BACKGROUND OF THE INVENTION <EOH>Modern, multiple story buildings may be formed with an external wall structure that is secured to a floor slab.\",\n \"The external wall structure, or curtain wall, is secured to the slab, which is made of concrete, and the curtain wall is at a distance spaced away from the slab.\",\n \"By creating a gap between the slab and the curtain wall, proper alignment of the curtain wall is ensured.\",\n \"For example, in the event that the slab for a particular floor is not entirely straight or the slabs of adjacent floors are not properly aligned, the size of the gap between the curtain wall and a slab may be adjusted at various points along the slab to align the curtain wall so that it is substantially straight along the entire length and/or height of the building.\",\n \"While the gap created between the curtain wall and the slabs of a building may be necessary to allow for proper alignment of the curtain wall, in the event of a fire, smoke, hot gasses, and/or flames, any of these conditions could pass from one floor to another through the gap between the curtain wall and the slabs.\",\n \"In order to prevent smoke, hot gasses, and/or fire from passing freely through this gap, safing insulation may be positioned between the slabs and spandrels of the curtain wall.\",\n \"Specifically, the spandrel areas of the curtain wall may be backed by a layer of spandrel insulation and the safing may be positioned between the spandrel insulation and the slabs in order to fill the gap between the spandrels and the slabs.\",\n \"While systems of installing the spandrel insulation are known, such systems are often labor intensive, requiring screws, other additional fasteners, and/or are dangerous, requiring sharp pins or impaling spikes.\",\n \"For example, U.S. Pat.\",\n \"No.\",\n \"7,886,491 to Shriver discloses an “Impasse” system used in today's curtain wall system using insulation hangers, which are steel base clips with a 12 GA steel pin swaged to the center.\",\n \"Such system requires screws to attach hangers and the insulation to be impaled onto the sharpened end, which is not always so easy to do in the field and may actually pose a safety risk to workers.\",\n \"Still, most other systems require multiple screws and attachment points to be anywhere from 8 to 12 inches O.C.\",\n \"As the cost for installing each screw may be as high as $1.00 for the extra time and material it takes, the cost for installing these systems may add up quickly.\",\n \"Further, sometimes mullions also serve to allow for drainage, so driving screws in can create points that could later leak.\",\n \"Other times, mullions may incorporate some steel into the aluminum for strength, and pilot holes need to be drilled in there.\",\n \"Thus, it is desirable to reduce or eliminate screws in the installation of curtain wall insulation system.\",\n \"This disclosure describes systems that address at least some of the technical issues discussed above, and/or other issues.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>In some embodiments, a curtain wall saddle bracket and clip assembly includes a bracket for securing insulation and/or a stiffener relative to a mullion or transom having a given width.\",\n \"The bracket includes a pair of legs extending from a bridge to define a receiving channel having a width equal to or smaller than the given width.\",\n \"At least one of the legs defines a first receiving slot configured to receive a clip leg of a respective clip configured to engage the insulation or configured to receive a face of the stiffener.\",\n \"In some embodiments, the first slot is configured to receive a clip leg of a respective clip configured to engage the insulation and is defined by a slot plate supported in spaced relation to a surface of the leg.\",\n \"In at least one embodiment, the leg also defines a second receiving slot configured to receive a face of the stiffener.\",\n \"In some embodiments, an insulation retaining system for a curtain wall includes a bracket and a clip.\",\n \"The bracket includes a pair of legs extending from a bridge to define a receiving channel having a width equal to or smaller than the given width.\",\n \"At least one of the legs defines a first receiving slot configured to receive a clip leg of a respective clip.\",\n \"The clip includes a pair of clip legs extending from a clip bridge with at least one of the clip legs including an inwardly extending projection configured to engage the slot plate once the clip leg has been extended through the first slot.\"\n ],\n [\n \"RELATED APPLICATION This patent document is a continuation-in-part of the U.S. patent application Ser.\",\n \"No.\",\n \"15/818,271 (the '271 Application) filed on Nov. 20, 2017.The '271 Application also claims priority to U.S.\",\n \"Provisional Patent Application No.\",\n \"62/424,772 (the '772 Application) filed Nov. 21, 2016.The disclosures of both '271 and '772 applications are incorporated herein by reference in full.\",\n \"FIELD OF THE INVENTION The present invention relates to a curtain wall insulation system, and in particular to a bracket and clip system for retaining wall insulation within the spandrel area of a curtain wall.\",\n \"BACKGROUND OF THE INVENTION Modern, multiple story buildings may be formed with an external wall structure that is secured to a floor slab.\",\n \"The external wall structure, or curtain wall, is secured to the slab, which is made of concrete, and the curtain wall is at a distance spaced away from the slab.\",\n \"By creating a gap between the slab and the curtain wall, proper alignment of the curtain wall is ensured.\",\n \"For example, in the event that the slab for a particular floor is not entirely straight or the slabs of adjacent floors are not properly aligned, the size of the gap between the curtain wall and a slab may be adjusted at various points along the slab to align the curtain wall so that it is substantially straight along the entire length and/or height of the building.\",\n \"While the gap created between the curtain wall and the slabs of a building may be necessary to allow for proper alignment of the curtain wall, in the event of a fire, smoke, hot gasses, and/or flames, any of these conditions could pass from one floor to another through the gap between the curtain wall and the slabs.\",\n \"In order to prevent smoke, hot gasses, and/or fire from passing freely through this gap, safing insulation may be positioned between the slabs and spandrels of the curtain wall.\",\n \"Specifically, the spandrel areas of the curtain wall may be backed by a layer of spandrel insulation and the safing may be positioned between the spandrel insulation and the slabs in order to fill the gap between the spandrels and the slabs.\",\n \"While systems of installing the spandrel insulation are known, such systems are often labor intensive, requiring screws, other additional fasteners, and/or are dangerous, requiring sharp pins or impaling spikes.\",\n \"For example, U.S. Pat.\",\n \"No.\",\n \"7,886,491 to Shriver discloses an “Impasse” system used in today's curtain wall system using insulation hangers, which are steel base clips with a 12 GA steel pin swaged to the center.\",\n \"Such system requires screws to attach hangers and the insulation to be impaled onto the sharpened end, which is not always so easy to do in the field and may actually pose a safety risk to workers.\",\n \"Still, most other systems require multiple screws and attachment points to be anywhere from 8 to 12 inches O.C.\",\n \"As the cost for installing each screw may be as high as $1.00 for the extra time and material it takes, the cost for installing these systems may add up quickly.\",\n \"Further, sometimes mullions also serve to allow for drainage, so driving screws in can create points that could later leak.\",\n \"Other times, mullions may incorporate some steel into the aluminum for strength, and pilot holes need to be drilled in there.\",\n \"Thus, it is desirable to reduce or eliminate screws in the installation of curtain wall insulation system.\",\n \"This disclosure describes systems that address at least some of the technical issues discussed above, and/or other issues.\",\n \"SUMMARY In some embodiments, a curtain wall saddle bracket and clip assembly includes a bracket for securing insulation and/or a stiffener relative to a mullion or transom having a given width.\",\n \"The bracket includes a pair of legs extending from a bridge to define a receiving channel having a width equal to or smaller than the given width.\",\n \"At least one of the legs defines a first receiving slot configured to receive a clip leg of a respective clip configured to engage the insulation or configured to receive a face of the stiffener.\",\n \"In some embodiments, the first slot is configured to receive a clip leg of a respective clip configured to engage the insulation and is defined by a slot plate supported in spaced relation to a surface of the leg.\",\n \"In at least one embodiment, the leg also defines a second receiving slot configured to receive a face of the stiffener.\",\n \"In some embodiments, an insulation retaining system for a curtain wall includes a bracket and a clip.\",\n \"The bracket includes a pair of legs extending from a bridge to define a receiving channel having a width equal to or smaller than the given width.\",\n \"At least one of the legs defines a first receiving slot configured to receive a clip leg of a respective clip.\",\n \"The clip includes a pair of clip legs extending from a clip bridge with at least one of the clip legs including an inwardly extending projection configured to engage the slot plate once the clip leg has been extended through the first slot.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate the presently preferred embodiments of the invention, and, together with the general description given above and the detailed description given below, serve to explain the features of various embodiments.\",\n \"In the drawings: FIG.\",\n \"1 is an isometric view of a wall system with mullions and transoms defining a spandrel area and brackets in accordance with some embodiments positioned on the mullions and transoms.\",\n \"The spandrel insulation is omitted from the figure for clarity.\",\n \"FIG.\",\n \"2 is an isometric view similar to FIG.\",\n \"1 with the spandrel insulation included.\",\n \"FIG.\",\n \"3 is an isometric view of an example of a bracket and clips, and a stiffener in some embodiments.\",\n \"FIG.\",\n \"4 is a cross-sectional view of the bracket along the lines 4-4 in FIG.\",\n \"3.FIG.\",\n \"5 is an isometric view of an example of a clip in some embodiments.\",\n \"FIG.\",\n \"6 is an isometric view of an example of a bracket in some embodiments.\",\n \"FIG.\",\n \"7 is an isometric view illustrating a pair of clips and a stiffener engaged with the bracket of FIG.\",\n \"3.FIGS.\",\n \"8-14 are isometric views illustrating installation of brackets and clips relative to spandrel insulation and positioning of stiffener in some embodiments.\",\n \"DETAILED DESCRIPTION OF THE INVENTION In the drawings, like numerals indicate like elements throughout.\",\n \"Certain terminology is used herein for convenience only and is not to be taken as a limitation on the present invention.\",\n \"The following describes preferred embodiments of the present invention.\",\n \"However, it should be understood, based on this disclosure, that the invention is not limited by the preferred embodiments described herein.\",\n \"Referring to FIGS.\",\n \"1 and 2, an exterior wall system is depicted generally at numeral 10.The wall system 10 is connected to a slab 12, which forms one of the floors of a multi-floor building.\",\n \"The wall system 10 includes spandrel areas 14 which are covered by spandrels (not shown) that, in one example, define the exterior facade of the building.\",\n \"In some scenarios, spandrel areas 14 extend between the sill of a first vision glass installation and the head of a second vision glass installation.\",\n \"Spandrel area 14 is defined between mullions 16, which provide the vertical framework for wall system 10, and transoms 18, which provide the horizontal framework for wall system 10.Additionally, vision glass 20 may be positioned between portions of mullions 16 and transoms 18.Referring to FIG.\",\n \"2, main spandrel insulation 22 is positioned with the spandrel area 14.Spandrel insulation 22 is preferably a fire-retardant insulation that provides a first layer of fire protection for exterior wall system 10.As discussed above, wall system 10 is positioned at a distance spaced from slab 12 and secured thereto.\",\n \"As a result, gap 13 (in FIG.\",\n \"1) is created between slab 12 and wall system 10.Thus, even though main spandrel insulation 22 is properly positioned, in the event of a fire, smoke, hot gasses, and/or flames any of these conditions may travel through gap 13 between slab 12 and wall system 10 and pass between adjacent floors of the building.\",\n \"In order to prevent and/or delay the passage of smoke, hot gasses, and/or fire between adjacent floors of a building, safing insulation is utilized.\",\n \"As shown in FIGS.\",\n \"1 and 2, safing insulation 24 is positioned between main spandrel insulation 22 and slab 12.Safing, as commonly used in construction industry, is made of noncombustible materials.\",\n \"It may be used as fire stop around the perimeter of a floor or around the protrusions or penetrations.\",\n \"In some embodiments, safing insulation 24 is mineral wool insulation.\",\n \"In order to increase the density of safing insulation 24 and, correspondingly, increase the ability of safing insulation 24 to delay and/or prevent the passage of smoke, hot gasses, and/or fire through gap 13 (in FIG.\",\n \"1), safing insulation 24 is compressed between slab 12 and main spandrel insulation 22.Due to the compression of safing insulation 24, safing insulation 24 exerts a force on both slab 12 and main spandrel insulation 22.As a result of the force applied by safing insulation 24 to main spandrel insulation 22, main spandrel insulation 22 may be deformed.\",\n \"In order to prevent main spandrel insulation 22 from deforming due to the forces exerted by compressed safing insulation 24, support structure, such as stiffeners 60 (in FIG.\",\n \"1) may be used.\",\n \"This support structure extends between opposing mullions 16 and provide a rigid area against which safing insulation 24 may press.\",\n \"For example, stiffeners 60 are sufficiently strong to resist deformation due to the forces exerted by compressed safing insulation 24.Thus, by utilizing support structure, such as stiffeners or other mechanical backer bars, such as metal angles or hat channel, deformation of main spandrel insulation 22 is substantially or entirely prevented.\",\n \"In FIG.\",\n \"3, in some embodiments, bracket 30 and clip 50 system configured to facilitate installation of the stiffeners 60 and the spandrel insulation are described.\",\n \"An example of a bracket 30 includes a bridge 32 extending between a pair of legs 34.Each leg 34 includes an outwardly extending flange 36 configured to engage and support the rear surface of the spandrel insulation 22, as will be described hereinafter.\",\n \"In FIG.\",\n \"4, legs 34 of bracket 30 are each about at a 90° angle with respect to bridge 32, although the angle can be more or less than 90°.\",\n \"An open channel 33 is defined between legs 34 having a width W which is approximately the same or slightly smaller than the width w of the mullions 16 or transoms 18 (see FIG.\",\n \"1).\",\n \"Bridge 32 has a width W′ that is not smaller than the width w of the mullions.\",\n \"With such configuration, bracket 30 is configured to receive either a mullion 16 or transom 18 into channel 33 with a friction fit.\",\n \"In this manner, bracket 30 may be installed onto mullion 16 or transom 18 by simple forcing thereon, for example, with a rubber mallet, and without the need for any fasteners or the like.\",\n \"Returning to FIG.\",\n \"3, alternatively, and/or additionally, bracket 30 may include one or more screw holes 31 on bridge 32 or on any of leg 34, the one or more screw holes 31 allow the bracket to be fixedly attached to the mullion or transom by screw.\",\n \"The screw may be used on either bridge 32 or leg 34 where permitted per the structure of the mullion or transom.\",\n \"In some embodiments, to assist in retaining spandrel insulation 22 (in FIG.\",\n \"2), each leg 34 includes a first receiving slot 39 defined between a slot plate 38 and leg 34.Slot plate 38 is supported by slot side walls 37 which extend between leg 34 and slot plate 38.Slot plate 38 and slot side walls 37 may be formed through a stamping process or otherwise formed.\",\n \"Each receiving slot 39 is configured to receive a clip leg 54 of a respective clip 50.Each clip 50 includes a clip bridge 52 extending between a pair of clip legs 54 such that clip 50 has a substantially U-shape.\",\n \"The free end 56 of each clip leg 54 has a tapered configuration.\",\n \"The tapered free end 56 facilitates passage into the receiving slot 39 or provides a sharpened tip for penetrating the spandrel insulation 22, as will be described hereinafter.\",\n \"In FIG.\",\n \"5, in some embodiments, at least one of the pair of clip legs 54 has a wing 53 that extends at a right angle from the surface of clip leg 54.Wing 53 has an outer edge 55 that is wedged from a portion distal from free end 56 towards free end 56 of the clip leg 54.When one of the pair of clip legs 54 is engaged into receiving slot 39 of the bracket 30 (FIG.\",\n \"3), wing 55 on the other leg is inserted into the spandrel insulation.\",\n \"This helps retain the spandrel insulation in the spandrel space and also prevent the spandrel insulation from moving longitudinally (or up and down) along the mullion.\",\n \"In some embodiments, each clip leg 54 defines an inwardly extending projection 58 extending from notch 57 defined in clip leg 54.As shown in FIGS.\",\n \"9 and 10, as clip leg 54 is passed through a respective bracket receiving slot 39, the inwardly extending projection 58 biases into notch 57 as it passes slot plate 38 and once fully inserted, returns to the natural inwardly extending position such that projection 58 engages slot plate 38 and maintains clip 50 engaged with bracket 30.FIG.\",\n \"6 illustrates an alternative bracket 30′, for which one of the legs 34′ may be free of the flange.\",\n \"For example, when bracket 30′ is to be used along transom 18 (FIG.\",\n \"1) or along a corner mullion 16 (FIG.\",\n \"1) which has a spandrel area on only one side of the mullion, the flange is not extending in front of vision glass 20 (FIG.\",\n \"1).\",\n \"Bracket 30′ illustrated in FIG.\",\n \"6 also illustrates other optional features including an inwardly extending projection 44 on each leg 34 to assist in securing the bracket.\",\n \"For example, extending projection 44 may be positioned to contact the mullion or transom and help to further retain the bracket in position.\",\n \"Bracket 30′ also may include reinforcing ribs 46.In other regards, bracket 30′ functions in the same manner as bracket 30 to be described hereinafter.\",\n \"Alternatively, and/or additionally, bracket 30 also may include the inwardly extending projections 44 on legs 34 and/or reinforcing ribs 46.Referring to FIGS.\",\n \"3 and 6, brackets 30, 30′ are also configured to support stiffeners 60 between two opposing mullions 16 (FIG.\",\n \"1).\",\n \"Each leg of bracket 30 may further include a second receiving slot 25 along the surface of flange 36.In some embodiments, receiving slot 25 may be formed by a cut plate 27 that is a portion of the flange 36 that is cut and raised from the surface of flange 36 to be at a distance therefrom, such that receiving slot 25 allows receiving a face plate of stiffener 60.Once the face plate of the stiffener is received by receiving slot 25, it is retained in place by cut plate 27.FIG.\",\n \"7 shows a stiffener that is received in the receiving slot behind cut plate 27.Returning to FIG.\",\n \"3, flange 36 may have an additional flange 47 extending from flange 36 at the bottom outwardly towards bridge 32 of the bracket.\",\n \"The additional flange 47 serves as a support for the stiffener.\",\n \"An embodiment of stiffener 60 as shown in FIG.\",\n \"3 is an L-shaped angle bar that has a vertical face plate 62 and a horizontal face plate 64.An end portion 63 of vertical face plate 62 of stiffener 60 may be received into receiving slot 25 of a first bracket 30 that is attached to a mullion, whereas horizontal face plate 64 is positioned to stay atop flange 47 of bracket 30.A second bracket (not shown) can be attached to an opposing mullion and can be used to receive an opposing end 65 of vertical side 62 of stiffener 60 and also support the stiffener.\",\n \"To install the angle bar as shown in FIG.\",\n \"3 between two opposing brackets, the stiffener may be installed from the bottom, in that vertical face plate 62 of the stiffener may first be slid upwardly at an angle from the bottom into receiving slots 25 of two opposing brackets, then tilted straight up while being slid into receiving slots 25 until horizontal face plate 64 of the stiffener passes above bottom flange 47 of the bracket.\",\n \"Then the stiffener may be dropped so that its horizontal face plate 64 rests on top of bottom flange 47, while vertical side 62 is maintained in position in receiving slots 25 of opposing two brackets.\",\n \"Bottom face plate 64 of the L-shaped angle bar provides support to the upper mineral wool panel that fills in the spandrel panel area.\",\n \"The stiffener also acts as a stiffener to reinforce the area at the edge of slab.\",\n \"Once installed, the stiffener maintains compression on the mineral wool safing insulation, but they also keep the over-compressed mineral wool safing sections from damaging the rigid curtain wall insulation.\",\n \"With reference to FIG.\",\n \"7, an alternative configuration of stiffener 60 is illustrated.\",\n \"In FIG.\",\n \"7, the stiffener is a hat channel that is rotated relative to its position in FIG.\",\n \"3 in that vertical face plate 62 becomes a front face and horizontal face plate 64 extends from vertical face plate 62 towards the rear face of the spandrel insulation away from bridge 32 of bracket 30.The L-shaped angle bar can be installed onto two opposing brackets 30 by directly sliding vertical face plate 62 into the receiving slots behind cut plates 27 of the two brackets from the top until horizontal face plate 64 rests on the top edge 48 of flange 36 (FIG.\",\n \"3).\",\n \"In such configuration, the curtain wall insulation can be placed inside the spandrel space, without split, past the stiffener and the floor slab.\",\n \"With reference to FIG.\",\n \"3, optionally, adjacent to the junction of each leg 34 and flange 36, corner tabs 40 are bent outwardly along line 41 such that a corner receiving slot 42 is defined between each corner tab 40 and flange 36.The corner receiving slot 42 has a width approximately equal to a thickness of vertical face plate 62 of stiffener 60.In the illustrated embodiment, stiffener 60 is a hat channel as shown in the configuration in FIG.\",\n \"7.Each end of vertical face plate 62 is received in corner receiving slots 42 of a pair of brackets 30 positioned on adjacent mullions 16 (see FIG.\",\n \"1) such that stiffener 60 is supported therebetween, with the respective flanges 36 extending behind vertical face plate 62 and preventing movement of stiffener 60 away from safing insulation 22 (FIG.\",\n \"2).\",\n \"Corner tab 40 serves two purposes.\",\n \"It helps to hold the L-shaped angle that will be used as a stiffener at the floor line.\",\n \"It also gives the bracket some rigidity and strength.\",\n \"Referring to FIGS.\",\n \"1, 2 and 8-10, an example of a process for installing the spandrel insulation is described.\",\n \"The process may include: attaching a plurality of spaced-apart brackets, each bracket having a first receiving slot; positioning the insulation in a space adjacent to the mullions and/or transoms; and engaging with each bracket a clip having a pair of clip legs with a first of the pair of clip legs extending through the first receiving slot of the bracket and a second of the pair of clip legs penetrating into the insulation, wherein the other clip leg has a tapered free end.\",\n \"The bracket can have various configurations.\",\n \"For example, using the bracket 30, 30′ (in FIGS.\",\n \"3 and 6), the process may include attaching a plurality of spaced-apart brackets 30, 30′ to mullions 16 and transoms 18 (FIG.\",\n \"1), either by friction fit or by screw or bolt or by other methods.\",\n \"In friction fit, each bracket 30, 30′ is positioned by aligning open channel 33 with mullion 16 or transom 18 and forcing bracket 30, 30′ as indicated by arrow A in FIG.\",\n \"8 into friction fit on mullion 16 or transom 18.With brackets 30, 30′ so positioned, the process may further position spandrel insulation 22 in spandrel space 14 with the rear surface thereof supported by flanges 36.Thereafter, the process may engage a clip 50 with each bracket 30, 30′, with one of clip legs 54 extending through a respective receiving slot 39 and the other clip leg 54 penetrating into spandrel insulation 22.As shown in FIG.\",\n \"3, bridge 32 of bracket 30 may have a mark 51 on the outside surface of the bridge to show the location of receiving slot 39, which is already covered by spandrel insulation 22.This allows easy installation of clip 50 after the leg of the bracket is covered by the spandrel insulation.\",\n \"Once each clip is engaged with the bracket, projection 58 of each clip leg 54 engages respective slot plate 38 such that clips 50, and thereby the spandrel insulation 22.is retained by brackets 30, 30′ and clips 50.Optionally, before positioning the insulation in the space adjacent to the mullion or transom, the process may include: attaching two opposing brackets onto two opposing mullions, respectively; and installing a stiffener onto the two opposing brackets by sliding a vertical face plate of the stiffener into a second receiving slot of each of the two opposing brackets.\",\n \"The second receiving slot for each bracket may be formed by a portion of the flange that is cut and raised from a surface of the flange of each respective opposing bracket.\",\n \"With reference to FIG.\",\n \"3, an example of the above process may include attaching two opposing brackets 30 on two opposing mullions proximate to the floor slab and installing stiffener 60 onto two opposing brackets 30.In some embodiments, the stiffener may be an L-shaped angle bar as shown in FIG.\",\n \"10, and the process may include sliding vertical face plate 62 of the angled bar at an angle upwardly into receiving slots 25 of each bracket 30 from the bottom, tilting vertical face plate 62 while being slid upwardly until horizontal face plate 64 of angled bar 60 passes above the bottom flange (47 in FIG.\",\n \"3), and dropping the stiffener to allow it to sit on top of bottom flange 47.Once stiffener 60 is installed, the process of positioning spandrel insulation 22 may include positioning a split panel of the spandrel insulation into the top of the bottom flange (47 in FIG.\",\n \"3).\",\n \"Alternatively, stiffener 60 is a hat channel, and the process may include sliding the vertical face plate of the hat channel to receiving slots 25 of each bracket 30 from the top until the horizontal face plate of the hat channel rests on the top edge 48 of flange 36 (FIG.\",\n \"3).\",\n \"In above various illustrated embodiments, bracket 30, 30′, clip 50, and stiffener 60 (FIG.\",\n \"3) can be made of steel or other metal.\",\n \"Bracket 30, 30′ also may be made of elastic materials to allow for friction fit on the mullion or transom.\",\n \"Other materials may be used as appreciated by one of ordinary skill in the art.\",\n \"With reference to FIG.\",\n \"11, the bracket may vary to accommodate different structures in the building in which the curtain wall insulation is installed.\",\n \"For example, a floor slab 12 may be attached to a mullion 16 by an anchor attachment 70, 72.This may interfere with the bracket (30 in FIG.\",\n \"1) near the floor line.\",\n \"In FIG.\",\n \"12, in some embodiments, a bracket 74 may include a side plate 76 defining at least one aperture 88 positioned to engage with a fastener for attaching the side plate 76 to a side surface of the mullion, which will be described in detail later in this document.\",\n \"Bracket 74 may also include a back plate 78 extending perpendicularly from the side plate 76 and defining a first receiving slot 86 formed by a portion 84 of the back plate 78 that is cut and raised from a surface of the back plate, wherein the first receiving slot 86 is configured to receive a face plate of a stiffener, which will be explained later.\",\n \"The back plate 78 may include a flange 94 extending outwardly from the bottom of the back plate 78 towards a front edge of the side plate 100.Back plate 78 may also have a top edge 102 near the first receiving slot 86.Aperture 88 in the side plate 76 may also include an opening through the front edge 100 of the side plate 76 to allow the side plate 76 to slide into an anchor attachment to the mullion so that the aperture in the side plate engages with a fastener of the anchor attachment.\",\n \"This is further explained with reference to FIG.\",\n \"13.In FIG.\",\n \"13, a part of an anchor attachment 70 is attached to a mullion 16, where part 70 is engaged with a second part 72 of the anchor attachment for attaching the slab to the mullion (see FIG.\",\n \"11).\",\n \"Part 70 of the anchor attachment is attached to the mullion via fasteners 96, such as bolts and screws.\",\n \"In attaching the bracket 74 to the mullion 16, a method may use existing fasteners 96 that fasten the anchor attachment 70 to the mullion 16 to fasten the bracket.\",\n \"In a non-limiting example, an installation method may include loosening the fasteners 96 and sliding the side plate 76 of the bracket 74 into the anchor attachment so that the apertures (88 in FIG.\",\n \"12) are engaged with the fasteners 96, such as bolts.\",\n \"This is further explained with reference to FIGS.\",\n \"12 and 13.The opening of the aperture 88 is positioned to be aligned with a bolt 96 of the anchor attachment 70 to allow the side plate 76 to slip right into the anchor attachment without having to remove the anchor attachment 70 from the mullion 16.While the bolt 96 is slipped into the respective aperture 88 of the side plate 76, the aperture 88 engages with the bolt 96.Then, the method may include tightening the fasteners 96 to secure both the anchor attachment 70 and the side plate 76 of the bracket 74 to the mullion 16.With further reference to FIG.\",\n \"13, similar to bracket 30 described earlier in this document (e.g., in FIG.\",\n \"10), a stiffener 60 may be an L-shaped bar, and the first receiving slot 84 of the back plate 78 may be positioned to receive a vertical face plate 62 of the stiffener 60.The flange of the back plate (94 in FIG.\",\n \"12) may be positioned to support a horizontal face plate 64 of the L-shaped bar 60.In some embodiments, with reference to FIGS.\",\n \"7 and 12, the stiffener 60 is a hat channel having a vertical face plate 62 positioned in the first receiving slot 84 of the back plate 78 of the bracket 74 and a horizontal face plate 64 extending inwardly from the vertical face plate further away from the front edge of the side plate of the bracket and positioned to rest on the top edge (102 in FIG.\",\n \"12) of the back plate 78.Returning to FIG.\",\n \"12, bracket 74 may additionally have a top plate 95 extending perpendicularly from the side plate 76 and defining a second receiving slot 90 that is configured to receive a clip leg of a respective clip to engage the insulation.\",\n \"The clip is described earlier in this document (e.g., clip 50 in FIG.\",\n \"3) and works the same way with the bracket 74 as it works with bracket 30.Referring to FIGS.\",\n \"1, 2 and 8-14, an example of a process for installing the spandrel insulation relative to a mullion and/or a transom may include: attaching two opposing brackets (e.g., 74 as described in FIG.\",\n \"12) onto two opposing mullions, respectively, by engaging each bracket into an anchor attachment for each respective mullion, wherein the anchor attachment attaches the mullion to a floor slab.\",\n \"The process may also include installing the stiffener onto the two opposing brackets by sliding a vertical face plate of the stiffener into the second receiving slot of each of the two opposing brackets, which was described in the embodiments in FIG.\",\n \"13.The process may also include positioning the insulation in a space defined between the two opposing mullions adjacent to the stiffener.\",\n \"With reference to FIG.\",\n \"14, the installation process may also include engaging the insulation by engaging each bracket with a clip having a pair of clip legs (e.g., a pair of clip legs described in the embodiments in FIG.\",\n \"3).\",\n \"In a non-limiting example, the installation process may include: extending inwardly from a front edge of the side plate towards the back plate the first clip leg of the pair 54 through a second receiving slot 86 of the bracket 74 formed on a top plate 95 that extends perpendicularly from the side plate.\",\n \"This is shown in the direction 98.The process may also include penetrating the second clip legs of the pair 54′ inwardly from a front side of the insulation towards the back plate of the bracket into the insulation (shown in direction 98).\",\n \"The above-illustrated embodiments provide advantages over the existing systems.\",\n \"For example, the brackets can be attached to the mullion or transom quickly by a friction fit or a single screw without laborious installation as in installation of curtain wall in a conventional manner.\",\n \"Further, once the insulation is installed, the clips that engage with the bracket can be quickly inserted into the first receiving slot of the bracket with accuracy because the location of the receiving slot on the leg of the bracket can be determined from the mark on outside surface of the bracket, which is exposed.\",\n \"This allows for easy alignment of the clip.\",\n \"Still further, the clip has both a tapered leg and a wing extending at a right angle from the tapered leg, so that when the clip is inserted into the spandrel insulation it allows the spandrel insulation to be retained inside the spandrel space without movement.\",\n \"Still further, the free end of the tapered leg of the clip is facing inward towards the spandrel insulation, thus, pushing the clips during installation creates no dangerous situation to the human installer as in other existing systems.\",\n \"Still further, the above-illustrated embodiments of the stiffener provide various ways to contend with floor slab attachment points for the curtain wall panels themselves that may be located at or near those points, which allows for proper installation.\",\n \"Still further, variations of the bracket are also shown above that may be attached to an anchor attachment that attaches the floor slab to the mullion so that the anchor attachment does not interfere with the bracket.\",\n \"These and other advantages of the present invention will be apparent to those skilled in the art from the foregoing specification.\",\n \"For example, an insulation retaining system may concurrently include one or more variations of the bracket illustrated above that attach to various locations of the mullion/transom.\",\n \"In such a system, one or more brackets (e.g., configurations shown in FIG.\",\n \"12) may be directly attached to the anchor attachment near the floor line, whereas one or more brackets (e.g., configurations shown in FIG.\",\n \"3) may be attached to the mullion via friction.\",\n \"Each of the various brackets may be positioned to receive a clip to engage the insulation.\",\n \"The features and functions described above, as well as alternatives, may be combined into many other different systems or applications as appreciated by one ordinarily skilled in the art.\",\n \"Accordingly, it will be recognized by those skilled in the art that changes or modifications may be made to the above-described embodiments without departing from the broad inventive concepts of the invention.\",\n \"It should, therefore, be understood that this invention is not limited to the particular embodiments described herein, but is intended to include all changes and modifications that are within the scope and spirit of the invention as defined in the claims.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874663"}}},{"rowIdx":4494663,"cells":{"text":{"kind":"list like","value":[["ARRANGEMENT WITH A MEMS DEVICE AND METHOD OF MANUFACTURING","An arrangement and a production method for the arrangement with at least one MEMS device, which comprises a package that closely encloses the MEMS device and seals it from ambient influences.","The package comprises as sealing a PFPE layer of a perfluoropolyether polymerized with the aid of functional groups."],["1.An apparatus, comprising: a substrate; a micro-electro-mechanical system (MEMS) device having device structures on a bottom surface of the MEMS device, wherein the MEMS device is on supporting structures such that the bottom surface of the MEMS device is facing a top surface of the substrate, and wherein the device structures are in a gap between the bottom surface of the MEMS device and the top surface of the substrate; and a perfluoropolyether (PFPE) layer on a top surface of the MEMS device.","2.The apparatus of claim 1, wherein the PFPE layer spans from the top surface of the substrate to the top surface of the MEMS device such that the MEMS device is encapsulated in the gap.","3.The apparatus of claim 1, wherein the supporting structures comprise solder balls used to electrically couple the MEMS device to the substrate.","4.The apparatus of claim 1, further comprising a covering layer over the PFPE layer.","5.The apparatus of claim 4, wherein the cover layer is disposed across an entirety of a top surface of the PFPE layer.","6.The apparatus of claim 1, wherein the MEMS device is a micro-structured electromechanical device with a movable part, a sensor or a device operating with acoustic waves.","7.The apparatus of claim 1, wherein the MEMS device is a radio-frequency (RF) device.","8.A method for manufacturing a micro-electro-mechanical system (MEMS) device, comprising: forming a substrate; arranging the MEMS device on supporting structures such that a bottom surface of the MEMS device is facing a top surface of the substrate, the MEMS device having device structures on the bottom surface of the MEMS device, and wherein the device structures are in a gap between the bottom surface of the MEMS device and the top surface of the substrate; and depositing a perfluoropolyether (PFPE) layer on a top surface of the MEMS device.","9.The method of claim 8, wherein the PFPE layer spans from the top surface of the substrate to the top surface of the MEMS device such that the MEMS device is encapsulated in the gap.","10.The method of claim 8, wherein the supporting structures comprise solder balls used to electrically couple the MEMS device to the substrate.","11.The method of claim 8, further comprising forming a covering layer over the PFPE layer.","12.The method of claim 11, wherein the cover layer is formed across an entirety of a top surface of the PFPE layer.","13.The method of claim 8, wherein the MEMS device is a micro-structured electromechanical device with a movable part, a sensor or a device operating with acoustic waves.","14.The method of claim 8, wherein the MEMS device is a radio-frequency (RF) device."],["<SOH> BACKGROUND <EOH>MEMS devices (MEMS=micro-electro-mechanical system) must be protected from mechanical and other environmental influences and for this purpose require a special form of packaging, in which the micromechanical structures are preferably arranged in a cavity, so that an undisturbed function of the structures that can move or vibrate during operation is possible.","As an additional requirement, an MEMS device may require a hermetically sealed package, which is sealed in particular from gases and moisture.","Various technologies for producing cavity packages are known, and have various advantages and disadvantages.","In what are known as CSP packages of the latest generation (CSP=chip sized package), the chip with the MEMS device structures is applied to a substrate in a flip-chip arrangement.","A frame surrounding the device structures of the MEMS chip serves as a spacing structure.","The flip-chip arrangement may subsequently be covered with a polymer, for example by means of lamination or encapsulation.","A better-sealed and easier-to-produce package is obtained if a cover wafer is placed onto a spacing structure enclosing the device structures of the MEMS chip, the device structures being enclosed in a cavity of the package created in this way.","Such cover wafers may consist of silicon, glass or piezoelectric materials and preferably coincide with the material of the MEMS chip.","The corresponding frame may consist of polymer, metal or metal alloys.","It is also possible to provide a cover wafer with an already pre-structured recess and to place this onto the MEMS chip as a covering in the form of a cap.","The bonding may take place with the aid of an adhesive or some other wafer bonding method.","However, the latter usually comprise a high-temperature step, which may lead to the MEMS device being damaged.","Other methods for producing a package comprise complex and elaborate steps that are difficult to implement in mass production or unnecessarily increase the effort required for the package, and consequently the costs."],["<SOH> SUMMARY <EOH>An object of the present disclosure is therefore to provide an arrangement with at least one MEMS device that can be produced in an easy and low-cost way, allowing the creation of a hermetic package for the MEMS device.","A further object is to provide a method of manufacturing thereof.","These and other objects are achieved according to the invention by an arrangement and method according to the independent claims as originally filed.","Advantageous refinements of the invention are provided by further claims.","It is proposed to use for the packaging of the arrangement at least one PFPE (perfluoropolyether) layer as a sealing or covering, which is obtained by polymerization of a perfluoropolyether having functional groups.","The MEMS device may in this case be arranged on a substrate and in the arrangement is protected from ambient influences by the package.","The PFPE layer serves in the package as a sealing layer.","In U.S. Patent Application Publication No.","2007/0254278 A1, PFPE has, because of its chemical inertness, already been proposed as a material for producing microstructured microfluidic devices, as they are known, which are used in the medical sector.","The PFPE layer comprises a polyether of perfluorinated branched or unbranched alkyl chains.","The polyether may comprise branched or unbranched chain links of varying lengths between the oxygen bridges of the polyether.","Similarly, the PFPE may have a structure branched by ether bridges.","A PFPE layer that is sealed from ambient influences and used in the invention is preferably completely polymerized and three-dimensionally crosslinked.","Such a crosslinked PFPE layer may be obtained from shorter-chain “monomers,” which are provided at the ends with polymerizable or crosslinkable functional groups.","Carbon-carbon bonds are preferably formed during the crosslinkage/polymerization, so that the functional groups of the monomers are correspondingly selected and for example comprise an olefinic double bond.","The monomers that can be used for producing a PFPE layer themselves represent perfluorinated polyethers, which are for example provided with methacrylate groups as functional crosslinkable groups.","Functionalization with crosslinkable styrene groups is also possible.","The perfluorinated alkyl radicals of the polyether give the polymerized material of the PFPE layer strongly hydrophobic properties and therefore make it possible to form a hermetically sealed layer.","Similar to TEFLON®, the PFPE material is also chemically inert and is therefore not attacked even under aggressive conditions.","It forms an intimate and close bond with frequently used substrate materials of MEMS devices and can therefore be used well as a sealing layer and as a bonding or adhesive layer.","A further advantage is that the monomers are liquid at room temperature and do not require any solvent for processing.","In the course of complete polymerization, the PFPE layer therefore does not lead to gas emissions, not even at elevated temperature.","The chemical stability is also combined with a thermal stability, so that no decomposition products or other gas emissions can escape from the PFPE layer, even at elevated temperature, and thereby destroy again the hermeticity of the package.","The PFPE layer may be applied by applying the liquid monomer to the surface to be sealed or covered, and subsequently polymerized by means of irradiation.","The irradiation/exposure may take place with a mask or in a structured form, so that the polymerization may result in a structured PFPE layer.","It is also possible, however, to apply the PFPE layer to an intermediate substrate and pre-polymerize it or transform it into a partially crosslinked state, possibly structured.","The pre-polymerized or partially crosslinked PFPE layer, which then has for example a gelatinous metastable consistency, may subsequently be transferred to the arrangement with the MEMS device.","There, the relatively soft partially crosslinked PFPE layer adapts itself to unevennesses on the underlying surface and can thus even out steps of up to several urn in height or closely envelop such steps.","The PFPE layer can therefore also be used for planarizing uneven surfaces and therefore takes the place of additional planarizing layers.","Before the final and complete curing of the PFPE layer by polymerization under irradiation, further PFPE layers may be applied over the first PFPE layer and then chemically crosslinked with this first layer during the curing.","In an embodiment, the PFPE layer is applied to the arrangement over a large surface area.","In this case, the PFPE layer covers at least the MEMS device or the device structures thereof.","Once the MEMS device has been mounted or arranged on a substrate, the PFPE layer can cover the MEMS device and at least parts of the entire substrate.","This has advantages whenever the MEMS device is mounted on the substrate as what is known as a bare die.","It is also possible in this way to cover further devices that are arranged on the substrate apart from the MEMS device.","In a further embodiment, the PFPE layer is structured.","It can in this form rest on the substrate and the MEMS device or only on the MEMS device or the substrate, covering only part of the arrangement.","In another embodiment, the PFPE layer is arranged in a structured form resting on the MEMS device or the substrate and represents a sealing intermediate layer for a covering.","Apart from the sealing function between the substrate or MEMS device and the covering, the intermediate layer may also perform a bonding and adhesive function, in particular if, in the production of the arrangement, application of the PFPE layer to a substrate is followed as a final step by complete crosslinking of the PFPE layer on the substrate.","In this case, a solid bond of the PFPE layer to frequently used substrate materials is created, in particular to ceramic, piezoelectric crystals and to metal and glass.","The covering, which lies on the PFPE layer as an intermediate layer, may therefore comprise a plate or a platelet of a ceramic or crystalline material.","For particularly sensitive MEMS devices, the properties of which may be impaired by mechanical stresses, particularly low-distortion packages are obtained if the substrate of the MEMS device comprises the same crystalline or ceramic material as the covering.","The PFPE layer may be formed particularly advantageously as an intermediate layer if it is structured in the form of a frame and at the same time forms a cavity-allowing spacing structure for the covering.","The PFPE layer structured in the form of a frame may enclose the device structures of the device on a surface of the MEMS device or may be arranged on the surface of the substrate and enclose at least the MEMS device as a whole.","The covering is then arranged in close contact on the PFPE layer structured in the form of a frame and is solidly bonded to it, so that a hermetically sealed cavity is formed between the covering, the PFPE layer and the surface of the MEMS device or of the substrate.","The PFPE layer may comprise at least a first and a second structured partial layer, which rest one on top of the other and are chemically bonded to one another.","The first and second PFPE partial layers may then form a three-dimensional structure.","In an embodiment, the PFPE layer forms a three-dimensional structure in the form of a cap, which has a recess which is open on one side and, when the cap is placed onto the substrate or the MEMS device, encloses a cavity for the MEMS device structures or for the MEMS device.","The cap then sits in a sealing manner on the MEMS device or the substrate and thus protects the MEMS device or the device structures thereof from ambient influences.","One partial layer may in this case be applied and structured before the next partial layer is created over it and structured.","In this way, a three-dimensional structure is successfully created from partial layers that are differently structured and arranged one on top of the other.","The three-dimensional structure of the PFPE layer may have on one side a multiplicity of recesses, which allow the formation of a corresponding number of cavities, in which an element to be encapsulated or hermetically sealed is then respectively arranged.","Each element may be an MEMS device or some other device or part thereof that is to be sealed.","The PFPE layer may also be applied over a large surface area as a sealing layer over an MEMS device mounted on the substrate by the flip-chip technique.","The MEMS device may be selected from micromechanical switches, variable capacitors, sensors, such as for example pressure sensors, or microphones or devices operating with acoustic waves such as SAW (=surface acoustic wave), BAW (=bulk acoustic wave) or GBAW (=guided acoustic wave) devices.","Other MEMS devices are also suitable.","Further devices that are sealed together with the MEMS device and a common covering may be provided on the substrate.","It is also possible, however, to seal only some of these devices with the PFPE layer or indeed only the MEMS device.","The additional devices may be semiconductor devices, MEMS devices or passive devices or modules that comprise integrated passive and active devices.","Integrated passive devices may for example take the form of multilayered structures in which structured metal layers are arranged alternately with dielectric and, in particular, ceramic layers.","Plated-through holes between the metallization levels create the electrical connections, so that a multiplicity of passive device structures may be integrated in such a device.","A further covering layer may be built up directly over a covering PFPE layer for sealing or shielding purposes.","Such further covering layers that can be applied by thin-film methods and have hermetic properties are preferred.","For example, metal layers or dielectric layers deposited from the vapour phase, such as for example oxide layers, nitride layers and the like, are therefore suitable as further covering layers.","It is also possible that the PFPE layer is arranged over a first covering layer formed from a different material.","The first covering layer may for example represent the uppermost layer of a thin-film package known per se for MEMS devices, also known as a zero level package.","In the case of such a package, a layer structure which comprises a cavity for the sensitive MEMS device structures is created with the aid of thin-film methods.","The cavity may be produced for example from a sacrificial layer, which is coated with the mentioned first covering layer.","The material of the sacrificial layer can be removed or etched out through preferably lateral etching openings or channels.","The etching openings and channels can subsequently be closed.","The PFPE layer may serve as a closing layer.","In an embodiment, the MEMS device is an RF device, for example an RF filter.","A possible way of producing the arrangement comprises at least the steps of applying the PFPE layer to the MEMS device or the substrate, the PFPE layer containing along with a perfluoropolyether provided with crosslinkable groups also a photoinitiator.","A further production step can comprise the crosslinking of the PFPE layer by means of irradiation, for example by means of UV light.","The crosslinking may be performed by polymerization of olefinic crosslinkable groups, for example of styrene or methacrylate groups.","The crosslinking make take place directly on the arrangement.","It is also possible, however, to divide the crosslinking into a number of partial steps, all of the partial steps apart from the last partial step leading to an incomplete crosslinkage of the PFPE layer.","The dividing into partial steps has the advantage that in this way a number of partial layers, which may be structured differently, can be applied one on top of the other and later bonded to one another.","In the last step of complete crosslinkage by means of a sufficient irradiating duration or intensity, the good bonding of the PFPE layer to all of the materials that are in close contact with the PFPE layer in the arrangement is also established.","Aspects of the present disclosure are explained in more detail below on the basis of exemplary embodiments and the associated figures.","The figures are only depicted schematically and not true to scale, so that neither absolute nor relative dimensions can be taken from the figures."],["CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of U.S. application Ser.","No.","13/472,980, filed May 16, 2012, entitled “Arrangement with a MEMS Device and method of Manufacturing”, which claims benefit under 35 U.S.C.","§ 119 of Germany Patent Application Serial No.","10 2011 102 266.3, filed in Germany on May 23, 2011, entitled “Arrangement with an MEMS Device and Method of Manufacturing.” COPYRIGHT A portion of the disclosure of this patent document contains material which is subject to copyright protection.","The copyright owner has no objection to the facsimile reproduction by anyone of the patent disclosure, as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyright rights whatsoever.","FIELD OF THE DISCLOSURE Aspects of the present disclosure relate to an arrangement with an MEMS device and methods of manufacturing the same.","BACKGROUND MEMS devices (MEMS=micro-electro-mechanical system) must be protected from mechanical and other environmental influences and for this purpose require a special form of packaging, in which the micromechanical structures are preferably arranged in a cavity, so that an undisturbed function of the structures that can move or vibrate during operation is possible.","As an additional requirement, an MEMS device may require a hermetically sealed package, which is sealed in particular from gases and moisture.","Various technologies for producing cavity packages are known, and have various advantages and disadvantages.","In what are known as CSP packages of the latest generation (CSP=chip sized package), the chip with the MEMS device structures is applied to a substrate in a flip-chip arrangement.","A frame surrounding the device structures of the MEMS chip serves as a spacing structure.","The flip-chip arrangement may subsequently be covered with a polymer, for example by means of lamination or encapsulation.","A better-sealed and easier-to-produce package is obtained if a cover wafer is placed onto a spacing structure enclosing the device structures of the MEMS chip, the device structures being enclosed in a cavity of the package created in this way.","Such cover wafers may consist of silicon, glass or piezoelectric materials and preferably coincide with the material of the MEMS chip.","The corresponding frame may consist of polymer, metal or metal alloys.","It is also possible to provide a cover wafer with an already pre-structured recess and to place this onto the MEMS chip as a covering in the form of a cap.","The bonding may take place with the aid of an adhesive or some other wafer bonding method.","However, the latter usually comprise a high-temperature step, which may lead to the MEMS device being damaged.","Other methods for producing a package comprise complex and elaborate steps that are difficult to implement in mass production or unnecessarily increase the effort required for the package, and consequently the costs.","SUMMARY An object of the present disclosure is therefore to provide an arrangement with at least one MEMS device that can be produced in an easy and low-cost way, allowing the creation of a hermetic package for the MEMS device.","A further object is to provide a method of manufacturing thereof.","These and other objects are achieved according to the invention by an arrangement and method according to the independent claims as originally filed.","Advantageous refinements of the invention are provided by further claims.","It is proposed to use for the packaging of the arrangement at least one PFPE (perfluoropolyether) layer as a sealing or covering, which is obtained by polymerization of a perfluoropolyether having functional groups.","The MEMS device may in this case be arranged on a substrate and in the arrangement is protected from ambient influences by the package.","The PFPE layer serves in the package as a sealing layer.","In U.S. Patent Application Publication No.","2007/0254278 A1, PFPE has, because of its chemical inertness, already been proposed as a material for producing microstructured microfluidic devices, as they are known, which are used in the medical sector.","The PFPE layer comprises a polyether of perfluorinated branched or unbranched alkyl chains.","The polyether may comprise branched or unbranched chain links of varying lengths between the oxygen bridges of the polyether.","Similarly, the PFPE may have a structure branched by ether bridges.","A PFPE layer that is sealed from ambient influences and used in the invention is preferably completely polymerized and three-dimensionally crosslinked.","Such a crosslinked PFPE layer may be obtained from shorter-chain “monomers,” which are provided at the ends with polymerizable or crosslinkable functional groups.","Carbon-carbon bonds are preferably formed during the crosslinkage/polymerization, so that the functional groups of the monomers are correspondingly selected and for example comprise an olefinic double bond.","The monomers that can be used for producing a PFPE layer themselves represent perfluorinated polyethers, which are for example provided with methacrylate groups as functional crosslinkable groups.","Functionalization with crosslinkable styrene groups is also possible.","The perfluorinated alkyl radicals of the polyether give the polymerized material of the PFPE layer strongly hydrophobic properties and therefore make it possible to form a hermetically sealed layer.","Similar to TEFLON®, the PFPE material is also chemically inert and is therefore not attacked even under aggressive conditions.","It forms an intimate and close bond with frequently used substrate materials of MEMS devices and can therefore be used well as a sealing layer and as a bonding or adhesive layer.","A further advantage is that the monomers are liquid at room temperature and do not require any solvent for processing.","In the course of complete polymerization, the PFPE layer therefore does not lead to gas emissions, not even at elevated temperature.","The chemical stability is also combined with a thermal stability, so that no decomposition products or other gas emissions can escape from the PFPE layer, even at elevated temperature, and thereby destroy again the hermeticity of the package.","The PFPE layer may be applied by applying the liquid monomer to the surface to be sealed or covered, and subsequently polymerized by means of irradiation.","The irradiation/exposure may take place with a mask or in a structured form, so that the polymerization may result in a structured PFPE layer.","It is also possible, however, to apply the PFPE layer to an intermediate substrate and pre-polymerize it or transform it into a partially crosslinked state, possibly structured.","The pre-polymerized or partially crosslinked PFPE layer, which then has for example a gelatinous metastable consistency, may subsequently be transferred to the arrangement with the MEMS device.","There, the relatively soft partially crosslinked PFPE layer adapts itself to unevennesses on the underlying surface and can thus even out steps of up to several urn in height or closely envelop such steps.","The PFPE layer can therefore also be used for planarizing uneven surfaces and therefore takes the place of additional planarizing layers.","Before the final and complete curing of the PFPE layer by polymerization under irradiation, further PFPE layers may be applied over the first PFPE layer and then chemically crosslinked with this first layer during the curing.","In an embodiment, the PFPE layer is applied to the arrangement over a large surface area.","In this case, the PFPE layer covers at least the MEMS device or the device structures thereof.","Once the MEMS device has been mounted or arranged on a substrate, the PFPE layer can cover the MEMS device and at least parts of the entire substrate.","This has advantages whenever the MEMS device is mounted on the substrate as what is known as a bare die.","It is also possible in this way to cover further devices that are arranged on the substrate apart from the MEMS device.","In a further embodiment, the PFPE layer is structured.","It can in this form rest on the substrate and the MEMS device or only on the MEMS device or the substrate, covering only part of the arrangement.","In another embodiment, the PFPE layer is arranged in a structured form resting on the MEMS device or the substrate and represents a sealing intermediate layer for a covering.","Apart from the sealing function between the substrate or MEMS device and the covering, the intermediate layer may also perform a bonding and adhesive function, in particular if, in the production of the arrangement, application of the PFPE layer to a substrate is followed as a final step by complete crosslinking of the PFPE layer on the substrate.","In this case, a solid bond of the PFPE layer to frequently used substrate materials is created, in particular to ceramic, piezoelectric crystals and to metal and glass.","The covering, which lies on the PFPE layer as an intermediate layer, may therefore comprise a plate or a platelet of a ceramic or crystalline material.","For particularly sensitive MEMS devices, the properties of which may be impaired by mechanical stresses, particularly low-distortion packages are obtained if the substrate of the MEMS device comprises the same crystalline or ceramic material as the covering.","The PFPE layer may be formed particularly advantageously as an intermediate layer if it is structured in the form of a frame and at the same time forms a cavity-allowing spacing structure for the covering.","The PFPE layer structured in the form of a frame may enclose the device structures of the device on a surface of the MEMS device or may be arranged on the surface of the substrate and enclose at least the MEMS device as a whole.","The covering is then arranged in close contact on the PFPE layer structured in the form of a frame and is solidly bonded to it, so that a hermetically sealed cavity is formed between the covering, the PFPE layer and the surface of the MEMS device or of the substrate.","The PFPE layer may comprise at least a first and a second structured partial layer, which rest one on top of the other and are chemically bonded to one another.","The first and second PFPE partial layers may then form a three-dimensional structure.","In an embodiment, the PFPE layer forms a three-dimensional structure in the form of a cap, which has a recess which is open on one side and, when the cap is placed onto the substrate or the MEMS device, encloses a cavity for the MEMS device structures or for the MEMS device.","The cap then sits in a sealing manner on the MEMS device or the substrate and thus protects the MEMS device or the device structures thereof from ambient influences.","One partial layer may in this case be applied and structured before the next partial layer is created over it and structured.","In this way, a three-dimensional structure is successfully created from partial layers that are differently structured and arranged one on top of the other.","The three-dimensional structure of the PFPE layer may have on one side a multiplicity of recesses, which allow the formation of a corresponding number of cavities, in which an element to be encapsulated or hermetically sealed is then respectively arranged.","Each element may be an MEMS device or some other device or part thereof that is to be sealed.","The PFPE layer may also be applied over a large surface area as a sealing layer over an MEMS device mounted on the substrate by the flip-chip technique.","The MEMS device may be selected from micromechanical switches, variable capacitors, sensors, such as for example pressure sensors, or microphones or devices operating with acoustic waves such as SAW (=surface acoustic wave), BAW (=bulk acoustic wave) or GBAW (=guided acoustic wave) devices.","Other MEMS devices are also suitable.","Further devices that are sealed together with the MEMS device and a common covering may be provided on the substrate.","It is also possible, however, to seal only some of these devices with the PFPE layer or indeed only the MEMS device.","The additional devices may be semiconductor devices, MEMS devices or passive devices or modules that comprise integrated passive and active devices.","Integrated passive devices may for example take the form of multilayered structures in which structured metal layers are arranged alternately with dielectric and, in particular, ceramic layers.","Plated-through holes between the metallization levels create the electrical connections, so that a multiplicity of passive device structures may be integrated in such a device.","A further covering layer may be built up directly over a covering PFPE layer for sealing or shielding purposes.","Such further covering layers that can be applied by thin-film methods and have hermetic properties are preferred.","For example, metal layers or dielectric layers deposited from the vapour phase, such as for example oxide layers, nitride layers and the like, are therefore suitable as further covering layers.","It is also possible that the PFPE layer is arranged over a first covering layer formed from a different material.","The first covering layer may for example represent the uppermost layer of a thin-film package known per se for MEMS devices, also known as a zero level package.","In the case of such a package, a layer structure which comprises a cavity for the sensitive MEMS device structures is created with the aid of thin-film methods.","The cavity may be produced for example from a sacrificial layer, which is coated with the mentioned first covering layer.","The material of the sacrificial layer can be removed or etched out through preferably lateral etching openings or channels.","The etching openings and channels can subsequently be closed.","The PFPE layer may serve as a closing layer.","In an embodiment, the MEMS device is an RF device, for example an RF filter.","A possible way of producing the arrangement comprises at least the steps of applying the PFPE layer to the MEMS device or the substrate, the PFPE layer containing along with a perfluoropolyether provided with crosslinkable groups also a photoinitiator.","A further production step can comprise the crosslinking of the PFPE layer by means of irradiation, for example by means of UV light.","The crosslinking may be performed by polymerization of olefinic crosslinkable groups, for example of styrene or methacrylate groups.","The crosslinking make take place directly on the arrangement.","It is also possible, however, to divide the crosslinking into a number of partial steps, all of the partial steps apart from the last partial step leading to an incomplete crosslinkage of the PFPE layer.","The dividing into partial steps has the advantage that in this way a number of partial layers, which may be structured differently, can be applied one on top of the other and later bonded to one another.","In the last step of complete crosslinkage by means of a sufficient irradiating duration or intensity, the good bonding of the PFPE layer to all of the materials that are in close contact with the PFPE layer in the arrangement is also established.","Aspects of the present disclosure are explained in more detail below on the basis of exemplary embodiments and the associated figures.","The figures are only depicted schematically and not true to scale, so that neither absolute nor relative dimensions can be taken from the figures.","BRIEF DESCRIPTION OF THE DRAWINGS FIGS.","1A to 1D show various arrangements with an MEMS device on a substrate and a PFPE layer, FIGS.","2A to 2C show various arrangements of an MEMS device in which the covering sits directly on the MEMS device, FIGS.","3A to 3E show various embodiments of an arrangement with a number of devices on a substrate and a covering comprising a PFPE layer, and FIGS.","4A to 4C show an arrangement according to an aspect incorporating an SAW device.","DETAILED DESCRIPTION FIG.","1A shows an embodiment of the arrangement according to an aspect of the present disclosure, in which an MEMS device MB is mounted in flip-chip arrangement on a substrate TR.","The electrical and mechanical attachment takes place by way of bumps, for example solder or stud bumps.","The bumps also act in this case as spacers, so that a gap remains between the substrate TR and the MEMS device MB, and the downwardly facing movable or vibrating device structures of the MEMS device can operate mechanically unimpeded.","For sealing the MEMS device MB from ambient influences, arranged on the upper side of the MEMS device MB is a PFPE layer PS formed as a covering layer AS.","This overlaps the edges of the MEMS device MB and finishes with the substrate TR.","The PFPE layer PS enters into an intimate, close and solid bond with conventional substrate materials, for example with ceramic, glass or metal, so that, with such a covering layer AS, a hermetically sealed cavity package having a cavity HR is created for the MEMS device.","At the same time, the gap is sealed off laterally, so that a sealed cavity HR is formed under the PFPE layer PS between the substrate TR and the MEMS device MB.","FIG.","1B shows a further arrangement, in which the MEMS device MB is again mounted on a substrate.","The MEMS device is covered by a covering cap AK and thereby forms a cavity HR, in which the MEMS device MB is arranged.","For secure sealing of the cavity HR, a structured intermediate layer ZS, which comprises a PFPE layer PS or consists of a PFPE layer PS, is arranged between the covering cap AK and the substrate TR.","The covering cap AK may be composed of materials that are mechanically adequately strong and can be structured.","The covering cap AK is preferably structured from a covering wafer, for example from a glass or ceramic plate of a semiconductor crystal or any other material that can be structured as a solid body.","This has the advantage that in this way a multiplicity of covering caps can be structured from the covering wafer, for example by forming corresponding recesses in the underside of the covering wafer, which are then placed on a panel with a multiplicity of MEMS devices and are only separated into individual devices after complete processing.","The PFPE layer PS, formed as an intermediate layer ZS, may be structured on the substrate TR or on the underside of the covering cap AK or be applied as an already structured layer to the substrate TR or the covering wafer.","FIG.","1C shows a further embodiment of an arrangement, in which the MEMS device MB is mounted on a substrate TR.","A structured PFPE layer PS forms an intermediate layer ZS, which surrounds the MEMS device on the substrate TR and at the same time forms a spacing element, on which a covering formed as a covering wafer AW rests.","This embodiment has the advantage that the covering wafer does not have to be structured and can be placed on as a level and thin wafer.","Only the intermediate layer ZS is structured, which once again can take place directly on the substrate TR, directly on the covering wafer AW or separately from the two parts by separate partial crosslinking of a PFPE layer and the subsequent arrangement thereof between the substrate and the covering wafer AW.","Here, too, an adequate cavity HR is ensured if the height of the intermediate layer ZS is greater than the height of the MEMS device above the surface of the substrate TR.","FIG.","1D shows an MEMS device MB on a substrate that is covered by a PFPE layer PS formed as a covering cap AK.","Such a covering cap AK may be formed by a number of partial layers of a PFPE layer, which are individually structured and in a final crosslinkage are bonded to one another to form a three-dimensional structure, indeed to form the covering cap.","In the embodiments that are shown in FIGS.","1B to 1D, it may remain open how exactly the MEMS device is mounted on the substrate TR.","It may be adhesively attached, soldered on or bonded to the substrate in the flip-chip manner of construction.","In the first two variants, the electrical connection to the substrate TR may take place by means of bonding wires.","Mounting by the SMD technique is also possible.","FIGS.","2A to 2C show various embodiments of arrangements according to aspects of the present disclosure, in which the sealing of the device structures takes place directly on the MEMS device MB and can therefore take place already at MEMS wafer level, that is to say before the individual separation of the MEMS devices.","In the figures, the MEMS devices MB are arranged on a substrate TR, but they may also represent complete arrangements according to the invention without a substrate.","FIG.","2A, a covering cap AK, which comprises a PFPE layer PS, is arranged on the MEMS device MB.","The covering cap AK encloses underneath it a cavity HR, in which the device structures BES are arranged and thus can operate undisturbed.","The covering cap AK may be formed completely by the PFPE layer PS, or comprise such a layer as a partial layer.","In particular, under the PFPE layer PS there may be arranged a further layer of a different material.","It is possible for example that the PFPE layer represents the uppermost sealing layer of a thin-film package, which is also known as a zero level package.","Various methods are already known for such packages that are produced in an integrated form and leave a cavity HR for the MEMS device structures.","In the case of wafer level packaging, a multiplicity of MEMS devices or MEMS device structures pre-structured on the MEMS wafer may be encapsulated together with a covering cap AK or with a PFPE layer PS provided with recesses.","After the individual separation of the MEMS devices, each MEMS device has a covering cap AK of its own.","FIG.","2B shows a covering of the device structures BES by means of a PFPE layer sitting directly on the MEMS device MB and structured to form an intermediate layer ZS, which forms a frame around the device structures BES and on which a covering formed as a covering wafer AW rests.","Here, too, the intermediate layer ZS acts as a spacer, so that a cavity HR for the device structures BES is formed between the MEMS device MB and the covering wafer AW.","FIG.","2C shows an arrangement with an MEMS device MB, in which the device structures BES are covered by a structured covering cap AK, which is for example formed from a rigid, preferably ceramic or crystalline material.","A PFPE layer PS structured to form an intermediate layer ZS is arranged between the covering cap AK and the surface of the MEMS device MB and provides a sealed closure of the cavity HR under the cap.","FIGS.","3A to 3E show embodiments of the arrangement in which an MEMS device and at least one further device WB are arranged on a substrate TR.","According to FIG.","3A, the two devices are covered by a common covering layer AS, which comprises a PFPE layer as a single layer or as a partial layer of a laminar structure.","The covering layer AS finishes in close contact with the substrate TR all around the devices and thus provides a sealed encapsulation of the devices on the substrate.","In the embodiment that is shown in FIG.","3B, only the MEMS device MB is covered by the covering layer AS.","FIG.","3C shows an arrangement in which the MEMS device MB and a further device WB are integrated in a package, which consists of an intermediate layer ZS and a covering, in particular a covering wafer AW.","The intermediate layer ZS is structured from a PFPE layer PS, sits on the substrate TR and surrounds the devices in the form of a frame.","At the same time, the intermediate layer ZS serves as a spacer and as a support for the preferably rigid covering AW, so that each frame formed in the intermediate layer encloses together with the covering a cavity HR for the respective device.","FIG.","3D shows an arrangement in which a structured PFPE layer PS is arranged as a sealing intermediate layer ZS between a covering, for example a structured covering wafer AW, and the substrate.","Respectively enclosed under the covering AW is a cavity HR for the respective device MB, WB, which is substantially formed by a recess in the covering.","FIG.","3E shows an arrangement in which the structured covering AW with the recesses is formed completely by a PFPE layer, which sits directly on the substrate.","It is possible here to dispense with the intermediate layer.","The covering AW may be built up from a number of structured partial layers.","FIG.","4A shows an arrangement in which the structure and possible functions of the substrate TR are presented in more detail.","The substrate TR is built up in a multilayered form from dielectric layers, between which structured metallization levels are arranged.","Different metallization levels are connected to one another by way of plated-through holes.","Provided on the upper side of the substrate TR are connection metallizations for the MEMS device MB and any other further devices there may be.","Arranged on the underside of the substrate TR are the external contacts KA, with the aid of which the arrangement can be connected to surrounding circuitry, for example by soldering.","The MEMS device MB is mechanically and electrically connected to the electrical terminal areas of the substrate TR by way of bumps.","The device structures BES face downwards and are arranged between the surface of the substrate TR and the MEMS device MB in a clear gap that remains there.","Laterally, the gap between the MEMS device and the substrate TR is sealed by means of a covering layer AS, which sits over a large surface area on the upper side of the MEMS device and of the substrate and is formed by a PFPE layer PS.","The covering layer AS may be applied with an approximately uniform layer thickness and conformal surface.","The covering layer AS may, however, also be applied with a greater layer thickness, for example in a layer thickness reaching up to the upper edge of the MEMS device, so that the MEMS device is virtually buried under the covering layer AS.","The MEMS device is represented here as an SAW device, which comprises a piezoelectric substrate and metallic device structures and terminal pads on the underside of the substrate.","The MEMS device may, however, also be a BAW device, in which a layer structure with BAW resonators is formed on the surface of a substrate, for example comprising crystalline silicon.","The MEMS device may also be a GBAW device, in which SAW-like device structures are covered by additional layers.","FIG.","4B shows a further refinement in which a relatively thin covering layer AS, formed by a PFPE layer PS, is provided with a further covering layer WA, which has been applied here for example as an encapsulating compound, which completely covers the MEMS device and has a planarized surface.","Such a further covering WA may be applied for example as an encapsulating compound and for example by injection molding.","FIG.","4C shows a further refinement of an arrangement with a further covering WA applied over the covering layer AS, in the form of a thin layer applied with a conformal surface.","Such a thin layer is preferably applied by means of thin-film methods from the vapour phase, for example by means of CVD methods, plasma depositing methods or sputtering.","It may for example comprise SiO2 or some other dielectric material.","It is also possible to apply the further covering layer WA as a metal layer and to deposit it for this purpose from a solution.","It is also possible to apply a base metallization from the vapour phase and galvanically or electrolessly reinforce it in a solution.","A metallic further covering layer WA may be used for electromagnetic shielding.","A metal layer can also increase the stability of the package as a whole, and consequently of the arrangement.","The present disclosure is not restricted to the exemplary embodiments that are represented in the figures and described.","However, all of these embodiments have in common that the hermetic sealing of the arrangement is performed by the package for the MEMS device by means of a PFPE layer.","The PFPE layer may provide the only sealing and covering or, as described, may be formed as an intermediate or bonding layer.","An arrangement disclosed herein may also comprise sub-combinations of the exemplary embodiments described or represented."]],"string":"[\n [\n \"ARRANGEMENT WITH A MEMS DEVICE AND METHOD OF MANUFACTURING\",\n \"An arrangement and a production method for the arrangement with at least one MEMS device, which comprises a package that closely encloses the MEMS device and seals it from ambient influences.\",\n \"The package comprises as sealing a PFPE layer of a perfluoropolyether polymerized with the aid of functional groups.\"\n ],\n [\n \"1.An apparatus, comprising: a substrate; a micro-electro-mechanical system (MEMS) device having device structures on a bottom surface of the MEMS device, wherein the MEMS device is on supporting structures such that the bottom surface of the MEMS device is facing a top surface of the substrate, and wherein the device structures are in a gap between the bottom surface of the MEMS device and the top surface of the substrate; and a perfluoropolyether (PFPE) layer on a top surface of the MEMS device.\",\n \"2.The apparatus of claim 1, wherein the PFPE layer spans from the top surface of the substrate to the top surface of the MEMS device such that the MEMS device is encapsulated in the gap.\",\n \"3.The apparatus of claim 1, wherein the supporting structures comprise solder balls used to electrically couple the MEMS device to the substrate.\",\n \"4.The apparatus of claim 1, further comprising a covering layer over the PFPE layer.\",\n \"5.The apparatus of claim 4, wherein the cover layer is disposed across an entirety of a top surface of the PFPE layer.\",\n \"6.The apparatus of claim 1, wherein the MEMS device is a micro-structured electromechanical device with a movable part, a sensor or a device operating with acoustic waves.\",\n \"7.The apparatus of claim 1, wherein the MEMS device is a radio-frequency (RF) device.\",\n \"8.A method for manufacturing a micro-electro-mechanical system (MEMS) device, comprising: forming a substrate; arranging the MEMS device on supporting structures such that a bottom surface of the MEMS device is facing a top surface of the substrate, the MEMS device having device structures on the bottom surface of the MEMS device, and wherein the device structures are in a gap between the bottom surface of the MEMS device and the top surface of the substrate; and depositing a perfluoropolyether (PFPE) layer on a top surface of the MEMS device.\",\n \"9.The method of claim 8, wherein the PFPE layer spans from the top surface of the substrate to the top surface of the MEMS device such that the MEMS device is encapsulated in the gap.\",\n \"10.The method of claim 8, wherein the supporting structures comprise solder balls used to electrically couple the MEMS device to the substrate.\",\n \"11.The method of claim 8, further comprising forming a covering layer over the PFPE layer.\",\n \"12.The method of claim 11, wherein the cover layer is formed across an entirety of a top surface of the PFPE layer.\",\n \"13.The method of claim 8, wherein the MEMS device is a micro-structured electromechanical device with a movable part, a sensor or a device operating with acoustic waves.\",\n \"14.The method of claim 8, wherein the MEMS device is a radio-frequency (RF) device.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>MEMS devices (MEMS=micro-electro-mechanical system) must be protected from mechanical and other environmental influences and for this purpose require a special form of packaging, in which the micromechanical structures are preferably arranged in a cavity, so that an undisturbed function of the structures that can move or vibrate during operation is possible.\",\n \"As an additional requirement, an MEMS device may require a hermetically sealed package, which is sealed in particular from gases and moisture.\",\n \"Various technologies for producing cavity packages are known, and have various advantages and disadvantages.\",\n \"In what are known as CSP packages of the latest generation (CSP=chip sized package), the chip with the MEMS device structures is applied to a substrate in a flip-chip arrangement.\",\n \"A frame surrounding the device structures of the MEMS chip serves as a spacing structure.\",\n \"The flip-chip arrangement may subsequently be covered with a polymer, for example by means of lamination or encapsulation.\",\n \"A better-sealed and easier-to-produce package is obtained if a cover wafer is placed onto a spacing structure enclosing the device structures of the MEMS chip, the device structures being enclosed in a cavity of the package created in this way.\",\n \"Such cover wafers may consist of silicon, glass or piezoelectric materials and preferably coincide with the material of the MEMS chip.\",\n \"The corresponding frame may consist of polymer, metal or metal alloys.\",\n \"It is also possible to provide a cover wafer with an already pre-structured recess and to place this onto the MEMS chip as a covering in the form of a cap.\",\n \"The bonding may take place with the aid of an adhesive or some other wafer bonding method.\",\n \"However, the latter usually comprise a high-temperature step, which may lead to the MEMS device being damaged.\",\n \"Other methods for producing a package comprise complex and elaborate steps that are difficult to implement in mass production or unnecessarily increase the effort required for the package, and consequently the costs.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>An object of the present disclosure is therefore to provide an arrangement with at least one MEMS device that can be produced in an easy and low-cost way, allowing the creation of a hermetic package for the MEMS device.\",\n \"A further object is to provide a method of manufacturing thereof.\",\n \"These and other objects are achieved according to the invention by an arrangement and method according to the independent claims as originally filed.\",\n \"Advantageous refinements of the invention are provided by further claims.\",\n \"It is proposed to use for the packaging of the arrangement at least one PFPE (perfluoropolyether) layer as a sealing or covering, which is obtained by polymerization of a perfluoropolyether having functional groups.\",\n \"The MEMS device may in this case be arranged on a substrate and in the arrangement is protected from ambient influences by the package.\",\n \"The PFPE layer serves in the package as a sealing layer.\",\n \"In U.S. Patent Application Publication No.\",\n \"2007/0254278 A1, PFPE has, because of its chemical inertness, already been proposed as a material for producing microstructured microfluidic devices, as they are known, which are used in the medical sector.\",\n \"The PFPE layer comprises a polyether of perfluorinated branched or unbranched alkyl chains.\",\n \"The polyether may comprise branched or unbranched chain links of varying lengths between the oxygen bridges of the polyether.\",\n \"Similarly, the PFPE may have a structure branched by ether bridges.\",\n \"A PFPE layer that is sealed from ambient influences and used in the invention is preferably completely polymerized and three-dimensionally crosslinked.\",\n \"Such a crosslinked PFPE layer may be obtained from shorter-chain “monomers,” which are provided at the ends with polymerizable or crosslinkable functional groups.\",\n \"Carbon-carbon bonds are preferably formed during the crosslinkage/polymerization, so that the functional groups of the monomers are correspondingly selected and for example comprise an olefinic double bond.\",\n \"The monomers that can be used for producing a PFPE layer themselves represent perfluorinated polyethers, which are for example provided with methacrylate groups as functional crosslinkable groups.\",\n \"Functionalization with crosslinkable styrene groups is also possible.\",\n \"The perfluorinated alkyl radicals of the polyether give the polymerized material of the PFPE layer strongly hydrophobic properties and therefore make it possible to form a hermetically sealed layer.\",\n \"Similar to TEFLON®, the PFPE material is also chemically inert and is therefore not attacked even under aggressive conditions.\",\n \"It forms an intimate and close bond with frequently used substrate materials of MEMS devices and can therefore be used well as a sealing layer and as a bonding or adhesive layer.\",\n \"A further advantage is that the monomers are liquid at room temperature and do not require any solvent for processing.\",\n \"In the course of complete polymerization, the PFPE layer therefore does not lead to gas emissions, not even at elevated temperature.\",\n \"The chemical stability is also combined with a thermal stability, so that no decomposition products or other gas emissions can escape from the PFPE layer, even at elevated temperature, and thereby destroy again the hermeticity of the package.\",\n \"The PFPE layer may be applied by applying the liquid monomer to the surface to be sealed or covered, and subsequently polymerized by means of irradiation.\",\n \"The irradiation/exposure may take place with a mask or in a structured form, so that the polymerization may result in a structured PFPE layer.\",\n \"It is also possible, however, to apply the PFPE layer to an intermediate substrate and pre-polymerize it or transform it into a partially crosslinked state, possibly structured.\",\n \"The pre-polymerized or partially crosslinked PFPE layer, which then has for example a gelatinous metastable consistency, may subsequently be transferred to the arrangement with the MEMS device.\",\n \"There, the relatively soft partially crosslinked PFPE layer adapts itself to unevennesses on the underlying surface and can thus even out steps of up to several urn in height or closely envelop such steps.\",\n \"The PFPE layer can therefore also be used for planarizing uneven surfaces and therefore takes the place of additional planarizing layers.\",\n \"Before the final and complete curing of the PFPE layer by polymerization under irradiation, further PFPE layers may be applied over the first PFPE layer and then chemically crosslinked with this first layer during the curing.\",\n \"In an embodiment, the PFPE layer is applied to the arrangement over a large surface area.\",\n \"In this case, the PFPE layer covers at least the MEMS device or the device structures thereof.\",\n \"Once the MEMS device has been mounted or arranged on a substrate, the PFPE layer can cover the MEMS device and at least parts of the entire substrate.\",\n \"This has advantages whenever the MEMS device is mounted on the substrate as what is known as a bare die.\",\n \"It is also possible in this way to cover further devices that are arranged on the substrate apart from the MEMS device.\",\n \"In a further embodiment, the PFPE layer is structured.\",\n \"It can in this form rest on the substrate and the MEMS device or only on the MEMS device or the substrate, covering only part of the arrangement.\",\n \"In another embodiment, the PFPE layer is arranged in a structured form resting on the MEMS device or the substrate and represents a sealing intermediate layer for a covering.\",\n \"Apart from the sealing function between the substrate or MEMS device and the covering, the intermediate layer may also perform a bonding and adhesive function, in particular if, in the production of the arrangement, application of the PFPE layer to a substrate is followed as a final step by complete crosslinking of the PFPE layer on the substrate.\",\n \"In this case, a solid bond of the PFPE layer to frequently used substrate materials is created, in particular to ceramic, piezoelectric crystals and to metal and glass.\",\n \"The covering, which lies on the PFPE layer as an intermediate layer, may therefore comprise a plate or a platelet of a ceramic or crystalline material.\",\n \"For particularly sensitive MEMS devices, the properties of which may be impaired by mechanical stresses, particularly low-distortion packages are obtained if the substrate of the MEMS device comprises the same crystalline or ceramic material as the covering.\",\n \"The PFPE layer may be formed particularly advantageously as an intermediate layer if it is structured in the form of a frame and at the same time forms a cavity-allowing spacing structure for the covering.\",\n \"The PFPE layer structured in the form of a frame may enclose the device structures of the device on a surface of the MEMS device or may be arranged on the surface of the substrate and enclose at least the MEMS device as a whole.\",\n \"The covering is then arranged in close contact on the PFPE layer structured in the form of a frame and is solidly bonded to it, so that a hermetically sealed cavity is formed between the covering, the PFPE layer and the surface of the MEMS device or of the substrate.\",\n \"The PFPE layer may comprise at least a first and a second structured partial layer, which rest one on top of the other and are chemically bonded to one another.\",\n \"The first and second PFPE partial layers may then form a three-dimensional structure.\",\n \"In an embodiment, the PFPE layer forms a three-dimensional structure in the form of a cap, which has a recess which is open on one side and, when the cap is placed onto the substrate or the MEMS device, encloses a cavity for the MEMS device structures or for the MEMS device.\",\n \"The cap then sits in a sealing manner on the MEMS device or the substrate and thus protects the MEMS device or the device structures thereof from ambient influences.\",\n \"One partial layer may in this case be applied and structured before the next partial layer is created over it and structured.\",\n \"In this way, a three-dimensional structure is successfully created from partial layers that are differently structured and arranged one on top of the other.\",\n \"The three-dimensional structure of the PFPE layer may have on one side a multiplicity of recesses, which allow the formation of a corresponding number of cavities, in which an element to be encapsulated or hermetically sealed is then respectively arranged.\",\n \"Each element may be an MEMS device or some other device or part thereof that is to be sealed.\",\n \"The PFPE layer may also be applied over a large surface area as a sealing layer over an MEMS device mounted on the substrate by the flip-chip technique.\",\n \"The MEMS device may be selected from micromechanical switches, variable capacitors, sensors, such as for example pressure sensors, or microphones or devices operating with acoustic waves such as SAW (=surface acoustic wave), BAW (=bulk acoustic wave) or GBAW (=guided acoustic wave) devices.\",\n \"Other MEMS devices are also suitable.\",\n \"Further devices that are sealed together with the MEMS device and a common covering may be provided on the substrate.\",\n \"It is also possible, however, to seal only some of these devices with the PFPE layer or indeed only the MEMS device.\",\n \"The additional devices may be semiconductor devices, MEMS devices or passive devices or modules that comprise integrated passive and active devices.\",\n \"Integrated passive devices may for example take the form of multilayered structures in which structured metal layers are arranged alternately with dielectric and, in particular, ceramic layers.\",\n \"Plated-through holes between the metallization levels create the electrical connections, so that a multiplicity of passive device structures may be integrated in such a device.\",\n \"A further covering layer may be built up directly over a covering PFPE layer for sealing or shielding purposes.\",\n \"Such further covering layers that can be applied by thin-film methods and have hermetic properties are preferred.\",\n \"For example, metal layers or dielectric layers deposited from the vapour phase, such as for example oxide layers, nitride layers and the like, are therefore suitable as further covering layers.\",\n \"It is also possible that the PFPE layer is arranged over a first covering layer formed from a different material.\",\n \"The first covering layer may for example represent the uppermost layer of a thin-film package known per se for MEMS devices, also known as a zero level package.\",\n \"In the case of such a package, a layer structure which comprises a cavity for the sensitive MEMS device structures is created with the aid of thin-film methods.\",\n \"The cavity may be produced for example from a sacrificial layer, which is coated with the mentioned first covering layer.\",\n \"The material of the sacrificial layer can be removed or etched out through preferably lateral etching openings or channels.\",\n \"The etching openings and channels can subsequently be closed.\",\n \"The PFPE layer may serve as a closing layer.\",\n \"In an embodiment, the MEMS device is an RF device, for example an RF filter.\",\n \"A possible way of producing the arrangement comprises at least the steps of applying the PFPE layer to the MEMS device or the substrate, the PFPE layer containing along with a perfluoropolyether provided with crosslinkable groups also a photoinitiator.\",\n \"A further production step can comprise the crosslinking of the PFPE layer by means of irradiation, for example by means of UV light.\",\n \"The crosslinking may be performed by polymerization of olefinic crosslinkable groups, for example of styrene or methacrylate groups.\",\n \"The crosslinking make take place directly on the arrangement.\",\n \"It is also possible, however, to divide the crosslinking into a number of partial steps, all of the partial steps apart from the last partial step leading to an incomplete crosslinkage of the PFPE layer.\",\n \"The dividing into partial steps has the advantage that in this way a number of partial layers, which may be structured differently, can be applied one on top of the other and later bonded to one another.\",\n \"In the last step of complete crosslinkage by means of a sufficient irradiating duration or intensity, the good bonding of the PFPE layer to all of the materials that are in close contact with the PFPE layer in the arrangement is also established.\",\n \"Aspects of the present disclosure are explained in more detail below on the basis of exemplary embodiments and the associated figures.\",\n \"The figures are only depicted schematically and not true to scale, so that neither absolute nor relative dimensions can be taken from the figures.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of U.S. application Ser.\",\n \"No.\",\n \"13/472,980, filed May 16, 2012, entitled “Arrangement with a MEMS Device and method of Manufacturing”, which claims benefit under 35 U.S.C.\",\n \"§ 119 of Germany Patent Application Serial No.\",\n \"10 2011 102 266.3, filed in Germany on May 23, 2011, entitled “Arrangement with an MEMS Device and Method of Manufacturing.” COPYRIGHT A portion of the disclosure of this patent document contains material which is subject to copyright protection.\",\n \"The copyright owner has no objection to the facsimile reproduction by anyone of the patent disclosure, as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyright rights whatsoever.\",\n \"FIELD OF THE DISCLOSURE Aspects of the present disclosure relate to an arrangement with an MEMS device and methods of manufacturing the same.\",\n \"BACKGROUND MEMS devices (MEMS=micro-electro-mechanical system) must be protected from mechanical and other environmental influences and for this purpose require a special form of packaging, in which the micromechanical structures are preferably arranged in a cavity, so that an undisturbed function of the structures that can move or vibrate during operation is possible.\",\n \"As an additional requirement, an MEMS device may require a hermetically sealed package, which is sealed in particular from gases and moisture.\",\n \"Various technologies for producing cavity packages are known, and have various advantages and disadvantages.\",\n \"In what are known as CSP packages of the latest generation (CSP=chip sized package), the chip with the MEMS device structures is applied to a substrate in a flip-chip arrangement.\",\n \"A frame surrounding the device structures of the MEMS chip serves as a spacing structure.\",\n \"The flip-chip arrangement may subsequently be covered with a polymer, for example by means of lamination or encapsulation.\",\n \"A better-sealed and easier-to-produce package is obtained if a cover wafer is placed onto a spacing structure enclosing the device structures of the MEMS chip, the device structures being enclosed in a cavity of the package created in this way.\",\n \"Such cover wafers may consist of silicon, glass or piezoelectric materials and preferably coincide with the material of the MEMS chip.\",\n \"The corresponding frame may consist of polymer, metal or metal alloys.\",\n \"It is also possible to provide a cover wafer with an already pre-structured recess and to place this onto the MEMS chip as a covering in the form of a cap.\",\n \"The bonding may take place with the aid of an adhesive or some other wafer bonding method.\",\n \"However, the latter usually comprise a high-temperature step, which may lead to the MEMS device being damaged.\",\n \"Other methods for producing a package comprise complex and elaborate steps that are difficult to implement in mass production or unnecessarily increase the effort required for the package, and consequently the costs.\",\n \"SUMMARY An object of the present disclosure is therefore to provide an arrangement with at least one MEMS device that can be produced in an easy and low-cost way, allowing the creation of a hermetic package for the MEMS device.\",\n \"A further object is to provide a method of manufacturing thereof.\",\n \"These and other objects are achieved according to the invention by an arrangement and method according to the independent claims as originally filed.\",\n \"Advantageous refinements of the invention are provided by further claims.\",\n \"It is proposed to use for the packaging of the arrangement at least one PFPE (perfluoropolyether) layer as a sealing or covering, which is obtained by polymerization of a perfluoropolyether having functional groups.\",\n \"The MEMS device may in this case be arranged on a substrate and in the arrangement is protected from ambient influences by the package.\",\n \"The PFPE layer serves in the package as a sealing layer.\",\n \"In U.S. Patent Application Publication No.\",\n \"2007/0254278 A1, PFPE has, because of its chemical inertness, already been proposed as a material for producing microstructured microfluidic devices, as they are known, which are used in the medical sector.\",\n \"The PFPE layer comprises a polyether of perfluorinated branched or unbranched alkyl chains.\",\n \"The polyether may comprise branched or unbranched chain links of varying lengths between the oxygen bridges of the polyether.\",\n \"Similarly, the PFPE may have a structure branched by ether bridges.\",\n \"A PFPE layer that is sealed from ambient influences and used in the invention is preferably completely polymerized and three-dimensionally crosslinked.\",\n \"Such a crosslinked PFPE layer may be obtained from shorter-chain “monomers,” which are provided at the ends with polymerizable or crosslinkable functional groups.\",\n \"Carbon-carbon bonds are preferably formed during the crosslinkage/polymerization, so that the functional groups of the monomers are correspondingly selected and for example comprise an olefinic double bond.\",\n \"The monomers that can be used for producing a PFPE layer themselves represent perfluorinated polyethers, which are for example provided with methacrylate groups as functional crosslinkable groups.\",\n \"Functionalization with crosslinkable styrene groups is also possible.\",\n \"The perfluorinated alkyl radicals of the polyether give the polymerized material of the PFPE layer strongly hydrophobic properties and therefore make it possible to form a hermetically sealed layer.\",\n \"Similar to TEFLON®, the PFPE material is also chemically inert and is therefore not attacked even under aggressive conditions.\",\n \"It forms an intimate and close bond with frequently used substrate materials of MEMS devices and can therefore be used well as a sealing layer and as a bonding or adhesive layer.\",\n \"A further advantage is that the monomers are liquid at room temperature and do not require any solvent for processing.\",\n \"In the course of complete polymerization, the PFPE layer therefore does not lead to gas emissions, not even at elevated temperature.\",\n \"The chemical stability is also combined with a thermal stability, so that no decomposition products or other gas emissions can escape from the PFPE layer, even at elevated temperature, and thereby destroy again the hermeticity of the package.\",\n \"The PFPE layer may be applied by applying the liquid monomer to the surface to be sealed or covered, and subsequently polymerized by means of irradiation.\",\n \"The irradiation/exposure may take place with a mask or in a structured form, so that the polymerization may result in a structured PFPE layer.\",\n \"It is also possible, however, to apply the PFPE layer to an intermediate substrate and pre-polymerize it or transform it into a partially crosslinked state, possibly structured.\",\n \"The pre-polymerized or partially crosslinked PFPE layer, which then has for example a gelatinous metastable consistency, may subsequently be transferred to the arrangement with the MEMS device.\",\n \"There, the relatively soft partially crosslinked PFPE layer adapts itself to unevennesses on the underlying surface and can thus even out steps of up to several urn in height or closely envelop such steps.\",\n \"The PFPE layer can therefore also be used for planarizing uneven surfaces and therefore takes the place of additional planarizing layers.\",\n \"Before the final and complete curing of the PFPE layer by polymerization under irradiation, further PFPE layers may be applied over the first PFPE layer and then chemically crosslinked with this first layer during the curing.\",\n \"In an embodiment, the PFPE layer is applied to the arrangement over a large surface area.\",\n \"In this case, the PFPE layer covers at least the MEMS device or the device structures thereof.\",\n \"Once the MEMS device has been mounted or arranged on a substrate, the PFPE layer can cover the MEMS device and at least parts of the entire substrate.\",\n \"This has advantages whenever the MEMS device is mounted on the substrate as what is known as a bare die.\",\n \"It is also possible in this way to cover further devices that are arranged on the substrate apart from the MEMS device.\",\n \"In a further embodiment, the PFPE layer is structured.\",\n \"It can in this form rest on the substrate and the MEMS device or only on the MEMS device or the substrate, covering only part of the arrangement.\",\n \"In another embodiment, the PFPE layer is arranged in a structured form resting on the MEMS device or the substrate and represents a sealing intermediate layer for a covering.\",\n \"Apart from the sealing function between the substrate or MEMS device and the covering, the intermediate layer may also perform a bonding and adhesive function, in particular if, in the production of the arrangement, application of the PFPE layer to a substrate is followed as a final step by complete crosslinking of the PFPE layer on the substrate.\",\n \"In this case, a solid bond of the PFPE layer to frequently used substrate materials is created, in particular to ceramic, piezoelectric crystals and to metal and glass.\",\n \"The covering, which lies on the PFPE layer as an intermediate layer, may therefore comprise a plate or a platelet of a ceramic or crystalline material.\",\n \"For particularly sensitive MEMS devices, the properties of which may be impaired by mechanical stresses, particularly low-distortion packages are obtained if the substrate of the MEMS device comprises the same crystalline or ceramic material as the covering.\",\n \"The PFPE layer may be formed particularly advantageously as an intermediate layer if it is structured in the form of a frame and at the same time forms a cavity-allowing spacing structure for the covering.\",\n \"The PFPE layer structured in the form of a frame may enclose the device structures of the device on a surface of the MEMS device or may be arranged on the surface of the substrate and enclose at least the MEMS device as a whole.\",\n \"The covering is then arranged in close contact on the PFPE layer structured in the form of a frame and is solidly bonded to it, so that a hermetically sealed cavity is formed between the covering, the PFPE layer and the surface of the MEMS device or of the substrate.\",\n \"The PFPE layer may comprise at least a first and a second structured partial layer, which rest one on top of the other and are chemically bonded to one another.\",\n \"The first and second PFPE partial layers may then form a three-dimensional structure.\",\n \"In an embodiment, the PFPE layer forms a three-dimensional structure in the form of a cap, which has a recess which is open on one side and, when the cap is placed onto the substrate or the MEMS device, encloses a cavity for the MEMS device structures or for the MEMS device.\",\n \"The cap then sits in a sealing manner on the MEMS device or the substrate and thus protects the MEMS device or the device structures thereof from ambient influences.\",\n \"One partial layer may in this case be applied and structured before the next partial layer is created over it and structured.\",\n \"In this way, a three-dimensional structure is successfully created from partial layers that are differently structured and arranged one on top of the other.\",\n \"The three-dimensional structure of the PFPE layer may have on one side a multiplicity of recesses, which allow the formation of a corresponding number of cavities, in which an element to be encapsulated or hermetically sealed is then respectively arranged.\",\n \"Each element may be an MEMS device or some other device or part thereof that is to be sealed.\",\n \"The PFPE layer may also be applied over a large surface area as a sealing layer over an MEMS device mounted on the substrate by the flip-chip technique.\",\n \"The MEMS device may be selected from micromechanical switches, variable capacitors, sensors, such as for example pressure sensors, or microphones or devices operating with acoustic waves such as SAW (=surface acoustic wave), BAW (=bulk acoustic wave) or GBAW (=guided acoustic wave) devices.\",\n \"Other MEMS devices are also suitable.\",\n \"Further devices that are sealed together with the MEMS device and a common covering may be provided on the substrate.\",\n \"It is also possible, however, to seal only some of these devices with the PFPE layer or indeed only the MEMS device.\",\n \"The additional devices may be semiconductor devices, MEMS devices or passive devices or modules that comprise integrated passive and active devices.\",\n \"Integrated passive devices may for example take the form of multilayered structures in which structured metal layers are arranged alternately with dielectric and, in particular, ceramic layers.\",\n \"Plated-through holes between the metallization levels create the electrical connections, so that a multiplicity of passive device structures may be integrated in such a device.\",\n \"A further covering layer may be built up directly over a covering PFPE layer for sealing or shielding purposes.\",\n \"Such further covering layers that can be applied by thin-film methods and have hermetic properties are preferred.\",\n \"For example, metal layers or dielectric layers deposited from the vapour phase, such as for example oxide layers, nitride layers and the like, are therefore suitable as further covering layers.\",\n \"It is also possible that the PFPE layer is arranged over a first covering layer formed from a different material.\",\n \"The first covering layer may for example represent the uppermost layer of a thin-film package known per se for MEMS devices, also known as a zero level package.\",\n \"In the case of such a package, a layer structure which comprises a cavity for the sensitive MEMS device structures is created with the aid of thin-film methods.\",\n \"The cavity may be produced for example from a sacrificial layer, which is coated with the mentioned first covering layer.\",\n \"The material of the sacrificial layer can be removed or etched out through preferably lateral etching openings or channels.\",\n \"The etching openings and channels can subsequently be closed.\",\n \"The PFPE layer may serve as a closing layer.\",\n \"In an embodiment, the MEMS device is an RF device, for example an RF filter.\",\n \"A possible way of producing the arrangement comprises at least the steps of applying the PFPE layer to the MEMS device or the substrate, the PFPE layer containing along with a perfluoropolyether provided with crosslinkable groups also a photoinitiator.\",\n \"A further production step can comprise the crosslinking of the PFPE layer by means of irradiation, for example by means of UV light.\",\n \"The crosslinking may be performed by polymerization of olefinic crosslinkable groups, for example of styrene or methacrylate groups.\",\n \"The crosslinking make take place directly on the arrangement.\",\n \"It is also possible, however, to divide the crosslinking into a number of partial steps, all of the partial steps apart from the last partial step leading to an incomplete crosslinkage of the PFPE layer.\",\n \"The dividing into partial steps has the advantage that in this way a number of partial layers, which may be structured differently, can be applied one on top of the other and later bonded to one another.\",\n \"In the last step of complete crosslinkage by means of a sufficient irradiating duration or intensity, the good bonding of the PFPE layer to all of the materials that are in close contact with the PFPE layer in the arrangement is also established.\",\n \"Aspects of the present disclosure are explained in more detail below on the basis of exemplary embodiments and the associated figures.\",\n \"The figures are only depicted schematically and not true to scale, so that neither absolute nor relative dimensions can be taken from the figures.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIGS.\",\n \"1A to 1D show various arrangements with an MEMS device on a substrate and a PFPE layer, FIGS.\",\n \"2A to 2C show various arrangements of an MEMS device in which the covering sits directly on the MEMS device, FIGS.\",\n \"3A to 3E show various embodiments of an arrangement with a number of devices on a substrate and a covering comprising a PFPE layer, and FIGS.\",\n \"4A to 4C show an arrangement according to an aspect incorporating an SAW device.\",\n \"DETAILED DESCRIPTION FIG.\",\n \"1A shows an embodiment of the arrangement according to an aspect of the present disclosure, in which an MEMS device MB is mounted in flip-chip arrangement on a substrate TR.\",\n \"The electrical and mechanical attachment takes place by way of bumps, for example solder or stud bumps.\",\n \"The bumps also act in this case as spacers, so that a gap remains between the substrate TR and the MEMS device MB, and the downwardly facing movable or vibrating device structures of the MEMS device can operate mechanically unimpeded.\",\n \"For sealing the MEMS device MB from ambient influences, arranged on the upper side of the MEMS device MB is a PFPE layer PS formed as a covering layer AS.\",\n \"This overlaps the edges of the MEMS device MB and finishes with the substrate TR.\",\n \"The PFPE layer PS enters into an intimate, close and solid bond with conventional substrate materials, for example with ceramic, glass or metal, so that, with such a covering layer AS, a hermetically sealed cavity package having a cavity HR is created for the MEMS device.\",\n \"At the same time, the gap is sealed off laterally, so that a sealed cavity HR is formed under the PFPE layer PS between the substrate TR and the MEMS device MB.\",\n \"FIG.\",\n \"1B shows a further arrangement, in which the MEMS device MB is again mounted on a substrate.\",\n \"The MEMS device is covered by a covering cap AK and thereby forms a cavity HR, in which the MEMS device MB is arranged.\",\n \"For secure sealing of the cavity HR, a structured intermediate layer ZS, which comprises a PFPE layer PS or consists of a PFPE layer PS, is arranged between the covering cap AK and the substrate TR.\",\n \"The covering cap AK may be composed of materials that are mechanically adequately strong and can be structured.\",\n \"The covering cap AK is preferably structured from a covering wafer, for example from a glass or ceramic plate of a semiconductor crystal or any other material that can be structured as a solid body.\",\n \"This has the advantage that in this way a multiplicity of covering caps can be structured from the covering wafer, for example by forming corresponding recesses in the underside of the covering wafer, which are then placed on a panel with a multiplicity of MEMS devices and are only separated into individual devices after complete processing.\",\n \"The PFPE layer PS, formed as an intermediate layer ZS, may be structured on the substrate TR or on the underside of the covering cap AK or be applied as an already structured layer to the substrate TR or the covering wafer.\",\n \"FIG.\",\n \"1C shows a further embodiment of an arrangement, in which the MEMS device MB is mounted on a substrate TR.\",\n \"A structured PFPE layer PS forms an intermediate layer ZS, which surrounds the MEMS device on the substrate TR and at the same time forms a spacing element, on which a covering formed as a covering wafer AW rests.\",\n \"This embodiment has the advantage that the covering wafer does not have to be structured and can be placed on as a level and thin wafer.\",\n \"Only the intermediate layer ZS is structured, which once again can take place directly on the substrate TR, directly on the covering wafer AW or separately from the two parts by separate partial crosslinking of a PFPE layer and the subsequent arrangement thereof between the substrate and the covering wafer AW.\",\n \"Here, too, an adequate cavity HR is ensured if the height of the intermediate layer ZS is greater than the height of the MEMS device above the surface of the substrate TR.\",\n \"FIG.\",\n \"1D shows an MEMS device MB on a substrate that is covered by a PFPE layer PS formed as a covering cap AK.\",\n \"Such a covering cap AK may be formed by a number of partial layers of a PFPE layer, which are individually structured and in a final crosslinkage are bonded to one another to form a three-dimensional structure, indeed to form the covering cap.\",\n \"In the embodiments that are shown in FIGS.\",\n \"1B to 1D, it may remain open how exactly the MEMS device is mounted on the substrate TR.\",\n \"It may be adhesively attached, soldered on or bonded to the substrate in the flip-chip manner of construction.\",\n \"In the first two variants, the electrical connection to the substrate TR may take place by means of bonding wires.\",\n \"Mounting by the SMD technique is also possible.\",\n \"FIGS.\",\n \"2A to 2C show various embodiments of arrangements according to aspects of the present disclosure, in which the sealing of the device structures takes place directly on the MEMS device MB and can therefore take place already at MEMS wafer level, that is to say before the individual separation of the MEMS devices.\",\n \"In the figures, the MEMS devices MB are arranged on a substrate TR, but they may also represent complete arrangements according to the invention without a substrate.\",\n \"FIG.\",\n \"2A, a covering cap AK, which comprises a PFPE layer PS, is arranged on the MEMS device MB.\",\n \"The covering cap AK encloses underneath it a cavity HR, in which the device structures BES are arranged and thus can operate undisturbed.\",\n \"The covering cap AK may be formed completely by the PFPE layer PS, or comprise such a layer as a partial layer.\",\n \"In particular, under the PFPE layer PS there may be arranged a further layer of a different material.\",\n \"It is possible for example that the PFPE layer represents the uppermost sealing layer of a thin-film package, which is also known as a zero level package.\",\n \"Various methods are already known for such packages that are produced in an integrated form and leave a cavity HR for the MEMS device structures.\",\n \"In the case of wafer level packaging, a multiplicity of MEMS devices or MEMS device structures pre-structured on the MEMS wafer may be encapsulated together with a covering cap AK or with a PFPE layer PS provided with recesses.\",\n \"After the individual separation of the MEMS devices, each MEMS device has a covering cap AK of its own.\",\n \"FIG.\",\n \"2B shows a covering of the device structures BES by means of a PFPE layer sitting directly on the MEMS device MB and structured to form an intermediate layer ZS, which forms a frame around the device structures BES and on which a covering formed as a covering wafer AW rests.\",\n \"Here, too, the intermediate layer ZS acts as a spacer, so that a cavity HR for the device structures BES is formed between the MEMS device MB and the covering wafer AW.\",\n \"FIG.\",\n \"2C shows an arrangement with an MEMS device MB, in which the device structures BES are covered by a structured covering cap AK, which is for example formed from a rigid, preferably ceramic or crystalline material.\",\n \"A PFPE layer PS structured to form an intermediate layer ZS is arranged between the covering cap AK and the surface of the MEMS device MB and provides a sealed closure of the cavity HR under the cap.\",\n \"FIGS.\",\n \"3A to 3E show embodiments of the arrangement in which an MEMS device and at least one further device WB are arranged on a substrate TR.\",\n \"According to FIG.\",\n \"3A, the two devices are covered by a common covering layer AS, which comprises a PFPE layer as a single layer or as a partial layer of a laminar structure.\",\n \"The covering layer AS finishes in close contact with the substrate TR all around the devices and thus provides a sealed encapsulation of the devices on the substrate.\",\n \"In the embodiment that is shown in FIG.\",\n \"3B, only the MEMS device MB is covered by the covering layer AS.\",\n \"FIG.\",\n \"3C shows an arrangement in which the MEMS device MB and a further device WB are integrated in a package, which consists of an intermediate layer ZS and a covering, in particular a covering wafer AW.\",\n \"The intermediate layer ZS is structured from a PFPE layer PS, sits on the substrate TR and surrounds the devices in the form of a frame.\",\n \"At the same time, the intermediate layer ZS serves as a spacer and as a support for the preferably rigid covering AW, so that each frame formed in the intermediate layer encloses together with the covering a cavity HR for the respective device.\",\n \"FIG.\",\n \"3D shows an arrangement in which a structured PFPE layer PS is arranged as a sealing intermediate layer ZS between a covering, for example a structured covering wafer AW, and the substrate.\",\n \"Respectively enclosed under the covering AW is a cavity HR for the respective device MB, WB, which is substantially formed by a recess in the covering.\",\n \"FIG.\",\n \"3E shows an arrangement in which the structured covering AW with the recesses is formed completely by a PFPE layer, which sits directly on the substrate.\",\n \"It is possible here to dispense with the intermediate layer.\",\n \"The covering AW may be built up from a number of structured partial layers.\",\n \"FIG.\",\n \"4A shows an arrangement in which the structure and possible functions of the substrate TR are presented in more detail.\",\n \"The substrate TR is built up in a multilayered form from dielectric layers, between which structured metallization levels are arranged.\",\n \"Different metallization levels are connected to one another by way of plated-through holes.\",\n \"Provided on the upper side of the substrate TR are connection metallizations for the MEMS device MB and any other further devices there may be.\",\n \"Arranged on the underside of the substrate TR are the external contacts KA, with the aid of which the arrangement can be connected to surrounding circuitry, for example by soldering.\",\n \"The MEMS device MB is mechanically and electrically connected to the electrical terminal areas of the substrate TR by way of bumps.\",\n \"The device structures BES face downwards and are arranged between the surface of the substrate TR and the MEMS device MB in a clear gap that remains there.\",\n \"Laterally, the gap between the MEMS device and the substrate TR is sealed by means of a covering layer AS, which sits over a large surface area on the upper side of the MEMS device and of the substrate and is formed by a PFPE layer PS.\",\n \"The covering layer AS may be applied with an approximately uniform layer thickness and conformal surface.\",\n \"The covering layer AS may, however, also be applied with a greater layer thickness, for example in a layer thickness reaching up to the upper edge of the MEMS device, so that the MEMS device is virtually buried under the covering layer AS.\",\n \"The MEMS device is represented here as an SAW device, which comprises a piezoelectric substrate and metallic device structures and terminal pads on the underside of the substrate.\",\n \"The MEMS device may, however, also be a BAW device, in which a layer structure with BAW resonators is formed on the surface of a substrate, for example comprising crystalline silicon.\",\n \"The MEMS device may also be a GBAW device, in which SAW-like device structures are covered by additional layers.\",\n \"FIG.\",\n \"4B shows a further refinement in which a relatively thin covering layer AS, formed by a PFPE layer PS, is provided with a further covering layer WA, which has been applied here for example as an encapsulating compound, which completely covers the MEMS device and has a planarized surface.\",\n \"Such a further covering WA may be applied for example as an encapsulating compound and for example by injection molding.\",\n \"FIG.\",\n \"4C shows a further refinement of an arrangement with a further covering WA applied over the covering layer AS, in the form of a thin layer applied with a conformal surface.\",\n \"Such a thin layer is preferably applied by means of thin-film methods from the vapour phase, for example by means of CVD methods, plasma depositing methods or sputtering.\",\n \"It may for example comprise SiO2 or some other dielectric material.\",\n \"It is also possible to apply the further covering layer WA as a metal layer and to deposit it for this purpose from a solution.\",\n \"It is also possible to apply a base metallization from the vapour phase and galvanically or electrolessly reinforce it in a solution.\",\n \"A metallic further covering layer WA may be used for electromagnetic shielding.\",\n \"A metal layer can also increase the stability of the package as a whole, and consequently of the arrangement.\",\n \"The present disclosure is not restricted to the exemplary embodiments that are represented in the figures and described.\",\n \"However, all of these embodiments have in common that the hermetic sealing of the arrangement is performed by the package for the MEMS device by means of a PFPE layer.\",\n \"The PFPE layer may provide the only sealing and covering or, as described, may be formed as an intermediate or bonding layer.\",\n \"An arrangement disclosed herein may also comprise sub-combinations of the exemplary embodiments described or represented.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874664"}}},{"rowIdx":4494664,"cells":{"text":{"kind":"list like","value":[["VISUALIZING CHANGES IN A MULTI-DIMENSIONAL DATASET USING THREE-DIMENSIONAL CUBES","A method, system and computer program product for visualizing changes in a multi-dimensional dataset.","A multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data, is received.","The number of dimensions in the multi-dimensional dataset of discrete data is then identified.","One or more levels of three-dimensional cubes of discrete data are then created equal to the number of dimensions in the multi-dimensional dataset divided by three rounded to the lowest positive integer.","The discrete data of the one or more levels of three-dimensional cubes is encoded.","A color palette is then associated with the encoded discrete data.","As a result, a user is able to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., adding/deleting/modifying business rules) in a more efficient and accurate manner."],["1.A method for visualizing changes in a multi-dimensional dataset, the method comprising: receiving a multi-dimensional dataset of discrete data; identifying a number of dimensions in said multi-dimensional dataset of discrete data; creating, by a processor, one or more levels of three-dimensional cubes of discrete data equal to said number of number of dimensions in said multi-dimensional dataset divided by three rounded to a lowest positive integer, wherein each of said one or more levels of three-dimensional cubes of discrete data contains three dimensions of discrete data; encoding, by said processor, said discrete data at each level of said one or more levels of three-dimensional cubes; and associating a color palette with said encoded discrete data.","2.The method as recited in claim 1 further comprising: computing a number equal to said number of dimensions in said multi-dimensional dataset of discrete data divided by three.","3.The method as recited in claim 2 further comprising: associating said one or more levels of three-dimensional cubes of discrete data with a one-dimensional straight line of three elements containing one-dimension of discrete data in response to said number ending in 1/3, wherein each of said three elements contains a pointer to a cell in one of said one or more levels of three-dimensional cubes.","4.The method as recited in claim 3 further comprising: associating said one or more levels of three-dimensional cubes of discrete data with a two-dimensional table of cells in response to said number ending in 2/3, wherein each row of said two-dimensional table represents an element from a first dimension and each column of said two-dimensional table represents an element from a second dimension, wherein each cell of said two-dimensional table represents a combination of elements from said first and second dimensions, wherein said combination of elements from said first and second dimensions is used as a pointer to a cell in one of said one or more levels of three-dimensional cubes.","5.The method as recited in claim 4, wherein each dimension in said multi-dimensional dataset of discrete data is represented by three elements, wherein said multi-dimensional dataset of discrete data is represented by a total of 3N total cells, where N is equal to said number of dimensions in said multi-dimensional dataset of discrete data.","6.The method as recited in claim 1, wherein color information from a lowest level three-dimensional cube is transferred upward to higher level three-dimensional cubes based on numeric weight of individual colors of each cell of said lowest level three-dimensional cube.","7.The method as recited in claim 1, wherein color information of each cell of a three-dimensional cube is transmitted to nearby cells of said three-dimensional cube.","8.The method as recited in claim 1, wherein said multi-dimensional dataset comprises online analytical processing based multi-dimensional data."],["<SOH> BACKGROUND <EOH>Analyzing data differences due to changes made in the system is often very difficult, especially for multi-dimensional datasets, such as online analytical processing (OLAP) based multi-dimensional datasets.","In computing, OLAP is an approach to answering multi-dimensional analytical queries swiftly.","Typical applications of OLAP include business reporting for sales, marketing, management reporting, business processing management, budgeting and forecasting, financial reporting and similar areas.","Currently, in attempting to quantify or understand the effects to the multi-dimensional data from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, month of January versus the month of April), the user will review and compare the data, such as comparing the data in two tables side by side.","However, such a process is time-consuming and inefficient and perhaps error-prone in quantifying or understanding the effects to the data from changes made in the system."],["<SOH> SUMMARY <EOH>In one embodiment of the present invention, a method for visualizing changes in a multi-dimensional dataset comprises receiving a multi-dimensional dataset of discrete data.","The method further comprises identifying a number of dimensions in the multi-dimensional dataset of discrete data.","The method additionally comprises creating, by a processor, one or more levels of three-dimensional cubes of discrete data equal to the number of number of dimensions in the multi-dimensional dataset divided by three rounded to a lowest positive integer, where each of the one or more levels of three-dimensional cubes of discrete data contains three dimensions of discrete data.","Furthermore, the method comprises encoding, by the processor, the discrete data at each level of the one or more levels of three-dimensional cubes.","Additionally, the method comprises associating a color palette with the encoded discrete data.","Other forms of the embodiment of the method described above are in a system and in a computer program product.","The foregoing has outlined rather generally the features and technical advantages of one or more embodiments of the present invention in order that the detailed description of the present invention that follows may be better understood.","Additional features and advantages of the present invention will be described hereinafter which may form the subject of the claims of the present invention."],["TECHNICAL FIELD The present invention relates generally to analyzing data, and more particularly to visualizing changes in a multi-dimensional dataset (e.g., online analytical processing (OLAP) based multi-dimensional data) using three-dimensional cubes associated with a two-dimensional table or a one-dimensional straight line, if necessary.","BACKGROUND Analyzing data differences due to changes made in the system is often very difficult, especially for multi-dimensional datasets, such as online analytical processing (OLAP) based multi-dimensional datasets.","In computing, OLAP is an approach to answering multi-dimensional analytical queries swiftly.","Typical applications of OLAP include business reporting for sales, marketing, management reporting, business processing management, budgeting and forecasting, financial reporting and similar areas.","Currently, in attempting to quantify or understand the effects to the multi-dimensional data from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, month of January versus the month of April), the user will review and compare the data, such as comparing the data in two tables side by side.","However, such a process is time-consuming and inefficient and perhaps error-prone in quantifying or understanding the effects to the data from changes made in the system.","SUMMARY In one embodiment of the present invention, a method for visualizing changes in a multi-dimensional dataset comprises receiving a multi-dimensional dataset of discrete data.","The method further comprises identifying a number of dimensions in the multi-dimensional dataset of discrete data.","The method additionally comprises creating, by a processor, one or more levels of three-dimensional cubes of discrete data equal to the number of number of dimensions in the multi-dimensional dataset divided by three rounded to a lowest positive integer, where each of the one or more levels of three-dimensional cubes of discrete data contains three dimensions of discrete data.","Furthermore, the method comprises encoding, by the processor, the discrete data at each level of the one or more levels of three-dimensional cubes.","Additionally, the method comprises associating a color palette with the encoded discrete data.","Other forms of the embodiment of the method described above are in a system and in a computer program product.","The foregoing has outlined rather generally the features and technical advantages of one or more embodiments of the present invention in order that the detailed description of the present invention that follows may be better understood.","Additional features and advantages of the present invention will be described hereinafter which may form the subject of the claims of the present invention.","BRIEF DESCRIPTION OF THE DRAWINGS A better understanding of the present invention can be obtained when the following detailed description is considered in conjunction with the following drawings, in which: FIG.","1 illustrates an embodiment of the present invention of a hardware configuration of a computing device which is representative of a hardware environment for practicing the present invention; FIG.","2 is a flowchart of a method for visualizing changes in a multi-dimensional dataset in accordance with an embodiment of the present invention; FIG.","3 illustrates a three-dimensional cube of discrete data with the dimensions of products, time and measures in accordance with an embodiment of the present invention; FIG.","4 illustrates a one-dimensional straight line of the fourth dimension of stores in accordance with an embodiment of the present invention; FIG.","5 graphically illustrates the number of cells in the 4 dimensional cube dataset by showing the 27 cells for each dimension of the three-dimensional cube in accordance with an embodiment of the present invention; FIG.","6 illustrates a two-dimensional table of the fourth and fifth dimensions of stores and locations, respectively, in accordance with an embodiment of the present invention; FIG.","7 illustrates three levels of a three-dimensional cube of discrete data in accordance with an embodiment of the present invention; and FIG.","8 illustrates a one-dimensional straight line of the tenth dimension in accordance with an embodiment of the present invention.","DETAILED DESCRIPTION The present invention comprises a method, system and computer program product for visualizing changes in a multi-dimensional dataset.","In one embodiment of the present invention, a multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data, is received.","The number of dimensions in the multi-dimensional dataset of discrete data is then identified.","For example, if the multi-dimensional dataset contains data for the dimensions of products, time, stores and measures, then the number of dimensions contained in the multi-dimensional dataset is four.","One or more levels of three-dimensional cubes of discrete data are then created equal to the number of dimensions in the multi-dimensional dataset divided by three rounded to the lowest positive integer.","For instance, referring to the above example, if the number of dimensions contained in the multi-dimensional dataset is four, then the number of four divided by three rounded to the lowest positive integer is one.","As a result, a single level of a three-dimensional cube of discrete data would be created.","The discrete data of the one or more levels of three-dimensional cubes is encoded.","A color palette is then associated with the encoded discrete data.","As a result of the present invention, a user is able to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.","In the following description, numerous specific details are set forth to provide a thorough understanding of the present invention.","However, it will be apparent to those skilled in the art that the present invention may be practiced without such specific details.","In other instances, well-known circuits have been shown in block diagram form in order not to obscure the present invention in unnecessary detail.","For the most part, details considering timing considerations and the like have been omitted inasmuch as such details are not necessary to obtain a complete understanding of the present invention and are within the skills of persons of ordinary skill in the relevant art.","Referring now to the Figures in detail, FIG.","1 illustrates an embodiment of the present invention of the hardware configuration of a computing device 100 which is representative of a hardware environment for practicing the present invention.","Computing device 100 may be any type of computing device (e.g., portable computing unit, Personal Digital Assistant (PDA), smartphone, laptop computer, mobile phone, navigation device, game console, desktop computer system, workstation, Internet appliance and the like) configured with the capability of visualizing changes in a multi-dimensional dataset (e.g., online analytical processing based multi-dimensional data).","Referring to FIG.","1, computing device 100 may have a processor 101 coupled to various other components by system bus 102.An operating system 103 may run on processor 101 and provide control and coordinate the functions of the various components of FIG.","1.An application 104 in accordance with the principles of the present invention may run in conjunction with operating system 103 and provide calls to operating system 103 where the calls implement the various functions or services to be performed by application 104.Application 104 may include, for example, a program for visualizing changes in a multi-dimensional dataset as discussed further below in connection with FIGS.","2-8.Referring again to FIG.","1, read-only memory (“ROM”) 105 may be coupled to system bus 102 and include a basic input/output system (“BIOS”) that controls certain basic functions of computing device 100.Random access memory (“RAM”) 106 and disk adapter 107 may also be coupled to system bus 102.It should be noted that software components including operating system 103 and application 104 may be loaded into RAM 106, which may be computing device's 100 main memory for execution.","Disk adapter 107 may be an integrated drive electronics (“IDE”) adapter that communicates with a disk unit 108, e.g., disk drive.","It is noted that the program for visualizing changes in a multi-dimensional dataset, as discussed further below in connection with FIGS.","2-8, may reside in disk unit 108 or in application 104.Computing device 100 may further include a communications adapter 109 coupled to bus 102.Communications adapter 109 may interconnect bus 102 with an outside network thereby allowing computing device 100 to communicate with other devices.","I/O devices may also be connected to computing device 100 via a user interface adapter 110 and a display adapter 111.Keyboard 112, mouse 113 and speaker 114 may all be interconnected to bus 102 through user interface adapter 110.A display monitor 115 may be connected to system bus 102 by display adapter 111.In this manner, a user is capable of inputting to computing device 100 through keyboard 112 or mouse 113 and receiving output from computing device 100 via display 115 or speaker 114.Other input mechanisms may be used to input data to computing device 100 that are not shown in FIG.","1, such as display 115 having touch-screen capability and keyboard 112 being a virtual keyboard.","Computing device 100 of FIG.","1 is not to be limited in scope to the elements depicted in FIG.","1 and may include fewer or additional elements than depicted in FIG.","1.The present invention may be a system, a method, and/or a computer program product.","The computer program product may include a computer readable storage medium (or media) having computer readable program instructions thereon for causing a processor to carry out aspects of the present invention.","The computer readable storage medium can be a tangible device that can retain and store instructions for use by an instruction execution device.","The computer readable storage medium may be, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing.","A non-exhaustive list of more specific examples of the computer readable storage medium includes the following: a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), a static random access memory (SRAM), a portable compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a memory stick, a floppy disk, a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon, and any suitable combination of the foregoing.","A computer readable storage medium, as used herein, is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g., light pulses passing through a fiber-optic cable), or electrical signals transmitted through a wire.","Computer readable program instructions described herein can be downloaded to respective computing/processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network and/or a wireless network.","The network may comprise copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers and/or edge servers.","A network adapter card or network interface in each computing/processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for storage in a computer readable storage medium within the respective computing/processing device.","Computer readable program instructions for carrying out operations of the present invention may be assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++ or the like, and conventional procedural programming languages, such as the “C” programming language or similar programming languages.","The computer readable program instructions may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server.","In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).","In some embodiments, electronic circuitry including, for example, programmable logic circuitry, field-programmable gate arrays (FPGA), or programmable logic arrays (PLA) may execute the computer readable program instructions by utilizing state information of the computer readable program instructions to personalize the electronic circuitry, in order to perform aspects of the present invention.","Aspects of the present invention are described herein with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention.","It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer readable program instructions.","These computer readable program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.","These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and/or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function/act specified in the flowchart and/or block diagram block or blocks.","The computer readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions/acts specified in the flowchart and/or block diagram block or blocks.","The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention.","In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function(s).","In some alternative implementations, the functions noted in the block may occur out of the order noted in the figures.","For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved.","It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts or carry out combinations of special purpose hardware and computer instructions.","As stated in the Background section, analyzing data differences due to changes made in the system is often very difficult, especially for multi-dimensional datasets, such as online analytical processing (OLAP) based multi-dimensional datasets.","In computing, OLAP is an approach to answering multi-dimensional analytical queries swiftly.","Typical applications of OLAP include business reporting for sales, marketing, management reporting, business processing management, budgeting and forecasting, financial reporting and similar areas.","Currently, in attempting to quantify or understand the effects to the multi-dimensional data from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, month of January versus the month of April), the user will review and compare the data, such as comparing the data in two tables side by side.","However, such a process is time-consuming and inefficient and perhaps error-prone in quantifying or understanding the effects to the data from changes made in the system.","The principles of the present invention provide a means for quantifying and understanding the effects to data in a multi-dimensional dataset from changes made in the system by visualizing changes in the multi-dimensional dataset using one or more levels of three-dimensional cubes of discrete data along with an associated two-dimensional table or one-dimensional straight line, if necessary, as discussed below in connection with FIGS.","2-8.For example, by using the principles of the present invention, a user will be able to quantify and understand the effects to data, such as the change in the frequency or quantum of data, in a multi-dimensional dataset from changes made in the system (e.g., adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.","As an example, the present invention would be able to assist the user in better understanding and quantifying what part of the country was most affected by a sales tax increase on a set of products.","FIG.","2 is a flowchart of a method for visualizing changes in a multi-dimensional dataset.","FIG.","3 illustrates a three-dimensional cube of discrete data with the dimensions of products, time and measures.","FIG.","4 illustrates a one-dimensional straight line of the fourth dimension of stores.","FIG.","5 graphically illustrates the number of cells in the 4 dimensional cube dataset by showing the 27 cells for each dimension of the three-dimensional cube.","FIG.","6 illustrates a two-dimensional table of the fourth and fifth dimensions of stores and locations, respectively.","FIG.","7 illustrates three levels of a three-dimensional cube of discrete data.","FIG.","8 illustrates a one-dimensional straight line of the tenth dimension.","As stated above, FIG.","2 is a flowchart of a method 200 for visualizing changes in a multi-dimensional dataset in accordance with an embodiment of the present invention.","Referring to FIG.","2, in conjunction with FIG.","1, in step 201, computing device 100 receives a multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data.","In step 202, computing device 100 identifies a number of dimensions in the multi-dimensional dataset of discrete data.","For example, if the multi-dimensional dataset contains data for the dimensions of products, time, stores and measures, then the number of dimensions contained in the multi-dimensional dataset is four.","In step 203, computing device 100 computes the number equal to the number of dimensions in the multi-dimensional dataset divided by three.","For example, if the number of dimensions contained in the multi-dimensional dataset is four, then computing device 100 computes the number 4/3 in step 203.In step 204, computing device 100 creates one or more levels of three-dimensional cubes of discrete data equal to the number of dimensions in the multi-dimensional dataset divided by three rounded to the lowest positive integer.","For instance, referring to the above example, if the number of dimensions contained in the multi-dimensional dataset is four, then the number of four divided by three rounded to the lowest positive integer is one.","As a result, computing device 100 would create a single level of a three-dimensional cube of discrete data.","In another example, if the number of dimensions contained in the multi-dimensional dataset is ten, then the number of ten divided by three rounded to the lowest positive integer is three.","As a result, computing device 100 would create three levels of three-dimensional cubes of discrete data.","In one embodiment, each level of the three-dimensional cubes contains three dimensions of discrete data.","In step 205, a determination is made by computing device 100 as to whether the number computed in step 203 ends in 1/3 or 2/3.If the number computed in step 203 ends in 1/3 or 2/3, then, in step 206, computing device 100 creates a one-dimensional straight line of three elements containing one-dimension of discrete data in response to the computed number ending in 1/3 or creates a two-dimensional table of cells with each row representing an element from a first dimension and each column representing an element of a second dimension in response to the computed number ending in 2/3.For example, suppose that the received multi-dimensional dataset is a four dimensional dataset of discrete data, such as data with the dimensions of products, time, stores and measures.","Since the number of dimensions divided by three is 1 and 1/3, computing device 100 will create one level of a three-dimensional cube of discrete data along with a one-dimensional straight line containing three elements as shown in FIGS.","3 and 4.FIG.","3 illustrates a three-dimensional cube 300 of discrete data with the dimensions of products, time and measures in accordance with an embodiment of the present invention.","As illustrated in FIG.","3, three-dimensional cube 300 contains cells 301 storing the discrete data.","FIG.","4 illustrates a one-dimensional straight line 400 of the fourth dimension of stores in accordance with an embodiment of the present invention.","Referring to FIGS.","3 and 4, in one embodiment, the one-dimensional straight line of the fourth dimension of stores contains three elements 401.In one embodiment, the content of elements 401 of one-dimensional straight line 400 contains a pointer to three-dimensional cube 300, which contains the data for that particular store.","In one embodiment, each dimension in the multi-dimensional dataset of discrete data is represented by three elements/items/members.","As a result, the multi-dimensional dataset of discrete data is represented by a total of 3N total cells, where N is equal to the number of dimensions in the multi-dimensional dataset of discrete data.","Hence, referring to the above example, if each dimension (four dimensions in the example) is represented by three elements/items/members, then the total cube will have 34 (81) cells as shown in FIG.","5.It is noted that the principles of the present invention are not to be limited in scope to having each dimension in the multi-dimensional dataset of discrete data being represented by three elements/items/members.","Instead, each dimension in the multi-dimensional dataset of discrete data may be represented by one or more elements/items/members.","A person of ordinary skill in the art would be capable of applying the principles of the present invention to such implementations.","Further, embodiments applying the principles of the present invention to such implementations would fall within the scope of the present invention.","FIG.","5 graphically illustrates the number of cells in the 4 dimensional cube dataset by showing the 27 cells for each dimension in space of the three-dimensional cube 300 (represented by cube 300′ for the first dimension, cube 300″ for the second dimension and cube 300″' for the third dimension) in accordance with an embodiment of the present invention.","In another example, suppose that the received multi-dimensional dataset is a five dimensional dataset of discrete data, such as data with the dimensions of products, time, stores, measures and locations.","Since the number of dimensions divided by three is 1 and 2/3, computing device 100 will create one level of a three-dimensional cube of discrete data along with a two-dimensional table as shown in FIGS.","3 and 6.As previously discussed, FIG.","3 illustrates a three-dimensional cube 300 of discrete data with the dimensions of products, time and measures in accordance with an embodiment of the present invention.","FIG.","6 illustrates a two-dimensional table 600 of the fourth and fifth dimensions of stores and locations, respectively, in accordance with an embodiment of the present invention.","Referring to FIG.","6, in one embodiment, each row in table 600 represents an element from the fourth dimension (stores) and each column represents an element from the fifth dimension (locations).","Each cell 601 in table 600 represents a combination of the fourth and fifth dimensions (stores and locations) and will act as a pointer to three-dimensional cube 300 comprised of the first, second and third dimensions (products, time and measures).","Since each dimension is represented by three elements/items/members in the exemplary embodiment, then the total cube (5 dimensional cube dataset), including the three-dimensional cube 300 and the two-dimensional table 600, will have 35 (243) cells as illustrated in FIG.","6.Since each cell 601 in table 600 points to a possible number of 27 cells of three-dimensional cube 300, then there is a total of 243 cells as illustrated in FIG.","6.It is noted that the principles of the present invention are not to be limited in scope to having each dimension of the three-dimensional cube 300 being represented by 27 cells based on each dimension of the multi-dimensional dataset being represented by three elements/items/members.","Instead, each dimension of the three-dimensional cube 300 may be represented by a different number of cells, such as the first dimension having twenty cells, the second dimension having twenty-five cells and the third dimension having a single cell.","In a further example, suppose that the received multi-dimensional dataset is a ten dimensional dataset of discrete data.","Since the number of dimensions divided by three is 3 and 1/3, computing device 100 will create three levels of a three-dimensional cube of discrete data along with a one-dimensional straight line as shown in FIGS.","7 and 8.FIG.","7 illustrates three levels of a three-dimensional cube of discrete data (identified by cubes 701,702 and 703) in accordance with an embodiment of the present invention.","Three-dimensional cube 701 is said to be the first level of a three-dimensional cube containing the discrete data for the first three dimensions, the first, second and third dimensions.","Three-dimensional cube 702 is said to be the second level of a three-dimensional cube containing the discrete data for the second three dimensions, the fourth, fifth and sixth dimensions.","Furthermore, three-dimensional cube 703 is said to be the third level of a three-dimensional cube containing the discrete data for the three dimensions, the seventh, eighth and ninth dimensions.","FIG.","8 illustrates a one-dimensional straight line 800 of the tenth dimension in accordance with an embodiment of the present invention.","Referring to FIGS.","7 and 8, in one embodiment, each element 801 of one-dimensional straight line 800 is a pointer to a cell 704 in the lowest-level three-dimensional cube (in this case the third level three-dimensional cube 703 containing the discrete data for the three dimensions, the seventh, eighth and ninth dimensions).","Each cell 704 in cube 703 will be a pointer to a cell 705 in the next highest-level three-dimensional cube (in this case the second level three-dimensional cube 702 containing the discrete data for the three dimensions, the fourth, fifth and sixth dimensions).","Furthermore, each cell 705 in cube 704 will be a pointer to a cell 706 in the highest-level three-dimensional cube 701 (the first level three-dimensional cube 701 containing the discrete data for the three dimensions, the first, second and third dimensions).","As a result, the 10 dimensional cube dataset includes a one-dimensional straight line 800 and three three-dimensional cubes 701, 702, 703, where the elements 801 of one-dimensional straight line 800 and cells 704, 705 of three-dimensional cubes 702, 703 contain pointers, whereas, cells 706 of the first level three-dimensional cube 701 will contain values (e.g., numeric values, string values).","Since each dimension is represented by three elements/items/members in the exemplary embodiment, then the total cube (10 dimensional cube dataset), including the three three-dimensional cubes 701, 702, 703 and the one-dimensional straight line 800, will have 310 (59,049) cells.","Returning to FIG.","2, in conjunction with FIGS.","1 and 3-8, upon creating a one-dimensional straight line or a two-dimensional table or if the number computed in step 203 did not end in 1/3 or 2/3, then, in step 207, computing device 100 encodes the discrete data of the one or more levels of the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) and any associated one-dimensional straight line (e.g., one-dimensional straight line 800) or two-dimensional table (e.g., two-dimensional table 600).","That is, in one embodiment, computing device 100 encodes the discrete data at each level of the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) and any associated one-dimensional straight line (e.g., one-dimensional straight line 800) or two-dimensional table (e.g., two-dimensional table 600).","“Encoding,” as used herein, refers to converting the discrete data into a proper range based discrete data so as to more easily identify the important data points or data sets.","In one embodiment, depending on the type of data contained in the cube dataset as well as the type of analysis to be performed on the data, various types of encoding functions could be used.","For example, if the frequency of change in a set of numbers needs to be viewed, then histograms may be utilized.","In another example, if the quantum of change in all the numbers needs to be viewed, then the data could be partitioned into various sets, where each set contains a number between a minimum and a maximum value.","In step 208, computing device 100 associates a color palette with the encoded data.","Since it may be difficult to identify important data points or data sets by presenting the data as a continuous color, the discrete data is encoded as discussed above, and later assigned a specific color (e.g., assign the color blue for data points between the values of x and y) so as to be able to easily analyze the data, such as analyzing data above or below a certain threshold as discussed below.","As a result of the present invention, a user is able to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.","In one embodiment, the discrete data that is encoded may be said to be “pseudo continuous” in that the difference between the values of the data may be small (i.e., the values of the various data may appear to be the same to the user).","For example, if the sales data for various months were plotted on a graph, the bar graphs representing the sales data for these months may be appear to be the same height to the user and hence causing the data to appear continuous.","Consequently, such data may be said to be “pseudo continuous.” As a result, a transformation function can be applied to these values thereby creating “proper discrete data” from the pseudo continuous data to enable a user to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.","As discussed above, computing device 100 associates a color palette with the encoded data.","For example, suppose that the numbers with a value between −10 and 2000 changed due a change in a factor in the system (e.g., modification of a business rule).","If a user would like to view the quantum of change in a single color, then the discrete data could be encoded by partitioning the data into various sets, such as a set with values between −10 and 2000, a set that contains numbers with values below −10 and a set that contains numbers with values greater than 2000.The partition that contains numbers between −10 and 2000 could then be associated with a color (e.g., blue) thereby enabling the user to more easily identify the quantum of change.","In another example, the user may want to further view the quantum of change within the partition containing the numbers between −10 and 2000.As a result, two partitions could be devised, where the first partition contains numbers between −10 and 1005 (1005 is the midpoint between the values of −10 and 2000) and the second partition contains numbers between 1006 and 2010.Each partition could then be associated with a color to enable the user to more easily identify the quantum of change within these ranges of values.","In one embodiment, when there are multiple levels of three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703), the color information in the lowest-level cube (e.g., three-dimensional cube 703) is transferred upwards to the “pointer” cubes (referring to those cubes with cells containing pointers to the next higher level cube) (e.g., three-dimensional cube 702) based on the numeric weight of the individual colors of each cell (e.g., cell 704) of the lowest-level cube (e.g., three-dimensional cube 703).","Furthermore, in one embodiment, functional transformation could also be applied to the weights to increase the quantum of change transferred and the redistribution of the transformed weights could be done based on the color palette.","In one embodiment, once the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) have been color coded, they may be traversed where a single color palette acts as a guiding mechanism.","In another embodiment, since the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) are represented in three-dimensions, there could be cube components or cells (e.g., cells 704, 705, 706) that are not visible in three-dimensions even after rotating the cube in 360 degrees.","In such a scenario, each cell (e.g., cells 704, 705, 706) could transfer its color information to nearby cells as well.","Once each cell (e.g., cells 704, 705, 706) transmits its color information to nearby cells and the calculated weighted information is kept within each cell, markers (such as in multiple of 3) could be utilized to identify the most important cells, such as by having those cells appear darker.","As a result, a user could more easily analyze even the hidden cells.","Furthermore, markers can be utilized to assist the user in identifying the data of interest in other levels of the three-dimensional cubes.","For instance, a user could review the data associated with a marker, such as on the highest level cube (e.g., three-dimensional cube 701).","The user could then select the data marker which would result in the user being shown the details of the marker in the next lower-level cube (e.g., three-dimensional cube 702).","The descriptions of the various embodiments of the present invention have been presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed.","Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments.","The terminology used herein was chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein."]],"string":"[\n [\n \"VISUALIZING CHANGES IN A MULTI-DIMENSIONAL DATASET USING THREE-DIMENSIONAL CUBES\",\n \"A method, system and computer program product for visualizing changes in a multi-dimensional dataset.\",\n \"A multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data, is received.\",\n \"The number of dimensions in the multi-dimensional dataset of discrete data is then identified.\",\n \"One or more levels of three-dimensional cubes of discrete data are then created equal to the number of dimensions in the multi-dimensional dataset divided by three rounded to the lowest positive integer.\",\n \"The discrete data of the one or more levels of three-dimensional cubes is encoded.\",\n \"A color palette is then associated with the encoded discrete data.\",\n \"As a result, a user is able to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., adding/deleting/modifying business rules) in a more efficient and accurate manner.\"\n ],\n [\n \"1.A method for visualizing changes in a multi-dimensional dataset, the method comprising: receiving a multi-dimensional dataset of discrete data; identifying a number of dimensions in said multi-dimensional dataset of discrete data; creating, by a processor, one or more levels of three-dimensional cubes of discrete data equal to said number of number of dimensions in said multi-dimensional dataset divided by three rounded to a lowest positive integer, wherein each of said one or more levels of three-dimensional cubes of discrete data contains three dimensions of discrete data; encoding, by said processor, said discrete data at each level of said one or more levels of three-dimensional cubes; and associating a color palette with said encoded discrete data.\",\n \"2.The method as recited in claim 1 further comprising: computing a number equal to said number of dimensions in said multi-dimensional dataset of discrete data divided by three.\",\n \"3.The method as recited in claim 2 further comprising: associating said one or more levels of three-dimensional cubes of discrete data with a one-dimensional straight line of three elements containing one-dimension of discrete data in response to said number ending in 1/3, wherein each of said three elements contains a pointer to a cell in one of said one or more levels of three-dimensional cubes.\",\n \"4.The method as recited in claim 3 further comprising: associating said one or more levels of three-dimensional cubes of discrete data with a two-dimensional table of cells in response to said number ending in 2/3, wherein each row of said two-dimensional table represents an element from a first dimension and each column of said two-dimensional table represents an element from a second dimension, wherein each cell of said two-dimensional table represents a combination of elements from said first and second dimensions, wherein said combination of elements from said first and second dimensions is used as a pointer to a cell in one of said one or more levels of three-dimensional cubes.\",\n \"5.The method as recited in claim 4, wherein each dimension in said multi-dimensional dataset of discrete data is represented by three elements, wherein said multi-dimensional dataset of discrete data is represented by a total of 3N total cells, where N is equal to said number of dimensions in said multi-dimensional dataset of discrete data.\",\n \"6.The method as recited in claim 1, wherein color information from a lowest level three-dimensional cube is transferred upward to higher level three-dimensional cubes based on numeric weight of individual colors of each cell of said lowest level three-dimensional cube.\",\n \"7.The method as recited in claim 1, wherein color information of each cell of a three-dimensional cube is transmitted to nearby cells of said three-dimensional cube.\",\n \"8.The method as recited in claim 1, wherein said multi-dimensional dataset comprises online analytical processing based multi-dimensional data.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Analyzing data differences due to changes made in the system is often very difficult, especially for multi-dimensional datasets, such as online analytical processing (OLAP) based multi-dimensional datasets.\",\n \"In computing, OLAP is an approach to answering multi-dimensional analytical queries swiftly.\",\n \"Typical applications of OLAP include business reporting for sales, marketing, management reporting, business processing management, budgeting and forecasting, financial reporting and similar areas.\",\n \"Currently, in attempting to quantify or understand the effects to the multi-dimensional data from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, month of January versus the month of April), the user will review and compare the data, such as comparing the data in two tables side by side.\",\n \"However, such a process is time-consuming and inefficient and perhaps error-prone in quantifying or understanding the effects to the data from changes made in the system.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>In one embodiment of the present invention, a method for visualizing changes in a multi-dimensional dataset comprises receiving a multi-dimensional dataset of discrete data.\",\n \"The method further comprises identifying a number of dimensions in the multi-dimensional dataset of discrete data.\",\n \"The method additionally comprises creating, by a processor, one or more levels of three-dimensional cubes of discrete data equal to the number of number of dimensions in the multi-dimensional dataset divided by three rounded to a lowest positive integer, where each of the one or more levels of three-dimensional cubes of discrete data contains three dimensions of discrete data.\",\n \"Furthermore, the method comprises encoding, by the processor, the discrete data at each level of the one or more levels of three-dimensional cubes.\",\n \"Additionally, the method comprises associating a color palette with the encoded discrete data.\",\n \"Other forms of the embodiment of the method described above are in a system and in a computer program product.\",\n \"The foregoing has outlined rather generally the features and technical advantages of one or more embodiments of the present invention in order that the detailed description of the present invention that follows may be better understood.\",\n \"Additional features and advantages of the present invention will be described hereinafter which may form the subject of the claims of the present invention.\"\n ],\n [\n \"TECHNICAL FIELD The present invention relates generally to analyzing data, and more particularly to visualizing changes in a multi-dimensional dataset (e.g., online analytical processing (OLAP) based multi-dimensional data) using three-dimensional cubes associated with a two-dimensional table or a one-dimensional straight line, if necessary.\",\n \"BACKGROUND Analyzing data differences due to changes made in the system is often very difficult, especially for multi-dimensional datasets, such as online analytical processing (OLAP) based multi-dimensional datasets.\",\n \"In computing, OLAP is an approach to answering multi-dimensional analytical queries swiftly.\",\n \"Typical applications of OLAP include business reporting for sales, marketing, management reporting, business processing management, budgeting and forecasting, financial reporting and similar areas.\",\n \"Currently, in attempting to quantify or understand the effects to the multi-dimensional data from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, month of January versus the month of April), the user will review and compare the data, such as comparing the data in two tables side by side.\",\n \"However, such a process is time-consuming and inefficient and perhaps error-prone in quantifying or understanding the effects to the data from changes made in the system.\",\n \"SUMMARY In one embodiment of the present invention, a method for visualizing changes in a multi-dimensional dataset comprises receiving a multi-dimensional dataset of discrete data.\",\n \"The method further comprises identifying a number of dimensions in the multi-dimensional dataset of discrete data.\",\n \"The method additionally comprises creating, by a processor, one or more levels of three-dimensional cubes of discrete data equal to the number of number of dimensions in the multi-dimensional dataset divided by three rounded to a lowest positive integer, where each of the one or more levels of three-dimensional cubes of discrete data contains three dimensions of discrete data.\",\n \"Furthermore, the method comprises encoding, by the processor, the discrete data at each level of the one or more levels of three-dimensional cubes.\",\n \"Additionally, the method comprises associating a color palette with the encoded discrete data.\",\n \"Other forms of the embodiment of the method described above are in a system and in a computer program product.\",\n \"The foregoing has outlined rather generally the features and technical advantages of one or more embodiments of the present invention in order that the detailed description of the present invention that follows may be better understood.\",\n \"Additional features and advantages of the present invention will be described hereinafter which may form the subject of the claims of the present invention.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS A better understanding of the present invention can be obtained when the following detailed description is considered in conjunction with the following drawings, in which: FIG.\",\n \"1 illustrates an embodiment of the present invention of a hardware configuration of a computing device which is representative of a hardware environment for practicing the present invention; FIG.\",\n \"2 is a flowchart of a method for visualizing changes in a multi-dimensional dataset in accordance with an embodiment of the present invention; FIG.\",\n \"3 illustrates a three-dimensional cube of discrete data with the dimensions of products, time and measures in accordance with an embodiment of the present invention; FIG.\",\n \"4 illustrates a one-dimensional straight line of the fourth dimension of stores in accordance with an embodiment of the present invention; FIG.\",\n \"5 graphically illustrates the number of cells in the 4 dimensional cube dataset by showing the 27 cells for each dimension of the three-dimensional cube in accordance with an embodiment of the present invention; FIG.\",\n \"6 illustrates a two-dimensional table of the fourth and fifth dimensions of stores and locations, respectively, in accordance with an embodiment of the present invention; FIG.\",\n \"7 illustrates three levels of a three-dimensional cube of discrete data in accordance with an embodiment of the present invention; and FIG.\",\n \"8 illustrates a one-dimensional straight line of the tenth dimension in accordance with an embodiment of the present invention.\",\n \"DETAILED DESCRIPTION The present invention comprises a method, system and computer program product for visualizing changes in a multi-dimensional dataset.\",\n \"In one embodiment of the present invention, a multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data, is received.\",\n \"The number of dimensions in the multi-dimensional dataset of discrete data is then identified.\",\n \"For example, if the multi-dimensional dataset contains data for the dimensions of products, time, stores and measures, then the number of dimensions contained in the multi-dimensional dataset is four.\",\n \"One or more levels of three-dimensional cubes of discrete data are then created equal to the number of dimensions in the multi-dimensional dataset divided by three rounded to the lowest positive integer.\",\n \"For instance, referring to the above example, if the number of dimensions contained in the multi-dimensional dataset is four, then the number of four divided by three rounded to the lowest positive integer is one.\",\n \"As a result, a single level of a three-dimensional cube of discrete data would be created.\",\n \"The discrete data of the one or more levels of three-dimensional cubes is encoded.\",\n \"A color palette is then associated with the encoded discrete data.\",\n \"As a result of the present invention, a user is able to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.\",\n \"In the following description, numerous specific details are set forth to provide a thorough understanding of the present invention.\",\n \"However, it will be apparent to those skilled in the art that the present invention may be practiced without such specific details.\",\n \"In other instances, well-known circuits have been shown in block diagram form in order not to obscure the present invention in unnecessary detail.\",\n \"For the most part, details considering timing considerations and the like have been omitted inasmuch as such details are not necessary to obtain a complete understanding of the present invention and are within the skills of persons of ordinary skill in the relevant art.\",\n \"Referring now to the Figures in detail, FIG.\",\n \"1 illustrates an embodiment of the present invention of the hardware configuration of a computing device 100 which is representative of a hardware environment for practicing the present invention.\",\n \"Computing device 100 may be any type of computing device (e.g., portable computing unit, Personal Digital Assistant (PDA), smartphone, laptop computer, mobile phone, navigation device, game console, desktop computer system, workstation, Internet appliance and the like) configured with the capability of visualizing changes in a multi-dimensional dataset (e.g., online analytical processing based multi-dimensional data).\",\n \"Referring to FIG.\",\n \"1, computing device 100 may have a processor 101 coupled to various other components by system bus 102.An operating system 103 may run on processor 101 and provide control and coordinate the functions of the various components of FIG.\",\n \"1.An application 104 in accordance with the principles of the present invention may run in conjunction with operating system 103 and provide calls to operating system 103 where the calls implement the various functions or services to be performed by application 104.Application 104 may include, for example, a program for visualizing changes in a multi-dimensional dataset as discussed further below in connection with FIGS.\",\n \"2-8.Referring again to FIG.\",\n \"1, read-only memory (“ROM”) 105 may be coupled to system bus 102 and include a basic input/output system (“BIOS”) that controls certain basic functions of computing device 100.Random access memory (“RAM”) 106 and disk adapter 107 may also be coupled to system bus 102.It should be noted that software components including operating system 103 and application 104 may be loaded into RAM 106, which may be computing device's 100 main memory for execution.\",\n \"Disk adapter 107 may be an integrated drive electronics (“IDE”) adapter that communicates with a disk unit 108, e.g., disk drive.\",\n \"It is noted that the program for visualizing changes in a multi-dimensional dataset, as discussed further below in connection with FIGS.\",\n \"2-8, may reside in disk unit 108 or in application 104.Computing device 100 may further include a communications adapter 109 coupled to bus 102.Communications adapter 109 may interconnect bus 102 with an outside network thereby allowing computing device 100 to communicate with other devices.\",\n \"I/O devices may also be connected to computing device 100 via a user interface adapter 110 and a display adapter 111.Keyboard 112, mouse 113 and speaker 114 may all be interconnected to bus 102 through user interface adapter 110.A display monitor 115 may be connected to system bus 102 by display adapter 111.In this manner, a user is capable of inputting to computing device 100 through keyboard 112 or mouse 113 and receiving output from computing device 100 via display 115 or speaker 114.Other input mechanisms may be used to input data to computing device 100 that are not shown in FIG.\",\n \"1, such as display 115 having touch-screen capability and keyboard 112 being a virtual keyboard.\",\n \"Computing device 100 of FIG.\",\n \"1 is not to be limited in scope to the elements depicted in FIG.\",\n \"1 and may include fewer or additional elements than depicted in FIG.\",\n \"1.The present invention may be a system, a method, and/or a computer program product.\",\n \"The computer program product may include a computer readable storage medium (or media) having computer readable program instructions thereon for causing a processor to carry out aspects of the present invention.\",\n \"The computer readable storage medium can be a tangible device that can retain and store instructions for use by an instruction execution device.\",\n \"The computer readable storage medium may be, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing.\",\n \"A non-exhaustive list of more specific examples of the computer readable storage medium includes the following: a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), a static random access memory (SRAM), a portable compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a memory stick, a floppy disk, a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon, and any suitable combination of the foregoing.\",\n \"A computer readable storage medium, as used herein, is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g., light pulses passing through a fiber-optic cable), or electrical signals transmitted through a wire.\",\n \"Computer readable program instructions described herein can be downloaded to respective computing/processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network and/or a wireless network.\",\n \"The network may comprise copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers and/or edge servers.\",\n \"A network adapter card or network interface in each computing/processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for storage in a computer readable storage medium within the respective computing/processing device.\",\n \"Computer readable program instructions for carrying out operations of the present invention may be assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++ or the like, and conventional procedural programming languages, such as the “C” programming language or similar programming languages.\",\n \"The computer readable program instructions may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server.\",\n \"In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).\",\n \"In some embodiments, electronic circuitry including, for example, programmable logic circuitry, field-programmable gate arrays (FPGA), or programmable logic arrays (PLA) may execute the computer readable program instructions by utilizing state information of the computer readable program instructions to personalize the electronic circuitry, in order to perform aspects of the present invention.\",\n \"Aspects of the present invention are described herein with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention.\",\n \"It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer readable program instructions.\",\n \"These computer readable program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.\",\n \"These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and/or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function/act specified in the flowchart and/or block diagram block or blocks.\",\n \"The computer readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions/acts specified in the flowchart and/or block diagram block or blocks.\",\n \"The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention.\",\n \"In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function(s).\",\n \"In some alternative implementations, the functions noted in the block may occur out of the order noted in the figures.\",\n \"For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved.\",\n \"It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts or carry out combinations of special purpose hardware and computer instructions.\",\n \"As stated in the Background section, analyzing data differences due to changes made in the system is often very difficult, especially for multi-dimensional datasets, such as online analytical processing (OLAP) based multi-dimensional datasets.\",\n \"In computing, OLAP is an approach to answering multi-dimensional analytical queries swiftly.\",\n \"Typical applications of OLAP include business reporting for sales, marketing, management reporting, business processing management, budgeting and forecasting, financial reporting and similar areas.\",\n \"Currently, in attempting to quantify or understand the effects to the multi-dimensional data from changes made in the system (e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, month of January versus the month of April), the user will review and compare the data, such as comparing the data in two tables side by side.\",\n \"However, such a process is time-consuming and inefficient and perhaps error-prone in quantifying or understanding the effects to the data from changes made in the system.\",\n \"The principles of the present invention provide a means for quantifying and understanding the effects to data in a multi-dimensional dataset from changes made in the system by visualizing changes in the multi-dimensional dataset using one or more levels of three-dimensional cubes of discrete data along with an associated two-dimensional table or one-dimensional straight line, if necessary, as discussed below in connection with FIGS.\",\n \"2-8.For example, by using the principles of the present invention, a user will be able to quantify and understand the effects to data, such as the change in the frequency or quantum of data, in a multi-dimensional dataset from changes made in the system (e.g., adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.\",\n \"As an example, the present invention would be able to assist the user in better understanding and quantifying what part of the country was most affected by a sales tax increase on a set of products.\",\n \"FIG.\",\n \"2 is a flowchart of a method for visualizing changes in a multi-dimensional dataset.\",\n \"FIG.\",\n \"3 illustrates a three-dimensional cube of discrete data with the dimensions of products, time and measures.\",\n \"FIG.\",\n \"4 illustrates a one-dimensional straight line of the fourth dimension of stores.\",\n \"FIG.\",\n \"5 graphically illustrates the number of cells in the 4 dimensional cube dataset by showing the 27 cells for each dimension of the three-dimensional cube.\",\n \"FIG.\",\n \"6 illustrates a two-dimensional table of the fourth and fifth dimensions of stores and locations, respectively.\",\n \"FIG.\",\n \"7 illustrates three levels of a three-dimensional cube of discrete data.\",\n \"FIG.\",\n \"8 illustrates a one-dimensional straight line of the tenth dimension.\",\n \"As stated above, FIG.\",\n \"2 is a flowchart of a method 200 for visualizing changes in a multi-dimensional dataset in accordance with an embodiment of the present invention.\",\n \"Referring to FIG.\",\n \"2, in conjunction with FIG.\",\n \"1, in step 201, computing device 100 receives a multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data.\",\n \"In step 202, computing device 100 identifies a number of dimensions in the multi-dimensional dataset of discrete data.\",\n \"For example, if the multi-dimensional dataset contains data for the dimensions of products, time, stores and measures, then the number of dimensions contained in the multi-dimensional dataset is four.\",\n \"In step 203, computing device 100 computes the number equal to the number of dimensions in the multi-dimensional dataset divided by three.\",\n \"For example, if the number of dimensions contained in the multi-dimensional dataset is four, then computing device 100 computes the number 4/3 in step 203.In step 204, computing device 100 creates one or more levels of three-dimensional cubes of discrete data equal to the number of dimensions in the multi-dimensional dataset divided by three rounded to the lowest positive integer.\",\n \"For instance, referring to the above example, if the number of dimensions contained in the multi-dimensional dataset is four, then the number of four divided by three rounded to the lowest positive integer is one.\",\n \"As a result, computing device 100 would create a single level of a three-dimensional cube of discrete data.\",\n \"In another example, if the number of dimensions contained in the multi-dimensional dataset is ten, then the number of ten divided by three rounded to the lowest positive integer is three.\",\n \"As a result, computing device 100 would create three levels of three-dimensional cubes of discrete data.\",\n \"In one embodiment, each level of the three-dimensional cubes contains three dimensions of discrete data.\",\n \"In step 205, a determination is made by computing device 100 as to whether the number computed in step 203 ends in 1/3 or 2/3.If the number computed in step 203 ends in 1/3 or 2/3, then, in step 206, computing device 100 creates a one-dimensional straight line of three elements containing one-dimension of discrete data in response to the computed number ending in 1/3 or creates a two-dimensional table of cells with each row representing an element from a first dimension and each column representing an element of a second dimension in response to the computed number ending in 2/3.For example, suppose that the received multi-dimensional dataset is a four dimensional dataset of discrete data, such as data with the dimensions of products, time, stores and measures.\",\n \"Since the number of dimensions divided by three is 1 and 1/3, computing device 100 will create one level of a three-dimensional cube of discrete data along with a one-dimensional straight line containing three elements as shown in FIGS.\",\n \"3 and 4.FIG.\",\n \"3 illustrates a three-dimensional cube 300 of discrete data with the dimensions of products, time and measures in accordance with an embodiment of the present invention.\",\n \"As illustrated in FIG.\",\n \"3, three-dimensional cube 300 contains cells 301 storing the discrete data.\",\n \"FIG.\",\n \"4 illustrates a one-dimensional straight line 400 of the fourth dimension of stores in accordance with an embodiment of the present invention.\",\n \"Referring to FIGS.\",\n \"3 and 4, in one embodiment, the one-dimensional straight line of the fourth dimension of stores contains three elements 401.In one embodiment, the content of elements 401 of one-dimensional straight line 400 contains a pointer to three-dimensional cube 300, which contains the data for that particular store.\",\n \"In one embodiment, each dimension in the multi-dimensional dataset of discrete data is represented by three elements/items/members.\",\n \"As a result, the multi-dimensional dataset of discrete data is represented by a total of 3N total cells, where N is equal to the number of dimensions in the multi-dimensional dataset of discrete data.\",\n \"Hence, referring to the above example, if each dimension (four dimensions in the example) is represented by three elements/items/members, then the total cube will have 34 (81) cells as shown in FIG.\",\n \"5.It is noted that the principles of the present invention are not to be limited in scope to having each dimension in the multi-dimensional dataset of discrete data being represented by three elements/items/members.\",\n \"Instead, each dimension in the multi-dimensional dataset of discrete data may be represented by one or more elements/items/members.\",\n \"A person of ordinary skill in the art would be capable of applying the principles of the present invention to such implementations.\",\n \"Further, embodiments applying the principles of the present invention to such implementations would fall within the scope of the present invention.\",\n \"FIG.\",\n \"5 graphically illustrates the number of cells in the 4 dimensional cube dataset by showing the 27 cells for each dimension in space of the three-dimensional cube 300 (represented by cube 300′ for the first dimension, cube 300″ for the second dimension and cube 300″' for the third dimension) in accordance with an embodiment of the present invention.\",\n \"In another example, suppose that the received multi-dimensional dataset is a five dimensional dataset of discrete data, such as data with the dimensions of products, time, stores, measures and locations.\",\n \"Since the number of dimensions divided by three is 1 and 2/3, computing device 100 will create one level of a three-dimensional cube of discrete data along with a two-dimensional table as shown in FIGS.\",\n \"3 and 6.As previously discussed, FIG.\",\n \"3 illustrates a three-dimensional cube 300 of discrete data with the dimensions of products, time and measures in accordance with an embodiment of the present invention.\",\n \"FIG.\",\n \"6 illustrates a two-dimensional table 600 of the fourth and fifth dimensions of stores and locations, respectively, in accordance with an embodiment of the present invention.\",\n \"Referring to FIG.\",\n \"6, in one embodiment, each row in table 600 represents an element from the fourth dimension (stores) and each column represents an element from the fifth dimension (locations).\",\n \"Each cell 601 in table 600 represents a combination of the fourth and fifth dimensions (stores and locations) and will act as a pointer to three-dimensional cube 300 comprised of the first, second and third dimensions (products, time and measures).\",\n \"Since each dimension is represented by three elements/items/members in the exemplary embodiment, then the total cube (5 dimensional cube dataset), including the three-dimensional cube 300 and the two-dimensional table 600, will have 35 (243) cells as illustrated in FIG.\",\n \"6.Since each cell 601 in table 600 points to a possible number of 27 cells of three-dimensional cube 300, then there is a total of 243 cells as illustrated in FIG.\",\n \"6.It is noted that the principles of the present invention are not to be limited in scope to having each dimension of the three-dimensional cube 300 being represented by 27 cells based on each dimension of the multi-dimensional dataset being represented by three elements/items/members.\",\n \"Instead, each dimension of the three-dimensional cube 300 may be represented by a different number of cells, such as the first dimension having twenty cells, the second dimension having twenty-five cells and the third dimension having a single cell.\",\n \"In a further example, suppose that the received multi-dimensional dataset is a ten dimensional dataset of discrete data.\",\n \"Since the number of dimensions divided by three is 3 and 1/3, computing device 100 will create three levels of a three-dimensional cube of discrete data along with a one-dimensional straight line as shown in FIGS.\",\n \"7 and 8.FIG.\",\n \"7 illustrates three levels of a three-dimensional cube of discrete data (identified by cubes 701,702 and 703) in accordance with an embodiment of the present invention.\",\n \"Three-dimensional cube 701 is said to be the first level of a three-dimensional cube containing the discrete data for the first three dimensions, the first, second and third dimensions.\",\n \"Three-dimensional cube 702 is said to be the second level of a three-dimensional cube containing the discrete data for the second three dimensions, the fourth, fifth and sixth dimensions.\",\n \"Furthermore, three-dimensional cube 703 is said to be the third level of a three-dimensional cube containing the discrete data for the three dimensions, the seventh, eighth and ninth dimensions.\",\n \"FIG.\",\n \"8 illustrates a one-dimensional straight line 800 of the tenth dimension in accordance with an embodiment of the present invention.\",\n \"Referring to FIGS.\",\n \"7 and 8, in one embodiment, each element 801 of one-dimensional straight line 800 is a pointer to a cell 704 in the lowest-level three-dimensional cube (in this case the third level three-dimensional cube 703 containing the discrete data for the three dimensions, the seventh, eighth and ninth dimensions).\",\n \"Each cell 704 in cube 703 will be a pointer to a cell 705 in the next highest-level three-dimensional cube (in this case the second level three-dimensional cube 702 containing the discrete data for the three dimensions, the fourth, fifth and sixth dimensions).\",\n \"Furthermore, each cell 705 in cube 704 will be a pointer to a cell 706 in the highest-level three-dimensional cube 701 (the first level three-dimensional cube 701 containing the discrete data for the three dimensions, the first, second and third dimensions).\",\n \"As a result, the 10 dimensional cube dataset includes a one-dimensional straight line 800 and three three-dimensional cubes 701, 702, 703, where the elements 801 of one-dimensional straight line 800 and cells 704, 705 of three-dimensional cubes 702, 703 contain pointers, whereas, cells 706 of the first level three-dimensional cube 701 will contain values (e.g., numeric values, string values).\",\n \"Since each dimension is represented by three elements/items/members in the exemplary embodiment, then the total cube (10 dimensional cube dataset), including the three three-dimensional cubes 701, 702, 703 and the one-dimensional straight line 800, will have 310 (59,049) cells.\",\n \"Returning to FIG.\",\n \"2, in conjunction with FIGS.\",\n \"1 and 3-8, upon creating a one-dimensional straight line or a two-dimensional table or if the number computed in step 203 did not end in 1/3 or 2/3, then, in step 207, computing device 100 encodes the discrete data of the one or more levels of the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) and any associated one-dimensional straight line (e.g., one-dimensional straight line 800) or two-dimensional table (e.g., two-dimensional table 600).\",\n \"That is, in one embodiment, computing device 100 encodes the discrete data at each level of the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) and any associated one-dimensional straight line (e.g., one-dimensional straight line 800) or two-dimensional table (e.g., two-dimensional table 600).\",\n \"“Encoding,” as used herein, refers to converting the discrete data into a proper range based discrete data so as to more easily identify the important data points or data sets.\",\n \"In one embodiment, depending on the type of data contained in the cube dataset as well as the type of analysis to be performed on the data, various types of encoding functions could be used.\",\n \"For example, if the frequency of change in a set of numbers needs to be viewed, then histograms may be utilized.\",\n \"In another example, if the quantum of change in all the numbers needs to be viewed, then the data could be partitioned into various sets, where each set contains a number between a minimum and a maximum value.\",\n \"In step 208, computing device 100 associates a color palette with the encoded data.\",\n \"Since it may be difficult to identify important data points or data sets by presenting the data as a continuous color, the discrete data is encoded as discussed above, and later assigned a specific color (e.g., assign the color blue for data points between the values of x and y) so as to be able to easily analyze the data, such as analyzing data above or below a certain threshold as discussed below.\",\n \"As a result of the present invention, a user is able to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.\",\n \"In one embodiment, the discrete data that is encoded may be said to be “pseudo continuous” in that the difference between the values of the data may be small (i.e., the values of the various data may appear to be the same to the user).\",\n \"For example, if the sales data for various months were plotted on a graph, the bar graphs representing the sales data for these months may be appear to be the same height to the user and hence causing the data to appear continuous.\",\n \"Consequently, such data may be said to be “pseudo continuous.” As a result, a transformation function can be applied to these values thereby creating “proper discrete data” from the pseudo continuous data to enable a user to quantify and understand the effects to data in a multi-dimensional dataset from changes made in the system (e.g., e.g., using version 2 instead of version 1, adding/deleting/modifying business rules, changes in the development model) in a more efficient and accurate manner.\",\n \"As discussed above, computing device 100 associates a color palette with the encoded data.\",\n \"For example, suppose that the numbers with a value between −10 and 2000 changed due a change in a factor in the system (e.g., modification of a business rule).\",\n \"If a user would like to view the quantum of change in a single color, then the discrete data could be encoded by partitioning the data into various sets, such as a set with values between −10 and 2000, a set that contains numbers with values below −10 and a set that contains numbers with values greater than 2000.The partition that contains numbers between −10 and 2000 could then be associated with a color (e.g., blue) thereby enabling the user to more easily identify the quantum of change.\",\n \"In another example, the user may want to further view the quantum of change within the partition containing the numbers between −10 and 2000.As a result, two partitions could be devised, where the first partition contains numbers between −10 and 1005 (1005 is the midpoint between the values of −10 and 2000) and the second partition contains numbers between 1006 and 2010.Each partition could then be associated with a color to enable the user to more easily identify the quantum of change within these ranges of values.\",\n \"In one embodiment, when there are multiple levels of three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703), the color information in the lowest-level cube (e.g., three-dimensional cube 703) is transferred upwards to the “pointer” cubes (referring to those cubes with cells containing pointers to the next higher level cube) (e.g., three-dimensional cube 702) based on the numeric weight of the individual colors of each cell (e.g., cell 704) of the lowest-level cube (e.g., three-dimensional cube 703).\",\n \"Furthermore, in one embodiment, functional transformation could also be applied to the weights to increase the quantum of change transferred and the redistribution of the transformed weights could be done based on the color palette.\",\n \"In one embodiment, once the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) have been color coded, they may be traversed where a single color palette acts as a guiding mechanism.\",\n \"In another embodiment, since the three-dimensional cubes (e.g., three-dimensional cubes 701, 702, 703) are represented in three-dimensions, there could be cube components or cells (e.g., cells 704, 705, 706) that are not visible in three-dimensions even after rotating the cube in 360 degrees.\",\n \"In such a scenario, each cell (e.g., cells 704, 705, 706) could transfer its color information to nearby cells as well.\",\n \"Once each cell (e.g., cells 704, 705, 706) transmits its color information to nearby cells and the calculated weighted information is kept within each cell, markers (such as in multiple of 3) could be utilized to identify the most important cells, such as by having those cells appear darker.\",\n \"As a result, a user could more easily analyze even the hidden cells.\",\n \"Furthermore, markers can be utilized to assist the user in identifying the data of interest in other levels of the three-dimensional cubes.\",\n \"For instance, a user could review the data associated with a marker, such as on the highest level cube (e.g., three-dimensional cube 701).\",\n \"The user could then select the data marker which would result in the user being shown the details of the marker in the next lower-level cube (e.g., three-dimensional cube 702).\",\n \"The descriptions of the various embodiments of the present invention have been presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed.\",\n \"Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments.\",\n \"The terminology used herein was chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874667"}}},{"rowIdx":4494665,"cells":{"text":{"kind":"list like","value":[["METHOD AND APPARATUS FOR TRANSMITTING ACK/NACK SIGNAL IN WIRELESS COMMUNICATION SYSTEM","The present invention relates to a method and apparatus for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) signal in a wireless communication system.","The method includes the steps of: receiving a transmission block; and transmitting an ACK/NACK signal for the transmission block in a first subframe or a second subframe according to the size of the transmission block, wherein, when the size of the transmission block is smaller than or equal to a reference value, the ACK/NACK signal is transmitted in the first frame, when the size of the transmission block is greater than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain."],["1-11.","(canceled) 12.A method for transmitting acknowledgement/not-acknowledgement (ACK/NACK) information, the method performed by a user equipment (UE) and comprising: receiving data scheduled by downlink control information (DCI) in a subframe n; and transmitting ACK/NACK information for the data in a subframe n+kadd, wherein each of the n and the kadd is an integer, and wherein a value of kadd depends on the DCI.","13.The method of claim 12, wherein the value of kadd is a natural number larger than 4.14.The method of claim 12, wherein the DCI includes a field informing the value of kadd.","15.The method of claim 12, wherein the value of kadd is larger than 4.16.The method of claim 12, wherein the UE uses a frequency division duplex (FDD) frame.","17.A user equipment (UE), comprising: a transceiver which transmits or receives a radio signal; and a processor connected with the transceiver, wherein the processor receives data scheduled by downlink control information (DCI) in a subframe n, and transmis ACK/NACK information for the data in a subframe n+kadd, wherein each of the n and the kadd is an integer, and wherein a value of kadd depends on the DCI.","18.The UE of claim 17, wherein the value of kadd is a natural number larger than 4.19.The UE of claim 17, wherein the DCI includes a field informing the value of kadd.","20.The UE of claim 17, wherein the value of kadd is larger than 4.21.The UE of claim 17, wherein the UE uses a frequency division duplex (FDD) frame."],["<SOH> BACKGROUND OF THE INVENTION <EOH>"],["<SOH> SUMMARY OF THE INVENTION <EOH>An object of the present invention is to provide a method and an apparatus for transmitting an ACK/NACK in a wireless communication system.","In accordance with an aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK signal for the transport block in a first subframe or a second subframe according to the size of the transport block, wherein, when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.","In accordance with another aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK for the transport block in a predetermined subframe when the size of the transport block is larger than a reference value, and not transmitting the ACK/NACK for the transport block when the size of the transport block is equal to or smaller than the reference value.","In accordance with yet another aspect of the present invention, a user equipment includes: a radio frequency (RF) unit which transmits or receives a radio signal; and a processor connected with the RF unit, wherein the processor receives a transport block and transmits an ACK/NACK for the transport block in a first subframe or a second subframe according to the size of the transport block, and when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.","An HARQ process can be efficiently performed under a situation in which a data decoding capability is limited.","Accordingly, system performance is improved."],["BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a wireless communication system, and more particularly, to a method and an apparatus for transmitting a reception acknowledgment for a hybrid automatic repeat request of a user equipment in a wireless communication system.","Related Art 3rd generation partnership project (3GPP) long term evolution (LTE) (hereinafter, referred to as LTE) is an influential next-generation wireless communication system standard.","In the LTE, when a base station transmits downlink data to a user equipment, the base station first transmits scheduling information on a downlink data channel through a control channel, allocates the downlink data channel according to the scheduling information, and transmits the downlink data through the allocated downlink data channel.","The user equipment transmits to the base station reception acknowledgement/non-acknowledgement (ACK/NACK) of the downlink data and the base station may transmit new downlink data or retransmit pretransmitted downlink data according to the ACK/NACK.","Such a data transmission scheme is called a hybrid automatic repeat request (HARQ).","The HARQ includes synchronous and asynchronous HARQs, and in the case of the synchronous HARQ, synchronization is set between an HARQ process and a subframe, and as a result, new transmission/retransmission of the same HARQ process is performed according to a predetermined timing.","On the contrary, in the case of the asynchronous HARQ, the use of the HARQ is directly instructed without the synchronization between the HARQ process and the subframe.","Meanwhile, 3GPP LTE-A (long term evolution-advanced) (hereinafter, referred to as LTE-A) is a next-generation wireless communication system standard developed by improving the LTE.","The LTE-A can support low price/low specification user equipments that primarily perform data communications such as meter reading, water level measurement, utilization of a monitoring camera, inventory reporting of a vending machine, and the like.","As described above, the low price/low specification user equipments that primarily perform low-capacity data communications are called a machine type communication (MTC) user equipment.","When the MTC user equipment exists in an area supported by the base station, it may be difficult to apply the ACK/NACK timing of the existing HARQ as it is.","For example, when the downlink data has a capacity larger than a capacity which the MTC user equipment can process within a specific time, the MTC user equipment may not decode all of the downlink data at the time of transmitting the ACK/NACK.","Further, in spite of not the MTC user equipment, data to be acknowledged/not acknowledged and a time up to the transmission timing of the ACK/NACK are insufficient, and as a result, an ACK/NACK response of the HARQ may not normally be performed during a predetermined time interval.","For example, the LTE-A can support carrier aggregation and support cross carrier scheduling.","In the cross carrier scheduling, scheduling information is simultaneously received through a specific cell, but data scheduled by the scheduling information may be received in different cells.","In this case, the different cells are not temporally aligned, and as a result, data may be received lately in some cells.","In this case, due to an insufficient time between the lately received data and an insufficient time and an ACK/NACK thereof, the lately received data may not normally be decoded.","Alternatively, in the LTE-A, a new control channel allocated to a data domain may be introduced in addition to the existing control channel allocated to a control domain.","Since the new control channel may exist in the data domain, a decoding time of data scheduled by the new control channel may be insufficient according to the user equipment.","Therefore, new ACK/NACK transmitting method and apparatus which can be applied to an advanced wireless communication system such as the LTE-A are required.","SUMMARY OF THE INVENTION An object of the present invention is to provide a method and an apparatus for transmitting an ACK/NACK in a wireless communication system.","In accordance with an aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK signal for the transport block in a first subframe or a second subframe according to the size of the transport block, wherein, when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.","In accordance with another aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK for the transport block in a predetermined subframe when the size of the transport block is larger than a reference value, and not transmitting the ACK/NACK for the transport block when the size of the transport block is equal to or smaller than the reference value.","In accordance with yet another aspect of the present invention, a user equipment includes: a radio frequency (RF) unit which transmits or receives a radio signal; and a processor connected with the RF unit, wherein the processor receives a transport block and transmits an ACK/NACK for the transport block in a first subframe or a second subframe according to the size of the transport block, and when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.","An HARQ process can be efficiently performed under a situation in which a data decoding capability is limited.","Accordingly, system performance is improved.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 illustrates a structure of an FDD radio frame.","FIG.","2 illustrates a structure of a TDD radio frame.","FIG.","3 illustrates one example of a resource grid for one downlink slot.","FIG.","4 illustrates a structure of a downlink subframe.","FIG.","5 illustrates a structure of an uplink subframe.","FIG.","6 illustrates a comparative example of a single carrier system and a carrier aggregation system.","FIG.","7 illustrates a channel coding process (channel coding chain) of a transport block.","FIG.","8 illustrates a method for transmitting an ACK/NACK of a user equipment according to an embodiment of the present invention.","FIG.","9 illustrates data receiving and ACK/NACK transmitting timings of the user equipment by the method of FIG.","8.FIG.","10 illustrates a method for transmitting an ACK/NACK of a user equipment according to another embodiment of the present invention.","FIG.","11 illustrates a method for transmitting an ACK/NACK according to the present invention.","FIG.","12 is a block diagram illustrating a wireless apparatus in which the embodiment of the present invention is implemented.","DESCRIPTION OF EXEMPLARY EMBODIMENTS The user equipment (UE) may be fixed or movable and may be called other terms such as a mobile station (MS), a mobile terminal (MT), a user terminal (UT), a subscriber station (SS), a wireless device, a personal digital assistant (PDA), a wireless modem, a handheld device, and the like.","The base station generally represents a fixed station that communicates with the user equipment, and may be called other terms such as an evolved-NodeB (eNB), a base transceiver system (BTS), an access point, and the like.","A communication from the base station to the user equipment is called a downlink DL and a communication from the user equipment to the base station is called an uplink UL.","A wireless communication system including the base station and the user equipment may be a time division duplex (TDD) or a frequency division duplex (FDD) system.","The TDD system is a wireless communication system that performs uplink and downlink transmission and reception by using different timings in the same frequency band.","The FDD system is a wireless communication system that can perform the uplink and downlink transmission and reception simultaneously by using different frequency bands.","The wireless communication system may perform the communication by using the radio frame.","FIG.","1 illustrates a structure of an FDD radio frame.","The FDD radio frame includes 10 subframes and one subframe two consecutive slots.","Slots included in the radio frames are indexed with 0 to 19.A time required to transmit one subframe is a transmission time interval (TTI) and the TTI may be a minimum scheduling unit.","For example, the length of one subframe may be 1 ms and the length of one slot may be 0.5 ms.","FIG.","2 illustrates a structure of a TDD radio frame.","Referring to FIG.","2, a subframe having index #1 and index #6 is called a special subframe and includes a downlink pilot time slot (DwPTS), a guard period (GP), and an uplink pilot time slot (UpPTS).","The DwPTS is used in initial cell search, synchronization, or channel estimation in the user equipment.","The UpPTS is used to match channel estimation in the base station and uplink transmission synchronization of the user equipment.","The GP is a period for removing an interference which occurs in the uplink due to a multipath delay of the downlink signal between the uplink and the downlink.","In the TDD, a downlink (DL) subframe and an uplink (UL) subframe coexist in one radio frame.","Table 1 illustrates one example of a UL-DL configuration of the radio frame.","TABLE 1 Downlink- to-uplink Uplink- Switch- downlink point Subframe n configuration periodicity 0 1 2 3 4 5 6 7 8 9 0 5 ms D S U U U D S U U U 1 5 ms D S U U D D S U U D 2 5 ms D S U D D D S U D D 3 10 ms D S U U U D D D D D 4 10 ms D S U U D D D D D D 5 10 ms D S U D D D D D D D 6 5 ms D S U U U D S U U D In Table 1, ‘D’ represents a DL subframe, IT represents a UL subframe, and ‘S’ represents the special subframe.","When the user equipment receives the UL-DL configuration from the base station, the user equipment may know whether each subframe is the DL subframe or the UL subframe in the radio frame.","Hereinafter, a UL-DL configuration N (N is any one of 0 to 6) may refer to Table 1.FIG.","3 illustrates one example of a resource grid for one downlink slot.","Referring to FIG.","3, the downlink slot may include a plurality of orthogonal frequency division multiplexing (OFDM) symbols in a time domain and NRB resource blocks (RBs) in a frequency domain.","The resource block as the resource allocation unit includes one slot in the time domain and a plurality of consecutive subcarriers in the frequency domain.","The number NRB of resource blocks included in the downlink slot is subordinate to a downlink bandwidth NDL set in a cell.","For example, in an LTE system, NRB may be any one of 6 to 110.A structure of an uplink slot may also be the same as that of the downlink slot.","Each element on the resource grid is called a resource element (RE).","The resource element on the resource grid may be identified by a pair of indexes (k,l) in the slot.","Herein, k (k=0, .",".",".",", NRB×12-1) represents a subcarrier index in the frequency domain and l (l=0, .",".",".",", 6) represents an OFDM symbol index in the time domain.","In FIG.","3, it is exemplarily described that one resource block is constituted by 7 OFDM symbols in the time domain and 12 subcarriers in the frequency domain and thus includes 7×12 resource elements, but the number of the OFDM symbols and the number of the subcarriers in the resource block are not limited thereto.","The number of the OFDM symbols and the number of the subcarriers may be variously changed depending on the length of a CP, frequency spacing, and the like.","As the number of subcarriers in one OFDM symbol, one may be selected and used among 128, 256, 512, 1024, 1536, and 2048.FIG.","4 illustrates a structure of a downlink subframe.","Referring to FIG.","4, the downlink (DL) subframe is divided into a control region and a data region.","The control region includes maximum three (maximum four in some cases) precedent OFDM symbols of a first slot in the subframe, but the number of OFDM symbols included in the control region may be changed.","A physical downlink control channel (PDCCH) and other control channel are allocated to the control region and a physical downlink shared channel (PDSCH) is allocated to the data region.","As disclosed in 3GPP TS 36.211 V8.7.0, a physical channel in 3GPP LTE may be divided into the physical downlink shared channel (PDSCH) and a physical uplink shared channel (PUSCH) which are data channels, and a physical downlink control channel (PDCCH), a physical control format indicator channel (PCFICH), a physical hybrid-ARQ indicator channel (PHICH), and a physical uplink control channel (PUCCH) which are data channels.","The PCFICH transmitted in a first OFDM symbol of the subframe transports a control format indicator regarding the number (that is, the size of the control region) of OFDM symbols used to transmit control channels in the subframe.","The user equipment first receives the CFI on the PCFICH and thereafter, monitors the PDCCH.","Unlike the PDCCH, the PCFICH is transmitted through a fixed PCFICH resource of the subframe without using blind decoding.","The PHICH transports a positive-acknowledgment (ACK)/negative-acknowledgement (NACK) signal for an uplink hybrid automatic repeat request (HARQ).","An ACK/NACK signal for uplink (UL) data on the PUSCH transmitted by the user equipment is transmitted on the PHICH.","A physical broadcast channel (PBCH) is transmitted in four precedent OFDM symbols of a second slot of the first subframe of the radio frame.","The PBCH transports system information required for the user equipment to communicate with the base station and the system information transmitted through the PBCH is called a master information block (MIB).","As compared therewith, system information transmitted on the PDSCH instructed by the PDCCH is called a system information block (SIB).","Control information transmitted through the PDCCH is called downlink control information (DCI).","The DCI may include resource allocation (also referred to as downlink (DL) grant) of the PDSCH, resource allocation (also referred to as uplink (UL) grant) of the PUSCH, a set of transmission power control commands for individual UEs in a predetermined UE group, and/or activation of a voice over Internet protocol (VoIP).","Table 2 shown below exemplifies a DCI format and a usage.","TABLE 2 DCI format USAGE DCI FORMAT 0 USED IN SCHEDULING PUSCH DCI FORMAT 1 USED IN SCHEDULING ONE PDSCH CODWORD DCI FORMAT 1A USED IN COMPACT SCHEDULING OF ONE PDSCH CODEWORD AND RANDOM ACCESS PROCESS DCI FORMAT 1B USED IN COMPACT SCHEDULING OF ONE PDSCH CODEWORD HAVING PRECODING INFORMATION DCI FORMAT 1C USED IN VERY COMPACT SCHEDULING OF ONE PDSCH CODWORD DCI FORMAT 1D USED IN COMPACT SCHEDULING OF ONE PDSCH CODEWORD HAVING PRECODING AND POWER OFFSET INFORMATION DCI FORMAT 2 USED IN SCHEDULING PDSCH OF USER EQUIPMENTS SET IN CLOSE LOOP SPATIAL MULTIPLEXING MODE DCI FORMAT 2A USED IN SCHEDULING PDSCH OF USER EQUIPMENTS SET IN OPEN LOOP SPATIAL MULTIPLEXING MODE DCI FORMAT 3 USED IN TRANSMITTING TPC COMMAND OF PUCCH AND PUSCH HAVING 2 BIT POWER ADJUSTMENTS DCI FORMAT 3A USED IN TRANSMITTING TPC COMMAND OF PUCCH AND PUSCH HAVING 1 BIT POWER ADJUSTMENT DCI FORMAT 4 USED IN SCHEDULING PUSCH IN ONE UL CELL IN MULTI ANTENNA TRANSMISSION MODE FIG.","5 illustrates a structure of an uplink subframe.","Referring to FIG.","5, the uplink subframe may be divided into a control region to which the physical uplink control channel (PUCCH) transporting the uplink control information is allocated and a data region to which the physical uplink shared channel (PUSCH) transporting user data is allocated, in the frequency domain.","The PUCCH is allocated as a pair of RBs in the subframe.","The RBs that belong to the pair of RBs occupy different subcarriers in first and second slots, respectively.","The pair of RBs have the same resource block index m. According to the 3GPP TS 36.211 V8.7.0, the PUCCH supports multiple formats.","PUCCH having different bit numbers for each subframe may be used according to a modulation scheme subordinate to the PUCCH format.","PUCCH format 1 is used to transmit a scheduling request (SR), PUCCH format 1a/1b is used to transmit the ACK/NACK signal for the HARQ, PUCCH format 2 is used to transmit a CQI, and PUCCH format 2a/2b is used to simultaneously transmit the CQI and the ACK/NACK signal.","PUCCH format 3 may be used to transmit a plurality of ACKs/NACKs.","In the 3GPP LTE, a resource index n(1)PUCCH is defined in order for the user equipment to configure the PUCCH.","The resource index is defined as n(1)PUCCH=nCCE+N(1)PUCCH, nCCE is No.","of a first CCE used to transmit the corresponding PDCCH (that is, PDCCH including downlink resource allocation used to receive the downlink data corresponding to the ACK/NACK signal), and N(1)PUCCH is a parameter which the base station notifies to the user equipment as a higher layer message.","The resource that transmits the ACK/NACK may be instructed by the n(1)PUCCH and in this case, implicit mapping of the CCE and the ACK/NACK resource is used.","Hereinafter, a carrier aggregation system will be described.","The carrier aggregation system is also referred to as a multiple carrier system or a multiple cell system.","The 3GPP LTE system supports a case in which a downlink bandwidth and an uplink bandwidth are set to be different from each other, but this premises one component carrier (CC).","The 3GPP LTE system supports maximum 20 MHz and the uplink bandwidth and the downlink bandwidth may be different from each other, but the 3GPP LTE system supports only one CC to each of the uplink and the downlink.","On the contrary, carrier aggregation supports a plurality of CCs.","For example, when five CCs are allocated as granularity of the unit of the carrier having a bandwidth of 20 MHz, a bandwidth of maximum 100 MHz may be supported.","One DL CC or a pair of UL CC and DL CC may correspond to one cell.","Therefore, the user equipment that communicates with the base station through a plurality of DL CCs may receive a service from a plurality of serving cells.","FIG.","6 illustrates a comparative example of a single carrier system and a carrier aggregation system.","A carrier aggregation system (FIG.","6(b)) has each of three DL CCs and UL CCs, but the numbers of DL CCs and UL CCs are not limited.","In each DL CC, the PDCCH and the PDSCH may be independently transmitted and in each UL CC, the PUCCH and the PUSCH may be independently transmitted.","Alternatively, the PUCCH may be transmitted through only a specific UL CC.","Since three pairs of the DL CC and the UL CC are defined, the user equipment may receive the service from three serving cells.","The user equipment may monitor the PDCCH in the plurality of DL CCs and receive a DL transport block simultaneously through the plurality of DL CCs.","The user equipment may transmit a plurality of UL transport blocks simultaneously through a plurality of UL CCs.","A pair of DL CC #A and UL CC #A may become a first serving cell, a pair of DL CC #B and UL CC #B may become a second serving cell, and a pair of DL CC #C and UL CC #C may become a third serving cell.","Each serving cell may be identified through a cell index (CI).","The CI may be unique in the cell or user equipment-specific.","The serving cell may be divided into a primary cell (PCell) and a secondary cell (SCell).","The primary cell is a cell designated as the primary cell while the user equipment performs an initial connection establishment process or starts a connection reestablishment process, or during a handover process.","The primary cell is also referred to as a reference cell.","The secondary cell may be set after an RRC connection is established and may be used to provide an additional radio resource.","At least one primary cell may be continuously set and the secondary cell may be add/modified/cancelled by higher layer signaling (e.g., an RRC message).","A CI of the primary cell may be fixed.","For example, a lowest CI may be designated as the CI of the primary cell.","The primary cell is constituted by a downlink primary component carrier (DL PCC) and an uplink primary component carrier (UL PCC) in terms of a component carrier.","The secondary cell may be constituted by only a downlink secondary component carrier or a pair of the DL SCC and an uplink secondary component carrier (UL SCC), in terms of the component carrier.","Hereinafter, ACK/NACK transmission for the HARQ in 3GPP LTE time division duplex (TDD) will be described.","In the TDD, the DL subframe and the UL subframe coexist in one radio frame unlike frequency division duplex (FDD).","In general, the number of UL subframes is smaller than the number of DL subframes.","Accordingly, against insufficient UL subframes for transmitting the ACK/NACK signal, it is supported that a plurality of ACK/NACK signals for downlink data (that is, DL transport blocks) received in the plurality of DL subframes is transmitted in one UL subframe.","In a table shown below, a DL subframe n-k associated with a UL subframe n depending on the UL-DL configuration, herein, k∈K, M represents the number of components of a set K. TABLE 3 UL-DL Subframe n Configuration 0 1 2 3 4 5 6 7 8 9 0 — — 6 — 4 — — 6 — 4 1 — — 7, 6 4 — — — 7, 6 4 — 2 — — 8, 7, 4, 6 — — — — 8, 7, 4, 6 — — 3 — — 7, 6, 11 6, 5 5, 4 — — — — — 4 — — 12, 8, 7, 11 6, 5, 4, 7 — — — — — — 5 — — 13, 12, 9, 8, 7, 5, 4, 11, 6 — — — — — — — 6 — — 7 7 5 — — 7 7 — If an ACK/NACK for data (for example, a downlink data channel (transport block) or a control channel requiring the ACK/NACK) received in the DL subframe n is transmitted in a UL subframe n+k(n), the k(n) may be expressed as shown in the following table.","TABLE 4 UL-DL Subframe n Configuration 0 1 2 3 4 5 6 7 8 9 0 4 6 — 4 6 — 1 7 6 4 7 6 4 2 7 6 4 8 7 6 4 8 3 4 11 7 6 6 5 5 4 12 11 8 7 7 6 5 4 5 12 11 9 8 7 6 5 4 13 6 7 7 7 7 5 In Table 4, when the user equipment receives the PDSCH or the PDCCH (for example, a DL SPS cancellation PDCCH) requiring the ACK/NACK response, the ACK/NACK is transmitted in the subframe n+k(n) and respective values of Table 4 represent the k(n) value.","For example, in the case where the UL-DL configuration is 0, when the PDSCH is received in subframe 0, the ACK/NACK is transmitted in subframe 4 after four subframes.","The user equipment requires a specific time in order to transmit the ACK/NACK after receiving the PDSCH or the DL SPS cancellation PDCCH.","Hereinafter, a minimum value of the specific time is expressed as kmin and a value thereof may be four subframes.","In Table 4, referring to the time of transmitting the ACK/NACK, it may be known that the ACK/NACK may be mostly transmitted in an initial uplink subframe in which kmin has elapsed.","However, a numerical figure underlined in Table 4 does not indicate the initial uplink subframe in which kmin has elapsed and indicates an uplink subframe positioned next thereto.","The reason is to prevent the ACK/NACK from being transmitted to too many downlink subframes in one uplink subframe.","Hereinafter, the size of the transport block (TB) and a channel coding process in the LTE will be described.","First, the size of the transport block is determined according to ITBS and NPRB as shown in Table 5.However, NPRB may have a predetermined value of 1 to 110 and represents only up to 10 in Table 5.TABLE 5 NPRB ITBS 1 2 3 4 5 6 7 8 9 10 0 16 32 56 88 120 152 176 208 224 256 1 24 56 88 144 176 208 224 256 328 344 2 32 72 144 176 208 256 296 328 376 424 3 40 104 176 208 256 328 392 440 504 568 4 56 120 208 256 328 408 488 552 632 696 5 72 144 224 328 424 504 600 680 776 872 6 328 176 256 392 504 600 712 808 936 1032 7 104 224 328 472 584 712 840 968 1096 1224 8 120 256 392 536 680 808 968 1096 1256 1384 9 136 296 456 616 776 936 1096 1256 1416 1544 10 144 328 504 680 872 1032 1224 1384 1544 1736 11 176 376 584 776 1000 1192 1384 1608 1800 2024 12 208 440 680 904 1128 1352 1608 1800 2024 2280 13 224 488 744 1000 1256 1544 1800 2024 2280 2536 14 256 552 840 1128 1416 1736 1992 2280 2600 2856 15 280 600 904 1224 1544 1800 2152 2472 2728 3112 16 328 632 968 1288 1608 1928 2280 2600 2984 3240 17 336 696 1064 1416 1800 2152 2536 2856 3240 3624 18 376 776 1160 1544 1992 2344 2792 3112 3624 4008 19 408 840 1288 1736 2152 2600 2984 3496 3880 4264 20 440 904 1384 1864 2344 2792 3240 3752 4136 4584 21 488 1000 1480 1992 2472 2984 3496 4008 4584 4968 22 520 1064 1608 2152 2664 3240 3752 4264 4776 5352 23 552 1128 1736 2280 2856 3496 4008 4584 5160 5736 24 584 1192 1800 2408 2984 3624 4264 4968 5544 5992 25 616 1256 1864 2536 3112 3752 4392 5160 5736 6200 26 712 1480 2216 2984 3752 4392 5160 5992 6712 7480 The transport block is channel-coded.","FIG.","7 illustrates a channel coding process (channel coding chain) of a transport block.","Referring to FIG.","7, a cyclic redundancy check (CRC) is added to the transport block (TB) (S701), which becomes a code block (CB).","When the size of the transport block is represented by A and the size of the CRC is represented by L, B (=A+L) which is a sum of the A and the L is compared with Z (=6144 bits) and when B is equal to or larger than Z, code block segmentation is performed (S702).","The CRC is added for each divided code block (S703) and the transport block is channel-coded (S704).","As the channel coding, turbo encoding may be used.","The divided code block added with the CRC becomes 6144 bits or less.","Thereafter, the code block is subjected to rate matching (S705) and code block concatenation (S706).","Hereinafter, the present invention will be described.","The LTE-A may support low price/low specification terminals that primarily perform data communications.","For example, meter reading, water level measurement, utilization of a monitoring camera, inventory reporting of a vending machine, and the like are primarily performed by the data communications and the data communications are sufficiently performed by even the low price/low specification user equipment.","The LTE-A may support the user equipment.","Hereinafter, the low price/low specification user equipment is called a machine type communication (MTC) user equipment.","In the case of the MTC user equipment, it may be important to simply/minimize a radio frequency (RF) chain or a channel coding chain in order to reduce manufacturing cost of the user equipment.","In the case of the downlink data channel that operates by the HARQ process, the ACK/NACK response representing whether to normally receive the data by processing the received data is transmitted.","In this case, in the HARQ process, a time required to transmit the ACK/NACK response is predetermined.","For example, in the case of the LTD FDD, the ACK/NACK is transmitted in a subframe after four subframes in the subframe receiving the PDSCH.","In the case of the LTE TDD, the subframe that transmits the ACK/NACK may vary according to the UL/DL configuration for each subframe, but the ACK/NACK is transmitted in the subframe after minimum four subframes in the subframe receiving the PDSCH (this has already been described).","Regardless of the FDD or the TDD, the user equipment decodes the downlink data (that is, the transport block) within a predetermined time and needs to generate/transmit the ACK/NACK therefor.","If the size of the transport block is larger than a predetermined value, the user equipment will allocate a plurality of channel coding chains to the transport block and parallelize the transport block in order to decode the transport block within a predetermined time or adjust a processing capability by increasing a clock speed.","However, in the case of the MTC user equipment, it is not preferable to set the processing capability to support the maximum transport block size within a predetermined time when an increase of the manufacturing cost, a low use frequency of the transport block having the maximum size, and the like are considered.","Hereinafter, a method for transmitting an ACK/NACK will be described, for a user equipment of which a decoding capability is limited, such as the MTC user equipment.","Further, a method for transmitting and receiving data between the user equipment of which the decoding capability is limited, such as the MTC user equipment and the base station will be described.","Hereinafter, the user equipment means the user equipment of which the decoding capability is limited, such as the MTC user equipment, but in the present invention, the user equipment is not limited thereto.","That is, the present invention may be applied to even a general LTE/LTE-A user equipment.","FIG.","8 illustrates a method for transmitting an ACK/NACK of a terminal according to an embodiment of the present invention.","Referring to FIG.","8, the user equipment judges whether the size of the transport block is larger than a predetermined value (S110).","Hereinafter, it will be assumed that the predetermined value is X. X may be 1) the maximum size of the transport block in an initial access and an initial configuration.","That is, it may not be known whether the user equipment is the existing user equipment or the MTD user equipment of which the decoding capability is limited in the initial access or the initial RRC configuration.","Accordingly, the maximum size of the transport block in the initial access and the initial RRC configuration may be set to X for counter compatibility.","As a result, the existing HARQ timing may be maintained in the initial access and the initial RRC configuration.","Alternatively, X may be determined 2) by considering code block segmentation and a code block processing capability of the MTD user equipment.","For example, if the block processing capability of the MTC user equipment is one code block, X=Z−L=6144−24=6120 (bits).","If the block processing capability of the MTC user equipment is two, X becomes 2*6120 (bits).","If the size of the transport block is equal to or smaller than a predetermined value, the ACK/NACK for the transport block is transmitted in the first subframe (S120).","Herein, the first subframe may be a subframe at a minimum ACK/NACK transmittable timing or the existing ACK/NACK transmission subframe.","In this sense, the first subframe may be called a default subframe.","For example, in the LTE 1-DD, when the transport block is received in subframe N, an ACK/NACK for the transport block is transmitted in subframe N+4.In this case, the subframe N+4 becomes the first subframe.","More generally, if subframes are consecutively indexed in an ascending order (if a last subframe of a frame is i, a first subframe of a next frame is represented by i+1), when a data unit (data to be acknowledged/not acknowledged, such as the PDSCH, the transport block, or the like) is received, the ACK/NACK for the data channel is transmitted in subframe n+kdefault.","In this case, the first subframe becomes the subframe n+kdefault based on the subframe n. In the FDD, kdefault may be 4 and in the TDD, kdefault may be a value of Table 4.If the size of the transport block is larger than the predetermined value, the ACK/NACK for the transport block is transmitted in the second subframe (S130).","The second subframe as the subframe in which the ACK/NACK is transmitted when the size of the transport block is larger than a predetermined value is a subframe temporally later than the first subframe.","For example, the data unit (data to be acknowledged/not acknowledged, such as the PDSCH, the transport block, or the like) is received in the subframe n and when the size of the data unit is larger than the predetermined value, the ACK/NACK for the data unit is transmitted in subframe n+kdefault+kadd(kadd>0).","Alternatively, a method for suspending (stopping) the ACK/NACK transmission may be used.","This shows the same effect as setting kadd to infinity and the base station performs scheduling by arbitrarily judging retransmission/new retransmission without the ACK/NACK response.","Suspending (stopping) the ACK/NACK transmission as described above may be applied to a case in which the data unit does not reach a predetermined value.","The reason is that loss may be small even though data having a small amount is arbitrarily retransmitted or the corresponding data is lost without the ACK/NACK response.","As the kadd, a value set by a higher layer signal such as a radio resource control (RRC) message may be used.","Alternatively, as kadd, a predetermined specific value (for example, any value of 1, 2, 3, and 4 and this just an example) may be used.","kadd may be determined by considering the number of code blocks, the size of the transport block, and the like.","In the case of the TDD, an HARQ ACK time delay, that is, k(n) may be set to be larger than kdefault according to subframe No.","n as shown in Table 4.In this case, when k(n) is equal to or larger than kdefault+kadd, k(n) is followed.","That is, a value of min(k(n), kdefault+kadd) may be used the HARQ ACK time delay.","Herein, min(x,y) represents a smaller value (the same value if x and y are the same as each other) of x and y. Alternatively, k(n) may be limited to schedule a transport block larger than predetermined X only in downlink subframe n in which k(n) is equal to or larger than kdefault+kadd.","In FIG.","8, an example of directly comparing whether the size of the transport block is larger than the predetermined value X is described, but the present invention is not limited thereto.","For example, it may be determined which subframe of the first and second subframes the ACK/NACK is transmitted based on specific ITBS and NPRB of Table 5 instead of X.","For example, ITBS has any value of 0 to 26 and NPRB has any value of 1 to 10, and the size of the transport block is determined according to ITBS and NPRB.","Therefore, the size of the transport block may be instructed by ITBS and NPRB.","Accordingly, sections for ITBS and NPRB are divided and thereafter, whether the ACK/NACK is transmitted in the first subframe or the second subframe may be discriminated based on a specific section or a specific value.","FIG.","9 illustrates data receiving and ACK/NACK transmitting timings of the user equipment by the method of FIG.","8.Referring to FIG.","9, the user equipment may receive a PDSCH 901 in which the size of the transport block is equal to or smaller than X and a PDSCH 902 in which the size of the transport block is larger than X in subframe n. The user equipment transmits an ACK/NACK for the PDSCH 901 in subframe n+kdefault and transmits an ACK/NACK for the PDSCH 902 in subframe n+kdefault+kadd.","FIG.","10 illustrates a method for transmitting an ACK/NACK of a user equipment according to another embodiment of the present invention.","Referring to FIG.","10, the user equipment judges whether a DCI format to schedule the PDSCH is a predetermined specific DCI format (S210).","For example, DCI format 1A is called a fallback DCI format as a DCI format which is continuously supported regardless of a downlink transmission mode.","The user equipment judges whether the DCI format detected in the PDCCH region is the fallback DCI format and if the detected DCI format is the fallback DCI format, the ACK/NACK for the transport block scheduled by the DCI format is transmitted in the first subframe (S220) and if not so, the ACK/NACK for the transport block scheduled by the DCI format is transmitted in the second subframe (S230).","The size of the transport block scheduled by the fallback DCI format may be limited by a scheduler according to a processing capability of the user equipment.","The present invention in which the transmission timing of the ACK/NACK may be differently applied according to a condition of the size of the data unit to be acknowledged/non acknowledged may be variously extended as described below.","For example, the subframe in which the ACK/NACK is transmitted may be divided according to search space in which the DCI is transmitted.","For example, different ACK/NACK transmission timings may be applied by considering which space of a common search space (CSS) which is a common search space for all user equipments in a cell and a user equipment specific search space (USS) which is a search space for a specific user equipment the DCI is received from.","Alternatively, different ACK/NACK transmission timings may be applied by considering whether being scheduled by the PDCCH or an E-PDCCH (enhanced-PDCCH, described below).","Alternatively, different transmission timings may be applied according to a subframe (alternatively, a cell) in which scheduling DCI is transmitted, different transmission timings may be applied according to a subframe (alternatively, a cell) in which a scheduled data channel is transmitted, different transmission timings may be applied according to whether a scheduling scheme being semi-persistent scheduling (SPS) (for example, a PDSCH without a corresponding PDCCH) or dynamic (a PDSCH with the corresponding PDCCH), different transmission timings may be applied according to a type of a radio network temporary identifier (RNTI) added to the DCI, or different transmission timings may be applied according to cross scheduling or non-cross scheduling.","FIG.","11 illustrates a method for transmitting an ACK/NACK according to the present invention.","Referring to FIG.","11, the user equipment receives the RRC message for setting X and kadd through the RRC message (S310).","The user equipment receives the transport block through the PDSCH of the subframe n (S320).","The user equipment compares the size of the transport block with X (S330), transmits the ACK/NACK in the subframe n+kdefault when the size of the transport block is equal to or smaller than X (S340-1), and transmits the ACK/NACK in the subframe n+kdefault+kadd when the size of the transport block is larger than X (S340-2).","In FIG.","11, a case in which both X and kadd are (directly or indirectly) set by the RRC message is exemplified for easy description.","However, the present invention is not limited thereto and only one of X and kadd may be set by one RRC message.","In this case, as a value not set by the RRC message, a predetermined value may be used between the user equipment and the base station.","Further, the base station may signal kdefault+kadd by the RRC message instead of kadd.","Alternatively, both X and kadd are not RRC-signaled and may be predetermined values.","Meanwhile, the base station may transmit information on the ACK/NACK transmission timing included in the DCI.","For example, information on kadd may be signaled by configuring a specific field in the DCI or combining states of other fields.","That is, the base station may instruct the second subframe to the user equipment through the DCI.","Alternatively, an instructor that disables the ACK/NACK to be transmitted may also be included in the DCI.","The user equipment does not transmit the ACK/NACK when it is judged that the ACK/NACK is instructed not to be transmitted through the instructor.","The instructor may be included separately from the specific field of the DCI.","Alternatively, in the case of the instructor, a value of the specific field itself may serve as the instructor.","For example, when the specific field is 2 bits and states of the specific field are ‘00’, ‘01’, ‘10’, and ‘11’ and ‘00’, ‘01’, and ‘10’ may sequentially represent that kadd is 0, 1, and 2 and ‘11’ may represent that kadd is infinite and thus the ACK/NACK is not transmitted.","In the above, when the size of the transport block is larger than a specific value X, a positive kadd value is added as an example, but the present invention is not limited thereto.","That is, kadd may have a negative value.","Alternatively, kminus may be signaled separately from kadd.","For example, when kdefault is set sufficiently, kminus may be subtracted.","Hereinafter, the resource allocation in the subframe in which the ACK/NACK is transmitted will be described.","In the FDD, when the ACK/NACK is transmitted, the resource allocation may be performed as follows.","1.When kdefault is applied (that is, when the ACK/NACK for the data unit received in the subframe n is transmitted in the subframe n+kdefault, hereinafter, the same as above), the ACK/NACK may be transmitted by using an implicit resource.","That is, the resource that transmits the ACK/NACK may be determined based on a lowest CCE of the PDCCH that schedules the transport block to be acknowledged/not acknowledged.","2.When kdefault+kadd is applied (that is, when the ACK/NACK for the data unit received in the subframe n is transmitted in the subframe n+kdefault+kadd, hereinafter, the same as above), the ACK/NACK may be transmitted by using an explicit resource set by the RRC.","When the implicit resource is used in the case where kdefault+kadd is applied, mapping of the CCE and the ACK/NACK resource different from the implicit resource determined in Clause 1 may be set.","In the TDD, when the ACK/NACK is transmitted, the resource allocation may be performed as follows.","1.When k(n) is applied, the ACK/NACK may be transmitted by using the implicit resource.","2.When kdefault+kadd is applied (for example, when k(n) of Table 4 is smaller than kdefault+kadd), the ACK/NACK may be transmitted by using the explicit resource set by the RRC.","When the implicit resource is used in the case where kdefault+kadd is applied, mapping of the CCE and the ACK/NACK resource different from the implicit resource determined in k(n) may be set.","Meanwhile, the present invention may be applied even to the carrier aggregation system.","That is, the present invention may be applied when multiple cells are set for the user equipment.","Reception timings of the PDSCH are different for each of multiple cells (alternatively, for each cell group) set for the user equipment, and as a result, multiple timing alignments (TAs) may be applied.","In this case, when a specific cell becomes a monitoring cell and cross carrier scheduling is applied between the cells, the reception timings of the PDCCH are the same as each other, but the reception timings of the PDSCH may be different from each other in respective cells.","For example, cells #1, 2 and 3 are set for the user equipment and the cross carrier scheduling is set, and as a result, the PDCCHs may be received through subframe #n of the cell #1.In this case, frame synchronization is not matched among the cells #1, 2, and 3, and as a result, the TA may be performed and then, the PDSCHs in the cells #1, 2, and 3 may be received different timings.","In this case, a decoding time of the PDSCH received late may be insufficient.","If the ACK/NACKs for the PDSCHs received in the cells #1, 2, and 3 need to be transmitted in the uplink subframe of one cell (for example, the primary cell), a problem may occur due to the insufficient decoding time for the PDSCH received late.","In this case, the ACK/NACK for the PDSCH received late may be transmitted in not the subframe #n+kdefault but the subframe #n+kdefault+kadd by modifying and applying the present invention.","Further, the present invention may be applied even to a wireless communication system including the enhanced-PDCCH (E-PDCCH).","Herein, the E-PDCCH is a control channel included in the data region in a subframe including the control region and the data region, and may be a control channel decoded through a common reference signal (CRS) common to all user equipments in the cell and a user equipment-specific reference signal.","The case of scheduling the PDSCH by the PDCCH and the case of scheduling the PDSCH by the E-PDCCH may be different from each other in a decoding start time of the PDSCH.","A decoding ability may be insufficient according to the user equipment in the case of scheduling the PDSCH by setting the E-PDCCH.","Even in this case, the present invention may be modified and applied.","For example, in the case of scheduling the PDSCH of the subframe n by the PDCCH of the subframe n, the ACK/NACK for the PDSCH may be transmitted in the subframe n+kdefault.","In addition, in the case of scheduling the PDSCH of the subframe n by the E-PDCCH of the subframe n, the ACK/NACK for the PDSCH may be transmitted in the subframe n kdefault+kadd.","In this case, kadd may be determined according to an amount in which the PDSCH decoding time is decreased in terms of the user equipment.","In the aforementioned methods, a method for controlling an HARQ ACK/NACK timing according to the size of the transport block has been described.","Meanwhile, according to yet another embodiment of the present invention, the user equipment may not transmit the ACK/NACK for the transport block according to the size of the transport block.","That is, when the size of the transport block is larger than predetermined X bits, the ACK/NACK is transmitted only when the size of the transport block is equal to or smaller than the X without transmitting the ACK/NACK.","This method is not limited to a case based on the size of the transport block and this method includes a method in which the ACK/NACK is not transmitted when the size of the transport block is larger than a predetermined reference based on the DCI format, ITBS and NPRB, and the like.","FIG.","12 is a block diagram illustrating a wireless apparatus in which the embodiment of the present invention is implemented.","The base station 100 includes a processor 110, a memory 120, and a radio frequency (RF) unit 130.The processor 110 implements a proposed function, a proposed process, and/or a proposed method.","For example, the processor 110 transmits a downlink grant to the user equipment and transmits downlink data such as the transport block through the radio resource allocated through the downlink grant.","A subframe that receives the ACK/NACK may be determined according to the size of the transport block.","Further, the processor 110 may transmit the reference value X and kadd (alternatively, kdefault+kadd) through the higher layer signal such as the RRC message.","Further, the processor 110 may determine the subframe that receives the ACK/NACK according to the DCI format.","The memory 120 is connected with the processor 110 to store various pieces of information for driving the processor 110.The RF unit 130 is connected with the processor 110 to transmit and/or receive a radio signal.","The user equipment 200 includes a processor 210, a memory 220, and an RF unit 230.The processor 210 implements a proposed function, a proposed process, and/or a proposed method.","For example, the processor 210 may receive the transport block and transmit the ACK/NACK for the transport block by using the subframe determined according to the size of the transport block.","The process of determining the subframe has been described with reference to FIGS.","8 and 9.Further, the processor 210 may determine the subframe to transmit the ACK/NACK according to the DCI format.","This process has been described with reference to FIG.","10.Further, the processor 210 may receive the reference value X and kadd (alternatively, kdefault+kadd) through the higher layer signal such as the RRC message and use the received reference value X and kadd (alternatively, kdefault+kadd).","The memory 220 is connected with the processor 210 to store various pieces of information for driving the processor 210.The RF unit 230 is connected with the processor 210 to transmit and/or receive a radio signal.","The processors 110 and 210 may include an application-specific integrated circuit (ASIC), other chipset, a logic circuit, a data processing device, and/or a converter that converts a baseband signal and a radio signal to each other.","The memories 120 and 220 may include a read-only memory (ROM), a random access memory (RAM0, a flash memory, a memory card, a storage medium, and/or other storage device.","The RF units 130 and 230 may include one or more antennas that transmit and/or receive the radio signal.","When the embodiment is implemented by software, the aforementioned technique may be implemented by a module (a process, a function, and the like) that perform the aforementioned function.","The module may be stored in the memories 120 and 220 and may be executed by the processors 110 and 210.The memories 120 and 220 may be present inside or outside the processors 110 and 210 and connected with the processors 110 and 210 by various well-known means."]],"string":"[\n [\n \"METHOD AND APPARATUS FOR TRANSMITTING ACK/NACK SIGNAL IN WIRELESS COMMUNICATION SYSTEM\",\n \"The present invention relates to a method and apparatus for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) signal in a wireless communication system.\",\n \"The method includes the steps of: receiving a transmission block; and transmitting an ACK/NACK signal for the transmission block in a first subframe or a second subframe according to the size of the transmission block, wherein, when the size of the transmission block is smaller than or equal to a reference value, the ACK/NACK signal is transmitted in the first frame, when the size of the transmission block is greater than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.\"\n ],\n [\n \"1-11.\",\n \"(canceled) 12.A method for transmitting acknowledgement/not-acknowledgement (ACK/NACK) information, the method performed by a user equipment (UE) and comprising: receiving data scheduled by downlink control information (DCI) in a subframe n; and transmitting ACK/NACK information for the data in a subframe n+kadd, wherein each of the n and the kadd is an integer, and wherein a value of kadd depends on the DCI.\",\n \"13.The method of claim 12, wherein the value of kadd is a natural number larger than 4.14.The method of claim 12, wherein the DCI includes a field informing the value of kadd.\",\n \"15.The method of claim 12, wherein the value of kadd is larger than 4.16.The method of claim 12, wherein the UE uses a frequency division duplex (FDD) frame.\",\n \"17.A user equipment (UE), comprising: a transceiver which transmits or receives a radio signal; and a processor connected with the transceiver, wherein the processor receives data scheduled by downlink control information (DCI) in a subframe n, and transmis ACK/NACK information for the data in a subframe n+kadd, wherein each of the n and the kadd is an integer, and wherein a value of kadd depends on the DCI.\",\n \"18.The UE of claim 17, wherein the value of kadd is a natural number larger than 4.19.The UE of claim 17, wherein the DCI includes a field informing the value of kadd.\",\n \"20.The UE of claim 17, wherein the value of kadd is larger than 4.21.The UE of claim 17, wherein the UE uses a frequency division duplex (FDD) frame.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>An object of the present invention is to provide a method and an apparatus for transmitting an ACK/NACK in a wireless communication system.\",\n \"In accordance with an aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK signal for the transport block in a first subframe or a second subframe according to the size of the transport block, wherein, when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.\",\n \"In accordance with another aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK for the transport block in a predetermined subframe when the size of the transport block is larger than a reference value, and not transmitting the ACK/NACK for the transport block when the size of the transport block is equal to or smaller than the reference value.\",\n \"In accordance with yet another aspect of the present invention, a user equipment includes: a radio frequency (RF) unit which transmits or receives a radio signal; and a processor connected with the RF unit, wherein the processor receives a transport block and transmits an ACK/NACK for the transport block in a first subframe or a second subframe according to the size of the transport block, and when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.\",\n \"An HARQ process can be efficiently performed under a situation in which a data decoding capability is limited.\",\n \"Accordingly, system performance is improved.\"\n ],\n [\n \"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a wireless communication system, and more particularly, to a method and an apparatus for transmitting a reception acknowledgment for a hybrid automatic repeat request of a user equipment in a wireless communication system.\",\n \"Related Art 3rd generation partnership project (3GPP) long term evolution (LTE) (hereinafter, referred to as LTE) is an influential next-generation wireless communication system standard.\",\n \"In the LTE, when a base station transmits downlink data to a user equipment, the base station first transmits scheduling information on a downlink data channel through a control channel, allocates the downlink data channel according to the scheduling information, and transmits the downlink data through the allocated downlink data channel.\",\n \"The user equipment transmits to the base station reception acknowledgement/non-acknowledgement (ACK/NACK) of the downlink data and the base station may transmit new downlink data or retransmit pretransmitted downlink data according to the ACK/NACK.\",\n \"Such a data transmission scheme is called a hybrid automatic repeat request (HARQ).\",\n \"The HARQ includes synchronous and asynchronous HARQs, and in the case of the synchronous HARQ, synchronization is set between an HARQ process and a subframe, and as a result, new transmission/retransmission of the same HARQ process is performed according to a predetermined timing.\",\n \"On the contrary, in the case of the asynchronous HARQ, the use of the HARQ is directly instructed without the synchronization between the HARQ process and the subframe.\",\n \"Meanwhile, 3GPP LTE-A (long term evolution-advanced) (hereinafter, referred to as LTE-A) is a next-generation wireless communication system standard developed by improving the LTE.\",\n \"The LTE-A can support low price/low specification user equipments that primarily perform data communications such as meter reading, water level measurement, utilization of a monitoring camera, inventory reporting of a vending machine, and the like.\",\n \"As described above, the low price/low specification user equipments that primarily perform low-capacity data communications are called a machine type communication (MTC) user equipment.\",\n \"When the MTC user equipment exists in an area supported by the base station, it may be difficult to apply the ACK/NACK timing of the existing HARQ as it is.\",\n \"For example, when the downlink data has a capacity larger than a capacity which the MTC user equipment can process within a specific time, the MTC user equipment may not decode all of the downlink data at the time of transmitting the ACK/NACK.\",\n \"Further, in spite of not the MTC user equipment, data to be acknowledged/not acknowledged and a time up to the transmission timing of the ACK/NACK are insufficient, and as a result, an ACK/NACK response of the HARQ may not normally be performed during a predetermined time interval.\",\n \"For example, the LTE-A can support carrier aggregation and support cross carrier scheduling.\",\n \"In the cross carrier scheduling, scheduling information is simultaneously received through a specific cell, but data scheduled by the scheduling information may be received in different cells.\",\n \"In this case, the different cells are not temporally aligned, and as a result, data may be received lately in some cells.\",\n \"In this case, due to an insufficient time between the lately received data and an insufficient time and an ACK/NACK thereof, the lately received data may not normally be decoded.\",\n \"Alternatively, in the LTE-A, a new control channel allocated to a data domain may be introduced in addition to the existing control channel allocated to a control domain.\",\n \"Since the new control channel may exist in the data domain, a decoding time of data scheduled by the new control channel may be insufficient according to the user equipment.\",\n \"Therefore, new ACK/NACK transmitting method and apparatus which can be applied to an advanced wireless communication system such as the LTE-A are required.\",\n \"SUMMARY OF THE INVENTION An object of the present invention is to provide a method and an apparatus for transmitting an ACK/NACK in a wireless communication system.\",\n \"In accordance with an aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK signal for the transport block in a first subframe or a second subframe according to the size of the transport block, wherein, when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.\",\n \"In accordance with another aspect of the present invention, a method for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) of a user equipment includes the steps of: receiving a transport block; and transmitting an ACK/NACK for the transport block in a predetermined subframe when the size of the transport block is larger than a reference value, and not transmitting the ACK/NACK for the transport block when the size of the transport block is equal to or smaller than the reference value.\",\n \"In accordance with yet another aspect of the present invention, a user equipment includes: a radio frequency (RF) unit which transmits or receives a radio signal; and a processor connected with the RF unit, wherein the processor receives a transport block and transmits an ACK/NACK for the transport block in a first subframe or a second subframe according to the size of the transport block, and when the size of the transport block is equal to or smaller than a preference value, the ACK/NACK signal is transmitted in the first subframe and when the size of the transport block is larger than the reference value, the ACK/NACK signal is transmitted in the second subframe, and the second subframe is behind the first subframe in a time domain.\",\n \"An HARQ process can be efficiently performed under a situation in which a data decoding capability is limited.\",\n \"Accordingly, system performance is improved.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 illustrates a structure of an FDD radio frame.\",\n \"FIG.\",\n \"2 illustrates a structure of a TDD radio frame.\",\n \"FIG.\",\n \"3 illustrates one example of a resource grid for one downlink slot.\",\n \"FIG.\",\n \"4 illustrates a structure of a downlink subframe.\",\n \"FIG.\",\n \"5 illustrates a structure of an uplink subframe.\",\n \"FIG.\",\n \"6 illustrates a comparative example of a single carrier system and a carrier aggregation system.\",\n \"FIG.\",\n \"7 illustrates a channel coding process (channel coding chain) of a transport block.\",\n \"FIG.\",\n \"8 illustrates a method for transmitting an ACK/NACK of a user equipment according to an embodiment of the present invention.\",\n \"FIG.\",\n \"9 illustrates data receiving and ACK/NACK transmitting timings of the user equipment by the method of FIG.\",\n \"8.FIG.\",\n \"10 illustrates a method for transmitting an ACK/NACK of a user equipment according to another embodiment of the present invention.\",\n \"FIG.\",\n \"11 illustrates a method for transmitting an ACK/NACK according to the present invention.\",\n \"FIG.\",\n \"12 is a block diagram illustrating a wireless apparatus in which the embodiment of the present invention is implemented.\",\n \"DESCRIPTION OF EXEMPLARY EMBODIMENTS The user equipment (UE) may be fixed or movable and may be called other terms such as a mobile station (MS), a mobile terminal (MT), a user terminal (UT), a subscriber station (SS), a wireless device, a personal digital assistant (PDA), a wireless modem, a handheld device, and the like.\",\n \"The base station generally represents a fixed station that communicates with the user equipment, and may be called other terms such as an evolved-NodeB (eNB), a base transceiver system (BTS), an access point, and the like.\",\n \"A communication from the base station to the user equipment is called a downlink DL and a communication from the user equipment to the base station is called an uplink UL.\",\n \"A wireless communication system including the base station and the user equipment may be a time division duplex (TDD) or a frequency division duplex (FDD) system.\",\n \"The TDD system is a wireless communication system that performs uplink and downlink transmission and reception by using different timings in the same frequency band.\",\n \"The FDD system is a wireless communication system that can perform the uplink and downlink transmission and reception simultaneously by using different frequency bands.\",\n \"The wireless communication system may perform the communication by using the radio frame.\",\n \"FIG.\",\n \"1 illustrates a structure of an FDD radio frame.\",\n \"The FDD radio frame includes 10 subframes and one subframe two consecutive slots.\",\n \"Slots included in the radio frames are indexed with 0 to 19.A time required to transmit one subframe is a transmission time interval (TTI) and the TTI may be a minimum scheduling unit.\",\n \"For example, the length of one subframe may be 1 ms and the length of one slot may be 0.5 ms.\",\n \"FIG.\",\n \"2 illustrates a structure of a TDD radio frame.\",\n \"Referring to FIG.\",\n \"2, a subframe having index #1 and index #6 is called a special subframe and includes a downlink pilot time slot (DwPTS), a guard period (GP), and an uplink pilot time slot (UpPTS).\",\n \"The DwPTS is used in initial cell search, synchronization, or channel estimation in the user equipment.\",\n \"The UpPTS is used to match channel estimation in the base station and uplink transmission synchronization of the user equipment.\",\n \"The GP is a period for removing an interference which occurs in the uplink due to a multipath delay of the downlink signal between the uplink and the downlink.\",\n \"In the TDD, a downlink (DL) subframe and an uplink (UL) subframe coexist in one radio frame.\",\n \"Table 1 illustrates one example of a UL-DL configuration of the radio frame.\",\n \"TABLE 1 Downlink- to-uplink Uplink- Switch- downlink point Subframe n configuration periodicity 0 1 2 3 4 5 6 7 8 9 0 5 ms D S U U U D S U U U 1 5 ms D S U U D D S U U D 2 5 ms D S U D D D S U D D 3 10 ms D S U U U D D D D D 4 10 ms D S U U D D D D D D 5 10 ms D S U D D D D D D D 6 5 ms D S U U U D S U U D In Table 1, ‘D’ represents a DL subframe, IT represents a UL subframe, and ‘S’ represents the special subframe.\",\n \"When the user equipment receives the UL-DL configuration from the base station, the user equipment may know whether each subframe is the DL subframe or the UL subframe in the radio frame.\",\n \"Hereinafter, a UL-DL configuration N (N is any one of 0 to 6) may refer to Table 1.FIG.\",\n \"3 illustrates one example of a resource grid for one downlink slot.\",\n \"Referring to FIG.\",\n \"3, the downlink slot may include a plurality of orthogonal frequency division multiplexing (OFDM) symbols in a time domain and NRB resource blocks (RBs) in a frequency domain.\",\n \"The resource block as the resource allocation unit includes one slot in the time domain and a plurality of consecutive subcarriers in the frequency domain.\",\n \"The number NRB of resource blocks included in the downlink slot is subordinate to a downlink bandwidth NDL set in a cell.\",\n \"For example, in an LTE system, NRB may be any one of 6 to 110.A structure of an uplink slot may also be the same as that of the downlink slot.\",\n \"Each element on the resource grid is called a resource element (RE).\",\n \"The resource element on the resource grid may be identified by a pair of indexes (k,l) in the slot.\",\n \"Herein, k (k=0, .\",\n \".\",\n \".\",\n \", NRB×12-1) represents a subcarrier index in the frequency domain and l (l=0, .\",\n \".\",\n \".\",\n \", 6) represents an OFDM symbol index in the time domain.\",\n \"In FIG.\",\n \"3, it is exemplarily described that one resource block is constituted by 7 OFDM symbols in the time domain and 12 subcarriers in the frequency domain and thus includes 7×12 resource elements, but the number of the OFDM symbols and the number of the subcarriers in the resource block are not limited thereto.\",\n \"The number of the OFDM symbols and the number of the subcarriers may be variously changed depending on the length of a CP, frequency spacing, and the like.\",\n \"As the number of subcarriers in one OFDM symbol, one may be selected and used among 128, 256, 512, 1024, 1536, and 2048.FIG.\",\n \"4 illustrates a structure of a downlink subframe.\",\n \"Referring to FIG.\",\n \"4, the downlink (DL) subframe is divided into a control region and a data region.\",\n \"The control region includes maximum three (maximum four in some cases) precedent OFDM symbols of a first slot in the subframe, but the number of OFDM symbols included in the control region may be changed.\",\n \"A physical downlink control channel (PDCCH) and other control channel are allocated to the control region and a physical downlink shared channel (PDSCH) is allocated to the data region.\",\n \"As disclosed in 3GPP TS 36.211 V8.7.0, a physical channel in 3GPP LTE may be divided into the physical downlink shared channel (PDSCH) and a physical uplink shared channel (PUSCH) which are data channels, and a physical downlink control channel (PDCCH), a physical control format indicator channel (PCFICH), a physical hybrid-ARQ indicator channel (PHICH), and a physical uplink control channel (PUCCH) which are data channels.\",\n \"The PCFICH transmitted in a first OFDM symbol of the subframe transports a control format indicator regarding the number (that is, the size of the control region) of OFDM symbols used to transmit control channels in the subframe.\",\n \"The user equipment first receives the CFI on the PCFICH and thereafter, monitors the PDCCH.\",\n \"Unlike the PDCCH, the PCFICH is transmitted through a fixed PCFICH resource of the subframe without using blind decoding.\",\n \"The PHICH transports a positive-acknowledgment (ACK)/negative-acknowledgement (NACK) signal for an uplink hybrid automatic repeat request (HARQ).\",\n \"An ACK/NACK signal for uplink (UL) data on the PUSCH transmitted by the user equipment is transmitted on the PHICH.\",\n \"A physical broadcast channel (PBCH) is transmitted in four precedent OFDM symbols of a second slot of the first subframe of the radio frame.\",\n \"The PBCH transports system information required for the user equipment to communicate with the base station and the system information transmitted through the PBCH is called a master information block (MIB).\",\n \"As compared therewith, system information transmitted on the PDSCH instructed by the PDCCH is called a system information block (SIB).\",\n \"Control information transmitted through the PDCCH is called downlink control information (DCI).\",\n \"The DCI may include resource allocation (also referred to as downlink (DL) grant) of the PDSCH, resource allocation (also referred to as uplink (UL) grant) of the PUSCH, a set of transmission power control commands for individual UEs in a predetermined UE group, and/or activation of a voice over Internet protocol (VoIP).\",\n \"Table 2 shown below exemplifies a DCI format and a usage.\",\n \"TABLE 2 DCI format USAGE DCI FORMAT 0 USED IN SCHEDULING PUSCH DCI FORMAT 1 USED IN SCHEDULING ONE PDSCH CODWORD DCI FORMAT 1A USED IN COMPACT SCHEDULING OF ONE PDSCH CODEWORD AND RANDOM ACCESS PROCESS DCI FORMAT 1B USED IN COMPACT SCHEDULING OF ONE PDSCH CODEWORD HAVING PRECODING INFORMATION DCI FORMAT 1C USED IN VERY COMPACT SCHEDULING OF ONE PDSCH CODWORD DCI FORMAT 1D USED IN COMPACT SCHEDULING OF ONE PDSCH CODEWORD HAVING PRECODING AND POWER OFFSET INFORMATION DCI FORMAT 2 USED IN SCHEDULING PDSCH OF USER EQUIPMENTS SET IN CLOSE LOOP SPATIAL MULTIPLEXING MODE DCI FORMAT 2A USED IN SCHEDULING PDSCH OF USER EQUIPMENTS SET IN OPEN LOOP SPATIAL MULTIPLEXING MODE DCI FORMAT 3 USED IN TRANSMITTING TPC COMMAND OF PUCCH AND PUSCH HAVING 2 BIT POWER ADJUSTMENTS DCI FORMAT 3A USED IN TRANSMITTING TPC COMMAND OF PUCCH AND PUSCH HAVING 1 BIT POWER ADJUSTMENT DCI FORMAT 4 USED IN SCHEDULING PUSCH IN ONE UL CELL IN MULTI ANTENNA TRANSMISSION MODE FIG.\",\n \"5 illustrates a structure of an uplink subframe.\",\n \"Referring to FIG.\",\n \"5, the uplink subframe may be divided into a control region to which the physical uplink control channel (PUCCH) transporting the uplink control information is allocated and a data region to which the physical uplink shared channel (PUSCH) transporting user data is allocated, in the frequency domain.\",\n \"The PUCCH is allocated as a pair of RBs in the subframe.\",\n \"The RBs that belong to the pair of RBs occupy different subcarriers in first and second slots, respectively.\",\n \"The pair of RBs have the same resource block index m. According to the 3GPP TS 36.211 V8.7.0, the PUCCH supports multiple formats.\",\n \"PUCCH having different bit numbers for each subframe may be used according to a modulation scheme subordinate to the PUCCH format.\",\n \"PUCCH format 1 is used to transmit a scheduling request (SR), PUCCH format 1a/1b is used to transmit the ACK/NACK signal for the HARQ, PUCCH format 2 is used to transmit a CQI, and PUCCH format 2a/2b is used to simultaneously transmit the CQI and the ACK/NACK signal.\",\n \"PUCCH format 3 may be used to transmit a plurality of ACKs/NACKs.\",\n \"In the 3GPP LTE, a resource index n(1)PUCCH is defined in order for the user equipment to configure the PUCCH.\",\n \"The resource index is defined as n(1)PUCCH=nCCE+N(1)PUCCH, nCCE is No.\",\n \"of a first CCE used to transmit the corresponding PDCCH (that is, PDCCH including downlink resource allocation used to receive the downlink data corresponding to the ACK/NACK signal), and N(1)PUCCH is a parameter which the base station notifies to the user equipment as a higher layer message.\",\n \"The resource that transmits the ACK/NACK may be instructed by the n(1)PUCCH and in this case, implicit mapping of the CCE and the ACK/NACK resource is used.\",\n \"Hereinafter, a carrier aggregation system will be described.\",\n \"The carrier aggregation system is also referred to as a multiple carrier system or a multiple cell system.\",\n \"The 3GPP LTE system supports a case in which a downlink bandwidth and an uplink bandwidth are set to be different from each other, but this premises one component carrier (CC).\",\n \"The 3GPP LTE system supports maximum 20 MHz and the uplink bandwidth and the downlink bandwidth may be different from each other, but the 3GPP LTE system supports only one CC to each of the uplink and the downlink.\",\n \"On the contrary, carrier aggregation supports a plurality of CCs.\",\n \"For example, when five CCs are allocated as granularity of the unit of the carrier having a bandwidth of 20 MHz, a bandwidth of maximum 100 MHz may be supported.\",\n \"One DL CC or a pair of UL CC and DL CC may correspond to one cell.\",\n \"Therefore, the user equipment that communicates with the base station through a plurality of DL CCs may receive a service from a plurality of serving cells.\",\n \"FIG.\",\n \"6 illustrates a comparative example of a single carrier system and a carrier aggregation system.\",\n \"A carrier aggregation system (FIG.\",\n \"6(b)) has each of three DL CCs and UL CCs, but the numbers of DL CCs and UL CCs are not limited.\",\n \"In each DL CC, the PDCCH and the PDSCH may be independently transmitted and in each UL CC, the PUCCH and the PUSCH may be independently transmitted.\",\n \"Alternatively, the PUCCH may be transmitted through only a specific UL CC.\",\n \"Since three pairs of the DL CC and the UL CC are defined, the user equipment may receive the service from three serving cells.\",\n \"The user equipment may monitor the PDCCH in the plurality of DL CCs and receive a DL transport block simultaneously through the plurality of DL CCs.\",\n \"The user equipment may transmit a plurality of UL transport blocks simultaneously through a plurality of UL CCs.\",\n \"A pair of DL CC #A and UL CC #A may become a first serving cell, a pair of DL CC #B and UL CC #B may become a second serving cell, and a pair of DL CC #C and UL CC #C may become a third serving cell.\",\n \"Each serving cell may be identified through a cell index (CI).\",\n \"The CI may be unique in the cell or user equipment-specific.\",\n \"The serving cell may be divided into a primary cell (PCell) and a secondary cell (SCell).\",\n \"The primary cell is a cell designated as the primary cell while the user equipment performs an initial connection establishment process or starts a connection reestablishment process, or during a handover process.\",\n \"The primary cell is also referred to as a reference cell.\",\n \"The secondary cell may be set after an RRC connection is established and may be used to provide an additional radio resource.\",\n \"At least one primary cell may be continuously set and the secondary cell may be add/modified/cancelled by higher layer signaling (e.g., an RRC message).\",\n \"A CI of the primary cell may be fixed.\",\n \"For example, a lowest CI may be designated as the CI of the primary cell.\",\n \"The primary cell is constituted by a downlink primary component carrier (DL PCC) and an uplink primary component carrier (UL PCC) in terms of a component carrier.\",\n \"The secondary cell may be constituted by only a downlink secondary component carrier or a pair of the DL SCC and an uplink secondary component carrier (UL SCC), in terms of the component carrier.\",\n \"Hereinafter, ACK/NACK transmission for the HARQ in 3GPP LTE time division duplex (TDD) will be described.\",\n \"In the TDD, the DL subframe and the UL subframe coexist in one radio frame unlike frequency division duplex (FDD).\",\n \"In general, the number of UL subframes is smaller than the number of DL subframes.\",\n \"Accordingly, against insufficient UL subframes for transmitting the ACK/NACK signal, it is supported that a plurality of ACK/NACK signals for downlink data (that is, DL transport blocks) received in the plurality of DL subframes is transmitted in one UL subframe.\",\n \"In a table shown below, a DL subframe n-k associated with a UL subframe n depending on the UL-DL configuration, herein, k∈K, M represents the number of components of a set K. TABLE 3 UL-DL Subframe n Configuration 0 1 2 3 4 5 6 7 8 9 0 — — 6 — 4 — — 6 — 4 1 — — 7, 6 4 — — — 7, 6 4 — 2 — — 8, 7, 4, 6 — — — — 8, 7, 4, 6 — — 3 — — 7, 6, 11 6, 5 5, 4 — — — — — 4 — — 12, 8, 7, 11 6, 5, 4, 7 — — — — — — 5 — — 13, 12, 9, 8, 7, 5, 4, 11, 6 — — — — — — — 6 — — 7 7 5 — — 7 7 — If an ACK/NACK for data (for example, a downlink data channel (transport block) or a control channel requiring the ACK/NACK) received in the DL subframe n is transmitted in a UL subframe n+k(n), the k(n) may be expressed as shown in the following table.\",\n \"TABLE 4 UL-DL Subframe n Configuration 0 1 2 3 4 5 6 7 8 9 0 4 6 — 4 6 — 1 7 6 4 7 6 4 2 7 6 4 8 7 6 4 8 3 4 11 7 6 6 5 5 4 12 11 8 7 7 6 5 4 5 12 11 9 8 7 6 5 4 13 6 7 7 7 7 5 In Table 4, when the user equipment receives the PDSCH or the PDCCH (for example, a DL SPS cancellation PDCCH) requiring the ACK/NACK response, the ACK/NACK is transmitted in the subframe n+k(n) and respective values of Table 4 represent the k(n) value.\",\n \"For example, in the case where the UL-DL configuration is 0, when the PDSCH is received in subframe 0, the ACK/NACK is transmitted in subframe 4 after four subframes.\",\n \"The user equipment requires a specific time in order to transmit the ACK/NACK after receiving the PDSCH or the DL SPS cancellation PDCCH.\",\n \"Hereinafter, a minimum value of the specific time is expressed as kmin and a value thereof may be four subframes.\",\n \"In Table 4, referring to the time of transmitting the ACK/NACK, it may be known that the ACK/NACK may be mostly transmitted in an initial uplink subframe in which kmin has elapsed.\",\n \"However, a numerical figure underlined in Table 4 does not indicate the initial uplink subframe in which kmin has elapsed and indicates an uplink subframe positioned next thereto.\",\n \"The reason is to prevent the ACK/NACK from being transmitted to too many downlink subframes in one uplink subframe.\",\n \"Hereinafter, the size of the transport block (TB) and a channel coding process in the LTE will be described.\",\n \"First, the size of the transport block is determined according to ITBS and NPRB as shown in Table 5.However, NPRB may have a predetermined value of 1 to 110 and represents only up to 10 in Table 5.TABLE 5 NPRB ITBS 1 2 3 4 5 6 7 8 9 10 0 16 32 56 88 120 152 176 208 224 256 1 24 56 88 144 176 208 224 256 328 344 2 32 72 144 176 208 256 296 328 376 424 3 40 104 176 208 256 328 392 440 504 568 4 56 120 208 256 328 408 488 552 632 696 5 72 144 224 328 424 504 600 680 776 872 6 328 176 256 392 504 600 712 808 936 1032 7 104 224 328 472 584 712 840 968 1096 1224 8 120 256 392 536 680 808 968 1096 1256 1384 9 136 296 456 616 776 936 1096 1256 1416 1544 10 144 328 504 680 872 1032 1224 1384 1544 1736 11 176 376 584 776 1000 1192 1384 1608 1800 2024 12 208 440 680 904 1128 1352 1608 1800 2024 2280 13 224 488 744 1000 1256 1544 1800 2024 2280 2536 14 256 552 840 1128 1416 1736 1992 2280 2600 2856 15 280 600 904 1224 1544 1800 2152 2472 2728 3112 16 328 632 968 1288 1608 1928 2280 2600 2984 3240 17 336 696 1064 1416 1800 2152 2536 2856 3240 3624 18 376 776 1160 1544 1992 2344 2792 3112 3624 4008 19 408 840 1288 1736 2152 2600 2984 3496 3880 4264 20 440 904 1384 1864 2344 2792 3240 3752 4136 4584 21 488 1000 1480 1992 2472 2984 3496 4008 4584 4968 22 520 1064 1608 2152 2664 3240 3752 4264 4776 5352 23 552 1128 1736 2280 2856 3496 4008 4584 5160 5736 24 584 1192 1800 2408 2984 3624 4264 4968 5544 5992 25 616 1256 1864 2536 3112 3752 4392 5160 5736 6200 26 712 1480 2216 2984 3752 4392 5160 5992 6712 7480 The transport block is channel-coded.\",\n \"FIG.\",\n \"7 illustrates a channel coding process (channel coding chain) of a transport block.\",\n \"Referring to FIG.\",\n \"7, a cyclic redundancy check (CRC) is added to the transport block (TB) (S701), which becomes a code block (CB).\",\n \"When the size of the transport block is represented by A and the size of the CRC is represented by L, B (=A+L) which is a sum of the A and the L is compared with Z (=6144 bits) and when B is equal to or larger than Z, code block segmentation is performed (S702).\",\n \"The CRC is added for each divided code block (S703) and the transport block is channel-coded (S704).\",\n \"As the channel coding, turbo encoding may be used.\",\n \"The divided code block added with the CRC becomes 6144 bits or less.\",\n \"Thereafter, the code block is subjected to rate matching (S705) and code block concatenation (S706).\",\n \"Hereinafter, the present invention will be described.\",\n \"The LTE-A may support low price/low specification terminals that primarily perform data communications.\",\n \"For example, meter reading, water level measurement, utilization of a monitoring camera, inventory reporting of a vending machine, and the like are primarily performed by the data communications and the data communications are sufficiently performed by even the low price/low specification user equipment.\",\n \"The LTE-A may support the user equipment.\",\n \"Hereinafter, the low price/low specification user equipment is called a machine type communication (MTC) user equipment.\",\n \"In the case of the MTC user equipment, it may be important to simply/minimize a radio frequency (RF) chain or a channel coding chain in order to reduce manufacturing cost of the user equipment.\",\n \"In the case of the downlink data channel that operates by the HARQ process, the ACK/NACK response representing whether to normally receive the data by processing the received data is transmitted.\",\n \"In this case, in the HARQ process, a time required to transmit the ACK/NACK response is predetermined.\",\n \"For example, in the case of the LTD FDD, the ACK/NACK is transmitted in a subframe after four subframes in the subframe receiving the PDSCH.\",\n \"In the case of the LTE TDD, the subframe that transmits the ACK/NACK may vary according to the UL/DL configuration for each subframe, but the ACK/NACK is transmitted in the subframe after minimum four subframes in the subframe receiving the PDSCH (this has already been described).\",\n \"Regardless of the FDD or the TDD, the user equipment decodes the downlink data (that is, the transport block) within a predetermined time and needs to generate/transmit the ACK/NACK therefor.\",\n \"If the size of the transport block is larger than a predetermined value, the user equipment will allocate a plurality of channel coding chains to the transport block and parallelize the transport block in order to decode the transport block within a predetermined time or adjust a processing capability by increasing a clock speed.\",\n \"However, in the case of the MTC user equipment, it is not preferable to set the processing capability to support the maximum transport block size within a predetermined time when an increase of the manufacturing cost, a low use frequency of the transport block having the maximum size, and the like are considered.\",\n \"Hereinafter, a method for transmitting an ACK/NACK will be described, for a user equipment of which a decoding capability is limited, such as the MTC user equipment.\",\n \"Further, a method for transmitting and receiving data between the user equipment of which the decoding capability is limited, such as the MTC user equipment and the base station will be described.\",\n \"Hereinafter, the user equipment means the user equipment of which the decoding capability is limited, such as the MTC user equipment, but in the present invention, the user equipment is not limited thereto.\",\n \"That is, the present invention may be applied to even a general LTE/LTE-A user equipment.\",\n \"FIG.\",\n \"8 illustrates a method for transmitting an ACK/NACK of a terminal according to an embodiment of the present invention.\",\n \"Referring to FIG.\",\n \"8, the user equipment judges whether the size of the transport block is larger than a predetermined value (S110).\",\n \"Hereinafter, it will be assumed that the predetermined value is X. X may be 1) the maximum size of the transport block in an initial access and an initial configuration.\",\n \"That is, it may not be known whether the user equipment is the existing user equipment or the MTD user equipment of which the decoding capability is limited in the initial access or the initial RRC configuration.\",\n \"Accordingly, the maximum size of the transport block in the initial access and the initial RRC configuration may be set to X for counter compatibility.\",\n \"As a result, the existing HARQ timing may be maintained in the initial access and the initial RRC configuration.\",\n \"Alternatively, X may be determined 2) by considering code block segmentation and a code block processing capability of the MTD user equipment.\",\n \"For example, if the block processing capability of the MTC user equipment is one code block, X=Z−L=6144−24=6120 (bits).\",\n \"If the block processing capability of the MTC user equipment is two, X becomes 2*6120 (bits).\",\n \"If the size of the transport block is equal to or smaller than a predetermined value, the ACK/NACK for the transport block is transmitted in the first subframe (S120).\",\n \"Herein, the first subframe may be a subframe at a minimum ACK/NACK transmittable timing or the existing ACK/NACK transmission subframe.\",\n \"In this sense, the first subframe may be called a default subframe.\",\n \"For example, in the LTE 1-DD, when the transport block is received in subframe N, an ACK/NACK for the transport block is transmitted in subframe N+4.In this case, the subframe N+4 becomes the first subframe.\",\n \"More generally, if subframes are consecutively indexed in an ascending order (if a last subframe of a frame is i, a first subframe of a next frame is represented by i+1), when a data unit (data to be acknowledged/not acknowledged, such as the PDSCH, the transport block, or the like) is received, the ACK/NACK for the data channel is transmitted in subframe n+kdefault.\",\n \"In this case, the first subframe becomes the subframe n+kdefault based on the subframe n. In the FDD, kdefault may be 4 and in the TDD, kdefault may be a value of Table 4.If the size of the transport block is larger than the predetermined value, the ACK/NACK for the transport block is transmitted in the second subframe (S130).\",\n \"The second subframe as the subframe in which the ACK/NACK is transmitted when the size of the transport block is larger than a predetermined value is a subframe temporally later than the first subframe.\",\n \"For example, the data unit (data to be acknowledged/not acknowledged, such as the PDSCH, the transport block, or the like) is received in the subframe n and when the size of the data unit is larger than the predetermined value, the ACK/NACK for the data unit is transmitted in subframe n+kdefault+kadd(kadd>0).\",\n \"Alternatively, a method for suspending (stopping) the ACK/NACK transmission may be used.\",\n \"This shows the same effect as setting kadd to infinity and the base station performs scheduling by arbitrarily judging retransmission/new retransmission without the ACK/NACK response.\",\n \"Suspending (stopping) the ACK/NACK transmission as described above may be applied to a case in which the data unit does not reach a predetermined value.\",\n \"The reason is that loss may be small even though data having a small amount is arbitrarily retransmitted or the corresponding data is lost without the ACK/NACK response.\",\n \"As the kadd, a value set by a higher layer signal such as a radio resource control (RRC) message may be used.\",\n \"Alternatively, as kadd, a predetermined specific value (for example, any value of 1, 2, 3, and 4 and this just an example) may be used.\",\n \"kadd may be determined by considering the number of code blocks, the size of the transport block, and the like.\",\n \"In the case of the TDD, an HARQ ACK time delay, that is, k(n) may be set to be larger than kdefault according to subframe No.\",\n \"n as shown in Table 4.In this case, when k(n) is equal to or larger than kdefault+kadd, k(n) is followed.\",\n \"That is, a value of min(k(n), kdefault+kadd) may be used the HARQ ACK time delay.\",\n \"Herein, min(x,y) represents a smaller value (the same value if x and y are the same as each other) of x and y. Alternatively, k(n) may be limited to schedule a transport block larger than predetermined X only in downlink subframe n in which k(n) is equal to or larger than kdefault+kadd.\",\n \"In FIG.\",\n \"8, an example of directly comparing whether the size of the transport block is larger than the predetermined value X is described, but the present invention is not limited thereto.\",\n \"For example, it may be determined which subframe of the first and second subframes the ACK/NACK is transmitted based on specific ITBS and NPRB of Table 5 instead of X.\",\n \"For example, ITBS has any value of 0 to 26 and NPRB has any value of 1 to 10, and the size of the transport block is determined according to ITBS and NPRB.\",\n \"Therefore, the size of the transport block may be instructed by ITBS and NPRB.\",\n \"Accordingly, sections for ITBS and NPRB are divided and thereafter, whether the ACK/NACK is transmitted in the first subframe or the second subframe may be discriminated based on a specific section or a specific value.\",\n \"FIG.\",\n \"9 illustrates data receiving and ACK/NACK transmitting timings of the user equipment by the method of FIG.\",\n \"8.Referring to FIG.\",\n \"9, the user equipment may receive a PDSCH 901 in which the size of the transport block is equal to or smaller than X and a PDSCH 902 in which the size of the transport block is larger than X in subframe n. The user equipment transmits an ACK/NACK for the PDSCH 901 in subframe n+kdefault and transmits an ACK/NACK for the PDSCH 902 in subframe n+kdefault+kadd.\",\n \"FIG.\",\n \"10 illustrates a method for transmitting an ACK/NACK of a user equipment according to another embodiment of the present invention.\",\n \"Referring to FIG.\",\n \"10, the user equipment judges whether a DCI format to schedule the PDSCH is a predetermined specific DCI format (S210).\",\n \"For example, DCI format 1A is called a fallback DCI format as a DCI format which is continuously supported regardless of a downlink transmission mode.\",\n \"The user equipment judges whether the DCI format detected in the PDCCH region is the fallback DCI format and if the detected DCI format is the fallback DCI format, the ACK/NACK for the transport block scheduled by the DCI format is transmitted in the first subframe (S220) and if not so, the ACK/NACK for the transport block scheduled by the DCI format is transmitted in the second subframe (S230).\",\n \"The size of the transport block scheduled by the fallback DCI format may be limited by a scheduler according to a processing capability of the user equipment.\",\n \"The present invention in which the transmission timing of the ACK/NACK may be differently applied according to a condition of the size of the data unit to be acknowledged/non acknowledged may be variously extended as described below.\",\n \"For example, the subframe in which the ACK/NACK is transmitted may be divided according to search space in which the DCI is transmitted.\",\n \"For example, different ACK/NACK transmission timings may be applied by considering which space of a common search space (CSS) which is a common search space for all user equipments in a cell and a user equipment specific search space (USS) which is a search space for a specific user equipment the DCI is received from.\",\n \"Alternatively, different ACK/NACK transmission timings may be applied by considering whether being scheduled by the PDCCH or an E-PDCCH (enhanced-PDCCH, described below).\",\n \"Alternatively, different transmission timings may be applied according to a subframe (alternatively, a cell) in which scheduling DCI is transmitted, different transmission timings may be applied according to a subframe (alternatively, a cell) in which a scheduled data channel is transmitted, different transmission timings may be applied according to whether a scheduling scheme being semi-persistent scheduling (SPS) (for example, a PDSCH without a corresponding PDCCH) or dynamic (a PDSCH with the corresponding PDCCH), different transmission timings may be applied according to a type of a radio network temporary identifier (RNTI) added to the DCI, or different transmission timings may be applied according to cross scheduling or non-cross scheduling.\",\n \"FIG.\",\n \"11 illustrates a method for transmitting an ACK/NACK according to the present invention.\",\n \"Referring to FIG.\",\n \"11, the user equipment receives the RRC message for setting X and kadd through the RRC message (S310).\",\n \"The user equipment receives the transport block through the PDSCH of the subframe n (S320).\",\n \"The user equipment compares the size of the transport block with X (S330), transmits the ACK/NACK in the subframe n+kdefault when the size of the transport block is equal to or smaller than X (S340-1), and transmits the ACK/NACK in the subframe n+kdefault+kadd when the size of the transport block is larger than X (S340-2).\",\n \"In FIG.\",\n \"11, a case in which both X and kadd are (directly or indirectly) set by the RRC message is exemplified for easy description.\",\n \"However, the present invention is not limited thereto and only one of X and kadd may be set by one RRC message.\",\n \"In this case, as a value not set by the RRC message, a predetermined value may be used between the user equipment and the base station.\",\n \"Further, the base station may signal kdefault+kadd by the RRC message instead of kadd.\",\n \"Alternatively, both X and kadd are not RRC-signaled and may be predetermined values.\",\n \"Meanwhile, the base station may transmit information on the ACK/NACK transmission timing included in the DCI.\",\n \"For example, information on kadd may be signaled by configuring a specific field in the DCI or combining states of other fields.\",\n \"That is, the base station may instruct the second subframe to the user equipment through the DCI.\",\n \"Alternatively, an instructor that disables the ACK/NACK to be transmitted may also be included in the DCI.\",\n \"The user equipment does not transmit the ACK/NACK when it is judged that the ACK/NACK is instructed not to be transmitted through the instructor.\",\n \"The instructor may be included separately from the specific field of the DCI.\",\n \"Alternatively, in the case of the instructor, a value of the specific field itself may serve as the instructor.\",\n \"For example, when the specific field is 2 bits and states of the specific field are ‘00’, ‘01’, ‘10’, and ‘11’ and ‘00’, ‘01’, and ‘10’ may sequentially represent that kadd is 0, 1, and 2 and ‘11’ may represent that kadd is infinite and thus the ACK/NACK is not transmitted.\",\n \"In the above, when the size of the transport block is larger than a specific value X, a positive kadd value is added as an example, but the present invention is not limited thereto.\",\n \"That is, kadd may have a negative value.\",\n \"Alternatively, kminus may be signaled separately from kadd.\",\n \"For example, when kdefault is set sufficiently, kminus may be subtracted.\",\n \"Hereinafter, the resource allocation in the subframe in which the ACK/NACK is transmitted will be described.\",\n \"In the FDD, when the ACK/NACK is transmitted, the resource allocation may be performed as follows.\",\n \"1.When kdefault is applied (that is, when the ACK/NACK for the data unit received in the subframe n is transmitted in the subframe n+kdefault, hereinafter, the same as above), the ACK/NACK may be transmitted by using an implicit resource.\",\n \"That is, the resource that transmits the ACK/NACK may be determined based on a lowest CCE of the PDCCH that schedules the transport block to be acknowledged/not acknowledged.\",\n \"2.When kdefault+kadd is applied (that is, when the ACK/NACK for the data unit received in the subframe n is transmitted in the subframe n+kdefault+kadd, hereinafter, the same as above), the ACK/NACK may be transmitted by using an explicit resource set by the RRC.\",\n \"When the implicit resource is used in the case where kdefault+kadd is applied, mapping of the CCE and the ACK/NACK resource different from the implicit resource determined in Clause 1 may be set.\",\n \"In the TDD, when the ACK/NACK is transmitted, the resource allocation may be performed as follows.\",\n \"1.When k(n) is applied, the ACK/NACK may be transmitted by using the implicit resource.\",\n \"2.When kdefault+kadd is applied (for example, when k(n) of Table 4 is smaller than kdefault+kadd), the ACK/NACK may be transmitted by using the explicit resource set by the RRC.\",\n \"When the implicit resource is used in the case where kdefault+kadd is applied, mapping of the CCE and the ACK/NACK resource different from the implicit resource determined in k(n) may be set.\",\n \"Meanwhile, the present invention may be applied even to the carrier aggregation system.\",\n \"That is, the present invention may be applied when multiple cells are set for the user equipment.\",\n \"Reception timings of the PDSCH are different for each of multiple cells (alternatively, for each cell group) set for the user equipment, and as a result, multiple timing alignments (TAs) may be applied.\",\n \"In this case, when a specific cell becomes a monitoring cell and cross carrier scheduling is applied between the cells, the reception timings of the PDCCH are the same as each other, but the reception timings of the PDSCH may be different from each other in respective cells.\",\n \"For example, cells #1, 2 and 3 are set for the user equipment and the cross carrier scheduling is set, and as a result, the PDCCHs may be received through subframe #n of the cell #1.In this case, frame synchronization is not matched among the cells #1, 2, and 3, and as a result, the TA may be performed and then, the PDSCHs in the cells #1, 2, and 3 may be received different timings.\",\n \"In this case, a decoding time of the PDSCH received late may be insufficient.\",\n \"If the ACK/NACKs for the PDSCHs received in the cells #1, 2, and 3 need to be transmitted in the uplink subframe of one cell (for example, the primary cell), a problem may occur due to the insufficient decoding time for the PDSCH received late.\",\n \"In this case, the ACK/NACK for the PDSCH received late may be transmitted in not the subframe #n+kdefault but the subframe #n+kdefault+kadd by modifying and applying the present invention.\",\n \"Further, the present invention may be applied even to a wireless communication system including the enhanced-PDCCH (E-PDCCH).\",\n \"Herein, the E-PDCCH is a control channel included in the data region in a subframe including the control region and the data region, and may be a control channel decoded through a common reference signal (CRS) common to all user equipments in the cell and a user equipment-specific reference signal.\",\n \"The case of scheduling the PDSCH by the PDCCH and the case of scheduling the PDSCH by the E-PDCCH may be different from each other in a decoding start time of the PDSCH.\",\n \"A decoding ability may be insufficient according to the user equipment in the case of scheduling the PDSCH by setting the E-PDCCH.\",\n \"Even in this case, the present invention may be modified and applied.\",\n \"For example, in the case of scheduling the PDSCH of the subframe n by the PDCCH of the subframe n, the ACK/NACK for the PDSCH may be transmitted in the subframe n+kdefault.\",\n \"In addition, in the case of scheduling the PDSCH of the subframe n by the E-PDCCH of the subframe n, the ACK/NACK for the PDSCH may be transmitted in the subframe n kdefault+kadd.\",\n \"In this case, kadd may be determined according to an amount in which the PDSCH decoding time is decreased in terms of the user equipment.\",\n \"In the aforementioned methods, a method for controlling an HARQ ACK/NACK timing according to the size of the transport block has been described.\",\n \"Meanwhile, according to yet another embodiment of the present invention, the user equipment may not transmit the ACK/NACK for the transport block according to the size of the transport block.\",\n \"That is, when the size of the transport block is larger than predetermined X bits, the ACK/NACK is transmitted only when the size of the transport block is equal to or smaller than the X without transmitting the ACK/NACK.\",\n \"This method is not limited to a case based on the size of the transport block and this method includes a method in which the ACK/NACK is not transmitted when the size of the transport block is larger than a predetermined reference based on the DCI format, ITBS and NPRB, and the like.\",\n \"FIG.\",\n \"12 is a block diagram illustrating a wireless apparatus in which the embodiment of the present invention is implemented.\",\n \"The base station 100 includes a processor 110, a memory 120, and a radio frequency (RF) unit 130.The processor 110 implements a proposed function, a proposed process, and/or a proposed method.\",\n \"For example, the processor 110 transmits a downlink grant to the user equipment and transmits downlink data such as the transport block through the radio resource allocated through the downlink grant.\",\n \"A subframe that receives the ACK/NACK may be determined according to the size of the transport block.\",\n \"Further, the processor 110 may transmit the reference value X and kadd (alternatively, kdefault+kadd) through the higher layer signal such as the RRC message.\",\n \"Further, the processor 110 may determine the subframe that receives the ACK/NACK according to the DCI format.\",\n \"The memory 120 is connected with the processor 110 to store various pieces of information for driving the processor 110.The RF unit 130 is connected with the processor 110 to transmit and/or receive a radio signal.\",\n \"The user equipment 200 includes a processor 210, a memory 220, and an RF unit 230.The processor 210 implements a proposed function, a proposed process, and/or a proposed method.\",\n \"For example, the processor 210 may receive the transport block and transmit the ACK/NACK for the transport block by using the subframe determined according to the size of the transport block.\",\n \"The process of determining the subframe has been described with reference to FIGS.\",\n \"8 and 9.Further, the processor 210 may determine the subframe to transmit the ACK/NACK according to the DCI format.\",\n \"This process has been described with reference to FIG.\",\n \"10.Further, the processor 210 may receive the reference value X and kadd (alternatively, kdefault+kadd) through the higher layer signal such as the RRC message and use the received reference value X and kadd (alternatively, kdefault+kadd).\",\n \"The memory 220 is connected with the processor 210 to store various pieces of information for driving the processor 210.The RF unit 230 is connected with the processor 210 to transmit and/or receive a radio signal.\",\n \"The processors 110 and 210 may include an application-specific integrated circuit (ASIC), other chipset, a logic circuit, a data processing device, and/or a converter that converts a baseband signal and a radio signal to each other.\",\n \"The memories 120 and 220 may include a read-only memory (ROM), a random access memory (RAM0, a flash memory, a memory card, a storage medium, and/or other storage device.\",\n \"The RF units 130 and 230 may include one or more antennas that transmit and/or receive the radio signal.\",\n \"When the embodiment is implemented by software, the aforementioned technique may be implemented by a module (a process, a function, and the like) that perform the aforementioned function.\",\n \"The module may be stored in the memories 120 and 220 and may be executed by the processors 110 and 210.The memories 120 and 220 may be present inside or outside the processors 110 and 210 and connected with the processors 110 and 210 by various well-known means.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874668"}}},{"rowIdx":4494666,"cells":{"text":{"kind":"list like","value":[["Method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof","A method of improving measurement speed of distributed optical fiber sensors by adopting orthogonal signals and the system thereof is disclosed, which is related to the optical fiber sensor field and solves the problems that conventional technology will increasing the bandwidth of the received signal, reducing the signal-to-noise ratio of the received signal or distortion the spatial resolution of the system.","The method comprises steps of generating N periodic orthogonal optical pulse sequence; injecting the N periodic orthogonal optical pulse sequence into the optical fiber under test(5); collecting the scattered light signal; demodulating the scattered light signal with the local oscillating light and then converting into digital signals; extracting the scatter information of the orthogonal optical pulses from the collected digital signals; and arranging the scattered information in order of precedence of the infusion.","The measurement speed of the distributed optical fiber sensors is improved by N−1 times."],["1.A method of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising steps of: step 1: generating a periodic orthogonal optical pulse sequence; step 2: injecting the periodic orthogonal optical pulse sequence into an optical fiber under test (5) in order of precedence and collecting scattered light signals; demodulating the scattered light signals with a local oscillating light, and transforming the demodulated signal into digital signals; and step 3: extracting scatter information of each of orthogonal optical pulses of the periodic orthogonal optical pulse sequence from collected digital signals; arranging the scatter information in order of precedence of the injecting into the optical fiber under test (5).","2.The method, as recited in claim 1, wherein the step 1 specifically comprises steps of: step 1.1: outputting a continuous wave laser emitted by a narrow linewidth laser (1) from a 90% port of a 90/10 coupler (2); and step 1.2: transforming the continuous wave laser into an up-conversion optical pulse signal or a down-conversion optical pulse signal which is a generated periodic orthogonal optical pulse sequence by a modulation unit (3) driven by shifting frequency electric signals.","3.The method, as recited in claim 1, wherein the step 2 specifically comprises steps of: step 2.1: injecting the periodic orthogonal optical pulse sequence into the optical fiber under test (5) by a circulator (4) to generate the scattered light signals; step 2.2: using a 90-degree optical hybrid (7) to carry out an IQ demodulation for the scattered light signals outputted by a 3rd port of the circulator (4) and the local oscillating light outputted by a 10 percent port of the 90/10 coupler (2); and step 2.3 transforming optical signals after IQ demodulation into electric signals by a balanced detector (8) and transforming the electric signals into the digital signals by a data acquisition card (9) or an oscilloscope.","4.The method, as recited in claim 2, wherein the step 3 specifically comprises steps of: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); wherein the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier Transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to an order of the orthogonal signals injected into the optical fiber under test.","5.The method, as recited in claim 3, wherein the step 3 comprises steps of: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); wherein the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier Transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.","6.The method, as recited in claim 4, wherein the signal generating unit generates two channels of orthogonal signals with a frequency of f1 in the step 1.2, which is: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I channel-signal, wherein a math expression of the I channel-signal is written as: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which are Q channel-signal, wherein a math expression of the Q-channel signal is as below: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T wherein L denotes a length of the optical fiber under test (5); c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test (5); nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f1 denotes a frequency shift of the modulation unit; VD denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] wherein, fc denotes a frequency of an incident light; Ec denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: E0=AR(z)exp{j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{−j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] wherein, j denotes an imaginary unit; A denotes a response factor of a probe; Tz denotes a delay of receiving a scattered light signal on point z on the optical fiber under test (5) at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test (5).","7.The method, as recited in claim 5, wherein the signal generating unit generates two channels of the orthogonal signals with a frequency of f1 in the step 1.2, wherein the following steps are comprised of: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I-channels, wherein a math expression of the I-channels is written as: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which are Q-channel signal, wherein a math expression of the Q-channel signal is as below: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T wherein L denotes a length of the optical fiber under test(5); c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test(5); nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f1 denotes a frequency shift of the modulation unit; VD denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] wherein, fc denotes a frequency of an incident light; Ec denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: E0=AR(z)exp{j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{−j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] wherein, j denotes an imaginary unit; A denotes a response factor of a probe; Tz denotes a delay of receiving a scattered light signal on point z on the optical fiber under test (5) at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test (5).","8.A system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising: a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the periodic orthogonal optical pulse signal sequence into an optical fiber under test (5) in order of precedence, collecting scattered light signals, demodulating with the local oscillating light and a scattered light, and then converting the signals after demodulation into digital signals; and a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to an order of the orthogonal signals injected into the optical fiber under test.","9.The system, as recited in claim 8, wherein the signal generating unit comprises a narrow linewidth laser (1); a modulation unit (3) for modulating laser emitted from the narrow linewidth laser (1) to an up-conversion optical pulse signal or a down-conversion optical pulse signal; and a signal generating unit (6) for shifting frequency electric signals to drive the modulation unit (3).","10.The system, as recited in claim 9, wherein the signal optical path detection unit comprises a circulator (4) connected to the modulation unit (3); a 90-degree optical hybrid (7) connected to the narrow linewidth laser (1) and a third port of the circulator (4) respectively; the optical fiber under test (5) connected to a second port of the circulator (4); a balance detector (8) connected to the 90-degree optical hybrid (7); a data acquisition card (9) or an oscilloscope connected to the balance detector (8); wherein the modulation unit (3) and the 90-degree optical hybrid (7) are connected to the narrow linewidth laser (1) through a 90/10 coupler (2); the modulation unit (3) is connected to a 90% port of the 90/10 coupler (2); the 90-degree optical hybrid (7) is connected to a 10% port of the 90/10 coupler (2).","11.The system, as recited in claim 9, wherein a phase difference of two channels of signals outputted by the signal generating unit (6) for the shifting frequency electric signals is 90° or −90° with an error of +/−10′; the signal generating unit (6) for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.","12.The system, as recited in claim 10, wherein a phase difference of two channels of signals outputted by the signal generating unit (6) for the shifting frequency electric signals is 90° or −90° with an error of +/−10°; the signal generating unit (6) for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.","13.The system, as recited in claim 9, wherein the modulation unit (3) is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal and the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal and the down-conversion optical pulse signal filtered by the optical filter.","14.The system, as recited in claim 10, wherein the modulation unit (3) is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal and the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal and the down-conversion optical pulse signal filtered by the optical filter."],["<SOH> BACKGROUND OF THE PRESENT INVENTION <EOH>"],["<SOH> SUMMARY OF THE PRESENT INVENTION <EOH>An object of the present invention is to provide a method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof to solve the problem that conventional technology will increase the bandwidth of the received signal, reduce the signal-to-noise ratio of the received signal or distort the spatial resolution of the system.","The technical solution of the present invention is as follow: A method of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising steps of: step 1: generating a periodic orthogonal optical pulse sequence; step 2: injecting the periodic orthogonal optical pulse sequence into an optical fiber under test in order of precedence and collecting scattered light signals; demodulating the scattered light signals with a local oscillating light, and transforming the demodulated signal into digital signals; step 3: extracting the scatter information of each of orthogonal optical pulses of the periodic orthogonal optical pulse sequence from collected digital signals; arranging the scatter information in order of precedence of the injecting into the optical fiber under test.","The step 1 further comprises the following steps: step 1.1: outputting a continuous wave laser emitted by the narrow linewidth laser from a 90% port of a 90/10 coupler; and step 1.2: transforming the continuous wave laser into an up-conversion optical pulse signal or a down-conversion optical pulse signal which is the generated periodic orthogonal optical pulse sequence by a modulation unit driven by shifting frequency electric signals.","The step 2 further comprises the following steps: step 2.1: injecting the periodic orthogonal optical pulse sequence into the optical fiber under test by a circulator to generate the scattered light signals; step 2.2: using a 90-degree optical hybrid to carry out an IQ demodulation for the scattered light signals outputted by 3rd port of the circulator and the local oscillating light outputted by a 10% port of the 90/10 coupler; and step 2.3 transforming optical signals after IQ demodulation into electric signals by a balanced detector and transforming the electric signals into the digital signals by a data acquisition card or an oscilloscope.","The step 3 further comprises the following steps: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details are as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); where the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.","Furthermore, a signal generator (SG) generating the two channels of orthogonal signals with a frequency of f 1 in the step 1.2, and more details are as follows: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I channel signal, where a math expression of the I channel signal is written as: in-line-formulae description=\"In-line Formulae\" end=\"lead\"?","V Ii ( t )= V D cos(2π f 1 t )rect( t/T )+ V D cos(2π f 1 t )rect[( t−nL/c )/ T] in-line-formulae description=\"In-line Formulae\" end=\"tail\"?","meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which called Q channel signals, where a math expression of the Q-signals is written as: in-line-formulae description=\"In-line Formulae\" end=\"lead\"?","V Qi ( t )= V D cos(2π f 1 t+π/ 2)rect( t/T )+ V D cos(2π f 1 t−π/ 2)rect[( t−nL/c )/ T in-line-formulae description=\"In-line Formulae\" end=\"tail\"?","where L denotes a length of the optical fiber under test; c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test; nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f 1 denotes a frequency shift of the modulation unit; V D denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: in-line-formulae description=\"In-line Formulae\" end=\"lead\"?","E i =E c cos [2π( f c +f 1 ) t ]rect( t/T )+ E c cos [2π( f c −f 1 ) t ]rect[( t−nL/c )/ T] in-line-formulae description=\"In-line Formulae\" end=\"tail\"?","where, f c denotes a frequency of an incident light; E c denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: in-line-formulae description=\"In-line Formulae\" end=\"lead\"?","E 0 =AR ( z )exp{ j[ 2π f 1 ( t−T z )−2π f c T z ]}·rect[( t−T z )/ T]+AR ( z )exp{− j[ 2π f 1 ( t−T z )+2π f c T z ]}·rect[( t−nL/c−T z )/ T] in-line-formulae description=\"In-line Formulae\" end=\"tail\"?","wherein, j denotes an imaginary unit; A denotes a response factor of a probe; T z denotes a delay of receiving scattered light signals on point z on the optical fiber under test at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test.","A system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising: a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the periodic orthogonal optical pulse signal sequence into an optical fiber under test in order of precedence, collecting scattered light signals, demodulating with the local oscillating light and the scattered light, and then converting the signals after demodulation into digital signals; a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.","Furthermore, the signal generating unit comprises a narrow linewidth laser; a modulation unit for modulating laser emitted from the narrow linewidth laser to the up-conversion optical pulse signal or the down-conversion optical pulse signal; and a signal generating unit for shifting frequency electric signals to drive the modulation unit.","Furthermore, the signal optical path detection unit comprises a circulator connected to the modulation unit; a 90-degree optical hybrid connected to the narrow linewidth laser and a third port of the circulator respectively; the optical fiber under test connected to a second port of the circulator; a balance detector connected to the 90-degree optical hybrid; a data acquisition card or an oscilloscope connected to the balance detector; where the modulation unit and the 90-degree optical hybrid are connected to the narrow linewidth laser through a 90/10 coupler; the modulation unit is connected to a 90% port of the 90/10 coupler; the 90-degree optical hybrid is connected to a 10% port of the 90/10 coupler.","Furthermore, a phase difference of two channels of signals outputted by the signal generating unit for the shifting frequency electric signals is 90° or −90° with an error of +/−10°; the signal generating unit for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel electric signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.","Furthermore, the modulation unit is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal or the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal or the down-conversion optical pulse signal filtered by the optical filter.","The benefits of the present invention by adopting the technical solution are as follow: 1 The present invention takes full advantage of the bandwidth of the measurement channel and breaks the limit of which the single measurement time must exceed the roundtrip time of a pulse.","The present invention improves the measurement speed by N−1 times without increasing the signal measurement bandwidth and decreasing the signal-to-noise ratio of the received signal; 2 For a φ-OTDR (Optical Time Domain Reflectometer) system, the spatial resolution is determined by the width of the pulse.","The width of the pulse is not changed by adopting the present invention.","For the OFDR system, the spatial resolution is determined by the range of sweep frequency.","The range of the sweep frequency is not changed by adopting the present invention.","So, the spatial resolution is not decreased by adopting the present invention.","3 The present invention is able to be applied in wide varieties of systems, which is able to be adopted by all the heterodyne detection with distributed optical fiber sensor system, such as the φ-OTDR of the heterodyne detection, or the OFDR system of the chirped pulse."],["CROSS REFERENCE OF RELATED APPLICATION This application claims priority under 35 U.S.C.","119(a-d) to CN 201710672585.5, filed Aug. 8, 2017.BACKGROUND OF THE PRESENT INVENTION Field of Invention The present invention relates to a method of improving measurement speed of a distributed optical fiber sensor by adopting orthogonal signals and a system thereof, and more particularly to optical fiber sensor field.","Description of Related Arts The distributed optical fiber sensor system is a remote detection system.","The measurement speed is an important parameter of the DOFS (Distributed Optical Fiber Sensor).","In most of the DOFS system, an object is located by calculating on the time interval between sending out a pulse and receiving the pulse reflection (scattering) light.","In order to avoid misjudgment, the pulse repeat frequency fscan can and the length of the optical fiber under test (L) should be satisfied fscan<2 nL/c, where c denotes a speed of light in vacuum; n denotes a refractive of the optical fiber.","The longer the sensing distance, the lower the measurement speed of the system.","There are several ways to improve the measurement speed.","A research team in Tel Aviv University in Israel improves the system pulse repeat frequency of OFDR (Optical Frequency-Domain Reflectometer) to a theory boundary of fscan<2L/v by adopting positive and negative beat signal.","A research team in Shanghai institute of optics and fine mechanics improves the pulse repeat frequency of a phase sensitive optical time-domain reflectometer with 9.6 km sensing range to 0.5 MHz by adopting a frequency-division multiplexing technique, but this method will increase the bandwidth of the received signal and decreases the signal-to noise ratio of the received signal significantly.","A research team in Shanghai Jiao Tong University improves pulse repeat frequency by 5 times by adopting the frequency-division multiplexing in TGD-OFDR (Time-Gated Digital Optical Frequency-Domain Reflectometer), this method needs to divide the frequency sweep range to 5 regions and will decrease the spatial resolution of the system by 5 times.","A new method for improving the measurement speed without increasing the bandwidth of the received signal, sacrificing the spatial resolution and decreasing the signal-to noise ratio of the received signal is required.","SUMMARY OF THE PRESENT INVENTION An object of the present invention is to provide a method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof to solve the problem that conventional technology will increase the bandwidth of the received signal, reduce the signal-to-noise ratio of the received signal or distort the spatial resolution of the system.","The technical solution of the present invention is as follow: A method of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising steps of: step 1: generating a periodic orthogonal optical pulse sequence; step 2: injecting the periodic orthogonal optical pulse sequence into an optical fiber under test in order of precedence and collecting scattered light signals; demodulating the scattered light signals with a local oscillating light, and transforming the demodulated signal into digital signals; step 3: extracting the scatter information of each of orthogonal optical pulses of the periodic orthogonal optical pulse sequence from collected digital signals; arranging the scatter information in order of precedence of the injecting into the optical fiber under test.","The step 1 further comprises the following steps: step 1.1: outputting a continuous wave laser emitted by the narrow linewidth laser from a 90% port of a 90/10 coupler; and step 1.2: transforming the continuous wave laser into an up-conversion optical pulse signal or a down-conversion optical pulse signal which is the generated periodic orthogonal optical pulse sequence by a modulation unit driven by shifting frequency electric signals.","The step 2 further comprises the following steps: step 2.1: injecting the periodic orthogonal optical pulse sequence into the optical fiber under test by a circulator to generate the scattered light signals; step 2.2: using a 90-degree optical hybrid to carry out an IQ demodulation for the scattered light signals outputted by 3rd port of the circulator and the local oscillating light outputted by a 10% port of the 90/10 coupler; and step 2.3 transforming optical signals after IQ demodulation into electric signals by a balanced detector and transforming the electric signals into the digital signals by a data acquisition card or an oscilloscope.","The step 3 further comprises the following steps: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details are as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); where the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.","Furthermore, a signal generator (SG) generating the two channels of orthogonal signals with a frequency of f1 in the step 1.2, and more details are as follows: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I channel signal, where a math expression of the I channel signal is written as: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which called Q channel signals, where a math expression of the Q-signals is written as: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T where L denotes a length of the optical fiber under test; c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test; nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f1 denotes a frequency shift of the modulation unit; VD denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] where, fc denotes a frequency of an incident light; Ec denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: E0=AR(z)exp{j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{−j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] wherein, j denotes an imaginary unit; A denotes a response factor of a probe; Tz denotes a delay of receiving scattered light signals on point z on the optical fiber under test at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test.","A system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising: a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the periodic orthogonal optical pulse signal sequence into an optical fiber under test in order of precedence, collecting scattered light signals, demodulating with the local oscillating light and the scattered light, and then converting the signals after demodulation into digital signals; a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.","Furthermore, the signal generating unit comprises a narrow linewidth laser; a modulation unit for modulating laser emitted from the narrow linewidth laser to the up-conversion optical pulse signal or the down-conversion optical pulse signal; and a signal generating unit for shifting frequency electric signals to drive the modulation unit.","Furthermore, the signal optical path detection unit comprises a circulator connected to the modulation unit; a 90-degree optical hybrid connected to the narrow linewidth laser and a third port of the circulator respectively; the optical fiber under test connected to a second port of the circulator; a balance detector connected to the 90-degree optical hybrid; a data acquisition card or an oscilloscope connected to the balance detector; where the modulation unit and the 90-degree optical hybrid are connected to the narrow linewidth laser through a 90/10 coupler; the modulation unit is connected to a 90% port of the 90/10 coupler; the 90-degree optical hybrid is connected to a 10% port of the 90/10 coupler.","Furthermore, a phase difference of two channels of signals outputted by the signal generating unit for the shifting frequency electric signals is 90° or −90° with an error of +/−10°; the signal generating unit for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel electric signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.","Furthermore, the modulation unit is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal or the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal or the down-conversion optical pulse signal filtered by the optical filter.","The benefits of the present invention by adopting the technical solution are as follow: 1 The present invention takes full advantage of the bandwidth of the measurement channel and breaks the limit of which the single measurement time must exceed the roundtrip time of a pulse.","The present invention improves the measurement speed by N−1 times without increasing the signal measurement bandwidth and decreasing the signal-to-noise ratio of the received signal; 2 For a φ-OTDR (Optical Time Domain Reflectometer) system, the spatial resolution is determined by the width of the pulse.","The width of the pulse is not changed by adopting the present invention.","For the OFDR system, the spatial resolution is determined by the range of sweep frequency.","The range of the sweep frequency is not changed by adopting the present invention.","So, the spatial resolution is not decreased by adopting the present invention.","3 The present invention is able to be applied in wide varieties of systems, which is able to be adopted by all the heterodyne detection with distributed optical fiber sensor system, such as the φ-OTDR of the heterodyne detection, or the OFDR system of the chirped pulse.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a schematic structural diagram of the system of the present invention; FIG.","2 is a schematic diagram of generating an up-converted optical pulse signal and a down-converted optical pulse signal according to the present invention; FIG.","3 is a schematic diagram of a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal of the present invention; FIG.","4 is a schematic diagram of processing the collected signals by adopting a positive and negative beat signal separation algorithm.","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT In order to better illustrate the target, technical solution and advantages of the present invention, referring to the figures and embodiment, the present invention is further explained.","The embodiment described is just for better illustrating the present invention and is not a limit.","As shown in FIG.","1, a system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprises a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the N periodic orthogonal optical pulse signal sequence into an optical fiber under test in order of precedence, collecting scattered light signals, modulating and converting a local oscillating light and the scattered light signals into digital signals; a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test; the signal generating unit for a periodic orthogonal optical pulse sequence comprises a narrow linewidth laser 1; a modulation unit 3 for modulating laser emitted from the narrow linewidth laser 1 to an up-conversion optical pulse signal or a down-conversion optical pulse signal; and a signal generating unit 6 for shifting frequency electric signals to drive the modulation unit 3.The modulation unit 3 is a dual parallel Mach-Zehnder modulator (I/Q modulator).","An up-conversion optical pulse signal and a down-conversion optical pulse signal are generated by changing a phase of two channels of signal outputted by the signal generating unit 6 to 90° or −90°; the signal generating unit is a two channels output signal generator; the signal optical path detection unit comprises a circulator 4 connected to the I/Q modulator; a 90/10 coupler 2 connected to the narrow linewidth laser 1; a 90-degree optical hybrid 7 connected to the 90/10 coupler 2 and a third port of the circulator 4 respectively; the optical fiber under test 5 connected to a second port of the circulator 4; a balance detector 8 connected to the 90-degree optical hybrid 7; a data acquisition card 9 or an oscilloscope connected to the balance detector 8; the signal processing unit separate scatted (reflected) light signals generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal by a positive and negative beat signal separation algorithm and demodulating sensing information contained in the separated two signals (positive frequency part and negative frequency part signal after IFFT) which is arranged in order of precedence of the infusion into the optical fiber under test.","The detailed structure of the embodiment is as follow: an output end of the narrow linewidth laser 1 is connected to an input port of the 90/10 coupler 2; the 10 percent port of the 90/10 coupler 2 is connected to the local oscillating signal (LO) input end of the 90-degree optical hybrid 7; the 90 percent port of the 90/10 coupler is connected to an input end of the UQ modulator; the radio frequency port of the UQ modulator is connected to the two channels of orthogonal signals of the signal generating unit; I/Q modulator is connected to the signal generating unit; the output port of the UQ modulator is connected to a first port of the circulator 4; the second port of the circulator 4 is connected to the optical fiber under test 5; the third port of the circulator 4 is connected to signal input (SI) port of the 90-degree optical hybrid 7; two channels of UQ output of the 90-degree optical hybrid 7 are connected to two input port of the balanced detector 8; the UQ demodulated light signals are converted to electric signals by the balanced detector 8; the electric signals are converted to the digital signals by the data acquisition card 9 or the oscilloscope.","L denotes a length of the optical fiber under test; c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2nL/c; nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; As shown in the FIG.","3, the rectangle with forward slash denotes the down-conversion optical pulse signal; the rectangle with back slash denotes the up-conversion optical pulse signal.","A denotes a response factor of a probe; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test.","Tz denotes a delay of receiving a scattered (reflected) light signal on point z on the optical fiber under test at a receiving end; fc denotes a frequency of incident light; f1 denotes a frequency shift of the modulation unit; Ec denotes a signal amplitude of an optical signal after modulation; VD denotes a radio-frequency signal amplitude of a modulation.","The method of improving measurement speed of a distributed optical fiber sensor by adopting orthogonal signals and a system thereof comprises steps of: (a) generating two channels of orthogonal signals with a frequency of f1 generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I-signals, where a math expression of the I-signals is as below: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which are Q-signals, where a math expression of the Q-signals is as below: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T where rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable.","(b) modulating the two channels UQ signal into the up-conversion optical pulse signal and the down-conversion optical pulse signal; where in the math expression of the output signal is: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] (c) UQ demodulating the backscatting sensing signal and the local oscillating light; where the demodulated signal is: E0=AR(z)exp{−j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] (d) processing the collected signal with the positive and negative beat signal separation algorithm; separating the scatted light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal; demodulating the sensing information of the separated two signals; arranging the two signals in order of precedence of infusion into the optical fiber; where a signal measurement with a measurement time of nL/c is carried out on the optical fiber of L. The processing is illustrated in FIG.","4.The scattered signal comprises positive and negative beat signals; where the scattered signal is covered into two parts of positive beat signal and negative beat signal by the positive and negative beat signal separation algorithm; demodulating the two parts and arranging the demodulated signal in order of precedence of infusion into the optical fiber; the sensing information along the optical fiber is captured.","Compared to the conventional measurement system, the present invention improves the measurement speed by N−1 times; where in the embodiment N=2.The embodiment is just an illustration of the present invention and not a limitation Any alteration and modification in the spirit and principle of the present invention is within the protection range of the present invention."]],"string":"[\n [\n \"Method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof\",\n \"A method of improving measurement speed of distributed optical fiber sensors by adopting orthogonal signals and the system thereof is disclosed, which is related to the optical fiber sensor field and solves the problems that conventional technology will increasing the bandwidth of the received signal, reducing the signal-to-noise ratio of the received signal or distortion the spatial resolution of the system.\",\n \"The method comprises steps of generating N periodic orthogonal optical pulse sequence; injecting the N periodic orthogonal optical pulse sequence into the optical fiber under test(5); collecting the scattered light signal; demodulating the scattered light signal with the local oscillating light and then converting into digital signals; extracting the scatter information of the orthogonal optical pulses from the collected digital signals; and arranging the scattered information in order of precedence of the infusion.\",\n \"The measurement speed of the distributed optical fiber sensors is improved by N−1 times.\"\n ],\n [\n \"1.A method of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising steps of: step 1: generating a periodic orthogonal optical pulse sequence; step 2: injecting the periodic orthogonal optical pulse sequence into an optical fiber under test (5) in order of precedence and collecting scattered light signals; demodulating the scattered light signals with a local oscillating light, and transforming the demodulated signal into digital signals; and step 3: extracting scatter information of each of orthogonal optical pulses of the periodic orthogonal optical pulse sequence from collected digital signals; arranging the scatter information in order of precedence of the injecting into the optical fiber under test (5).\",\n \"2.The method, as recited in claim 1, wherein the step 1 specifically comprises steps of: step 1.1: outputting a continuous wave laser emitted by a narrow linewidth laser (1) from a 90% port of a 90/10 coupler (2); and step 1.2: transforming the continuous wave laser into an up-conversion optical pulse signal or a down-conversion optical pulse signal which is a generated periodic orthogonal optical pulse sequence by a modulation unit (3) driven by shifting frequency electric signals.\",\n \"3.The method, as recited in claim 1, wherein the step 2 specifically comprises steps of: step 2.1: injecting the periodic orthogonal optical pulse sequence into the optical fiber under test (5) by a circulator (4) to generate the scattered light signals; step 2.2: using a 90-degree optical hybrid (7) to carry out an IQ demodulation for the scattered light signals outputted by a 3rd port of the circulator (4) and the local oscillating light outputted by a 10 percent port of the 90/10 coupler (2); and step 2.3 transforming optical signals after IQ demodulation into electric signals by a balanced detector (8) and transforming the electric signals into the digital signals by a data acquisition card (9) or an oscilloscope.\",\n \"4.The method, as recited in claim 2, wherein the step 3 specifically comprises steps of: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); wherein the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier Transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to an order of the orthogonal signals injected into the optical fiber under test.\",\n \"5.The method, as recited in claim 3, wherein the step 3 comprises steps of: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); wherein the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier Transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.\",\n \"6.The method, as recited in claim 4, wherein the signal generating unit generates two channels of orthogonal signals with a frequency of f1 in the step 1.2, which is: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I channel-signal, wherein a math expression of the I channel-signal is written as: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which are Q channel-signal, wherein a math expression of the Q-channel signal is as below: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T wherein L denotes a length of the optical fiber under test (5); c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test (5); nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f1 denotes a frequency shift of the modulation unit; VD denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] wherein, fc denotes a frequency of an incident light; Ec denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: E0=AR(z)exp{j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{−j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] wherein, j denotes an imaginary unit; A denotes a response factor of a probe; Tz denotes a delay of receiving a scattered light signal on point z on the optical fiber under test (5) at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test (5).\",\n \"7.The method, as recited in claim 5, wherein the signal generating unit generates two channels of the orthogonal signals with a frequency of f1 in the step 1.2, wherein the following steps are comprised of: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I-channels, wherein a math expression of the I-channels is written as: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which are Q-channel signal, wherein a math expression of the Q-channel signal is as below: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T wherein L denotes a length of the optical fiber under test(5); c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test(5); nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f1 denotes a frequency shift of the modulation unit; VD denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] wherein, fc denotes a frequency of an incident light; Ec denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: E0=AR(z)exp{j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{−j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] wherein, j denotes an imaginary unit; A denotes a response factor of a probe; Tz denotes a delay of receiving a scattered light signal on point z on the optical fiber under test (5) at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test (5).\",\n \"8.A system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising: a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the periodic orthogonal optical pulse signal sequence into an optical fiber under test (5) in order of precedence, collecting scattered light signals, demodulating with the local oscillating light and a scattered light, and then converting the signals after demodulation into digital signals; and a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to an order of the orthogonal signals injected into the optical fiber under test.\",\n \"9.The system, as recited in claim 8, wherein the signal generating unit comprises a narrow linewidth laser (1); a modulation unit (3) for modulating laser emitted from the narrow linewidth laser (1) to an up-conversion optical pulse signal or a down-conversion optical pulse signal; and a signal generating unit (6) for shifting frequency electric signals to drive the modulation unit (3).\",\n \"10.The system, as recited in claim 9, wherein the signal optical path detection unit comprises a circulator (4) connected to the modulation unit (3); a 90-degree optical hybrid (7) connected to the narrow linewidth laser (1) and a third port of the circulator (4) respectively; the optical fiber under test (5) connected to a second port of the circulator (4); a balance detector (8) connected to the 90-degree optical hybrid (7); a data acquisition card (9) or an oscilloscope connected to the balance detector (8); wherein the modulation unit (3) and the 90-degree optical hybrid (7) are connected to the narrow linewidth laser (1) through a 90/10 coupler (2); the modulation unit (3) is connected to a 90% port of the 90/10 coupler (2); the 90-degree optical hybrid (7) is connected to a 10% port of the 90/10 coupler (2).\",\n \"11.The system, as recited in claim 9, wherein a phase difference of two channels of signals outputted by the signal generating unit (6) for the shifting frequency electric signals is 90° or −90° with an error of +/−10′; the signal generating unit (6) for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.\",\n \"12.The system, as recited in claim 10, wherein a phase difference of two channels of signals outputted by the signal generating unit (6) for the shifting frequency electric signals is 90° or −90° with an error of +/−10°; the signal generating unit (6) for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.\",\n \"13.The system, as recited in claim 9, wherein the modulation unit (3) is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal and the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal and the down-conversion optical pulse signal filtered by the optical filter.\",\n \"14.The system, as recited in claim 10, wherein the modulation unit (3) is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal and the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal and the down-conversion optical pulse signal filtered by the optical filter.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE PRESENT INVENTION <EOH>\"\n ],\n [\n \"<SOH> SUMMARY OF THE PRESENT INVENTION <EOH>An object of the present invention is to provide a method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof to solve the problem that conventional technology will increase the bandwidth of the received signal, reduce the signal-to-noise ratio of the received signal or distort the spatial resolution of the system.\",\n \"The technical solution of the present invention is as follow: A method of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising steps of: step 1: generating a periodic orthogonal optical pulse sequence; step 2: injecting the periodic orthogonal optical pulse sequence into an optical fiber under test in order of precedence and collecting scattered light signals; demodulating the scattered light signals with a local oscillating light, and transforming the demodulated signal into digital signals; step 3: extracting the scatter information of each of orthogonal optical pulses of the periodic orthogonal optical pulse sequence from collected digital signals; arranging the scatter information in order of precedence of the injecting into the optical fiber under test.\",\n \"The step 1 further comprises the following steps: step 1.1: outputting a continuous wave laser emitted by the narrow linewidth laser from a 90% port of a 90/10 coupler; and step 1.2: transforming the continuous wave laser into an up-conversion optical pulse signal or a down-conversion optical pulse signal which is the generated periodic orthogonal optical pulse sequence by a modulation unit driven by shifting frequency electric signals.\",\n \"The step 2 further comprises the following steps: step 2.1: injecting the periodic orthogonal optical pulse sequence into the optical fiber under test by a circulator to generate the scattered light signals; step 2.2: using a 90-degree optical hybrid to carry out an IQ demodulation for the scattered light signals outputted by 3rd port of the circulator and the local oscillating light outputted by a 10% port of the 90/10 coupler; and step 2.3 transforming optical signals after IQ demodulation into electric signals by a balanced detector and transforming the electric signals into the digital signals by a data acquisition card or an oscilloscope.\",\n \"The step 3 further comprises the following steps: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details are as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); where the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.\",\n \"Furthermore, a signal generator (SG) generating the two channels of orthogonal signals with a frequency of f 1 in the step 1.2, and more details are as follows: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I channel signal, where a math expression of the I channel signal is written as: in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"lead\\\"?\",\n \"V Ii ( t )= V D cos(2π f 1 t )rect( t/T )+ V D cos(2π f 1 t )rect[( t−nL/c )/ T] in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"tail\\\"?\",\n \"meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which called Q channel signals, where a math expression of the Q-signals is written as: in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"lead\\\"?\",\n \"V Qi ( t )= V D cos(2π f 1 t+π/ 2)rect( t/T )+ V D cos(2π f 1 t−π/ 2)rect[( t−nL/c )/ T in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"tail\\\"?\",\n \"where L denotes a length of the optical fiber under test; c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test; nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f 1 denotes a frequency shift of the modulation unit; V D denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"lead\\\"?\",\n \"E i =E c cos [2π( f c +f 1 ) t ]rect( t/T )+ E c cos [2π( f c −f 1 ) t ]rect[( t−nL/c )/ T] in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"tail\\\"?\",\n \"where, f c denotes a frequency of an incident light; E c denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"lead\\\"?\",\n \"E 0 =AR ( z )exp{ j[ 2π f 1 ( t−T z )−2π f c T z ]}·rect[( t−T z )/ T]+AR ( z )exp{− j[ 2π f 1 ( t−T z )+2π f c T z ]}·rect[( t−nL/c−T z )/ T] in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"tail\\\"?\",\n \"wherein, j denotes an imaginary unit; A denotes a response factor of a probe; T z denotes a delay of receiving scattered light signals on point z on the optical fiber under test at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test.\",\n \"A system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising: a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the periodic orthogonal optical pulse signal sequence into an optical fiber under test in order of precedence, collecting scattered light signals, demodulating with the local oscillating light and the scattered light, and then converting the signals after demodulation into digital signals; a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.\",\n \"Furthermore, the signal generating unit comprises a narrow linewidth laser; a modulation unit for modulating laser emitted from the narrow linewidth laser to the up-conversion optical pulse signal or the down-conversion optical pulse signal; and a signal generating unit for shifting frequency electric signals to drive the modulation unit.\",\n \"Furthermore, the signal optical path detection unit comprises a circulator connected to the modulation unit; a 90-degree optical hybrid connected to the narrow linewidth laser and a third port of the circulator respectively; the optical fiber under test connected to a second port of the circulator; a balance detector connected to the 90-degree optical hybrid; a data acquisition card or an oscilloscope connected to the balance detector; where the modulation unit and the 90-degree optical hybrid are connected to the narrow linewidth laser through a 90/10 coupler; the modulation unit is connected to a 90% port of the 90/10 coupler; the 90-degree optical hybrid is connected to a 10% port of the 90/10 coupler.\",\n \"Furthermore, a phase difference of two channels of signals outputted by the signal generating unit for the shifting frequency electric signals is 90° or −90° with an error of +/−10°; the signal generating unit for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel electric signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.\",\n \"Furthermore, the modulation unit is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal or the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal or the down-conversion optical pulse signal filtered by the optical filter.\",\n \"The benefits of the present invention by adopting the technical solution are as follow: 1 The present invention takes full advantage of the bandwidth of the measurement channel and breaks the limit of which the single measurement time must exceed the roundtrip time of a pulse.\",\n \"The present invention improves the measurement speed by N−1 times without increasing the signal measurement bandwidth and decreasing the signal-to-noise ratio of the received signal; 2 For a φ-OTDR (Optical Time Domain Reflectometer) system, the spatial resolution is determined by the width of the pulse.\",\n \"The width of the pulse is not changed by adopting the present invention.\",\n \"For the OFDR system, the spatial resolution is determined by the range of sweep frequency.\",\n \"The range of the sweep frequency is not changed by adopting the present invention.\",\n \"So, the spatial resolution is not decreased by adopting the present invention.\",\n \"3 The present invention is able to be applied in wide varieties of systems, which is able to be adopted by all the heterodyne detection with distributed optical fiber sensor system, such as the φ-OTDR of the heterodyne detection, or the OFDR system of the chirped pulse.\"\n ],\n [\n \"CROSS REFERENCE OF RELATED APPLICATION This application claims priority under 35 U.S.C.\",\n \"119(a-d) to CN 201710672585.5, filed Aug. 8, 2017.BACKGROUND OF THE PRESENT INVENTION Field of Invention The present invention relates to a method of improving measurement speed of a distributed optical fiber sensor by adopting orthogonal signals and a system thereof, and more particularly to optical fiber sensor field.\",\n \"Description of Related Arts The distributed optical fiber sensor system is a remote detection system.\",\n \"The measurement speed is an important parameter of the DOFS (Distributed Optical Fiber Sensor).\",\n \"In most of the DOFS system, an object is located by calculating on the time interval between sending out a pulse and receiving the pulse reflection (scattering) light.\",\n \"In order to avoid misjudgment, the pulse repeat frequency fscan can and the length of the optical fiber under test (L) should be satisfied fscan<2 nL/c, where c denotes a speed of light in vacuum; n denotes a refractive of the optical fiber.\",\n \"The longer the sensing distance, the lower the measurement speed of the system.\",\n \"There are several ways to improve the measurement speed.\",\n \"A research team in Tel Aviv University in Israel improves the system pulse repeat frequency of OFDR (Optical Frequency-Domain Reflectometer) to a theory boundary of fscan<2L/v by adopting positive and negative beat signal.\",\n \"A research team in Shanghai institute of optics and fine mechanics improves the pulse repeat frequency of a phase sensitive optical time-domain reflectometer with 9.6 km sensing range to 0.5 MHz by adopting a frequency-division multiplexing technique, but this method will increase the bandwidth of the received signal and decreases the signal-to noise ratio of the received signal significantly.\",\n \"A research team in Shanghai Jiao Tong University improves pulse repeat frequency by 5 times by adopting the frequency-division multiplexing in TGD-OFDR (Time-Gated Digital Optical Frequency-Domain Reflectometer), this method needs to divide the frequency sweep range to 5 regions and will decrease the spatial resolution of the system by 5 times.\",\n \"A new method for improving the measurement speed without increasing the bandwidth of the received signal, sacrificing the spatial resolution and decreasing the signal-to noise ratio of the received signal is required.\",\n \"SUMMARY OF THE PRESENT INVENTION An object of the present invention is to provide a method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof to solve the problem that conventional technology will increase the bandwidth of the received signal, reduce the signal-to-noise ratio of the received signal or distort the spatial resolution of the system.\",\n \"The technical solution of the present invention is as follow: A method of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising steps of: step 1: generating a periodic orthogonal optical pulse sequence; step 2: injecting the periodic orthogonal optical pulse sequence into an optical fiber under test in order of precedence and collecting scattered light signals; demodulating the scattered light signals with a local oscillating light, and transforming the demodulated signal into digital signals; step 3: extracting the scatter information of each of orthogonal optical pulses of the periodic orthogonal optical pulse sequence from collected digital signals; arranging the scatter information in order of precedence of the injecting into the optical fiber under test.\",\n \"The step 1 further comprises the following steps: step 1.1: outputting a continuous wave laser emitted by the narrow linewidth laser from a 90% port of a 90/10 coupler; and step 1.2: transforming the continuous wave laser into an up-conversion optical pulse signal or a down-conversion optical pulse signal which is the generated periodic orthogonal optical pulse sequence by a modulation unit driven by shifting frequency electric signals.\",\n \"The step 2 further comprises the following steps: step 2.1: injecting the periodic orthogonal optical pulse sequence into the optical fiber under test by a circulator to generate the scattered light signals; step 2.2: using a 90-degree optical hybrid to carry out an IQ demodulation for the scattered light signals outputted by 3rd port of the circulator and the local oscillating light outputted by a 10% port of the 90/10 coupler; and step 2.3 transforming optical signals after IQ demodulation into electric signals by a balanced detector and transforming the electric signals into the digital signals by a data acquisition card or an oscilloscope.\",\n \"The step 3 further comprises the following steps: step 3.1: processing collected digital signals by a positive and negative beat signal separation algorithm and separating the scattered light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal, and more details are as follows: converting the collected digital signals to a frequency domain by FFT (Fast Fourier Transform); where the orthogonal signals are a positive frequency part and a negative frequency part of the frequency domain respectively; obtaining time domain signals of the orthogonal signals by IFFT (Inverse Fast Fourier transform) of the positive frequency part and the negative frequency part; and step 3.2: sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.\",\n \"Furthermore, a signal generator (SG) generating the two channels of orthogonal signals with a frequency of f1 in the step 1.2, and more details are as follows: generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I channel signal, where a math expression of the I channel signal is written as: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which called Q channel signals, where a math expression of the Q-signals is written as: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T where L denotes a length of the optical fiber under test; c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test; nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2 nL/c; f1 denotes a frequency shift of the modulation unit; VD denotes a radio-frequency signal amplitude of a modulation; rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable; an output expression of the up-conversion optical pulse signal and the down-conversion optical pulse signal outputted by the modulation unit in the step 1.2 is as follow: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] where, fc denotes a frequency of an incident light; Ec denotes a signal amplitude of an optical signal after modulation; a modulated signal in the step 2.2 is as below: E0=AR(z)exp{j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{−j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] wherein, j denotes an imaginary unit; A denotes a response factor of a probe; Tz denotes a delay of receiving scattered light signals on point z on the optical fiber under test at a receiver; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test.\",\n \"A system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprising: a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the periodic orthogonal optical pulse signal sequence into an optical fiber under test in order of precedence, collecting scattered light signals, demodulating with the local oscillating light and the scattered light, and then converting the signals after demodulation into digital signals; a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test.\",\n \"Furthermore, the signal generating unit comprises a narrow linewidth laser; a modulation unit for modulating laser emitted from the narrow linewidth laser to the up-conversion optical pulse signal or the down-conversion optical pulse signal; and a signal generating unit for shifting frequency electric signals to drive the modulation unit.\",\n \"Furthermore, the signal optical path detection unit comprises a circulator connected to the modulation unit; a 90-degree optical hybrid connected to the narrow linewidth laser and a third port of the circulator respectively; the optical fiber under test connected to a second port of the circulator; a balance detector connected to the 90-degree optical hybrid; a data acquisition card or an oscilloscope connected to the balance detector; where the modulation unit and the 90-degree optical hybrid are connected to the narrow linewidth laser through a 90/10 coupler; the modulation unit is connected to a 90% port of the 90/10 coupler; the 90-degree optical hybrid is connected to a 10% port of the 90/10 coupler.\",\n \"Furthermore, a phase difference of two channels of signals outputted by the signal generating unit for the shifting frequency electric signals is 90° or −90° with an error of +/−10°; the signal generating unit for the shifting frequency electric signals is a signal generator with two channels of output; or a single channel signal generator and a 90-degree bridge which transforms a single channel electric signal generated by the single channel signal generator into two channels of signals; or a single channel signal generator.\",\n \"Furthermore, the modulation unit is an I/Q modulator; or an intensity modulator which generates the up-conversion optical pulse signal and the down-conversion optical pulse signal, an optical filter for filtering the up-conversion optical pulse signal or the down-conversion optical pulse signal generated by the intensity modulator and an optical switch for selecting the up-conversion optical pulse signal or the down-conversion optical pulse signal filtered by the optical filter.\",\n \"The benefits of the present invention by adopting the technical solution are as follow: 1 The present invention takes full advantage of the bandwidth of the measurement channel and breaks the limit of which the single measurement time must exceed the roundtrip time of a pulse.\",\n \"The present invention improves the measurement speed by N−1 times without increasing the signal measurement bandwidth and decreasing the signal-to-noise ratio of the received signal; 2 For a φ-OTDR (Optical Time Domain Reflectometer) system, the spatial resolution is determined by the width of the pulse.\",\n \"The width of the pulse is not changed by adopting the present invention.\",\n \"For the OFDR system, the spatial resolution is determined by the range of sweep frequency.\",\n \"The range of the sweep frequency is not changed by adopting the present invention.\",\n \"So, the spatial resolution is not decreased by adopting the present invention.\",\n \"3 The present invention is able to be applied in wide varieties of systems, which is able to be adopted by all the heterodyne detection with distributed optical fiber sensor system, such as the φ-OTDR of the heterodyne detection, or the OFDR system of the chirped pulse.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a schematic structural diagram of the system of the present invention; FIG.\",\n \"2 is a schematic diagram of generating an up-converted optical pulse signal and a down-converted optical pulse signal according to the present invention; FIG.\",\n \"3 is a schematic diagram of a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal of the present invention; FIG.\",\n \"4 is a schematic diagram of processing the collected signals by adopting a positive and negative beat signal separation algorithm.\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT In order to better illustrate the target, technical solution and advantages of the present invention, referring to the figures and embodiment, the present invention is further explained.\",\n \"The embodiment described is just for better illustrating the present invention and is not a limit.\",\n \"As shown in FIG.\",\n \"1, a system of improving a measurement speed of distributed optical fiber sensors by adopting orthogonal signals, comprises a signal generating unit for a periodic orthogonal optical pulse sequence; a signal optical path detection unit for injecting the N periodic orthogonal optical pulse signal sequence into an optical fiber under test in order of precedence, collecting scattered light signals, modulating and converting a local oscillating light and the scattered light signals into digital signals; a signal processing unit for extracting scatter information of each of orthogonal optical pulses respectively from collected digital signals and sorting sensing information contained in demodulated two signals according to the order of the orthogonal signals injected into the optical fiber under test; the signal generating unit for a periodic orthogonal optical pulse sequence comprises a narrow linewidth laser 1; a modulation unit 3 for modulating laser emitted from the narrow linewidth laser 1 to an up-conversion optical pulse signal or a down-conversion optical pulse signal; and a signal generating unit 6 for shifting frequency electric signals to drive the modulation unit 3.The modulation unit 3 is a dual parallel Mach-Zehnder modulator (I/Q modulator).\",\n \"An up-conversion optical pulse signal and a down-conversion optical pulse signal are generated by changing a phase of two channels of signal outputted by the signal generating unit 6 to 90° or −90°; the signal generating unit is a two channels output signal generator; the signal optical path detection unit comprises a circulator 4 connected to the I/Q modulator; a 90/10 coupler 2 connected to the narrow linewidth laser 1; a 90-degree optical hybrid 7 connected to the 90/10 coupler 2 and a third port of the circulator 4 respectively; the optical fiber under test 5 connected to a second port of the circulator 4; a balance detector 8 connected to the 90-degree optical hybrid 7; a data acquisition card 9 or an oscilloscope connected to the balance detector 8; the signal processing unit separate scatted (reflected) light signals generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal by a positive and negative beat signal separation algorithm and demodulating sensing information contained in the separated two signals (positive frequency part and negative frequency part signal after IFFT) which is arranged in order of precedence of the infusion into the optical fiber under test.\",\n \"The detailed structure of the embodiment is as follow: an output end of the narrow linewidth laser 1 is connected to an input port of the 90/10 coupler 2; the 10 percent port of the 90/10 coupler 2 is connected to the local oscillating signal (LO) input end of the 90-degree optical hybrid 7; the 90 percent port of the 90/10 coupler is connected to an input end of the UQ modulator; the radio frequency port of the UQ modulator is connected to the two channels of orthogonal signals of the signal generating unit; I/Q modulator is connected to the signal generating unit; the output port of the UQ modulator is connected to a first port of the circulator 4; the second port of the circulator 4 is connected to the optical fiber under test 5; the third port of the circulator 4 is connected to signal input (SI) port of the 90-degree optical hybrid 7; two channels of UQ output of the 90-degree optical hybrid 7 are connected to two input port of the balanced detector 8; the UQ demodulated light signals are converted to electric signals by the balanced detector 8; the electric signals are converted to the digital signals by the data acquisition card 9 or the oscilloscope.\",\n \"L denotes a length of the optical fiber under test; c denotes a speed of light in vacuum; n denotes a refractive index of the optical fiber under test; a periodic repetition of the up-conversion optical pulse signal and the down-conversion optical pulse optical pulse signal is 2nL/c; nL/c denotes a time interval between the up-conversion optical pulse signal and the down-conversion optical pulse signal; As shown in the FIG.\",\n \"3, the rectangle with forward slash denotes the down-conversion optical pulse signal; the rectangle with back slash denotes the up-conversion optical pulse signal.\",\n \"A denotes a response factor of a probe; R(z) denotes a distribution of a scattered light signal amplitude along the optical fiber under test.\",\n \"Tz denotes a delay of receiving a scattered (reflected) light signal on point z on the optical fiber under test at a receiving end; fc denotes a frequency of incident light; f1 denotes a frequency shift of the modulation unit; Ec denotes a signal amplitude of an optical signal after modulation; VD denotes a radio-frequency signal amplitude of a modulation.\",\n \"The method of improving measurement speed of a distributed optical fiber sensor by adopting orthogonal signals and a system thereof comprises steps of: (a) generating two channels of orthogonal signals with a frequency of f1 generating two pulses with an initial phase of 0° and a delay of nL/c as in-phase signals which are I-signals, where a math expression of the I-signals is as below: VIi(t)=VD cos(2πf1t)rect(t/T)+VD cos(2πf1t)rect[(t−nL/c)/T] meanwhile, generating two pulses with initial phases of 90° and −90° respectively and a delay of nL/c as the orthogonal signals which are Q-signals, where a math expression of the Q-signals is as below: VQi(t)=VD cos(2πf1t+π/2)rect(t/T)+VD cos(2πf1t−π/2)rect[(t−nL/c)/T where rect denotes a rectangular function; T denotes a pulse width; t denotes a time variable.\",\n \"(b) modulating the two channels UQ signal into the up-conversion optical pulse signal and the down-conversion optical pulse signal; where in the math expression of the output signal is: Ei=Ec cos [2π(fc+f1)t]rect(t/T)+Ec cos [2π(fc−f1)t]rect[(t−nL/c)/T] (c) UQ demodulating the backscatting sensing signal and the local oscillating light; where the demodulated signal is: E0=AR(z)exp{−j[2πf1(t−Tz)−2πfcTz]}·rect[(t−Tz)/T]+AR(z)exp{j[2πf1(t−Tz)+2πfcTz]}·rect[(t−nL/c−Tz)/T] (d) processing the collected signal with the positive and negative beat signal separation algorithm; separating the scatted light generated by the up-conversion optical pulse signal and the down-conversion optical pulse signal; demodulating the sensing information of the separated two signals; arranging the two signals in order of precedence of infusion into the optical fiber; where a signal measurement with a measurement time of nL/c is carried out on the optical fiber of L. The processing is illustrated in FIG.\",\n \"4.The scattered signal comprises positive and negative beat signals; where the scattered signal is covered into two parts of positive beat signal and negative beat signal by the positive and negative beat signal separation algorithm; demodulating the two parts and arranging the demodulated signal in order of precedence of infusion into the optical fiber; the sensing information along the optical fiber is captured.\",\n \"Compared to the conventional measurement system, the present invention improves the measurement speed by N−1 times; where in the embodiment N=2.The embodiment is just an illustration of the present invention and not a limitation Any alteration and modification in the spirit and principle of the present invention is within the protection range of the present invention.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874672"}}},{"rowIdx":4494667,"cells":{"text":{"kind":"list like","value":[["POWER ADAPTATION BASED ON ERROR RATE","A host device is configured to increase the power output by an internal amplifier of its wireless chipset in response to requests from a remote device.","Once the internal amplifier has reached its maximum power, further requests for power increases from the remove device do not similarly lead to automatic power increases being delivered by a external amplifier of the host device.","Rather, the host device determines the strength of the link between it and the remote device.","If the signal strength is too low, it is an indication that the signal power output by the remote device may not be sufficient to maintain the link and that any further increases in signal power by the host device will have little or no effect on the link.","However, if the signal strength from the remote device is sufficient, the host device determines an error rate between it and the remote device.","If the error rate is sufficiently low to maintain the link, then the host device will not further increase its signal output power.","However, if the error rate is too high, the host device will turn on and/or increase power from its external amplifier to boost the power of its output signal and, thus, improve the error rate between it and the remote device."],["1.An electronic device configured to communicate via a wireless communications link with a remote device, comprising: an input/output interface having a wireless communication circuitry comprising: a wireless chipset configured to generate a radio frequency signal, wherein the wireless chipset comprises an internal amplifier configured to amplify the radio frequency signal; and an external amplifier operatively coupled to the wireless chipset and configured to further amplify the radio frequency signal; and a processor configured to: determine whether the internal amplifier is at a maximum amplification level in response to receiving a request from the remote device to increase power of the radio frequency signal; determine a signal strength received by the electronic device from the remote device based at least in part on an error rate of the wireless communication link; and manage the external amplifier based at least in part on the signal strength, wherein managing the external amplifier comprises turning on, turning off, increasing the power, decreasing the power, or maintaining the power of the external amplifier.","2.The electronic device of claim 1, wherein managing the external amplifier based at least on the signal strength comprises: comparing the error rate an upper error rate boundary; when the error rate is above the upper error rate boundary, determining a power of the signal received by the electronic device from the remote device and determining whether the power is below a power threshold; when the power of the received signal is below the power threshold, maintaining the power of the external amplifier; and when the power of the signal is above the power threshold, increasing the power of the external amplifier or turning on the external amplifier.","3.The electronic device of claim 2, wherein the wireless communications link comprises a Bluetooth communications link, and wherein the power of the signal comprises a received signal strength indication (RSSI).","4.The electronic device of claim 1, wherein managing the external amplifier based at least on the signal strength comprises: comparing the error rate with a lower error rate boundary; when the error rate is above the lower error rate boundary, maintaining the power of the external amplifier; and when the error rate is below the lower error rate boundary, decreasing the power of the external amplifier or turning off the external amplifier.","5.The electronic device of claim 4, wherein managing the external amplifier when the error rate is below the lower error rate boundary comprises determining if the external amplifier is at minimum, decreasing the power of the external amplifier when the external amplifier is not at a minimum power setting, and turning off the external amplifier when the external amplifier is at a minimum power setting.","6.The electronic device of claim 1, wherein the processor is configured to manage the internal amplifier based at least in part on the request from the remote device to increase power of the radio frequency signal when the internal amplifier is not at a maximum power.","7.A method for controlling a power of a radio frequency signal generated by an electronic device wirelessly communicating via a communications link with a remote device, the method comprising: receiving at the electronic device a request for more power from the remote device; determining an error rate of the communications link and a power of a radio frequency signal received by the electronic device from the remote device; and determining whether to increase, decrease, or maintain a power setting of an amplifier external to a wireless chipset that generates the radio frequency signal based at least in part on the error rate and on a power of the radio frequency signal.","8.The method of claim 7, wherein the communications link comprises a Bluetooth communications link and wherein the power of the radio frequency signal comprises a received signal strength indicator (RS SI).","9.The method of claim 8, wherein increasing the power setting of the amplifier comprises turning on the amplifier when the amplifier is turned off, and wherein decreasing the power setting of the amplifier comprises turning off the amplifier when the amplifier is at a minimum power setting.","10.The method of claim 7, wherein determining whether to increase, decrease, or maintain the power setting of the amplifier comprises: comparing the error rate with an upper error rate boundary; if the error rate is above the upper error rate boundary, comparing the power of the radio frequency signal with a power threshold; if the power of the radio frequency signal is below the power threshold, increasing the power setting of the amplifier; if the power of the radio frequency signal is above the power threshold, maintaining the power setting of the amplifier; if the error rate is below the lower error rate boundary, decreasing the power setting of the amplifier; and if the error rate is above the lower error rate boundary and not above the upper rate boundary, maintaining the power setting of the amplifier.","11.The method of claim 7, wherein the error rate comprises a packet error rate (PER).","12.The method of claim 7, comprising: determining if a power setting of a second amplifier internal to the wireless chipset is at a maximum setting; and adjusting the second amplifier internal based at least in part on the request for more power if the second amplifier is below the maximum setting.","13.A tangible, non-transitory computer-readable medium having instructions that, when executed by a processor of an electronic device in wireless communication with a remote device via a communications link, causes the electronic device to: determine, in response to the electronic device receiving a request for more power from a remote device, whether an internal amplifier of a wireless chipset generating a radio frequency signal of the electronic device is at a maximum amplification level; increase an amplification level of the internal amplifier in response to the request for more power when the internal amplifier is below the maximum amplification level; determine an error rate and a signal strength of the communications link when the internal amplifier is at the maximum amplification level; and manage a power level of an external amplifier based at least in part on the error rate and the signal strength, wherein managing the power level of the external amplifier comprises increasing, decreasing, or maintaining the power level of the external amplifier.","14.The computer-readable medium of claim 13, wherein the communications link comprises a Bluetooth communications link or a wireless large area network (WLAN) communications link.","15.The computer-readable medium of claim 13, wherein the signal strength comprises a received signal strength indication (RSSI).","16.The computer-readable medium of claim 15, wherein the error rate comprises a packet error rate (PER).","17.The computer-readable medium of claim 13, wherein the managing the power level of an external amplifier based at least in part on the error rate and the signal strength comprises: increasing the power level of the external amplifier when the error rate is above an upper error rate boundary and the signal strength is below a signal strength threshold; maintaining the power level of the external amplifier when the error rate is above the upper error rate boundary and the signal strength is below the signal strength threshold; maintaining the power level of the external amplifier when the error rate is above a lower error rate boundary and below an upper error rate boundary; and decreasing the power level of the external amplifier when the error rate is below the lower error rate boundary.","18.The computer-readable medium of claim 17, wherein the lower error rate boundary and the upper error rate boundary are equal.","19.The computer-readable medium of claim 17, wherein decreasing the power level of the external amplifier comprises disabling the external amplifier when the power level of the external amplifier is at a minimum setting.","20.The computer-readable medium of claim 17, wherein increasing the power level of the external amplifier comprises enabling the external amplifier when the external amplifier is disabled."],["<SOH> BACKGROUND <EOH>The present disclosure relates generally to techniques for facilitating communication between two electronic devices and, more particularly, to techniques for controlling the power of communications signals between electronic devices, such as Bluetooth® enabled devices.","This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure, which are described and/or claimed below.","This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.","Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.","In the marketplace today, there are a wide variety of electronic devices available for a wide variety of purposes.","Such devices include cellular telephones, tablet computers, laptop computers, personal computers, televisions, headphones, Bluetooth® enabled watches, printers, and cameras, just to name a few.","It is often desirable for one electronic device to communicate with one or more other electronic devices.","Traditionally, such connections have been “hard-wired”, such that the devices had to be connected directly to one another by some sort of cabling or by cabling via a network interface.","Such cabling is typically terminated by standardized connectors (e.g., USB, RS232, etc.)","or by proprietary connectors, e.g.","Apple's Lightning® connector, etc.","Hence, not only does the cabling solution require a plethora of unsightly wires, it often requires specific types of cables and/or adaptors because of the wide variety of connectors and signaling schemes.","To address many of these concerns, various wireless technologies have become popular for facilitating communication between electronic devices.","For example radio frequency (RF) technologies, such as WiFi (IEEE 802.11) and Bluetooth® (IEEE 802.15), are now commonly used by many electronic devices to facilitate communication without the need for cabling.","Although such wireless interfaces address some of the problems with cabling, they are subject to their own disadvantages.","For example, because wireless signals typically need to be amplified more than signals that travel on an actual conductor, electronic devices typically utilize more power when communicating wirelessly, thus reducing battery life.","In one particular example, two electronic devices may communicate with one another using Bluetooth®.","In such situations, one device is typically the host, and the other device is typically considered a remote device.","Once the devices are paired, the remote device will determine a received signal strength indication (RSSI), which is a measurement of the power present in the RF signal it receives from the host device.","The higher the RSSI, the stronger the signal.","When the remote device determines that the RSSI of the signal it receives falls below a certain level, it sends a signal to the host device to request that it increase the power of the signal it transmits.","Typically, when a host device receives such a request, it increases the power of an internal amplifier that is typically part of its Bluetooth® chip set.","While such internal amplifiers typically do not lead to undue power consumption by the host device, it may be undesirable to allow a remote device to dictate the output power of a host device in situations that could lead to undue power consumption by the host device."],["<SOH> SUMMARY <EOH>A summary of certain embodiments disclosed herein is set forth below.","It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.","Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.","In accordance with the present techniques, certain devices, such as host devices, may include a wireless module that has an amplifier that is external to one or more of the wireless chip sets on the wireless module.","In one example, a wireless module may include a Bluetooth® chipset having an internal amplifier, as well as an amplifier that is externally coupled to the Bluetooth® chipset to further increase the output power of the Bluetooth signal after the internal amplifier has reached its maximum power.","In one embodiment, the host device is configured to increase the power output by the internal amplifier of its wireless chipset in response to requests from the remote device.","However, once the internal amplifier has reached its maximum power, further requests for power increases from the remove device do not similarly lead to automatic power increases being delivered by the external amplifier of the host device.","Rather, the host device determines the strength of the link between it and the remote device, by determining the RSSI of the signal it receives from the host device, for example.","If the RSSI is too low, it is an indication that the signal power output by the remote device may not be sufficient to maintain the link and that any further increases in signal power by the host device will have little or no effect on the link.","However, if the RSSI from the remote device is sufficient, the host device determines an error rate, such as an average packet error rate (PER), between it and the remote device.","If the error rate is sufficiently low to maintain the link, then the host device will not further increase its signal output power.","However, if the error rate is too high, the host device will turn on and/or increase power from its external amplifier to boost the power of its output signal and, thus, improve the error rate between it and the remote device.","Utilizing such a technique, the host device does not unduly consume power by driving its external amplifier harder than required to maintain a sufficient communications link between it and the remote device."],["CROSS-REFERENCE TO RELATED APPLICATIONS Under 35 U.S.C.","§ 120, this application is a continuation of U.S. patent application Ser.","No.","14/746,133 filed on Jun.","22, 2015, which is incorporated by reference herein in its entirety for all purposes.","BACKGROUND The present disclosure relates generally to techniques for facilitating communication between two electronic devices and, more particularly, to techniques for controlling the power of communications signals between electronic devices, such as Bluetooth® enabled devices.","This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure, which are described and/or claimed below.","This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.","Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.","In the marketplace today, there are a wide variety of electronic devices available for a wide variety of purposes.","Such devices include cellular telephones, tablet computers, laptop computers, personal computers, televisions, headphones, Bluetooth® enabled watches, printers, and cameras, just to name a few.","It is often desirable for one electronic device to communicate with one or more other electronic devices.","Traditionally, such connections have been “hard-wired”, such that the devices had to be connected directly to one another by some sort of cabling or by cabling via a network interface.","Such cabling is typically terminated by standardized connectors (e.g., USB, RS232, etc.)","or by proprietary connectors, e.g.","Apple's Lightning® connector, etc.","Hence, not only does the cabling solution require a plethora of unsightly wires, it often requires specific types of cables and/or adaptors because of the wide variety of connectors and signaling schemes.","To address many of these concerns, various wireless technologies have become popular for facilitating communication between electronic devices.","For example radio frequency (RF) technologies, such as WiFi (IEEE 802.11) and Bluetooth® (IEEE 802.15), are now commonly used by many electronic devices to facilitate communication without the need for cabling.","Although such wireless interfaces address some of the problems with cabling, they are subject to their own disadvantages.","For example, because wireless signals typically need to be amplified more than signals that travel on an actual conductor, electronic devices typically utilize more power when communicating wirelessly, thus reducing battery life.","In one particular example, two electronic devices may communicate with one another using Bluetooth®.","In such situations, one device is typically the host, and the other device is typically considered a remote device.","Once the devices are paired, the remote device will determine a received signal strength indication (RSSI), which is a measurement of the power present in the RF signal it receives from the host device.","The higher the RSSI, the stronger the signal.","When the remote device determines that the RSSI of the signal it receives falls below a certain level, it sends a signal to the host device to request that it increase the power of the signal it transmits.","Typically, when a host device receives such a request, it increases the power of an internal amplifier that is typically part of its Bluetooth® chip set.","While such internal amplifiers typically do not lead to undue power consumption by the host device, it may be undesirable to allow a remote device to dictate the output power of a host device in situations that could lead to undue power consumption by the host device.","SUMMARY A summary of certain embodiments disclosed herein is set forth below.","It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.","Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.","In accordance with the present techniques, certain devices, such as host devices, may include a wireless module that has an amplifier that is external to one or more of the wireless chip sets on the wireless module.","In one example, a wireless module may include a Bluetooth® chipset having an internal amplifier, as well as an amplifier that is externally coupled to the Bluetooth® chipset to further increase the output power of the Bluetooth signal after the internal amplifier has reached its maximum power.","In one embodiment, the host device is configured to increase the power output by the internal amplifier of its wireless chipset in response to requests from the remote device.","However, once the internal amplifier has reached its maximum power, further requests for power increases from the remove device do not similarly lead to automatic power increases being delivered by the external amplifier of the host device.","Rather, the host device determines the strength of the link between it and the remote device, by determining the RSSI of the signal it receives from the host device, for example.","If the RSSI is too low, it is an indication that the signal power output by the remote device may not be sufficient to maintain the link and that any further increases in signal power by the host device will have little or no effect on the link.","However, if the RSSI from the remote device is sufficient, the host device determines an error rate, such as an average packet error rate (PER), between it and the remote device.","If the error rate is sufficiently low to maintain the link, then the host device will not further increase its signal output power.","However, if the error rate is too high, the host device will turn on and/or increase power from its external amplifier to boost the power of its output signal and, thus, improve the error rate between it and the remote device.","Utilizing such a technique, the host device does not unduly consume power by driving its external amplifier harder than required to maintain a sufficient communications link between it and the remote device.","BRIEF DESCRIPTION OF THE DRAWINGS Various aspects of this disclosure may be better understood upon reading the following detailed description and upon reference to the drawings in which: FIG.","1 is a schematic block diagram of an electronic device including display control circuitry, in accordance with an embodiment; FIG.","2 is a perspective view of a notebook computer representing an embodiment of the electronic device of FIG.","1, in accordance with an embodiment; FIG.","3 is a front view of a hand-held device representing another embodiment of the electronic device of FIG.","1, in accordance with an embodiment; FIG.","4 is a front view of another hand-held device representing another embodiment of the electronic device of FIG.","1, in accordance with an embodiment; FIG.","5 is a front view of a desktop computer representing another embodiment of the electronic device of FIG.","1, in accordance with an embodiment; FIG.","6 is a front view of a wearable electronic device representing another embodiment of the electronic device of FIG.","1, in accordance with an embodiment; FIG.","7 is a diagram illustrating a host electronic device, such as a smart phone, communicating with a remote device, such as a wireless speaker, via a wireless link; FIG.","8 is block diagram of a portion of the input/output (I/O) interface of FIG.","1, illustrating that the I/O interface may include, among other things, a wireless module having an external amplifier that may be used in conjunction with a wireless chipset having an internal amplifier; FIG.","9 is a flowchart demonstrating an example of a technique that an electronic device, such as the host device illustrated in FIG.","7, may use to control the output power of a wireless signal emitted by the electronic device; FIG.","10 is a flowchart illustrating one example of the technique illustrated in FIG.","9; and FIG.","11 is a flowchart illustrating another example of the technique illustrated in FIG.","9.DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS One or more specific embodiments will be described below.","In an effort to provide a concise description of these embodiments, not all features of an actual implementation are described in the specification.","It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another.","Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.","As discussed above, when electronic devices wirelessly communicate with one another, one of the devices may request that another device increase the output power of its wireless signal.","In some situations, the request may cause the receiving device (after referred to as a host device) to increase its output power more than required to sufficiently maintain the link, and this can lead to undue power consumption and reduced battery life.","For instance, if the power request from the remote device caused the host device to turn on an additional amplifier and increase its power more than required to sufficiently maintain the communications link, the host device may unduly consume power.","To address this concern, the techniques described herein may reduce power consumption of the host device.","In one embodiment, the host device will increase output power of its wireless signal in response to requests from a remote device until the internal amplifier of its wireless chip set has reached its maximum level.","Thereafter, the host device will monitor the communications link between it and the remote device to determine whether any further power increases may be desirable.","For example, the host device may determine the RSSI of the signal it receives from the remote device to determine whether the signal strength of the remove device is sufficient to maintain the link.","If not, it will not increase the output power of its signal since it would have little or no effect on the quality of the communications link.","If so, however, the host device may determine the error rate of the communications link and whether that error rate is sufficiently low to adequately maintain the communications link.","If so, it will not provide further power increases, such as by turning on or increasing the power of an amplifier external to the wireless chipset.","If not, however, it may further increase signal output power, such as by providing power increases using the external amplifier, until the error rate is sufficiently low to adequately maintain the communications link.","Although the techniques described below use a Bluetooth communications link as an example, the techniques may apply to other types of wireless communications as well.","For example, it may apply to other types of Bluetooth, such as Bluetooth Low Energy (BLE), WLAN, cellular, etc.","With these features in mind, a general description of suitable electronic devices that may use error based power adaptation is provided.","Turning first to FIG.","1, an electronic device 10 according to an embodiment of the present disclosure may include, among other things, one or more processor(s) 12, memory 14, nonvolatile storage 16, a display 18 input structures 22, an input/output (I/O) interface 24 and a power source 26.The various functional blocks shown in FIG.","1 may include hardware elements (e.g., including circuitry), software elements (e.g., including computer code stored on a computer-readable medium) or a combination of both hardware and software elements.","It should be noted that FIG.","1 is merely one example of a particular implementation and is intended to illustrate the types of components that may be present in electronic device 10.By way of example, the electronic device 10 may represent a block diagram of the notebook computer depicted in FIG.","2, the handheld device depicted in either of FIG.","3 or FIG.","4, the desktop computer depicted in FIG.","5, the wearable electronic device depicted in FIG.6, or similar devices.","It should be noted that the processor(s) 12 and/or other data processing circuitry may be generally referred to herein as “data processing circuitry.” Such data processing circuitry may be embodied wholly or in part as software, firmware, hardware, or any combination thereof.","Furthermore, the data processing circuitry may be a single contained processing module or may be incorporated wholly or partially within any of the other elements within the electronic device 10.In the electronic device 10 of FIG.","1, the processor(s) 12 and/or other data processing circuitry may be operably coupled with the memory 14 and the nonvolatile memory 16 to perform various algorithms.","Such programs or instructions, including those for executing the techniques described herein, executed by the processor(s) 12 may be stored in any suitable article of manufacture that includes one or more tangible, computer-readable media at least collectively storing the instructions or routines, such as the memory 14 and the nonvolatile storage 16.The memory 14 and the nonvolatile storage 16 may include any suitable articles of manufacture for storing data and executable instructions, such as random-access memory, read-only memory, rewritable flash memory, hard drives, and optical discs.","Also, programs (e.g., e.g., an operating system) encoded on such a computer program product may also include instructions that may be executed by the processor(s) 12 to enable the electronic device 10 to provide various functionalities.","In certain embodiments, the display 18 may be a liquid crystal display (e.g., LCD), which may allow users to view images generated on the electronic device 10.In some embodiments, the display 18 may include a touch screen, which may allow users to interact with a user interface of the electronic device 10.Furthermore, it should be appreciated that, in some embodiments, the display 18 may include one or more light emitting diode (e.g., LED) displays, or some combination of LCD panels and LED panels.","The input structures 22 of the electronic device 10 may enable a user to interact with the electronic device 10 (e.g., e.g., pressing a button to increase or decrease a volume level).","The I/O interface 24 may enable electronic device 10 to interface with various other electronic devices.","The I/O interface 24 may include various types of ports that may be connected to cabling.","These ports may include standardized and/or proprietary ports, such as USB, RS232, Apple's Lightning® connector, as well as one or more ports for a conducted RF link.","The I/O interface 24 may also include, for example, interfaces for a personal area network (e.g., PAN), such as a Bluetooth network, for a local area network (e.g., LAN) or wireless local area network (e.g., WLAN), such as an 802.11x Wi-Fi network, and/or for a wide area network (e.g., WAN), such as a 3rd generation (e.g., 3G) cellular network, 4th generation (e.g., 4G) cellular network, or long term evolution (e.g., LTE) cellular network.","The I/O interface 24 may also include interfaces for, for example, broadband fixed wireless access networks (e.g., WiMAX), mobile broadband Wireless networks (e.g., mobile WiMAX), and so forth.","As further illustrated, the electronic device 10 may include a power source 26.The power source 26 may include any suitable source of power, such as a rechargeable lithium polymer (e.g., Li-poly) battery and/or an alternating current (e.g., AC) power converter.","The power source 26 may be removable, such as replaceable battery cell.","In certain embodiments, the electronic device 10 may take the form of a computer, a portable electronic device, a wearable electronic device, or other type of electronic device.","Such computers may include computers that are generally portable (e.g., such as laptop, notebook, and tablet computers) as well as computers that are generally used in one place (e.g., such as conventional desktop computers, workstations and/or servers).","In certain embodiments, the electronic device 10 in the form of a computer may be a model of a MacBook®, MacBook® Pro, MacBook Air®, iMac®, Mac® mini, or Mac Pro® available from Apple Inc. By way of example, the electronic device 10, taking the form of a notebook computer 30A, is illustrated in FIG.","2 in accordance with one embodiment of the present disclosure.","The depicted computer 30A may include a housing or enclosure 32, a display 18, input structures 22, and ports of the I/O interface 24.In one embodiment, the input structures 22 (e.g., such as a keyboard and/or touchpad) may be used to interact with the computer 30A, such as to start, control, or operate a GUI or applications running on computer 30A.","For example, a keyboard and/or touchpad may allow a user to navigate a user interface or application interface displayed on display 18.FIG.","3 depicts a front view of a handheld device 30B, which represents one embodiment of the electronic device 10.The handheld device 34 may represent, for example, a portable phone, a media player, a personal data organizer, a handheld game platform, or any combination of such devices.","By way of example, the handheld device 34 may be a model of an iPod® or iPhone® available from Apple Inc. of Cupertino, Calif.","The handheld device 30B may include an enclosure 36 to protect interior components from physical damage and to shield them from electromagnetic interference.","The enclosure 36 may surround the display 18, which may display indicator icons 39.The indicator icons 38 may indicate, among other things, a cellular signal strength, Bluetooth connection, and/or battery life.","The I/O interfaces 24 may open through the enclosure 36 and may include, for example, an I/O port for a hard wired connection for charging and/or content manipulation using a connector and protocol, such as the Lightning connector provided by Apple Inc., a universal serial bus (e.g., USB), one or more conducted RF connectors, or other connectors and protocols.","User input structures 40 and 42, in combination with the display 18, may allow a user to control the handheld device 30B.","For example, the input structure 40 may activate or deactivate the handheld device 30B, one of the input structures 42 may navigate user interface to a home screen, a user-configurable application screen, and/or activate a voice-recognition feature of the handheld device 30B, while other of the input structures 42 may provide volume control, or may toggle between vibrate and ring modes.","Additional input structures 42 may also include a microphone may obtain a user's voice for various voice-related features, and a speaker to allow for audio playback and/or certain phone capabilities.","The input structures 42 may also include a headphone input to provide a connection to external speakers and/or headphones.","FIG.","4 depicts a front view of another handheld device 30C, which represents another embodiment of the electronic device 10.The handheld device 30C may represent, for example, a tablet computer, or one of various portable computing devices.","By way of example, the handheld device 30C may be a tablet-sized embodiment of the electronic device 10, which may be, for example, a model of an iPad® available from Apple Inc. of Cupertino, Calif.","Turning to FIG.","5, a computer 30D may represent another embodiment of the electronic device 10 of FIG.","1.The computer 30D may be any computer, such as a desktop computer, a server, or a notebook computer, but may also be a standalone media player or video gaming machine.","By way of example, the computer 30D may be an iMac®, a MacBook®, or other similar device by Apple Inc.","It should be noted that the computer 30D may also represent a personal computer (e.g., PC) by another manufacturer.","A similar enclosure 36 may be provided to protect and enclose internal components of the computer 30D such as the dual-layer display 18.In certain embodiments, a user of the computer 30D may interact with the computer 30D using various peripheral input devices, such as the keyboard 22 or mouse 38, which may connect to the computer 30D via a wired and/or wireless I/O interface 24.Similarly, FIG.","6 depicts a wearable electronic device 30E representing another embodiment of the electronic device 10 of FIG.","1 that may be configured to operate using the techniques described herein.","By way of example, the wearable electronic device 30E, which may include a wristband 43, may be an Apple Watch® by Apple, Inc.","However, in other embodiments, the wearable electronic device 30E may include any wearable electronic device such as, for example, a wearable exercise monitoring device (e.g., e.g., pedometer, accelerometer, heart rate monitor), or other device by another manufacturer.","The display 18 of the wearable electronic device 30E may include a touch screen (e.g., e.g., LCD, OLED display, active-matrix organic light emitting diode (e.g., AMOLED) display, and so forth), which may allow users to interact with a user interface of the wearable electronic device 30E.","As discussed previously, when electronic devices wirelessly communicate with one another, one of the devices may act as a host device while another of the devices may act as a remote device.","An example of one such situation is illustrated in FIG.","7, which depicts a handheld device 30B acting as the host device.","The host device 30B is wirelessly communicating with a remote device 50, here illustrated as a wireless speaker, via a communications link 52.As discussed previously, some communications protocols, such as Bluetooth®, operate in a manner where the remote device 50 will send a request to the host device 32B to increase its signal power if the RSSI at the remote device 52 falls below a certain level.","In situations where the host device 30B includes an I/O interface 24 having a wireless module without any external amplifiers to further power the communications link 52, such requests from the remote device 50 to increase power will typically not result in undue power consumption by the host device 30B.","However, in situations where the host device 30B includes such an I/O interface 24, such as that illustrated in FIG.","8, raising output power in response to every request from the remote device 50 could cause the host device 30B to unduly consume power.","In this case, the wireless module 54 includes a wireless chipset, such as a Bluetooth® chipset 56 that includes its own internal amplifier 58.In addition, the wireless module 54 includes an external amplifier 60 that is coupled to the chipset 56 to further amplify the wireless signal produced by the chipset 56.Because the external amplifier 60 can consume much more power than the internal amplifier 58 of the chipset 56, turning it on and increasing its power when it is not necessary to do so to maintain the communications link 52 can cause the host device 30B to unduly consume power.","This is particularly problematic if the host device 30B is a battery powered device.","One technique to address this concern is illustrated by the flowchart 62 in FIG.","9.According to this technique, if the RSSI at the remote device 50 is too low, it will send a request for more power to the host device 30B (Block 64).","The host device 30B will check to see if the internal amplifier 58 is at its maximum output level (Block 66).","If it is not, the host device 30B will increase the power output by the internal amplifier 58 based on the RSSI at the remote device 50 (Block 68).","If so, however, the host device 30B will control its output power based on the error rate of the communications link 52 and the RSSI of the signal from the remote device 50 that is the received by the host device 30B (Block 69).","As understood by those of ordinary skill in the art, this technique may be executed by any suitable data processing circuitry, including the processor(s) 12, a processor of the I/O interface 24, a processor of the wireless module 54 or chipset 56, or any combination thereof.","It should be appreciated that the technique discussed with respect to FIG.","9 may be executed in a variety of ways, and one way for executing this technique is illustrated by the flowchart 70 in FIG.","10.Here, the remote device 50 sends a request to the host device 30B to increase its signal power (Block 72).","The host device 30B checks its internal amplifier 58 to determine whether it is at its maximum output level (Block 74).","If not, the host device 30B increases power of its internal amplifier and waits to see if it will receive another request from the remote device 50 (Block 76).","However, it the internal amplifier 58 is at its maximum power level, the host device 34 sends a message to the remote device 50 that maximum power has been reached (Block 78).","This may have the effect of causing the remove device 50 to cease sending requests for more power to the host device 30B.","Next, the host device 30B determines whether any further increases in power will improve the communications link 52.One way it may do this is by checking the RSSI of the signal that it receives from the remote device 50 (Block 80).","If the RSSI is below a certain threshold (Block 82), the host device 30B determines that the communications link 52 is limited by the signal output by the remote device 50 and, thus, does not turn on the external amplifier 60 (Block 84).","However, if the RSSI of the signal from the remote device 50 is above the threshold, then it is possible that further power increases will improve the communications link 52.To make this determination, the host device 30B may check for the retransmission rate and/or packet error rate of the communications link 52 (Block 86).","If the error rate is sufficient to maintain the communications link 52, the host device 30B will not turn on the external amplifier 60 or further increase power (Block 88).","Rather, it will continue to monitor the communications link 52 as described above.","If, however, the error rate is not sufficient to adequately maintain the communications link 52, the host device 30B will turn on the external amplifier 60 (Block 90).","With the external amplifier 60 on, the host device 30B will again check the retransmission rate and/or package rate to determine whether it is sufficient to maintain the communications link 52 (Blocks 92 and 94).","If not, it will again determine whether the RSSI from the remote device 50 is below a certain threshold (Block 95).","If not, it will increase the power of the external amplifier 60 (Block 96).","Otherwise, the communications link 52 is limited by the remote device 50, so the host device 30B will continue to check on the quality of the communications link 52 as described above.","Once the external amplifier 60 has been turned on so that it is providing additional power to the communications link 52, the host device 30B will determine whether it is able to turn off the external amplifier 60 or decrease its power while still maintaining an adequate communications link 52.Accordingly, if the error rate is sufficient to maintain the link, the host device 30B determines whether the external amplifier is at its minimal power level (Blocks 94 and 98).","If not, it will decrease power from the external amplifier 60 and again check on the quality of the communications link 52 as described above (Block 100).","However, if the external amplifier is at its minimum power level, the host device 30B will determine whether the external amplifier can be turned off (Blocks 98 and 102).","If not, then the host 30B will continue to check on the quality of the communications link 52.If so, however, the host device 30B will turn off the external amplifier 60and again wait for any requests to increase power from the remote device 50 (Blocks 104 and 72).","As mentioned above, there are a variety of ways to execute the technique set forth in FIG.","9, and another specific technique is illustrated by the flowchart 110 in FIG.","11.Here the remote device 50 sends a request to the host device 30B to increase its signal power (Block 112).","When the host device 30B receives this request, it checks its internal amplifier 58 to determine whether it is at its maximum power level (Block 114).","If not, the devices 30B and 50 will continue to operate under “classic power control” and the host device 30B will increase the power of its internal amplifier 58 (Block 116).","However, if its internal amplifier is at its maximum power level, the host device 30B determines the error rate and/or retransmission rate of communications link 52 (Block 118).","For example, the host device 30B may determine an average packet error rate over a given amount of time.","If the error rate is greater than an upper boundary, the host device 30B checks to determine whether the RSSI of the signal that it received from the remote device 50 is below a threshold (Blocks 120 and 122).","If the RSSI is too low, then the communications link 52 is limited by the remote device 50, so the host device 30B does not need to increase power using the external amplifier 60 (Block 124).","However, if the signal strength from the remove device 50 is sufficient, the host device 30B will increase power using the external amplifier 60 (Block 126).","On the other hand, if the measured error rate is below the upper boundary, the host device 30B determines whether the error rate is below a lower boundary (Blocks 120 and 128).","If not, then the host device 30B continues to monitor the quality of the communications link 52 as described above.","However, if the measured error rate is below the lower boundary, this suggests that the power of the output signal from the host device 30B may be greater than needed to maintain the quality of the communications link 52.Accordingly, the host device 30B will check to see if the external amplifier 60 is at its minimum level (Block 130).","If so, it will turn off the external amplifier 60 and the devices 30B and 50 will return to classic power control (Block 132 and 116).","If not, the host 30B will decrease the power output by the external amplifier 60 and continue to monitor the communications link 52 as described above (Block 134).","The specific embodiments described above have been shown by way of example, and it should be understood that these embodiments may be susceptible to various modifications and alternative forms.","It should be further understood that the claims are not intended to be limited to the particular forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure."]],"string":"[\n [\n \"POWER ADAPTATION BASED ON ERROR RATE\",\n \"A host device is configured to increase the power output by an internal amplifier of its wireless chipset in response to requests from a remote device.\",\n \"Once the internal amplifier has reached its maximum power, further requests for power increases from the remove device do not similarly lead to automatic power increases being delivered by a external amplifier of the host device.\",\n \"Rather, the host device determines the strength of the link between it and the remote device.\",\n \"If the signal strength is too low, it is an indication that the signal power output by the remote device may not be sufficient to maintain the link and that any further increases in signal power by the host device will have little or no effect on the link.\",\n \"However, if the signal strength from the remote device is sufficient, the host device determines an error rate between it and the remote device.\",\n \"If the error rate is sufficiently low to maintain the link, then the host device will not further increase its signal output power.\",\n \"However, if the error rate is too high, the host device will turn on and/or increase power from its external amplifier to boost the power of its output signal and, thus, improve the error rate between it and the remote device.\"\n ],\n [\n \"1.An electronic device configured to communicate via a wireless communications link with a remote device, comprising: an input/output interface having a wireless communication circuitry comprising: a wireless chipset configured to generate a radio frequency signal, wherein the wireless chipset comprises an internal amplifier configured to amplify the radio frequency signal; and an external amplifier operatively coupled to the wireless chipset and configured to further amplify the radio frequency signal; and a processor configured to: determine whether the internal amplifier is at a maximum amplification level in response to receiving a request from the remote device to increase power of the radio frequency signal; determine a signal strength received by the electronic device from the remote device based at least in part on an error rate of the wireless communication link; and manage the external amplifier based at least in part on the signal strength, wherein managing the external amplifier comprises turning on, turning off, increasing the power, decreasing the power, or maintaining the power of the external amplifier.\",\n \"2.The electronic device of claim 1, wherein managing the external amplifier based at least on the signal strength comprises: comparing the error rate an upper error rate boundary; when the error rate is above the upper error rate boundary, determining a power of the signal received by the electronic device from the remote device and determining whether the power is below a power threshold; when the power of the received signal is below the power threshold, maintaining the power of the external amplifier; and when the power of the signal is above the power threshold, increasing the power of the external amplifier or turning on the external amplifier.\",\n \"3.The electronic device of claim 2, wherein the wireless communications link comprises a Bluetooth communications link, and wherein the power of the signal comprises a received signal strength indication (RSSI).\",\n \"4.The electronic device of claim 1, wherein managing the external amplifier based at least on the signal strength comprises: comparing the error rate with a lower error rate boundary; when the error rate is above the lower error rate boundary, maintaining the power of the external amplifier; and when the error rate is below the lower error rate boundary, decreasing the power of the external amplifier or turning off the external amplifier.\",\n \"5.The electronic device of claim 4, wherein managing the external amplifier when the error rate is below the lower error rate boundary comprises determining if the external amplifier is at minimum, decreasing the power of the external amplifier when the external amplifier is not at a minimum power setting, and turning off the external amplifier when the external amplifier is at a minimum power setting.\",\n \"6.The electronic device of claim 1, wherein the processor is configured to manage the internal amplifier based at least in part on the request from the remote device to increase power of the radio frequency signal when the internal amplifier is not at a maximum power.\",\n \"7.A method for controlling a power of a radio frequency signal generated by an electronic device wirelessly communicating via a communications link with a remote device, the method comprising: receiving at the electronic device a request for more power from the remote device; determining an error rate of the communications link and a power of a radio frequency signal received by the electronic device from the remote device; and determining whether to increase, decrease, or maintain a power setting of an amplifier external to a wireless chipset that generates the radio frequency signal based at least in part on the error rate and on a power of the radio frequency signal.\",\n \"8.The method of claim 7, wherein the communications link comprises a Bluetooth communications link and wherein the power of the radio frequency signal comprises a received signal strength indicator (RS SI).\",\n \"9.The method of claim 8, wherein increasing the power setting of the amplifier comprises turning on the amplifier when the amplifier is turned off, and wherein decreasing the power setting of the amplifier comprises turning off the amplifier when the amplifier is at a minimum power setting.\",\n \"10.The method of claim 7, wherein determining whether to increase, decrease, or maintain the power setting of the amplifier comprises: comparing the error rate with an upper error rate boundary; if the error rate is above the upper error rate boundary, comparing the power of the radio frequency signal with a power threshold; if the power of the radio frequency signal is below the power threshold, increasing the power setting of the amplifier; if the power of the radio frequency signal is above the power threshold, maintaining the power setting of the amplifier; if the error rate is below the lower error rate boundary, decreasing the power setting of the amplifier; and if the error rate is above the lower error rate boundary and not above the upper rate boundary, maintaining the power setting of the amplifier.\",\n \"11.The method of claim 7, wherein the error rate comprises a packet error rate (PER).\",\n \"12.The method of claim 7, comprising: determining if a power setting of a second amplifier internal to the wireless chipset is at a maximum setting; and adjusting the second amplifier internal based at least in part on the request for more power if the second amplifier is below the maximum setting.\",\n \"13.A tangible, non-transitory computer-readable medium having instructions that, when executed by a processor of an electronic device in wireless communication with a remote device via a communications link, causes the electronic device to: determine, in response to the electronic device receiving a request for more power from a remote device, whether an internal amplifier of a wireless chipset generating a radio frequency signal of the electronic device is at a maximum amplification level; increase an amplification level of the internal amplifier in response to the request for more power when the internal amplifier is below the maximum amplification level; determine an error rate and a signal strength of the communications link when the internal amplifier is at the maximum amplification level; and manage a power level of an external amplifier based at least in part on the error rate and the signal strength, wherein managing the power level of the external amplifier comprises increasing, decreasing, or maintaining the power level of the external amplifier.\",\n \"14.The computer-readable medium of claim 13, wherein the communications link comprises a Bluetooth communications link or a wireless large area network (WLAN) communications link.\",\n \"15.The computer-readable medium of claim 13, wherein the signal strength comprises a received signal strength indication (RSSI).\",\n \"16.The computer-readable medium of claim 15, wherein the error rate comprises a packet error rate (PER).\",\n \"17.The computer-readable medium of claim 13, wherein the managing the power level of an external amplifier based at least in part on the error rate and the signal strength comprises: increasing the power level of the external amplifier when the error rate is above an upper error rate boundary and the signal strength is below a signal strength threshold; maintaining the power level of the external amplifier when the error rate is above the upper error rate boundary and the signal strength is below the signal strength threshold; maintaining the power level of the external amplifier when the error rate is above a lower error rate boundary and below an upper error rate boundary; and decreasing the power level of the external amplifier when the error rate is below the lower error rate boundary.\",\n \"18.The computer-readable medium of claim 17, wherein the lower error rate boundary and the upper error rate boundary are equal.\",\n \"19.The computer-readable medium of claim 17, wherein decreasing the power level of the external amplifier comprises disabling the external amplifier when the power level of the external amplifier is at a minimum setting.\",\n \"20.The computer-readable medium of claim 17, wherein increasing the power level of the external amplifier comprises enabling the external amplifier when the external amplifier is disabled.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>The present disclosure relates generally to techniques for facilitating communication between two electronic devices and, more particularly, to techniques for controlling the power of communications signals between electronic devices, such as Bluetooth® enabled devices.\",\n \"This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure, which are described and/or claimed below.\",\n \"This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.\",\n \"Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.\",\n \"In the marketplace today, there are a wide variety of electronic devices available for a wide variety of purposes.\",\n \"Such devices include cellular telephones, tablet computers, laptop computers, personal computers, televisions, headphones, Bluetooth® enabled watches, printers, and cameras, just to name a few.\",\n \"It is often desirable for one electronic device to communicate with one or more other electronic devices.\",\n \"Traditionally, such connections have been “hard-wired”, such that the devices had to be connected directly to one another by some sort of cabling or by cabling via a network interface.\",\n \"Such cabling is typically terminated by standardized connectors (e.g., USB, RS232, etc.)\",\n \"or by proprietary connectors, e.g.\",\n \"Apple's Lightning® connector, etc.\",\n \"Hence, not only does the cabling solution require a plethora of unsightly wires, it often requires specific types of cables and/or adaptors because of the wide variety of connectors and signaling schemes.\",\n \"To address many of these concerns, various wireless technologies have become popular for facilitating communication between electronic devices.\",\n \"For example radio frequency (RF) technologies, such as WiFi (IEEE 802.11) and Bluetooth® (IEEE 802.15), are now commonly used by many electronic devices to facilitate communication without the need for cabling.\",\n \"Although such wireless interfaces address some of the problems with cabling, they are subject to their own disadvantages.\",\n \"For example, because wireless signals typically need to be amplified more than signals that travel on an actual conductor, electronic devices typically utilize more power when communicating wirelessly, thus reducing battery life.\",\n \"In one particular example, two electronic devices may communicate with one another using Bluetooth®.\",\n \"In such situations, one device is typically the host, and the other device is typically considered a remote device.\",\n \"Once the devices are paired, the remote device will determine a received signal strength indication (RSSI), which is a measurement of the power present in the RF signal it receives from the host device.\",\n \"The higher the RSSI, the stronger the signal.\",\n \"When the remote device determines that the RSSI of the signal it receives falls below a certain level, it sends a signal to the host device to request that it increase the power of the signal it transmits.\",\n \"Typically, when a host device receives such a request, it increases the power of an internal amplifier that is typically part of its Bluetooth® chip set.\",\n \"While such internal amplifiers typically do not lead to undue power consumption by the host device, it may be undesirable to allow a remote device to dictate the output power of a host device in situations that could lead to undue power consumption by the host device.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>A summary of certain embodiments disclosed herein is set forth below.\",\n \"It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.\",\n \"Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.\",\n \"In accordance with the present techniques, certain devices, such as host devices, may include a wireless module that has an amplifier that is external to one or more of the wireless chip sets on the wireless module.\",\n \"In one example, a wireless module may include a Bluetooth® chipset having an internal amplifier, as well as an amplifier that is externally coupled to the Bluetooth® chipset to further increase the output power of the Bluetooth signal after the internal amplifier has reached its maximum power.\",\n \"In one embodiment, the host device is configured to increase the power output by the internal amplifier of its wireless chipset in response to requests from the remote device.\",\n \"However, once the internal amplifier has reached its maximum power, further requests for power increases from the remove device do not similarly lead to automatic power increases being delivered by the external amplifier of the host device.\",\n \"Rather, the host device determines the strength of the link between it and the remote device, by determining the RSSI of the signal it receives from the host device, for example.\",\n \"If the RSSI is too low, it is an indication that the signal power output by the remote device may not be sufficient to maintain the link and that any further increases in signal power by the host device will have little or no effect on the link.\",\n \"However, if the RSSI from the remote device is sufficient, the host device determines an error rate, such as an average packet error rate (PER), between it and the remote device.\",\n \"If the error rate is sufficiently low to maintain the link, then the host device will not further increase its signal output power.\",\n \"However, if the error rate is too high, the host device will turn on and/or increase power from its external amplifier to boost the power of its output signal and, thus, improve the error rate between it and the remote device.\",\n \"Utilizing such a technique, the host device does not unduly consume power by driving its external amplifier harder than required to maintain a sufficient communications link between it and the remote device.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS Under 35 U.S.C.\",\n \"§ 120, this application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/746,133 filed on Jun.\",\n \"22, 2015, which is incorporated by reference herein in its entirety for all purposes.\",\n \"BACKGROUND The present disclosure relates generally to techniques for facilitating communication between two electronic devices and, more particularly, to techniques for controlling the power of communications signals between electronic devices, such as Bluetooth® enabled devices.\",\n \"This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure, which are described and/or claimed below.\",\n \"This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.\",\n \"Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.\",\n \"In the marketplace today, there are a wide variety of electronic devices available for a wide variety of purposes.\",\n \"Such devices include cellular telephones, tablet computers, laptop computers, personal computers, televisions, headphones, Bluetooth® enabled watches, printers, and cameras, just to name a few.\",\n \"It is often desirable for one electronic device to communicate with one or more other electronic devices.\",\n \"Traditionally, such connections have been “hard-wired”, such that the devices had to be connected directly to one another by some sort of cabling or by cabling via a network interface.\",\n \"Such cabling is typically terminated by standardized connectors (e.g., USB, RS232, etc.)\",\n \"or by proprietary connectors, e.g.\",\n \"Apple's Lightning® connector, etc.\",\n \"Hence, not only does the cabling solution require a plethora of unsightly wires, it often requires specific types of cables and/or adaptors because of the wide variety of connectors and signaling schemes.\",\n \"To address many of these concerns, various wireless technologies have become popular for facilitating communication between electronic devices.\",\n \"For example radio frequency (RF) technologies, such as WiFi (IEEE 802.11) and Bluetooth® (IEEE 802.15), are now commonly used by many electronic devices to facilitate communication without the need for cabling.\",\n \"Although such wireless interfaces address some of the problems with cabling, they are subject to their own disadvantages.\",\n \"For example, because wireless signals typically need to be amplified more than signals that travel on an actual conductor, electronic devices typically utilize more power when communicating wirelessly, thus reducing battery life.\",\n \"In one particular example, two electronic devices may communicate with one another using Bluetooth®.\",\n \"In such situations, one device is typically the host, and the other device is typically considered a remote device.\",\n \"Once the devices are paired, the remote device will determine a received signal strength indication (RSSI), which is a measurement of the power present in the RF signal it receives from the host device.\",\n \"The higher the RSSI, the stronger the signal.\",\n \"When the remote device determines that the RSSI of the signal it receives falls below a certain level, it sends a signal to the host device to request that it increase the power of the signal it transmits.\",\n \"Typically, when a host device receives such a request, it increases the power of an internal amplifier that is typically part of its Bluetooth® chip set.\",\n \"While such internal amplifiers typically do not lead to undue power consumption by the host device, it may be undesirable to allow a remote device to dictate the output power of a host device in situations that could lead to undue power consumption by the host device.\",\n \"SUMMARY A summary of certain embodiments disclosed herein is set forth below.\",\n \"It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.\",\n \"Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.\",\n \"In accordance with the present techniques, certain devices, such as host devices, may include a wireless module that has an amplifier that is external to one or more of the wireless chip sets on the wireless module.\",\n \"In one example, a wireless module may include a Bluetooth® chipset having an internal amplifier, as well as an amplifier that is externally coupled to the Bluetooth® chipset to further increase the output power of the Bluetooth signal after the internal amplifier has reached its maximum power.\",\n \"In one embodiment, the host device is configured to increase the power output by the internal amplifier of its wireless chipset in response to requests from the remote device.\",\n \"However, once the internal amplifier has reached its maximum power, further requests for power increases from the remove device do not similarly lead to automatic power increases being delivered by the external amplifier of the host device.\",\n \"Rather, the host device determines the strength of the link between it and the remote device, by determining the RSSI of the signal it receives from the host device, for example.\",\n \"If the RSSI is too low, it is an indication that the signal power output by the remote device may not be sufficient to maintain the link and that any further increases in signal power by the host device will have little or no effect on the link.\",\n \"However, if the RSSI from the remote device is sufficient, the host device determines an error rate, such as an average packet error rate (PER), between it and the remote device.\",\n \"If the error rate is sufficiently low to maintain the link, then the host device will not further increase its signal output power.\",\n \"However, if the error rate is too high, the host device will turn on and/or increase power from its external amplifier to boost the power of its output signal and, thus, improve the error rate between it and the remote device.\",\n \"Utilizing such a technique, the host device does not unduly consume power by driving its external amplifier harder than required to maintain a sufficient communications link between it and the remote device.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Various aspects of this disclosure may be better understood upon reading the following detailed description and upon reference to the drawings in which: FIG.\",\n \"1 is a schematic block diagram of an electronic device including display control circuitry, in accordance with an embodiment; FIG.\",\n \"2 is a perspective view of a notebook computer representing an embodiment of the electronic device of FIG.\",\n \"1, in accordance with an embodiment; FIG.\",\n \"3 is a front view of a hand-held device representing another embodiment of the electronic device of FIG.\",\n \"1, in accordance with an embodiment; FIG.\",\n \"4 is a front view of another hand-held device representing another embodiment of the electronic device of FIG.\",\n \"1, in accordance with an embodiment; FIG.\",\n \"5 is a front view of a desktop computer representing another embodiment of the electronic device of FIG.\",\n \"1, in accordance with an embodiment; FIG.\",\n \"6 is a front view of a wearable electronic device representing another embodiment of the electronic device of FIG.\",\n \"1, in accordance with an embodiment; FIG.\",\n \"7 is a diagram illustrating a host electronic device, such as a smart phone, communicating with a remote device, such as a wireless speaker, via a wireless link; FIG.\",\n \"8 is block diagram of a portion of the input/output (I/O) interface of FIG.\",\n \"1, illustrating that the I/O interface may include, among other things, a wireless module having an external amplifier that may be used in conjunction with a wireless chipset having an internal amplifier; FIG.\",\n \"9 is a flowchart demonstrating an example of a technique that an electronic device, such as the host device illustrated in FIG.\",\n \"7, may use to control the output power of a wireless signal emitted by the electronic device; FIG.\",\n \"10 is a flowchart illustrating one example of the technique illustrated in FIG.\",\n \"9; and FIG.\",\n \"11 is a flowchart illustrating another example of the technique illustrated in FIG.\",\n \"9.DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS One or more specific embodiments will be described below.\",\n \"In an effort to provide a concise description of these embodiments, not all features of an actual implementation are described in the specification.\",\n \"It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another.\",\n \"Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.\",\n \"As discussed above, when electronic devices wirelessly communicate with one another, one of the devices may request that another device increase the output power of its wireless signal.\",\n \"In some situations, the request may cause the receiving device (after referred to as a host device) to increase its output power more than required to sufficiently maintain the link, and this can lead to undue power consumption and reduced battery life.\",\n \"For instance, if the power request from the remote device caused the host device to turn on an additional amplifier and increase its power more than required to sufficiently maintain the communications link, the host device may unduly consume power.\",\n \"To address this concern, the techniques described herein may reduce power consumption of the host device.\",\n \"In one embodiment, the host device will increase output power of its wireless signal in response to requests from a remote device until the internal amplifier of its wireless chip set has reached its maximum level.\",\n \"Thereafter, the host device will monitor the communications link between it and the remote device to determine whether any further power increases may be desirable.\",\n \"For example, the host device may determine the RSSI of the signal it receives from the remote device to determine whether the signal strength of the remove device is sufficient to maintain the link.\",\n \"If not, it will not increase the output power of its signal since it would have little or no effect on the quality of the communications link.\",\n \"If so, however, the host device may determine the error rate of the communications link and whether that error rate is sufficiently low to adequately maintain the communications link.\",\n \"If so, it will not provide further power increases, such as by turning on or increasing the power of an amplifier external to the wireless chipset.\",\n \"If not, however, it may further increase signal output power, such as by providing power increases using the external amplifier, until the error rate is sufficiently low to adequately maintain the communications link.\",\n \"Although the techniques described below use a Bluetooth communications link as an example, the techniques may apply to other types of wireless communications as well.\",\n \"For example, it may apply to other types of Bluetooth, such as Bluetooth Low Energy (BLE), WLAN, cellular, etc.\",\n \"With these features in mind, a general description of suitable electronic devices that may use error based power adaptation is provided.\",\n \"Turning first to FIG.\",\n \"1, an electronic device 10 according to an embodiment of the present disclosure may include, among other things, one or more processor(s) 12, memory 14, nonvolatile storage 16, a display 18 input structures 22, an input/output (I/O) interface 24 and a power source 26.The various functional blocks shown in FIG.\",\n \"1 may include hardware elements (e.g., including circuitry), software elements (e.g., including computer code stored on a computer-readable medium) or a combination of both hardware and software elements.\",\n \"It should be noted that FIG.\",\n \"1 is merely one example of a particular implementation and is intended to illustrate the types of components that may be present in electronic device 10.By way of example, the electronic device 10 may represent a block diagram of the notebook computer depicted in FIG.\",\n \"2, the handheld device depicted in either of FIG.\",\n \"3 or FIG.\",\n \"4, the desktop computer depicted in FIG.\",\n \"5, the wearable electronic device depicted in FIG.6, or similar devices.\",\n \"It should be noted that the processor(s) 12 and/or other data processing circuitry may be generally referred to herein as “data processing circuitry.” Such data processing circuitry may be embodied wholly or in part as software, firmware, hardware, or any combination thereof.\",\n \"Furthermore, the data processing circuitry may be a single contained processing module or may be incorporated wholly or partially within any of the other elements within the electronic device 10.In the electronic device 10 of FIG.\",\n \"1, the processor(s) 12 and/or other data processing circuitry may be operably coupled with the memory 14 and the nonvolatile memory 16 to perform various algorithms.\",\n \"Such programs or instructions, including those for executing the techniques described herein, executed by the processor(s) 12 may be stored in any suitable article of manufacture that includes one or more tangible, computer-readable media at least collectively storing the instructions or routines, such as the memory 14 and the nonvolatile storage 16.The memory 14 and the nonvolatile storage 16 may include any suitable articles of manufacture for storing data and executable instructions, such as random-access memory, read-only memory, rewritable flash memory, hard drives, and optical discs.\",\n \"Also, programs (e.g., e.g., an operating system) encoded on such a computer program product may also include instructions that may be executed by the processor(s) 12 to enable the electronic device 10 to provide various functionalities.\",\n \"In certain embodiments, the display 18 may be a liquid crystal display (e.g., LCD), which may allow users to view images generated on the electronic device 10.In some embodiments, the display 18 may include a touch screen, which may allow users to interact with a user interface of the electronic device 10.Furthermore, it should be appreciated that, in some embodiments, the display 18 may include one or more light emitting diode (e.g., LED) displays, or some combination of LCD panels and LED panels.\",\n \"The input structures 22 of the electronic device 10 may enable a user to interact with the electronic device 10 (e.g., e.g., pressing a button to increase or decrease a volume level).\",\n \"The I/O interface 24 may enable electronic device 10 to interface with various other electronic devices.\",\n \"The I/O interface 24 may include various types of ports that may be connected to cabling.\",\n \"These ports may include standardized and/or proprietary ports, such as USB, RS232, Apple's Lightning® connector, as well as one or more ports for a conducted RF link.\",\n \"The I/O interface 24 may also include, for example, interfaces for a personal area network (e.g., PAN), such as a Bluetooth network, for a local area network (e.g., LAN) or wireless local area network (e.g., WLAN), such as an 802.11x Wi-Fi network, and/or for a wide area network (e.g., WAN), such as a 3rd generation (e.g., 3G) cellular network, 4th generation (e.g., 4G) cellular network, or long term evolution (e.g., LTE) cellular network.\",\n \"The I/O interface 24 may also include interfaces for, for example, broadband fixed wireless access networks (e.g., WiMAX), mobile broadband Wireless networks (e.g., mobile WiMAX), and so forth.\",\n \"As further illustrated, the electronic device 10 may include a power source 26.The power source 26 may include any suitable source of power, such as a rechargeable lithium polymer (e.g., Li-poly) battery and/or an alternating current (e.g., AC) power converter.\",\n \"The power source 26 may be removable, such as replaceable battery cell.\",\n \"In certain embodiments, the electronic device 10 may take the form of a computer, a portable electronic device, a wearable electronic device, or other type of electronic device.\",\n \"Such computers may include computers that are generally portable (e.g., such as laptop, notebook, and tablet computers) as well as computers that are generally used in one place (e.g., such as conventional desktop computers, workstations and/or servers).\",\n \"In certain embodiments, the electronic device 10 in the form of a computer may be a model of a MacBook®, MacBook® Pro, MacBook Air®, iMac®, Mac® mini, or Mac Pro® available from Apple Inc. By way of example, the electronic device 10, taking the form of a notebook computer 30A, is illustrated in FIG.\",\n \"2 in accordance with one embodiment of the present disclosure.\",\n \"The depicted computer 30A may include a housing or enclosure 32, a display 18, input structures 22, and ports of the I/O interface 24.In one embodiment, the input structures 22 (e.g., such as a keyboard and/or touchpad) may be used to interact with the computer 30A, such as to start, control, or operate a GUI or applications running on computer 30A.\",\n \"For example, a keyboard and/or touchpad may allow a user to navigate a user interface or application interface displayed on display 18.FIG.\",\n \"3 depicts a front view of a handheld device 30B, which represents one embodiment of the electronic device 10.The handheld device 34 may represent, for example, a portable phone, a media player, a personal data organizer, a handheld game platform, or any combination of such devices.\",\n \"By way of example, the handheld device 34 may be a model of an iPod® or iPhone® available from Apple Inc. of Cupertino, Calif.\",\n \"The handheld device 30B may include an enclosure 36 to protect interior components from physical damage and to shield them from electromagnetic interference.\",\n \"The enclosure 36 may surround the display 18, which may display indicator icons 39.The indicator icons 38 may indicate, among other things, a cellular signal strength, Bluetooth connection, and/or battery life.\",\n \"The I/O interfaces 24 may open through the enclosure 36 and may include, for example, an I/O port for a hard wired connection for charging and/or content manipulation using a connector and protocol, such as the Lightning connector provided by Apple Inc., a universal serial bus (e.g., USB), one or more conducted RF connectors, or other connectors and protocols.\",\n \"User input structures 40 and 42, in combination with the display 18, may allow a user to control the handheld device 30B.\",\n \"For example, the input structure 40 may activate or deactivate the handheld device 30B, one of the input structures 42 may navigate user interface to a home screen, a user-configurable application screen, and/or activate a voice-recognition feature of the handheld device 30B, while other of the input structures 42 may provide volume control, or may toggle between vibrate and ring modes.\",\n \"Additional input structures 42 may also include a microphone may obtain a user's voice for various voice-related features, and a speaker to allow for audio playback and/or certain phone capabilities.\",\n \"The input structures 42 may also include a headphone input to provide a connection to external speakers and/or headphones.\",\n \"FIG.\",\n \"4 depicts a front view of another handheld device 30C, which represents another embodiment of the electronic device 10.The handheld device 30C may represent, for example, a tablet computer, or one of various portable computing devices.\",\n \"By way of example, the handheld device 30C may be a tablet-sized embodiment of the electronic device 10, which may be, for example, a model of an iPad® available from Apple Inc. of Cupertino, Calif.\",\n \"Turning to FIG.\",\n \"5, a computer 30D may represent another embodiment of the electronic device 10 of FIG.\",\n \"1.The computer 30D may be any computer, such as a desktop computer, a server, or a notebook computer, but may also be a standalone media player or video gaming machine.\",\n \"By way of example, the computer 30D may be an iMac®, a MacBook®, or other similar device by Apple Inc.\",\n \"It should be noted that the computer 30D may also represent a personal computer (e.g., PC) by another manufacturer.\",\n \"A similar enclosure 36 may be provided to protect and enclose internal components of the computer 30D such as the dual-layer display 18.In certain embodiments, a user of the computer 30D may interact with the computer 30D using various peripheral input devices, such as the keyboard 22 or mouse 38, which may connect to the computer 30D via a wired and/or wireless I/O interface 24.Similarly, FIG.\",\n \"6 depicts a wearable electronic device 30E representing another embodiment of the electronic device 10 of FIG.\",\n \"1 that may be configured to operate using the techniques described herein.\",\n \"By way of example, the wearable electronic device 30E, which may include a wristband 43, may be an Apple Watch® by Apple, Inc.\",\n \"However, in other embodiments, the wearable electronic device 30E may include any wearable electronic device such as, for example, a wearable exercise monitoring device (e.g., e.g., pedometer, accelerometer, heart rate monitor), or other device by another manufacturer.\",\n \"The display 18 of the wearable electronic device 30E may include a touch screen (e.g., e.g., LCD, OLED display, active-matrix organic light emitting diode (e.g., AMOLED) display, and so forth), which may allow users to interact with a user interface of the wearable electronic device 30E.\",\n \"As discussed previously, when electronic devices wirelessly communicate with one another, one of the devices may act as a host device while another of the devices may act as a remote device.\",\n \"An example of one such situation is illustrated in FIG.\",\n \"7, which depicts a handheld device 30B acting as the host device.\",\n \"The host device 30B is wirelessly communicating with a remote device 50, here illustrated as a wireless speaker, via a communications link 52.As discussed previously, some communications protocols, such as Bluetooth®, operate in a manner where the remote device 50 will send a request to the host device 32B to increase its signal power if the RSSI at the remote device 52 falls below a certain level.\",\n \"In situations where the host device 30B includes an I/O interface 24 having a wireless module without any external amplifiers to further power the communications link 52, such requests from the remote device 50 to increase power will typically not result in undue power consumption by the host device 30B.\",\n \"However, in situations where the host device 30B includes such an I/O interface 24, such as that illustrated in FIG.\",\n \"8, raising output power in response to every request from the remote device 50 could cause the host device 30B to unduly consume power.\",\n \"In this case, the wireless module 54 includes a wireless chipset, such as a Bluetooth® chipset 56 that includes its own internal amplifier 58.In addition, the wireless module 54 includes an external amplifier 60 that is coupled to the chipset 56 to further amplify the wireless signal produced by the chipset 56.Because the external amplifier 60 can consume much more power than the internal amplifier 58 of the chipset 56, turning it on and increasing its power when it is not necessary to do so to maintain the communications link 52 can cause the host device 30B to unduly consume power.\",\n \"This is particularly problematic if the host device 30B is a battery powered device.\",\n \"One technique to address this concern is illustrated by the flowchart 62 in FIG.\",\n \"9.According to this technique, if the RSSI at the remote device 50 is too low, it will send a request for more power to the host device 30B (Block 64).\",\n \"The host device 30B will check to see if the internal amplifier 58 is at its maximum output level (Block 66).\",\n \"If it is not, the host device 30B will increase the power output by the internal amplifier 58 based on the RSSI at the remote device 50 (Block 68).\",\n \"If so, however, the host device 30B will control its output power based on the error rate of the communications link 52 and the RSSI of the signal from the remote device 50 that is the received by the host device 30B (Block 69).\",\n \"As understood by those of ordinary skill in the art, this technique may be executed by any suitable data processing circuitry, including the processor(s) 12, a processor of the I/O interface 24, a processor of the wireless module 54 or chipset 56, or any combination thereof.\",\n \"It should be appreciated that the technique discussed with respect to FIG.\",\n \"9 may be executed in a variety of ways, and one way for executing this technique is illustrated by the flowchart 70 in FIG.\",\n \"10.Here, the remote device 50 sends a request to the host device 30B to increase its signal power (Block 72).\",\n \"The host device 30B checks its internal amplifier 58 to determine whether it is at its maximum output level (Block 74).\",\n \"If not, the host device 30B increases power of its internal amplifier and waits to see if it will receive another request from the remote device 50 (Block 76).\",\n \"However, it the internal amplifier 58 is at its maximum power level, the host device 34 sends a message to the remote device 50 that maximum power has been reached (Block 78).\",\n \"This may have the effect of causing the remove device 50 to cease sending requests for more power to the host device 30B.\",\n \"Next, the host device 30B determines whether any further increases in power will improve the communications link 52.One way it may do this is by checking the RSSI of the signal that it receives from the remote device 50 (Block 80).\",\n \"If the RSSI is below a certain threshold (Block 82), the host device 30B determines that the communications link 52 is limited by the signal output by the remote device 50 and, thus, does not turn on the external amplifier 60 (Block 84).\",\n \"However, if the RSSI of the signal from the remote device 50 is above the threshold, then it is possible that further power increases will improve the communications link 52.To make this determination, the host device 30B may check for the retransmission rate and/or packet error rate of the communications link 52 (Block 86).\",\n \"If the error rate is sufficient to maintain the communications link 52, the host device 30B will not turn on the external amplifier 60 or further increase power (Block 88).\",\n \"Rather, it will continue to monitor the communications link 52 as described above.\",\n \"If, however, the error rate is not sufficient to adequately maintain the communications link 52, the host device 30B will turn on the external amplifier 60 (Block 90).\",\n \"With the external amplifier 60 on, the host device 30B will again check the retransmission rate and/or package rate to determine whether it is sufficient to maintain the communications link 52 (Blocks 92 and 94).\",\n \"If not, it will again determine whether the RSSI from the remote device 50 is below a certain threshold (Block 95).\",\n \"If not, it will increase the power of the external amplifier 60 (Block 96).\",\n \"Otherwise, the communications link 52 is limited by the remote device 50, so the host device 30B will continue to check on the quality of the communications link 52 as described above.\",\n \"Once the external amplifier 60 has been turned on so that it is providing additional power to the communications link 52, the host device 30B will determine whether it is able to turn off the external amplifier 60 or decrease its power while still maintaining an adequate communications link 52.Accordingly, if the error rate is sufficient to maintain the link, the host device 30B determines whether the external amplifier is at its minimal power level (Blocks 94 and 98).\",\n \"If not, it will decrease power from the external amplifier 60 and again check on the quality of the communications link 52 as described above (Block 100).\",\n \"However, if the external amplifier is at its minimum power level, the host device 30B will determine whether the external amplifier can be turned off (Blocks 98 and 102).\",\n \"If not, then the host 30B will continue to check on the quality of the communications link 52.If so, however, the host device 30B will turn off the external amplifier 60and again wait for any requests to increase power from the remote device 50 (Blocks 104 and 72).\",\n \"As mentioned above, there are a variety of ways to execute the technique set forth in FIG.\",\n \"9, and another specific technique is illustrated by the flowchart 110 in FIG.\",\n \"11.Here the remote device 50 sends a request to the host device 30B to increase its signal power (Block 112).\",\n \"When the host device 30B receives this request, it checks its internal amplifier 58 to determine whether it is at its maximum power level (Block 114).\",\n \"If not, the devices 30B and 50 will continue to operate under “classic power control” and the host device 30B will increase the power of its internal amplifier 58 (Block 116).\",\n \"However, if its internal amplifier is at its maximum power level, the host device 30B determines the error rate and/or retransmission rate of communications link 52 (Block 118).\",\n \"For example, the host device 30B may determine an average packet error rate over a given amount of time.\",\n \"If the error rate is greater than an upper boundary, the host device 30B checks to determine whether the RSSI of the signal that it received from the remote device 50 is below a threshold (Blocks 120 and 122).\",\n \"If the RSSI is too low, then the communications link 52 is limited by the remote device 50, so the host device 30B does not need to increase power using the external amplifier 60 (Block 124).\",\n \"However, if the signal strength from the remove device 50 is sufficient, the host device 30B will increase power using the external amplifier 60 (Block 126).\",\n \"On the other hand, if the measured error rate is below the upper boundary, the host device 30B determines whether the error rate is below a lower boundary (Blocks 120 and 128).\",\n \"If not, then the host device 30B continues to monitor the quality of the communications link 52 as described above.\",\n \"However, if the measured error rate is below the lower boundary, this suggests that the power of the output signal from the host device 30B may be greater than needed to maintain the quality of the communications link 52.Accordingly, the host device 30B will check to see if the external amplifier 60 is at its minimum level (Block 130).\",\n \"If so, it will turn off the external amplifier 60 and the devices 30B and 50 will return to classic power control (Block 132 and 116).\",\n \"If not, the host 30B will decrease the power output by the external amplifier 60 and continue to monitor the communications link 52 as described above (Block 134).\",\n \"The specific embodiments described above have been shown by way of example, and it should be understood that these embodiments may be susceptible to various modifications and alternative forms.\",\n \"It should be further understood that the claims are not intended to be limited to the particular forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874678"}}},{"rowIdx":4494668,"cells":{"text":{"kind":"list like","value":[["SELF-ALIGNED REPLACEMENT METAL GATE SPACERLESS VERTICAL FIELD EFFECT TRANSISTOR","A method of making a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.","A first sacrificial layer is deposited over the substrate surface, and a second sacrificial layer is deposited over the first sacrificial layer such that each of the first and second sacrificial layers are formed peripheral to the nanowire.","The second sacrificial layer is then patterned to form a dummy gate structure.","Thereafter, the first sacrificial layer is removed and source and drain regions are deposited via epitaxy directly over respective portions of the nanowire."],["1.A structure comprising: a semiconductor nanowire having a channel segment between source and drain segments located in distal ends of the nanowire, the semiconductor nanowire extending from a substrate surface; an epitaxial source region located on the source segment of the nanowire; an epitaxial drain region located one the drain segment of the nanowire; and a gate stack comprising a gate dielectric layer formed over the channel segment of the nanowire and a conductive electrode formed over the dielectric layer.","2.The structure of claim 1, wherein the gate stack extends between a pair of adjacent semiconductor nanowires.","3.The structure of claim 1, wherein the gate dielectric layer is present over a lower surface of the drain region and over an upper surface of the source region.","4.The structure of claim 1, wherein the gate dielectric layer comprises a high-k dielectric material.","5.The structure of claim 1, wherein the substrate surface comprises an isolation layer.","6.The structure of claim 1, further comprising a dielectric layer located adjacent the source and drain regions and surrounding the gate stack.","7.The structure of claim 6, wherein a topmost surface of one of the source region or the drain region is coplanar with a topmost surface of the dielectric layer.","8.The structure of claim 1, wherein the semiconductor nanowire has a height from 50 nm to 200 nm, and a circular cross section having a diameter from 1 nm to 50 nm.","9.The structure of claim 1, wherein the semiconductor nanowire has a height from 50 nm to 200 nm, and a rectangular or square cross section having a length from 1 nm to 50 nm, and a width from 1 nm to 50 nm.","10.The structure of claim 1, wherein the source region and the drain region are annular in shape.","11.The structure of claim 1, wherein the source region and the drain region have an epitaxial relationship with the semiconductor nanowire.","12.The structure of claim 1, further comprising a first dielectric material laterally surrounding the semiconductor nanowire and the gate stack, wherein the first dielectric material has a topmost surface that is located above the topmost surface of the semiconductor and is coplanar with a topmost surface of the gate dielectric of the gate stack.","13.The structure of claim 12, wherein the topmost surface of the first dielectric material is coplanar with a topmost surface of one of the source region or the drain region.","14.The structure of claim 12, further comprising a second dielectric material located above the first dielectric material that laterally surrounds the semiconductor nanowire and the gate stack.","15.The structure of claim 14, wherein the source segment and the source region are located beneath the drain segment and the drain region.","16.The structure of claim 15, further comprising a first source/drain contact extending through the second dielectric material and the first dielectric material and directly contacting a sidewall surface of the source region, and a second source/drain contact extending through the second dielectric material and directly contacting the topmost surface of the drain region.","17.The structure of claim 14, wherein the source segment and the source region are located above the drain segment and the drain region.","18.The structure of claim 15, further comprising a first source/drain contact extending through the second dielectric material and the first dielectric material and directly contacting a sidewall surface of the drain region, and a second source/drain contact extending through the second dielectric material and directly contacting the topmost surface of the source region."],["<SOH> BACKGROUND <EOH>The present application relates generally to semiconductor devices, and more specifically to vertical field effect transistors (VFETs) and their methods of production.","Conventional vertical FETs are devices where the source-drain current flows in a direction normal to the substrate surface.","In such devices, a vertical pillar defines the channel with the source and drain located at opposing ends of the pillar.","An advantage of the vertical FET is that the channel length is not defined by lithography, but by methods such as epitaxy or layer deposition, which enable precise dimensional control.","Modern transistors are manufactured using gate-first or gate-last (also known as replacement metal gate) process flows, which may include hybrid approaches such as a gate-first method for NMOS and a gate-last method for the more difficult PMOS transistor.","With the proliferation of high-k dielectrics (e.g., dielectric materials having a dielectric constant greater than silicon nitride), it has been suggested that the high-temperature steps that follow high-k and metal gate depositions cause an adverse shift in threshold voltage, affecting PMOS performance in particular.","In view of the foregoing, it would be advantageous to provide a manufacturing process for a vertical field effect transistor that is compatible with a gate-last approach."],["<SOH> SUMMARY <EOH>In accordance with embodiments of the present application, a method of fabricating a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.","A first sacrificial layer is deposited over the substrate surface, and a second sacrificial layer is deposited over the first sacrificial layer where each of the first and second sacrificial layers are formed peripheral to the nanowire.","The second sacrificial layer is patterned to form a dummy gate structure.","Thereafter, the first sacrificial layer is removed and source and drain regions are deposited via epitaxy directly over respective portions of the nanowire.","According to further embodiments, a semiconductor structure includes a semiconductor nanowire having a channel segment between source and drain segments that are located in distal ends of the nanowire, where the semiconductor nanowire extends from a substrate surface.","An epitaxial source region is located over the source segment of the nanowire, and an epitaxial drain region is located over the drain segment of the nanowire.","A gate stack includes a conformal dielectric layer that is located over the channel segment of the nanowire and a conductive layer located over the dielectric layer."],["BACKGROUND The present application relates generally to semiconductor devices, and more specifically to vertical field effect transistors (VFETs) and their methods of production.","Conventional vertical FETs are devices where the source-drain current flows in a direction normal to the substrate surface.","In such devices, a vertical pillar defines the channel with the source and drain located at opposing ends of the pillar.","An advantage of the vertical FET is that the channel length is not defined by lithography, but by methods such as epitaxy or layer deposition, which enable precise dimensional control.","Modern transistors are manufactured using gate-first or gate-last (also known as replacement metal gate) process flows, which may include hybrid approaches such as a gate-first method for NMOS and a gate-last method for the more difficult PMOS transistor.","With the proliferation of high-k dielectrics (e.g., dielectric materials having a dielectric constant greater than silicon nitride), it has been suggested that the high-temperature steps that follow high-k and metal gate depositions cause an adverse shift in threshold voltage, affecting PMOS performance in particular.","In view of the foregoing, it would be advantageous to provide a manufacturing process for a vertical field effect transistor that is compatible with a gate-last approach.","SUMMARY In accordance with embodiments of the present application, a method of fabricating a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.","A first sacrificial layer is deposited over the substrate surface, and a second sacrificial layer is deposited over the first sacrificial layer where each of the first and second sacrificial layers are formed peripheral to the nanowire.","The second sacrificial layer is patterned to form a dummy gate structure.","Thereafter, the first sacrificial layer is removed and source and drain regions are deposited via epitaxy directly over respective portions of the nanowire.","According to further embodiments, a semiconductor structure includes a semiconductor nanowire having a channel segment between source and drain segments that are located in distal ends of the nanowire, where the semiconductor nanowire extends from a substrate surface.","An epitaxial source region is located over the source segment of the nanowire, and an epitaxial drain region is located over the drain segment of the nanowire.","A gate stack includes a conformal dielectric layer that is located over the channel segment of the nanowire and a conductive layer located over the dielectric layer.","BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS The following detailed description of specific embodiments of the present application can be best understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which: FIG.","1 shows an example semiconductor substrate used in conjunction with various embodiments; FIG.","2 is a schematic diagram of vertically-oriented nanowires formed over an isolation layer of a substrate according to various embodiments; FIG.","3 shows the formation of a first sacrificial layer adjacent to the nanowires and over the isolation layer; FIG.","4 shows the formation of a second sacrificial layer adjacent to the nanowires and over the first sacrificial layer; FIGS.","5A and 5B are cross-sectional and top-down plan view images of the structure of FIG.","4 after patterning the second sacrificial layer to form a sacrificial gate; FIGS.","6A and 6B show removal of the first sacrificial layer; FIGS.","7A and 7B show the formation of source and drain regions adjacent to the nanowires and respectively below and above the sacrificial gate; FIGS.","8A and 8B show the deposition and planarization of an interlayer dielectric; FIGS.","9A and 9B show the partial removal of the drain; FIGS.","10A and 10B show the deposition and planarization of an interlayer dielectric; FIGS.","11A and 11B show the etching of gate contact vias into the dielectric layers of FIGS.","8 and 10; FIGS.","12A and 12B reveal an intermediate architecture after removal of the sacrificial gate and deposition of a replacement gate stack; and FIGS.","13A and 13B show the deposition of a further interlayer dielectric and the formation of source and drain contacts.","DETAILED DESCRIPTION Reference will now be made in greater detail to various embodiments of the subject matter of the present application, some embodiments of which are illustrated in the accompanying drawings.","The same reference numerals will be used throughout the drawings to refer to the same or similar parts.","With reference to FIGS.","1 and 2, a plurality of nanowires 202 are formed on an isolation layer 120 of substrate 100; substrate 100 may include a handle substrate 110 which may be composed of any semiconductor material or a remaining portion of a bulk semiconductor substrate.","Substrate 100 may be a semiconductor material such as silicon or a silicon-containing material, including a bulk substrate.","Silicon-containing materials include, but are not limited to, single crystal Si, polycrystalline Si, single crystal silicon germanium (SiGe), polycrystalline silicon germanium, silicon doped with carbon (Si:C), amorphous Si, as well as combinations and multi-layers thereof.","Example silicon substrates include silicon-on-insulator (SOI) substrates, silicon-on-sapphire (SOS) substrates, and the like.","As used herein, the term “single crystal” denotes a crystalline solid, in which the crystal lattice of the entire sample is substantially continuous and substantially unbroken to the edges of the sample with substantially no grain boundaries.","Substrate 100 is not limited to silicon-containing materials, as the substrate 100 may comprise other semiconductor materials, including Ge and compound semiconductors such as GaAs, InAs and other like semiconductors.","The isolation layer 120 may comprise the buried oxide (BOX) layer of a semiconductor-on-insulator (SOI) substrate, or an oxidized layer of a bulk silicon substrate.","The thickness of the isolation layer 120 may range from 30 to 300 nm, e.g., 30, 50, 100, 150, 200, 250 or 300 nm, including ranges between any of the foregoing values.","The isolation layer 120 may comprise, for example, silicon dioxide (SiO2).","The supporting substrate 110 may comprise (100)-oriented silicon or (111)-oriented silicon, for example.","The substrate 100 may have dimensions as typically used in the art.","Example substrate diameters include, but are not limited to, 50, 100, 150, 200, 300 and 450 mm.","The total substrate thickness may range from 250 microns to 1500 microns, though in particular embodiments the substrate thickness is in the range of 725 to 775 microns, which corresponds to thickness dimensions commonly used in silicon CMOS processing.","Nanowires 202 comprise a semiconductor material such as silicon, and may be formed by patterning and then etching a layer 200 of semiconductor material disposed on substrate 100.As an alternative to silicon, nanowires may comprise germanium (Ge), silicon germanium (SiGe), III-V compound semiconductors such as GaAs, GaN, GaP, InAs, InSb, ZnSe, and ZnS, and II-VI compound semiconductors such as CdSe, CdS, CdTe, ZnSe, ZnS and ZnTe.","The patterning process may comprise photolithography, which includes forming a layer of photoresist material (not shown) atop a material or material stack to be patterned.","The photoresist material may include a positive-tone photoresist composition, a negative-tone photoresist composition, or a hybrid-tone photoresist composition.","A layer of photoresist material may be formed by a deposition process such as, for example, spin-on coating.","The deposited photoresist is then subjected to a pattern of irradiation, and the exposed photoresist material is developed utilizing a conventional resist developer.","In the instant embodiment, this provides a patterned layer of photoresist atop a portion of the semiconductor layer 200.The pattern provided by the patterned photoresist material is thereafter transferred into the underlying material layer or material layers utilizing at least one pattern transfer etching process.","The pattern transfer etching process is an anisotropic etch.","In embodiments, a dry etching process such as, for example, reactive ion etching can be used.","In other embodiments, a wet chemical etchant can be used.","In still further embodiments, a combination of dry etching and wet etching can be used.","The pattern transfer etching may stop on the isolation layer 120, or a portion of the isolation layer 120 may be removed during the formation of the nanowires 202.In some embodiments of the present application, the nanowires 202 may be formed utilizing a sidewall image transfer (SIT) patterning process.","SIT includes forming mandrel structures on a material or material stack to be patterned, then forming spacers along the sidewalls of each mandrel structure, and thereafter removing each mandrel structure.","An etch, as described above, is then employed utilizing each spacer as an etch mask.","After etching, i.e., pattern transfer, each spacer is then removed from the structure.","In embodiments, nanowires 202 are formed from a crystalline semiconductor material.","The semiconductor material forming nanowires 202 may be doped, undoped, or contain doped and undoped regions therein.","Each doped region within the semiconductor nanowires 202 may have the same or different doping concentrations and/or conductivities.","Doped regions that are present can be formed, for example, by ion implantation, gas phase doping, or by dopants that are present in the material used to form the nanowires.","For instance, semiconductor layer 200 may comprise a dopant prior to forming the nanowires 202.By way of example, semiconductor layer 200 and hence nanowires 202 may be initially and uniformly doped and have a dopant concentration in the range of 1×1015 atoms/cm3 to 1×1018 atoms/cm3.In embodiments, nanowires 202 are free standing, i.e., supported only by the substrate 100.The nanowires 202 have a uniform height H of 50 to 200 nm, e.g., 50, 100, 150 or 200 nm, including ranges between any of the foregoing values.","The nanowires 202 may have a circular cross section characterized by a diameter of 1 to 50 nm, e.g., 1, 2, 5, 10, 20 or 50 nm, including ranges between any of the foregoing values.","In alternate embodiments, nanowires 202 have a rectangular or square cross section characterized by a length L and a width W that may independently range from 1 to 50 nm, e.g., 1, 2, 5, 10, 20 or 50 nm, including ranges between any of the foregoing values.","The nanowires 202 may be arranged in a regular array that, in embodiments, has a nanowire-to-nanowire spacing (i.e., pitch) of 10 to 1000 nm.","As depicted in FIG.","3, after formation of nanowires 202, a first sacrificial layer 320 is formed over the isolation layer 120 and adjacent to the nanowires 202.In embodiments, first sacrificial layer 320 is in direct physical contact with the isolation layer 120 and with lower portions of the sidewalls of the nanowires 202.In embodiments, first sacrificial layer 320 can be selectively etched with respect to one or more of silicon, silicon dioxide and silicon nitride.","First sacrificial layer 320 is configured to be later removed selective to both the isolation layer and nanowire materials.","By way of example, the first sacrificial layer 320 may comprise amorphous carbon or a porous dielectric and may have a thickness of 10 to 50 nm.","An amorphous carbon (a-C) layer or hydrogenated amorphous carbon (a-C:H) layer may be deposited from an argon/hydrocarbon gas/hydrogen/oxygen plasma or an argon/acetylene-helium/hydrogen/oxygen plasma, for example.","In embodiments, the hydrocarbon gas used to form an amorphous carbon layer may be any hydrocarbon compound that capable of forming a plasma.","The term ‘hydrocarbon’ refers to a compound that contains only carbon and hydrogen atoms, and may be either a saturated hydrocarbon or an unsaturated hydrocarbon.","A saturated hydrocarbon compound contains only carbon single bonds, while an unsaturated compound contains carbon double or triple bonds.","Suitable hydrocarbon compounds include alkanes, alkenes and alkynes.","Methods of depositing an amorphous carbon layer include optionally pre-mixing and introducing process gases to a substrate at both a pressure and temperature effective to form amorphous carbon.","In embodiments, a total pressure of the process gases (or process gas mixture) may range from 1 to 50 mTorr.","The substrate temperature may range from 25° C. to 400° C. Porous dielectric thin films may be formed by selective removal of soluble porogens as known by those skilled in the art.","A silicon-containing dielectric layer, for example, that initially contains soluble porogen material dispersed therein may be formed by chemical vapor deposition (CVD).","Example porogen materials include germanium oxide and boron oxide, and example CVD precursors include germanic acid (H4GeO4) and boric acid (H3BO3) in addition to a suitable silicon source, such as an organosilicon compound.","As seen with reference to FIG.","4, a second sacrificial layer 420 is then formed over the first sacrificial layer 320 and adjacent to the nanowires 202.The second sacrificial layer 420 may comprise a dielectric material such as silicon nitride, for example, and have a thickness of 10 to 20 nm.","Other dielectric materials may be employed as the second sacrificial layer 420 so long as the dielectric material that provides the second sacrificial layer 420 has a different etch selectivity than the material that provides the first sacrificial layer 320.Turning to FIGS.","5A and 5B, photolithography and etching steps may be used to pattern the second sacrificial layer 420 to form a sacrificial gate 422.In embodiments, patterning and etching of the second sacrificial layer 420 exposes the first sacrificial layer 320, though nanowires 202 remain enveloped along a portion of their periphery by the sacrificial gate 422.Then, as illustrated in FIGS.","6A and 6B, first sacrificial layer 320 is removed.","A wet or dry etch may be used to selectively remove the first sacrificial layer 320.For example, the first sacrificial layer 320 formed from amorphous carbon may be removed using a wet etching comprising an acid such as sulfuric acid.","Alternatively, the first sacrificial layer may be removed using a plasma ashing process, e.g., using an oxygen-based plasma such as an O2/N2-containing plasma.","After removal of the first sacrificial layer 320, sacrificial gate 422 is anchored by nanowires 202 and suspended over substrate 100 to form a gap 326 there between.","As shown in FIGS.","7A and 7B, source and drain regions 520, 620 are formed below and above sacrificial gate 422, respectively, via epitaxial growth on exposed surfaces of nanowires 202.Source regions 520 are formed within the gap 326.In embodiments, source and drain regions are formed simultaneously and may have a radial thickness (i.e., with respect to nanowires 202) of 10 to 30 nm.","Thus, source and drain regions 520, 620 have an annular shape when viewed along a direction normal to the substrate.","The thickness of the source and drain regions with respect to the surface of the nanowires 202 may be constant or variable.","Referring to FIG.","7A, for example, the thickness of the source and drain regions may vary along with length of the nanowires due to shadowing or other geometric effects associated with the epitaxial growth.","The source and drain regions may comprise silicon, e.g., single crystal silicon.","By forming source and drain regions separately from the sacrificial gate, parasitic capacitance is advantageously reduced.","Although the present application describes and illustrates the source region 520 being formed beneath the drain region 620, it is possible to form the drain region beneath the source region.","The terms “epitaxy,” “epitaxial” and/or “epitaxial growth and/or deposition” refer to the growth of a semiconductor material layer on a deposition surface of a semiconductor material, in which the semiconductor material layer being grown assumes the same crystalline habit as the semiconductor material of the deposition surface.","For example, in an epitaxial deposition process, chemical reactants provided by source gases are controlled and the system parameters are set so that depositing atoms alight on the deposition surface and remain sufficiently mobile via surface diffusion to orient themselves according to the crystalline orientation of the atoms of the deposition surface.","Therefore, an epitaxial semiconductor material has the same crystalline characteristics as the deposition surface on which it is formed.","For example, an epitaxial semiconductor material deposited on a (100) crystal surface will take on a (100) orientation.","The epitaxial source and drain regions 520, 620 may be doped.","Doping changes the electron and hole carrier concentrations of an intrinsic semiconductor at thermal equilibrium.","A doped layer or region may be p-type or n-type.","A p-type dopant is used to manufacture a PFET and an n-type dopant is used to manufacture an NFET.","As used herein, “p-type” refers to the addition of impurities to an intrinsic semiconductor that creates a deficiency of valence electrons.","For silicon, example p-type dopants, i.e., impurities, include but are not limited to, boron, aluminum, gallium, and indium.","As used herein, “n-type” refers to the addition of impurities that contribute free electrons to an intrinsic semiconductor.","For silicon, example n-type dopants, i.e., impurities, include but are not limited to, antimony, arsenic, and phosphorus.","The dopant(s) may be introduced by plasma doping, or may be introduced, for example, in situ, i.e., during a process sequence used to form the layer.","By way of example, a dopant region may in-situ doped with arsenic or phosphorus to form an n-type region.","The dopant concentration within the source and drain regions may range from 1×1019 atoms/cm3 to 1×1022 atoms/cm3, e.g., 1×1020 atoms/cm3 to 1×1021 atoms/cm3.In another example, a dopant region is in-situ doped with boron or BF2 to form a p-type region.","The dopant concentration within the source and drain regions may range from 1×1019 atoms/cm3 to 1×1022 atoms/cm3, e.g., 1×1020 atoms/cm3 to 1×1021 atoms/cm3.An optional drive-in anneal can be used to diffuse dopant species and generate a desired dopant profile.","In embodiments, dopant atoms within the source and drain regions 520, 620 may be diffused into the adjacent nanowires 202 using a post-epitaxy anneal (e.g., at a temperature of 600 to 1400° C.) to create a dopant profile within the nanowires proximate to the source and drain regions 520, 620.The dopant profile within the nanowires 202 may be constant or variable.","For instance, the dopant concentration within the nanowires may vary radially, with a minimum dopant concentration (e.g., 1×1019 to 1×1022 atoms/cm3) along a central axis of the nanowires and a maximum dopant concentration (e.g., 1×1019 to 1×1022 atoms/cm3) at the periphery.","With reference to FIGS.","8A and 8B, following the formation of epitaxial source and drain regions 520, 620, a dielectric layer 720 is deposited over exposed surfaces of the structure.","In some embodiments, the dielectric layer 720 is then planarized and etched back so as to cover source regions 520 and sacrificial gate 422.The dielectric layer 720 may be self-planarizing, or the top surface of the dielectric layer 720 can be planarized, for example, by chemical mechanical planarization (CMP).","Chemical mechanical polishing (CMP) is a material removal process that uses both chemical reactions and mechanical forces to remove material and planarize a surface.","Drain regions 620 may function as a CMP etch stop.","In embodiments, the thickness of dielectric layer 720 over the sacrificial gate may be 0 to 10 nm.","A vertical transistor architecture is shown that includes one or more vertical nanowires 202 connecting a source region 520 with a drain region 620.Dielectric layer 720 may comprise silicon dioxide, silicon nitride, silicon oxynitride, a low-k material (i.e., a dielectric material having a dielectric constant of less than silicon dioxide), or any suitable combination of these materials.","Exemplary low-k materials include but are not limited to, amorphous carbon, fluorine-doped oxides, carbon-doped oxides, SiCOH or SiBCN.","Commercially-available low-k dielectric products and materials include Dow Corning's SiLK™ and porous SiLK™, Applied Materials' Black Diamond™, Texas Instrument's Coral™ and TSMC's Black Diamond™ and Coral™.","The dielectric layer 720 may be deposited by plasma enhanced chemical vapor deposition (PECVD).","Referring next to FIGS.","9A, 9B, 10A and 10B, lithography and etching steps are used to optionally remove a portion of drain 620 in order to decrease a projected cross-sectional area thereof and create space adjacent to nanowires 202 through which contact vias will be formed in later steps.","The resulting structure is backfilled with an additional dielectric layer 730, which is planarized to a height of the drain regions 620.Dielectric layer 730 may comprise the same dielectric material used for dielectric layer 720.As seen with reference to FIGS.","11A and 11B, vias 736 are then etched into dielectric layers 720 and 730 to expose sacrificial gate 422.In the illustrated embodiment, both a sidewall surface and a top surface of the sacrificial gate 422 are exposed.","As known to those skilled in the art, a wet and/or dry etch is used to selectively remove the sacrificial gate 422.Then, as shown in FIGS.","12A and 12B, a gate stack is formed within vias 736 and the volume previously filled with the sacrificial gate.","The gate stack comprises a gate dielectric 810 and a gate electrode 820, which are deposited in succession.","The gate dielectric 810 may be a conformal layer that is formed over exposed surfaces within the aforementioned volume, including a top surface of epitaxial source region 520, a bottom surface of epitaxial drain region 620, and sidewalls of the intermediate (channel) segment of nanowires 202.Gate dielectric 810 may comprise silicon dioxide, silicon nitride, silicon oxynitride, a high-k dielectric, or other suitable material.","As used herein, a high-k material has a dielectric constant greater than that of silicon nitride.","A high-k dielectric may include a binary or ternary compound such as hafnium oxide (HfO2).","Further exemplary high-k dielectrics include, but are not limited to, ZrO2, La2O3, Al2O3, TiO2, SrTiO3, BaTiO3, LaAlO3, Y2O3, HfOxNy, HfSiOxNy, ZrOxNy, La2OxNy, Al2OxNy, TiOxNy, SrTiOxNy, LaAlOxNy, Y2OxNy, SiOxNy, SiNx, a silicate thereof, and an alloy thereof.","Each value of x may independently vary from 0.5 to 3, and each value of y may independently vary from 0 to 2.The gate dielectric 810 may be deposited by a suitable process such as atomic layer deposition (ALD), chemical vapor deposition (CVD), physical vapor deposition (PVD), thermal oxidation, UV-ozone oxidation, or combinations thereof.","The gate dielectric thickness may range from 1 nm to 10 nm, e.g., 1, 2, 4, 6, 8 or 10 nm, including ranges between any of the foregoing.","The gate electrode 820 may include a conductive material such as polysilicon, silicon-germanium, a conductive metal such as Al, W, Cu, Ti, Ta, W, Pt, Ag, Au, Ru, Ir, Rh and Re, alloys of conductive metals, e.g., Al—Cu, silicides of a conductive metal, e.g., W silicide, and Pt silicide, or other conductive metal compounds such as TiN, TiC, TiSiN, TiTaN, TaN, TaAlN, TaSiN, TaRuN, WSiN, NiSi, CoSi, as well as combinations thereof.","The gate electrode 820 may comprise one or more layers of such materials such as, for example, a metal stack including a work function metal layer and/or a liner.","The gate electrode 820 can be formed utilizing a conventional deposition process such as, for example, ALD, CVD, metalorganic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), PVD, sputtering, plating, evaporation, ion beam deposition, electron beam deposition, laser assisted deposition, or chemical solution deposition.","In embodiments, the overlap area can be minimized between each of the source region and the gate stack, and the drain region and the gate stack, e.g., by forming source and drain regions with tapered sidewalls.","As seen in FIGS.","13A and 13B, a further dielectric layer 740 is deposited over the architecture of FIGS.","12A and 12B, and source/drain contacts 850, 860 are formed extending through a portion of at least one of the dielectric layers 720, 730, 740.Source/drain contacts 850, 860 may be formed using a deposition process such as ALD, CVD, metalorganic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), PVD, sputtering, plating, evaporation, ion beam deposition, electron beam deposition, laser assisted deposition, or chemical solution deposition, and may comprise a conductive metal such as Al, W, Cu, Ti, Ta, W, Pt, Ag, Au, Ru, Ir, Rh and Re, alloys of conductive metals, e.g., Al—Cu, silicides of a conductive metal, e.g., W silicide, and Pt silicide, or other conductive metal compounds such as TiN, TiC, TiSiN, TiTaN, TaN, TaAlN, TaSiN, TaRuN, WSiN, NiSi, CoSi, as well as combinations thereof.","Illustrated in FIGS.","1-13 are embodiments of a process to form a vertical field effect transistor as well as the resulting structure.","Absent from the gate of the resulting structure is a sidewall spacer, which simplifies the process flow.","As used herein, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.","Thus, for example, reference to a “nanowire” includes examples having two or more such “nanowires” unless the context clearly indicates otherwise.","Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order.","Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that any particular order be inferred.","Any recited single or multiple feature or aspect in any one claim can be combined or permuted with any other recited feature or aspect in any other claim or claims.","It will be understood that when an element such as a layer, region or substrate is referred to as being formed on, deposited on, or disposed “on” or “over” another element, it can be directly on the other element or intervening elements may also be present.","In contrast, when an element is referred to as being “directly on” or “directly over” another element, no intervening elements are present.","While various features, elements or steps of particular embodiments may be disclosed using the transitional phrase “comprising,” it is to be understood that alternative embodiments, including those that may be described using the transitional phrases “consisting” or “consisting essentially of,” are implied.","Thus, for example, implied alternative embodiments to a dielectric layer that comprises silicon nitride include embodiments where a dielectric layer consists essentially of silicon nitride and embodiments where a dielectric layer consists of silicon nitride.","It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit and scope of the invention.","Since modifications, combinations, sub-combinations and variations of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed to include everything within the scope of the appended claims and their equivalents."]],"string":"[\n [\n \"SELF-ALIGNED REPLACEMENT METAL GATE SPACERLESS VERTICAL FIELD EFFECT TRANSISTOR\",\n \"A method of making a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.\",\n \"A first sacrificial layer is deposited over the substrate surface, and a second sacrificial layer is deposited over the first sacrificial layer such that each of the first and second sacrificial layers are formed peripheral to the nanowire.\",\n \"The second sacrificial layer is then patterned to form a dummy gate structure.\",\n \"Thereafter, the first sacrificial layer is removed and source and drain regions are deposited via epitaxy directly over respective portions of the nanowire.\"\n ],\n [\n \"1.A structure comprising: a semiconductor nanowire having a channel segment between source and drain segments located in distal ends of the nanowire, the semiconductor nanowire extending from a substrate surface; an epitaxial source region located on the source segment of the nanowire; an epitaxial drain region located one the drain segment of the nanowire; and a gate stack comprising a gate dielectric layer formed over the channel segment of the nanowire and a conductive electrode formed over the dielectric layer.\",\n \"2.The structure of claim 1, wherein the gate stack extends between a pair of adjacent semiconductor nanowires.\",\n \"3.The structure of claim 1, wherein the gate dielectric layer is present over a lower surface of the drain region and over an upper surface of the source region.\",\n \"4.The structure of claim 1, wherein the gate dielectric layer comprises a high-k dielectric material.\",\n \"5.The structure of claim 1, wherein the substrate surface comprises an isolation layer.\",\n \"6.The structure of claim 1, further comprising a dielectric layer located adjacent the source and drain regions and surrounding the gate stack.\",\n \"7.The structure of claim 6, wherein a topmost surface of one of the source region or the drain region is coplanar with a topmost surface of the dielectric layer.\",\n \"8.The structure of claim 1, wherein the semiconductor nanowire has a height from 50 nm to 200 nm, and a circular cross section having a diameter from 1 nm to 50 nm.\",\n \"9.The structure of claim 1, wherein the semiconductor nanowire has a height from 50 nm to 200 nm, and a rectangular or square cross section having a length from 1 nm to 50 nm, and a width from 1 nm to 50 nm.\",\n \"10.The structure of claim 1, wherein the source region and the drain region are annular in shape.\",\n \"11.The structure of claim 1, wherein the source region and the drain region have an epitaxial relationship with the semiconductor nanowire.\",\n \"12.The structure of claim 1, further comprising a first dielectric material laterally surrounding the semiconductor nanowire and the gate stack, wherein the first dielectric material has a topmost surface that is located above the topmost surface of the semiconductor and is coplanar with a topmost surface of the gate dielectric of the gate stack.\",\n \"13.The structure of claim 12, wherein the topmost surface of the first dielectric material is coplanar with a topmost surface of one of the source region or the drain region.\",\n \"14.The structure of claim 12, further comprising a second dielectric material located above the first dielectric material that laterally surrounds the semiconductor nanowire and the gate stack.\",\n \"15.The structure of claim 14, wherein the source segment and the source region are located beneath the drain segment and the drain region.\",\n \"16.The structure of claim 15, further comprising a first source/drain contact extending through the second dielectric material and the first dielectric material and directly contacting a sidewall surface of the source region, and a second source/drain contact extending through the second dielectric material and directly contacting the topmost surface of the drain region.\",\n \"17.The structure of claim 14, wherein the source segment and the source region are located above the drain segment and the drain region.\",\n \"18.The structure of claim 15, further comprising a first source/drain contact extending through the second dielectric material and the first dielectric material and directly contacting a sidewall surface of the drain region, and a second source/drain contact extending through the second dielectric material and directly contacting the topmost surface of the source region.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>The present application relates generally to semiconductor devices, and more specifically to vertical field effect transistors (VFETs) and their methods of production.\",\n \"Conventional vertical FETs are devices where the source-drain current flows in a direction normal to the substrate surface.\",\n \"In such devices, a vertical pillar defines the channel with the source and drain located at opposing ends of the pillar.\",\n \"An advantage of the vertical FET is that the channel length is not defined by lithography, but by methods such as epitaxy or layer deposition, which enable precise dimensional control.\",\n \"Modern transistors are manufactured using gate-first or gate-last (also known as replacement metal gate) process flows, which may include hybrid approaches such as a gate-first method for NMOS and a gate-last method for the more difficult PMOS transistor.\",\n \"With the proliferation of high-k dielectrics (e.g., dielectric materials having a dielectric constant greater than silicon nitride), it has been suggested that the high-temperature steps that follow high-k and metal gate depositions cause an adverse shift in threshold voltage, affecting PMOS performance in particular.\",\n \"In view of the foregoing, it would be advantageous to provide a manufacturing process for a vertical field effect transistor that is compatible with a gate-last approach.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>In accordance with embodiments of the present application, a method of fabricating a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.\",\n \"A first sacrificial layer is deposited over the substrate surface, and a second sacrificial layer is deposited over the first sacrificial layer where each of the first and second sacrificial layers are formed peripheral to the nanowire.\",\n \"The second sacrificial layer is patterned to form a dummy gate structure.\",\n \"Thereafter, the first sacrificial layer is removed and source and drain regions are deposited via epitaxy directly over respective portions of the nanowire.\",\n \"According to further embodiments, a semiconductor structure includes a semiconductor nanowire having a channel segment between source and drain segments that are located in distal ends of the nanowire, where the semiconductor nanowire extends from a substrate surface.\",\n \"An epitaxial source region is located over the source segment of the nanowire, and an epitaxial drain region is located over the drain segment of the nanowire.\",\n \"A gate stack includes a conformal dielectric layer that is located over the channel segment of the nanowire and a conductive layer located over the dielectric layer.\"\n ],\n [\n \"BACKGROUND The present application relates generally to semiconductor devices, and more specifically to vertical field effect transistors (VFETs) and their methods of production.\",\n \"Conventional vertical FETs are devices where the source-drain current flows in a direction normal to the substrate surface.\",\n \"In such devices, a vertical pillar defines the channel with the source and drain located at opposing ends of the pillar.\",\n \"An advantage of the vertical FET is that the channel length is not defined by lithography, but by methods such as epitaxy or layer deposition, which enable precise dimensional control.\",\n \"Modern transistors are manufactured using gate-first or gate-last (also known as replacement metal gate) process flows, which may include hybrid approaches such as a gate-first method for NMOS and a gate-last method for the more difficult PMOS transistor.\",\n \"With the proliferation of high-k dielectrics (e.g., dielectric materials having a dielectric constant greater than silicon nitride), it has been suggested that the high-temperature steps that follow high-k and metal gate depositions cause an adverse shift in threshold voltage, affecting PMOS performance in particular.\",\n \"In view of the foregoing, it would be advantageous to provide a manufacturing process for a vertical field effect transistor that is compatible with a gate-last approach.\",\n \"SUMMARY In accordance with embodiments of the present application, a method of fabricating a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.\",\n \"A first sacrificial layer is deposited over the substrate surface, and a second sacrificial layer is deposited over the first sacrificial layer where each of the first and second sacrificial layers are formed peripheral to the nanowire.\",\n \"The second sacrificial layer is patterned to form a dummy gate structure.\",\n \"Thereafter, the first sacrificial layer is removed and source and drain regions are deposited via epitaxy directly over respective portions of the nanowire.\",\n \"According to further embodiments, a semiconductor structure includes a semiconductor nanowire having a channel segment between source and drain segments that are located in distal ends of the nanowire, where the semiconductor nanowire extends from a substrate surface.\",\n \"An epitaxial source region is located over the source segment of the nanowire, and an epitaxial drain region is located over the drain segment of the nanowire.\",\n \"A gate stack includes a conformal dielectric layer that is located over the channel segment of the nanowire and a conductive layer located over the dielectric layer.\",\n \"BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS The following detailed description of specific embodiments of the present application can be best understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which: FIG.\",\n \"1 shows an example semiconductor substrate used in conjunction with various embodiments; FIG.\",\n \"2 is a schematic diagram of vertically-oriented nanowires formed over an isolation layer of a substrate according to various embodiments; FIG.\",\n \"3 shows the formation of a first sacrificial layer adjacent to the nanowires and over the isolation layer; FIG.\",\n \"4 shows the formation of a second sacrificial layer adjacent to the nanowires and over the first sacrificial layer; FIGS.\",\n \"5A and 5B are cross-sectional and top-down plan view images of the structure of FIG.\",\n \"4 after patterning the second sacrificial layer to form a sacrificial gate; FIGS.\",\n \"6A and 6B show removal of the first sacrificial layer; FIGS.\",\n \"7A and 7B show the formation of source and drain regions adjacent to the nanowires and respectively below and above the sacrificial gate; FIGS.\",\n \"8A and 8B show the deposition and planarization of an interlayer dielectric; FIGS.\",\n \"9A and 9B show the partial removal of the drain; FIGS.\",\n \"10A and 10B show the deposition and planarization of an interlayer dielectric; FIGS.\",\n \"11A and 11B show the etching of gate contact vias into the dielectric layers of FIGS.\",\n \"8 and 10; FIGS.\",\n \"12A and 12B reveal an intermediate architecture after removal of the sacrificial gate and deposition of a replacement gate stack; and FIGS.\",\n \"13A and 13B show the deposition of a further interlayer dielectric and the formation of source and drain contacts.\",\n \"DETAILED DESCRIPTION Reference will now be made in greater detail to various embodiments of the subject matter of the present application, some embodiments of which are illustrated in the accompanying drawings.\",\n \"The same reference numerals will be used throughout the drawings to refer to the same or similar parts.\",\n \"With reference to FIGS.\",\n \"1 and 2, a plurality of nanowires 202 are formed on an isolation layer 120 of substrate 100; substrate 100 may include a handle substrate 110 which may be composed of any semiconductor material or a remaining portion of a bulk semiconductor substrate.\",\n \"Substrate 100 may be a semiconductor material such as silicon or a silicon-containing material, including a bulk substrate.\",\n \"Silicon-containing materials include, but are not limited to, single crystal Si, polycrystalline Si, single crystal silicon germanium (SiGe), polycrystalline silicon germanium, silicon doped with carbon (Si:C), amorphous Si, as well as combinations and multi-layers thereof.\",\n \"Example silicon substrates include silicon-on-insulator (SOI) substrates, silicon-on-sapphire (SOS) substrates, and the like.\",\n \"As used herein, the term “single crystal” denotes a crystalline solid, in which the crystal lattice of the entire sample is substantially continuous and substantially unbroken to the edges of the sample with substantially no grain boundaries.\",\n \"Substrate 100 is not limited to silicon-containing materials, as the substrate 100 may comprise other semiconductor materials, including Ge and compound semiconductors such as GaAs, InAs and other like semiconductors.\",\n \"The isolation layer 120 may comprise the buried oxide (BOX) layer of a semiconductor-on-insulator (SOI) substrate, or an oxidized layer of a bulk silicon substrate.\",\n \"The thickness of the isolation layer 120 may range from 30 to 300 nm, e.g., 30, 50, 100, 150, 200, 250 or 300 nm, including ranges between any of the foregoing values.\",\n \"The isolation layer 120 may comprise, for example, silicon dioxide (SiO2).\",\n \"The supporting substrate 110 may comprise (100)-oriented silicon or (111)-oriented silicon, for example.\",\n \"The substrate 100 may have dimensions as typically used in the art.\",\n \"Example substrate diameters include, but are not limited to, 50, 100, 150, 200, 300 and 450 mm.\",\n \"The total substrate thickness may range from 250 microns to 1500 microns, though in particular embodiments the substrate thickness is in the range of 725 to 775 microns, which corresponds to thickness dimensions commonly used in silicon CMOS processing.\",\n \"Nanowires 202 comprise a semiconductor material such as silicon, and may be formed by patterning and then etching a layer 200 of semiconductor material disposed on substrate 100.As an alternative to silicon, nanowires may comprise germanium (Ge), silicon germanium (SiGe), III-V compound semiconductors such as GaAs, GaN, GaP, InAs, InSb, ZnSe, and ZnS, and II-VI compound semiconductors such as CdSe, CdS, CdTe, ZnSe, ZnS and ZnTe.\",\n \"The patterning process may comprise photolithography, which includes forming a layer of photoresist material (not shown) atop a material or material stack to be patterned.\",\n \"The photoresist material may include a positive-tone photoresist composition, a negative-tone photoresist composition, or a hybrid-tone photoresist composition.\",\n \"A layer of photoresist material may be formed by a deposition process such as, for example, spin-on coating.\",\n \"The deposited photoresist is then subjected to a pattern of irradiation, and the exposed photoresist material is developed utilizing a conventional resist developer.\",\n \"In the instant embodiment, this provides a patterned layer of photoresist atop a portion of the semiconductor layer 200.The pattern provided by the patterned photoresist material is thereafter transferred into the underlying material layer or material layers utilizing at least one pattern transfer etching process.\",\n \"The pattern transfer etching process is an anisotropic etch.\",\n \"In embodiments, a dry etching process such as, for example, reactive ion etching can be used.\",\n \"In other embodiments, a wet chemical etchant can be used.\",\n \"In still further embodiments, a combination of dry etching and wet etching can be used.\",\n \"The pattern transfer etching may stop on the isolation layer 120, or a portion of the isolation layer 120 may be removed during the formation of the nanowires 202.In some embodiments of the present application, the nanowires 202 may be formed utilizing a sidewall image transfer (SIT) patterning process.\",\n \"SIT includes forming mandrel structures on a material or material stack to be patterned, then forming spacers along the sidewalls of each mandrel structure, and thereafter removing each mandrel structure.\",\n \"An etch, as described above, is then employed utilizing each spacer as an etch mask.\",\n \"After etching, i.e., pattern transfer, each spacer is then removed from the structure.\",\n \"In embodiments, nanowires 202 are formed from a crystalline semiconductor material.\",\n \"The semiconductor material forming nanowires 202 may be doped, undoped, or contain doped and undoped regions therein.\",\n \"Each doped region within the semiconductor nanowires 202 may have the same or different doping concentrations and/or conductivities.\",\n \"Doped regions that are present can be formed, for example, by ion implantation, gas phase doping, or by dopants that are present in the material used to form the nanowires.\",\n \"For instance, semiconductor layer 200 may comprise a dopant prior to forming the nanowires 202.By way of example, semiconductor layer 200 and hence nanowires 202 may be initially and uniformly doped and have a dopant concentration in the range of 1×1015 atoms/cm3 to 1×1018 atoms/cm3.In embodiments, nanowires 202 are free standing, i.e., supported only by the substrate 100.The nanowires 202 have a uniform height H of 50 to 200 nm, e.g., 50, 100, 150 or 200 nm, including ranges between any of the foregoing values.\",\n \"The nanowires 202 may have a circular cross section characterized by a diameter of 1 to 50 nm, e.g., 1, 2, 5, 10, 20 or 50 nm, including ranges between any of the foregoing values.\",\n \"In alternate embodiments, nanowires 202 have a rectangular or square cross section characterized by a length L and a width W that may independently range from 1 to 50 nm, e.g., 1, 2, 5, 10, 20 or 50 nm, including ranges between any of the foregoing values.\",\n \"The nanowires 202 may be arranged in a regular array that, in embodiments, has a nanowire-to-nanowire spacing (i.e., pitch) of 10 to 1000 nm.\",\n \"As depicted in FIG.\",\n \"3, after formation of nanowires 202, a first sacrificial layer 320 is formed over the isolation layer 120 and adjacent to the nanowires 202.In embodiments, first sacrificial layer 320 is in direct physical contact with the isolation layer 120 and with lower portions of the sidewalls of the nanowires 202.In embodiments, first sacrificial layer 320 can be selectively etched with respect to one or more of silicon, silicon dioxide and silicon nitride.\",\n \"First sacrificial layer 320 is configured to be later removed selective to both the isolation layer and nanowire materials.\",\n \"By way of example, the first sacrificial layer 320 may comprise amorphous carbon or a porous dielectric and may have a thickness of 10 to 50 nm.\",\n \"An amorphous carbon (a-C) layer or hydrogenated amorphous carbon (a-C:H) layer may be deposited from an argon/hydrocarbon gas/hydrogen/oxygen plasma or an argon/acetylene-helium/hydrogen/oxygen plasma, for example.\",\n \"In embodiments, the hydrocarbon gas used to form an amorphous carbon layer may be any hydrocarbon compound that capable of forming a plasma.\",\n \"The term ‘hydrocarbon’ refers to a compound that contains only carbon and hydrogen atoms, and may be either a saturated hydrocarbon or an unsaturated hydrocarbon.\",\n \"A saturated hydrocarbon compound contains only carbon single bonds, while an unsaturated compound contains carbon double or triple bonds.\",\n \"Suitable hydrocarbon compounds include alkanes, alkenes and alkynes.\",\n \"Methods of depositing an amorphous carbon layer include optionally pre-mixing and introducing process gases to a substrate at both a pressure and temperature effective to form amorphous carbon.\",\n \"In embodiments, a total pressure of the process gases (or process gas mixture) may range from 1 to 50 mTorr.\",\n \"The substrate temperature may range from 25° C. to 400° C. Porous dielectric thin films may be formed by selective removal of soluble porogens as known by those skilled in the art.\",\n \"A silicon-containing dielectric layer, for example, that initially contains soluble porogen material dispersed therein may be formed by chemical vapor deposition (CVD).\",\n \"Example porogen materials include germanium oxide and boron oxide, and example CVD precursors include germanic acid (H4GeO4) and boric acid (H3BO3) in addition to a suitable silicon source, such as an organosilicon compound.\",\n \"As seen with reference to FIG.\",\n \"4, a second sacrificial layer 420 is then formed over the first sacrificial layer 320 and adjacent to the nanowires 202.The second sacrificial layer 420 may comprise a dielectric material such as silicon nitride, for example, and have a thickness of 10 to 20 nm.\",\n \"Other dielectric materials may be employed as the second sacrificial layer 420 so long as the dielectric material that provides the second sacrificial layer 420 has a different etch selectivity than the material that provides the first sacrificial layer 320.Turning to FIGS.\",\n \"5A and 5B, photolithography and etching steps may be used to pattern the second sacrificial layer 420 to form a sacrificial gate 422.In embodiments, patterning and etching of the second sacrificial layer 420 exposes the first sacrificial layer 320, though nanowires 202 remain enveloped along a portion of their periphery by the sacrificial gate 422.Then, as illustrated in FIGS.\",\n \"6A and 6B, first sacrificial layer 320 is removed.\",\n \"A wet or dry etch may be used to selectively remove the first sacrificial layer 320.For example, the first sacrificial layer 320 formed from amorphous carbon may be removed using a wet etching comprising an acid such as sulfuric acid.\",\n \"Alternatively, the first sacrificial layer may be removed using a plasma ashing process, e.g., using an oxygen-based plasma such as an O2/N2-containing plasma.\",\n \"After removal of the first sacrificial layer 320, sacrificial gate 422 is anchored by nanowires 202 and suspended over substrate 100 to form a gap 326 there between.\",\n \"As shown in FIGS.\",\n \"7A and 7B, source and drain regions 520, 620 are formed below and above sacrificial gate 422, respectively, via epitaxial growth on exposed surfaces of nanowires 202.Source regions 520 are formed within the gap 326.In embodiments, source and drain regions are formed simultaneously and may have a radial thickness (i.e., with respect to nanowires 202) of 10 to 30 nm.\",\n \"Thus, source and drain regions 520, 620 have an annular shape when viewed along a direction normal to the substrate.\",\n \"The thickness of the source and drain regions with respect to the surface of the nanowires 202 may be constant or variable.\",\n \"Referring to FIG.\",\n \"7A, for example, the thickness of the source and drain regions may vary along with length of the nanowires due to shadowing or other geometric effects associated with the epitaxial growth.\",\n \"The source and drain regions may comprise silicon, e.g., single crystal silicon.\",\n \"By forming source and drain regions separately from the sacrificial gate, parasitic capacitance is advantageously reduced.\",\n \"Although the present application describes and illustrates the source region 520 being formed beneath the drain region 620, it is possible to form the drain region beneath the source region.\",\n \"The terms “epitaxy,” “epitaxial” and/or “epitaxial growth and/or deposition” refer to the growth of a semiconductor material layer on a deposition surface of a semiconductor material, in which the semiconductor material layer being grown assumes the same crystalline habit as the semiconductor material of the deposition surface.\",\n \"For example, in an epitaxial deposition process, chemical reactants provided by source gases are controlled and the system parameters are set so that depositing atoms alight on the deposition surface and remain sufficiently mobile via surface diffusion to orient themselves according to the crystalline orientation of the atoms of the deposition surface.\",\n \"Therefore, an epitaxial semiconductor material has the same crystalline characteristics as the deposition surface on which it is formed.\",\n \"For example, an epitaxial semiconductor material deposited on a (100) crystal surface will take on a (100) orientation.\",\n \"The epitaxial source and drain regions 520, 620 may be doped.\",\n \"Doping changes the electron and hole carrier concentrations of an intrinsic semiconductor at thermal equilibrium.\",\n \"A doped layer or region may be p-type or n-type.\",\n \"A p-type dopant is used to manufacture a PFET and an n-type dopant is used to manufacture an NFET.\",\n \"As used herein, “p-type” refers to the addition of impurities to an intrinsic semiconductor that creates a deficiency of valence electrons.\",\n \"For silicon, example p-type dopants, i.e., impurities, include but are not limited to, boron, aluminum, gallium, and indium.\",\n \"As used herein, “n-type” refers to the addition of impurities that contribute free electrons to an intrinsic semiconductor.\",\n \"For silicon, example n-type dopants, i.e., impurities, include but are not limited to, antimony, arsenic, and phosphorus.\",\n \"The dopant(s) may be introduced by plasma doping, or may be introduced, for example, in situ, i.e., during a process sequence used to form the layer.\",\n \"By way of example, a dopant region may in-situ doped with arsenic or phosphorus to form an n-type region.\",\n \"The dopant concentration within the source and drain regions may range from 1×1019 atoms/cm3 to 1×1022 atoms/cm3, e.g., 1×1020 atoms/cm3 to 1×1021 atoms/cm3.In another example, a dopant region is in-situ doped with boron or BF2 to form a p-type region.\",\n \"The dopant concentration within the source and drain regions may range from 1×1019 atoms/cm3 to 1×1022 atoms/cm3, e.g., 1×1020 atoms/cm3 to 1×1021 atoms/cm3.An optional drive-in anneal can be used to diffuse dopant species and generate a desired dopant profile.\",\n \"In embodiments, dopant atoms within the source and drain regions 520, 620 may be diffused into the adjacent nanowires 202 using a post-epitaxy anneal (e.g., at a temperature of 600 to 1400° C.) to create a dopant profile within the nanowires proximate to the source and drain regions 520, 620.The dopant profile within the nanowires 202 may be constant or variable.\",\n \"For instance, the dopant concentration within the nanowires may vary radially, with a minimum dopant concentration (e.g., 1×1019 to 1×1022 atoms/cm3) along a central axis of the nanowires and a maximum dopant concentration (e.g., 1×1019 to 1×1022 atoms/cm3) at the periphery.\",\n \"With reference to FIGS.\",\n \"8A and 8B, following the formation of epitaxial source and drain regions 520, 620, a dielectric layer 720 is deposited over exposed surfaces of the structure.\",\n \"In some embodiments, the dielectric layer 720 is then planarized and etched back so as to cover source regions 520 and sacrificial gate 422.The dielectric layer 720 may be self-planarizing, or the top surface of the dielectric layer 720 can be planarized, for example, by chemical mechanical planarization (CMP).\",\n \"Chemical mechanical polishing (CMP) is a material removal process that uses both chemical reactions and mechanical forces to remove material and planarize a surface.\",\n \"Drain regions 620 may function as a CMP etch stop.\",\n \"In embodiments, the thickness of dielectric layer 720 over the sacrificial gate may be 0 to 10 nm.\",\n \"A vertical transistor architecture is shown that includes one or more vertical nanowires 202 connecting a source region 520 with a drain region 620.Dielectric layer 720 may comprise silicon dioxide, silicon nitride, silicon oxynitride, a low-k material (i.e., a dielectric material having a dielectric constant of less than silicon dioxide), or any suitable combination of these materials.\",\n \"Exemplary low-k materials include but are not limited to, amorphous carbon, fluorine-doped oxides, carbon-doped oxides, SiCOH or SiBCN.\",\n \"Commercially-available low-k dielectric products and materials include Dow Corning's SiLK™ and porous SiLK™, Applied Materials' Black Diamond™, Texas Instrument's Coral™ and TSMC's Black Diamond™ and Coral™.\",\n \"The dielectric layer 720 may be deposited by plasma enhanced chemical vapor deposition (PECVD).\",\n \"Referring next to FIGS.\",\n \"9A, 9B, 10A and 10B, lithography and etching steps are used to optionally remove a portion of drain 620 in order to decrease a projected cross-sectional area thereof and create space adjacent to nanowires 202 through which contact vias will be formed in later steps.\",\n \"The resulting structure is backfilled with an additional dielectric layer 730, which is planarized to a height of the drain regions 620.Dielectric layer 730 may comprise the same dielectric material used for dielectric layer 720.As seen with reference to FIGS.\",\n \"11A and 11B, vias 736 are then etched into dielectric layers 720 and 730 to expose sacrificial gate 422.In the illustrated embodiment, both a sidewall surface and a top surface of the sacrificial gate 422 are exposed.\",\n \"As known to those skilled in the art, a wet and/or dry etch is used to selectively remove the sacrificial gate 422.Then, as shown in FIGS.\",\n \"12A and 12B, a gate stack is formed within vias 736 and the volume previously filled with the sacrificial gate.\",\n \"The gate stack comprises a gate dielectric 810 and a gate electrode 820, which are deposited in succession.\",\n \"The gate dielectric 810 may be a conformal layer that is formed over exposed surfaces within the aforementioned volume, including a top surface of epitaxial source region 520, a bottom surface of epitaxial drain region 620, and sidewalls of the intermediate (channel) segment of nanowires 202.Gate dielectric 810 may comprise silicon dioxide, silicon nitride, silicon oxynitride, a high-k dielectric, or other suitable material.\",\n \"As used herein, a high-k material has a dielectric constant greater than that of silicon nitride.\",\n \"A high-k dielectric may include a binary or ternary compound such as hafnium oxide (HfO2).\",\n \"Further exemplary high-k dielectrics include, but are not limited to, ZrO2, La2O3, Al2O3, TiO2, SrTiO3, BaTiO3, LaAlO3, Y2O3, HfOxNy, HfSiOxNy, ZrOxNy, La2OxNy, Al2OxNy, TiOxNy, SrTiOxNy, LaAlOxNy, Y2OxNy, SiOxNy, SiNx, a silicate thereof, and an alloy thereof.\",\n \"Each value of x may independently vary from 0.5 to 3, and each value of y may independently vary from 0 to 2.The gate dielectric 810 may be deposited by a suitable process such as atomic layer deposition (ALD), chemical vapor deposition (CVD), physical vapor deposition (PVD), thermal oxidation, UV-ozone oxidation, or combinations thereof.\",\n \"The gate dielectric thickness may range from 1 nm to 10 nm, e.g., 1, 2, 4, 6, 8 or 10 nm, including ranges between any of the foregoing.\",\n \"The gate electrode 820 may include a conductive material such as polysilicon, silicon-germanium, a conductive metal such as Al, W, Cu, Ti, Ta, W, Pt, Ag, Au, Ru, Ir, Rh and Re, alloys of conductive metals, e.g., Al—Cu, silicides of a conductive metal, e.g., W silicide, and Pt silicide, or other conductive metal compounds such as TiN, TiC, TiSiN, TiTaN, TaN, TaAlN, TaSiN, TaRuN, WSiN, NiSi, CoSi, as well as combinations thereof.\",\n \"The gate electrode 820 may comprise one or more layers of such materials such as, for example, a metal stack including a work function metal layer and/or a liner.\",\n \"The gate electrode 820 can be formed utilizing a conventional deposition process such as, for example, ALD, CVD, metalorganic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), PVD, sputtering, plating, evaporation, ion beam deposition, electron beam deposition, laser assisted deposition, or chemical solution deposition.\",\n \"In embodiments, the overlap area can be minimized between each of the source region and the gate stack, and the drain region and the gate stack, e.g., by forming source and drain regions with tapered sidewalls.\",\n \"As seen in FIGS.\",\n \"13A and 13B, a further dielectric layer 740 is deposited over the architecture of FIGS.\",\n \"12A and 12B, and source/drain contacts 850, 860 are formed extending through a portion of at least one of the dielectric layers 720, 730, 740.Source/drain contacts 850, 860 may be formed using a deposition process such as ALD, CVD, metalorganic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), PVD, sputtering, plating, evaporation, ion beam deposition, electron beam deposition, laser assisted deposition, or chemical solution deposition, and may comprise a conductive metal such as Al, W, Cu, Ti, Ta, W, Pt, Ag, Au, Ru, Ir, Rh and Re, alloys of conductive metals, e.g., Al—Cu, silicides of a conductive metal, e.g., W silicide, and Pt silicide, or other conductive metal compounds such as TiN, TiC, TiSiN, TiTaN, TaN, TaAlN, TaSiN, TaRuN, WSiN, NiSi, CoSi, as well as combinations thereof.\",\n \"Illustrated in FIGS.\",\n \"1-13 are embodiments of a process to form a vertical field effect transistor as well as the resulting structure.\",\n \"Absent from the gate of the resulting structure is a sidewall spacer, which simplifies the process flow.\",\n \"As used herein, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.\",\n \"Thus, for example, reference to a “nanowire” includes examples having two or more such “nanowires” unless the context clearly indicates otherwise.\",\n \"Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order.\",\n \"Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that any particular order be inferred.\",\n \"Any recited single or multiple feature or aspect in any one claim can be combined or permuted with any other recited feature or aspect in any other claim or claims.\",\n \"It will be understood that when an element such as a layer, region or substrate is referred to as being formed on, deposited on, or disposed “on” or “over” another element, it can be directly on the other element or intervening elements may also be present.\",\n \"In contrast, when an element is referred to as being “directly on” or “directly over” another element, no intervening elements are present.\",\n \"While various features, elements or steps of particular embodiments may be disclosed using the transitional phrase “comprising,” it is to be understood that alternative embodiments, including those that may be described using the transitional phrases “consisting” or “consisting essentially of,” are implied.\",\n \"Thus, for example, implied alternative embodiments to a dielectric layer that comprises silicon nitride include embodiments where a dielectric layer consists essentially of silicon nitride and embodiments where a dielectric layer consists of silicon nitride.\",\n \"It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit and scope of the invention.\",\n \"Since modifications, combinations, sub-combinations and variations of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed to include everything within the scope of the appended claims and their equivalents.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874680"}}},{"rowIdx":4494669,"cells":{"text":{"kind":"list like","value":[["BACKLIGHT UNIT AND DISPLAY DEVICE HAVING BACKLIGHT UNIT","A display device including a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a reflecting sheet on the substrate.","The reflecting sheet includes a first sheet part on the bottom and having a rectangular shape with a first long side, a second long side opposite the first long side, a first short side adjacent to the first long side and the second long side, and a second short side opposite the first short side, the first sheet part comprising a plurality of holes corresponding to the plurality of light sources; a second sheet part extended from the first sheet part toward the side wall of the frame; and a plurality of dots on the second sheet part, wherein the plurality of dots reduces a reflectance of light, and wherein a size of the plurality of dots increases from a corner of the second sheet part in a first direction parallel to the long sides and a second direction parallel to the short sides."],["1.A display device comprising: a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a reflecting sheet on the substrate, wherein the reflecting sheet includes: a first sheet part on the bottom and having a rectangular shape with a first long side, a second long side opposite the first long side, a first short side adjacent to the first long side and the second long side, and a second short side opposite the first short side, the first sheet part comprising a plurality of holes corresponding to the plurality of light sources; a second sheet part extended from the first sheet part toward the side wall of the frame; and a plurality of dots on the second sheet part, wherein the plurality of dots reduces a reflectance of light, and wherein a size of the plurality of dots increases from a corner of the second sheet part in a first direction parallel to the long sides and a second direction parallel to the short sides.","2.The display device of claim 1, wherein the size of the plurality of dots gradually changes along an outer side of the second sheet part from each corner of the second sheet part in the first direction and the second direction.","3.The display device of claim 1, wherein the second sheet part comprises a cut line between a horizontal portion of the second sheet part arranged along the first direction and a vertical portion of the second sheet part arranged along the second direction.","4.The display device of claim 3, wherein the second sheet part comprises a first dot area, and a second dot area next to the first dot area, wherein the first dot area is a closest area to the corner of the second sheet part and the second dot area is farther from the corner of the second sheet part than the first dot area.","5.The display device of claim 4, wherein a first border line between the first dot area and the second dot area is not straight.","6.The display device of claim 4, wherein the second sheet part further comprises a third dot area next to the second dot area, the third dot area is the farthest area from the corner of the second sheet part among the first dot area, the second dot area and the third dot area.","7.The display device of claim 6, wherein a second border line between the second dot area and the third dot area is not straight.","8.The display device of claim 6, wherein a size of the dots in the first dot area is the same and is smaller than a size of the dots in the second dot area, and the size of the dots in the second dot area is the same and is smaller than a size of the dots in the third dot area, the size of the dots in the third dot area being the same.","9.The display device of claim 6, wherein the first dot area, the second dot area, and the third dot area on the second sheet part along the long side form a horizontal dot area, and wherein the first dot area, the second dot area, and the third dot area on the second sheet part along the short side form a vertical dot area, and wherein a width of the vertical dot area is different from a width of the horizontal dot area.","10.The display device of claim 9, wherein the second dot area of the horizontal dot area is separated from the cutting portion by a first angle and the second dot area of the vertical dot area is separated from the cutting portion by a second angle, and wherein the first angle is different from the second angle.","11.The display device of claim 9, wherein the first vertical dot area is the closest to the cut line among the first to third vertical dot areas, wherein the first horizontal dot area is the closest to the cut line among the first to third horizontal dot areas, and wherein an empty area without dots is positioned between the first vertical dot area and the first horizontal dot area around the cut line.","12.The display device of claim 9, wherein the vertical dot area has a different shape than the horizontal dot area.","13.The display device of claim 12, the width of the vertical dot area is greater than the width of the horizontal dot area.","14.The display device of claim 9, wherein an outline of the vertical dot area or the horizontal dot area adjacent to the cut line is inclined with respect to the cut line.","15.The display device of claim 7, wherein the first border line is substantially parallel with the second border line.","16.The display device of claim 1, further comprising a separation space between the second sheet part of the reflecting sheet and the frame.","17.The display device of claim 1, further comprising a signal line electrically connected to the substrate, wherein the frame includes a hole on the bottom of the frame, and wherein the signal line passes through the hole.","18.A display device comprising: a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a reflecting sheet on the substrate, wherein the reflecting sheet includes: a first sheet part on the bottom and being a rectangular shape, the first sheet part comprising a plurality of holes corresponding to the plurality of light sources; a second sheet part extended from the first sheet part toward the side wall of the frame; and a plurality of dot areas on the second sheet part, the plurality of dot areas forming a gradation in a direction along a side of the first sheet part, wherein the gradation of the plurality of dot areas becomes darker as the dot areas go farther from a corner of the first sheet part and the gradation of the plurality of dot areas becomes brighter as the dot areas go closer to another corner of the first sheet part.","19.The display device of claim 18, wherein a size of dots in the plurality of dot areas becomes greater as the dot areas go farther from a corner of the first sheet part and the size of dots in the plurality of dot areas becomes smaller as the dot areas go closer to another corner of the first sheet part.","20.The display device of claim 18, wherein the frame is a rectangular plate having a short side and a long side, the second sheet part includes a vertical sheet part adjacent to the short side of the frame and a horizontal sheet part adjacent to the long side of the frame, and wherein the plurality of dot areas includes a vertical dot area and a horizontal dot area, the vertical dot area is positioned on the vertical sheet part and the horizontal dot area is positioned on the horizontal sheet part.","21.The display device of claim 20, further comprising a cut line between the vertical sheet part and the horizontal sheet part of the second sheet part, wherein the vertical dot area includes a plurality of vertical dot areas forming a gradation in a vertical direction along the short side of the frame, wherein the horizontal dot area includes a plurality of horizontal dot areas forming a gradation in a horizontal direction along the long side of the frame, and wherein a shape of the vertical dot area and a shape of the horizontal dot area are asymmetric with respect to the cut line.","22.The display device of claim 21, wherein the plurality of vertical dot areas comprises a first vertical area, a second vertical area next to the first vertical area, the first vertical area is the closest area to the cut line among the plurality of vertical dot areas and the second vertical area is farther from the cut line than the first vertical area, wherein the plurality of horizontal dot areas comprises a first horizontal area, a second horizontal area next to the first horizontal area, the first horizontal area is the closest area to the cut line among the plurality of horizontal dot areas and the second horizontal area is farther from the cut line than the first horizontal area, and wherein an empty area without dots is positioned between the first vertical area and the first horizontal area around the cut line.","23.The display device of claim 22, wherein the empty area without dots is gradually narrower as the empty area goes closer to a corner of the second sheet part.","24.The display device of claim 18, wherein the gradation of the plurality of dot areas darker as the dot areas go from a border between the first sheet part and the second sheet part toward the side wall of the frame."],["<SOH> BACKGROUND OF THE INVENTION <EOH>"],["<SOH> SUMMARY OF THE INVENTION <EOH>The present disclosure provides a backlight unit including a reflecting sheet having a dot area.","In one aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, and wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.","The backlight unit may further include at least one of a diffusion plate and an optical sheet positioned on the reflecting sheet.","The backlight unit may further include a plurality of lenses positioned on the plurality of light sources.","The backlight unit may further include a plurality of pins fixing the reflecting sheet to the frame.","The plurality of pins maybe arranged outside the plurality of holes.","The plurality of pins maybe arranged in a row.","The first sheet part and the second sheet part may be delineated by the plurality of pins.","At least one of the plurality of pins maybe positioned between at least two outermost holes among the plurality of holes positioned on a short side of the reflecting sheet.","A distance between a dot area on a long side of the reflecting sheet and an outermost hole of the plurality of holes on the long side maybe greater than a distance between a dot area on a short side of the reflecting sheet and an outermost hole of the plurality of holes on the short side.","A bent area maybe positioned at a boundary between the first sheet part and the second sheet part and a boundary between the second sheet part and third sheet part.","The second sheet part may be rounded.","A slope of the second sheet part may increase as the slope goes towards the third sheet part.","Sizes of the plurality of dots in the second sheet area may vary depending on an increase in the slope.","The sizes of the plurality of dots in the second sheet area may increase as the slope increases.","In a corner of the reflecting sheet, a shape of a dot area on a long side of the reflecting sheet and a shape of a dot area on a short side of the reflecting sheet maybe asymmetric.","The backlight unit may further include a cutting line on a corner of the reflecting sheet.","A distance between a specific point on the cutting line and a dot nearest to the cutting line in a direction parallel to a long side of the reflecting sheet maybe different from a distance between the specific point and a dot nearest to the cutting line in a direction parallel to a short side of the reflecting sheet.","The second sheet area may include a non-dot area adjacent to the third sheet part.","A width of the non-dot area maybe greater than a distance between adjacent dots of the plurality of dots.","The first sheet part and the third sheet part may contact the frame, and the second sheet part may be separated from the frame.","A distance between adjacent dots of the plurality of dots in the first dot area maybe different from a distance between adjacent dots of the plurality of dots in the second dot area.","The first dot area may be located closer to the first sheet part than the second dot area.","In another aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas include a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a distance of adjacent dots of the plurality of dots in the first dot area is different from a distance of adjacent dots of the plurality of dots in the second dot area.","In another aspect, there is a display device including: a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; a reflecting sheet located on the at least one substrate; an optical sheet located on the reflecting sheet; and a display panel located on the optical sheet, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area."],["This application is a Continuation of co-pending application Ser.","No.","14/929,828, filed on Nov. 2, 2015, which claims priority under 35 U.S.C.","§ 119(e) to U.S.","Provisional Application No.","62/073,509, filed on Oct. 31, 2014, and under 35 U.S.C.","§ 119(a) to Application Nos.","10-2015-0109165 and 10-2015-0109155, both filed in Republic of Korea on Jul.","31, 2015, all of which are hereby expressly incorporated by reference into the present application.","BACKGROUND OF THE INVENTION Field of the Invention The present disclosure relates to a backlight unit and a display device including the backlight unit.","Discussion of the Related Art With the development of the information society, various demands for display devices have been increasing.","Various display devices, such as liquid crystal displays (LCDs), plasma display panels (PDPs), electroluminescent displays (ELDs), and vacuum fluorescent displays (VFDs), have been recently studied and used to meet various demands for the display devices.","Among the display devices, a liquid crystal display panel of the liquid crystal display includes a liquid crystal layer, and a thin film transistor (TFT) substrate and a color filter substrate which are positioned opposite each other with the liquid crystal layer interposed there between.","The liquid crystal display panel displays an image using light provided by a backlight unit of the liquid crystal display.","SUMMARY OF THE INVENTION The present disclosure provides a backlight unit including a reflecting sheet having a dot area.","In one aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, and wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.","The backlight unit may further include at least one of a diffusion plate and an optical sheet positioned on the reflecting sheet.","The backlight unit may further include a plurality of lenses positioned on the plurality of light sources.","The backlight unit may further include a plurality of pins fixing the reflecting sheet to the frame.","The plurality of pins maybe arranged outside the plurality of holes.","The plurality of pins maybe arranged in a row.","The first sheet part and the second sheet part may be delineated by the plurality of pins.","At least one of the plurality of pins maybe positioned between at least two outermost holes among the plurality of holes positioned on a short side of the reflecting sheet.","A distance between a dot area on a long side of the reflecting sheet and an outermost hole of the plurality of holes on the long side maybe greater than a distance between a dot area on a short side of the reflecting sheet and an outermost hole of the plurality of holes on the short side.","A bent area maybe positioned at a boundary between the first sheet part and the second sheet part and a boundary between the second sheet part and third sheet part.","The second sheet part may be rounded.","A slope of the second sheet part may increase as the slope goes towards the third sheet part.","Sizes of the plurality of dots in the second sheet area may vary depending on an increase in the slope.","The sizes of the plurality of dots in the second sheet area may increase as the slope increases.","In a corner of the reflecting sheet, a shape of a dot area on a long side of the reflecting sheet and a shape of a dot area on a short side of the reflecting sheet maybe asymmetric.","The backlight unit may further include a cutting line on a corner of the reflecting sheet.","A distance between a specific point on the cutting line and a dot nearest to the cutting line in a direction parallel to a long side of the reflecting sheet maybe different from a distance between the specific point and a dot nearest to the cutting line in a direction parallel to a short side of the reflecting sheet.","The second sheet area may include a non-dot area adjacent to the third sheet part.","A width of the non-dot area maybe greater than a distance between adjacent dots of the plurality of dots.","The first sheet part and the third sheet part may contact the frame, and the second sheet part may be separated from the frame.","A distance between adjacent dots of the plurality of dots in the first dot area maybe different from a distance between adjacent dots of the plurality of dots in the second dot area.","The first dot area may be located closer to the first sheet part than the second dot area.","In another aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas include a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a distance of adjacent dots of the plurality of dots in the first dot area is different from a distance of adjacent dots of the plurality of dots in the second dot area.","In another aspect, there is a display device including: a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; a reflecting sheet located on the at least one substrate; an optical sheet located on the reflecting sheet; and a display panel located on the optical sheet, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention.","In the drawings: FIGS.","1 and 2 illustrate a display device according to an example embodiment of the invention; FIGS.","3 to 7 illustrate configuration of a display device related to an example embodiment of the invention; FIGS.","8 and 9 illustrate a light source according to an example embodiment of the invention; FIG.","10 illustrates a connection relationship between a reflecting sheet and components around the reflecting sheet according to an example embodiment of the invention; FIGS.","11 to 13 illustrate configuration of a reflecting sheet according to an example embodiment of the invention; FIGS.","14 to 23B illustrate a dot distribution of a reflecting sheet according to an example embodiment of the invention; FIGS.","24 and 25 illustrate a reflecting sheet according to an example embodiment of the invention; FIGS.","26 to 28 illustrate configuration of a cutting portion of a reflecting sheet according to an example embodiment of the invention; FIGS.","29 and 30 illustrate a dot area according to an example embodiment of the invention; FIGS.","31 to 38 illustrate configuration related to a lens hole of a reflecting sheet according to an example embodiment of the invention; FIGS.","39 to 43 illustrate configuration related to a lens hole reflecting sheet according to an example embodiment of the invention; FIGS.","44 and 45 illustrate configuration related to horizontal and vertical coupling units of a reflecting sheet according to an example embodiment of the invention; FIGS.","46 to 48B illustrate configuration related to a cutting portion of a reflecting sheet according to an example embodiment of the invention; FIGS.","49 and 50 illustrate configuration related to a supporter hole of a reflecting sheet according to an example embodiment of the invention; FIG.","51 shows a light assembly including a light source shown in FIG.","19; FIGS.","52 and 53 show a lens according to an example embodiment of the invention; FIG.","54 shows an example of a light path of a lens shown in FIG.","52; FIGS.","55 to 60 show a lens according to another example embodiment of the invention; and FIGS.","61 and 62 show a disposition of a light assembly according to another example embodiment of the invention.","DETAILED DESCRIPTION OF THE EMBODIMENTS Reference will now be made in detail to embodiments of the invention, examples of which are illustrated in the accompanying drawings.","Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.","A suffix such as “module” and “unit” may be assigned or used interchangeably to refer to elements or components.","Use of such a suffix herein is merely intended to facilitate the description of the embodiments of the invention, and the suffix itself is not intended to give any special meaning or function.","It will be paid attention that detailed description of known arts will be omitted if it is determined that the detailed description of the know arts can obscure the embodiments of the invention.","The accompanying drawings are merely intended to easily describe the embodiments of the invention, and the spirit and technical scope of the present invention is not limited by the accompanying drawings.","It should be understood that the present invention is not limited to specific disclosed embodiments, but includes all modifications, equivalents and substitutes included within the spirit and technical scope of the present invention.","Hereinafter, the embodiments of the invention are described using a liquid crystal display panel as an example of a display panel.","Other display panels may be used.","For example, a plasma display panel (PDP), a field emission display (FED) panel, and an organic light emitting diode (OLED) display panel may be used.","In what follows, a display panel may include a first long side LS1, a second long side LS2 opposite the first long side LS1, a first short side SS1 adjacent to the first long side LS1 and the second long side LS2, and a second short side SS2 opposite the first short side SS1.In the embodiment disclosed herein, the first short side SS1 may be referred to as a first side area; the second short side SS2 may be referred to as a second side area opposite the first side area; the first long side LS1 may be referred to as a third side area which is adjacent to the first side area and the second side area and is positioned between the first side area and the second side area; and the second long side LS2 may be referred to as a fourth side area which is adjacent to the first side area and the second side area, is positioned between the first side area and the second side area, and is opposite to the third side area.","The embodiment of the invention describes that lengths of the first and second long sides LS1 and LS2 are longer than lengths of the first and second short sides SS1 and SS2 for the sake of brevity and ease of reading.","However, the lengths of the first and second long sides LS1 and LS2 may be almost equal to the lengths of the first and second short sides SS1 and SS2.In the following description, a first direction DR1 may be a direction parallel to the long sides LS1 and LS2 of the display panel, and a second direction DR2 may be a direction parallel to the short sides SS1 and SS2 of the display panel.","Further, a third direction DR3 may be a direction vertical to the first direction DR1 and/or the second direction DR2.In the embodiment disclosed herein, the first direction DR1 and the second direction DR2 may be commonly referred to as a horizontal direction.","Further, the third direction DR3 may be referred to as a vertical direction.","FIGS.","1 and 2 illustrate a display device according to an example embodiment of the invention.","As shown in FIGS.","1 and 2, a display device 100 according to the embodiment of the invention may include a display panel 110 and a back cover 150 positioned in the rear of the display panel 110.The back cover 150 may be connected to the display panel 110 in a sliding manner in a direction (i.e., the second direction DR2) from the first long side LS1 to the second long side LS2.In other words, the back cover 150 may be inserted into the first short side SS1, the second short side SS2 opposite the first short side SS1, and the first long side LS1 which is adjacent to the first and second short sides SS1 and SS2 and is positioned between the first short side SS1 and the second short side SS2, of the display panel 110 in the sliding manner.","The back cover 150 and/or other components adjacent to the back cover 150 may include a protrusion, a sliding unit, a connection unit, etc., so that the back cover 150 is connected to the display panel 110 in the sliding manner.","FIGS.","3 to 7 illustrate configuration of a display device related to the embodiment of the invention.","As shown in FIG.","3, the display device 100 according to the embodiment of the invention may include a front cover 105, the display panel 110, a backlight unit 120, a frame 130, and the back cover 150.The front cover 105 may cover at least a portion of a front surface and a side surface of the display panel 110.The front cover 105 may have a rectangular fame shape, in which a center portion is empty.","Because the center portion of the front cover 105 is empty, an image displayed on the display panel 110 may be seen to the outside.","The front cover 105 may include a front cover and a side cover.","Namely, the front cover 105 may include the front cover positioned at the front surface of the display panel 110 and the side cover at the side surface of the display panel 110.The front cover and the side cover may be separately configured.","One of the front cover and the side cover may be omitted.","For example, the front cover may be omitted, and only the side cover may be absent in terms of a beautiful appearance of the display device 100.The display panel 110 may be positioned in front of the display device 100 and may display an image.","The display panel 110 may divide the image into a plurality of pixels and may output the image while controlling color, brightness, and chroma of each pixel.","The display panel 110 may include an active area, on which the image is displayed, and an inactive area, on which the image is not displayed.","The display panel 110 may include a front substrate and a back substrate which are positioned opposite each other with a liquid crystal layer interposed there between.","The front substrate may include a plurality of pixels each including red, green, and blue subpixels.","The front substrate may generate an image corresponding to the red, green, or blue color in response to a control signal.","The back substrate may include switching elements.","The back substrate may turn on pixel electrodes.","For example, the pixel electrode may change a molecule arrangement of the liquid crystal layer in response to a control signal received from the outside.","The liquid crystal layer may include a plurality of liquid crystal molecules.","The arrangement of the liquid crystal molecules may change depending on a voltage difference between the pixel electrode and a common electrode.","The liquid crystal layer may transmit light provided by the backlight unit 120 to the front substrate.","The backlight unit 120 may be positioned at a back surface of the display panel 110.The backlight unit 120 may include a plurality of light sources.","The light sources of the backlight unit 120 may be arranged in an edge type or a direct type.","In the instance of the edge type backlight unit 120, a light guide plate may be added.","The backlight unit 120 may be coupled to a front surface of the frame 130.For example, the plurality of light sources may be disposed at the front surface of the frame 130.In this instance, the backlight unit 120 may be commonly called the direct type backlight unit 120.The backlight unit 120 may be driven in an entire driving method or a partial driving method such as a local dimming method and an impulsive driving method.","The backlight unit 120 may include an optical sheet 125 and an optical layer 123.The optical sheet 125 can cause light of the light sources to be uniformly transferred to the display panel 110.The optical sheet 125 may include a plurality of layers.","For example, the optical sheet 125 may include at least one prism sheet and/or at least one diffusion sheet.","The optical sheet 125 may further include at least one coupling unit 125d.","The coupling unit 125d may be coupled to the front cover 105 and/or the back cover 150.Namely, the coupling unit 125d may be directly coupled to the front cover 105 and/or the back cover 150.Alternatively, the coupling unit 125d may be coupled to a structure formed on the front cover 105 and/or the back cover 150.Namely, the coupling unit 125d may be indirectly coupled to the front cover 105 and/or the back cover 150.The optical layer 123 may include the light source, etc.","The detailed configuration of the optical layer 123 will be described in the corresponding paragraphs.","The frame 130 may support components constituting the display device 100.For example, the frame 130 may be coupled to the backlight unit 120.The frame 130 may be formed of a metal material, for example, an aluminum alloy.","The back cover 150 may be positioned at a back surface of the display device 100.The back cover 150 may protect inner configuration of the display device 100 from the outside.","At least a portion of the back cover 150 may be coupled to the frame 130 and/or the front cover 105.The back cover 150 may be an injection production (or injection molded) formed of a resin material.","FIG.","4 shows the configuration of the optical sheet 125.As shown in (a) of FIG.","4, the optical sheet 125 and/or a diffusion plate 129 may be positioned on the frame 130.The optical sheet 125 and/or the diffusion plate 129 may be coupled to the frame 130 at an edge of the frame 130.The optical sheet 125 and/or the diffusion plate 129 may be directly placed at the edge of the frame 130.Namely, an outer perimeter of the optical sheet 125 and/or the diffusion plate 129 may be supported by the frame 130.An upper surface of an edge of the optical sheet 125 and/or the diffusion plate 129 may be surrounded by a first guide panel 117.For example, the optical sheet 125 and/or the diffusion plate 129 may be positioned between the edge of the frame 130 and a flange 117a of the first guide panel 117.The display panel 110 may be positioned at a front surface of the optical sheet 125.An edge of the display panel 110 may be coupled to the first guide panel 117.Namely, the display panel 110 may be supported by the first guide panel 117.An edge area of the front surface of the display panel 110 may be surrounded by the front cover 105.For example, the display panel 110 may be positioned between the first guide panel 117 and the front cover 105.As shown in (b) of FIG.","4, the display device 100 according to the embodiment of the invention may further include a second guide panel 113.The optical sheet 125 and/or the diffusion plate 129 may be coupled to the second guide panel 113.Namely, the second guide panel 113 may have a shape, in which the second guide panel 113 is coupled to the frame 130 and the optical sheet 125 and/or the diffusion plate 129 are/is coupled to the second guide panel 113.The second guide panel 113 may be formed of a material different from the frame 130.The frame 130 may have a shape surrounding the first and second guide panels 117 and 113.As shown in (c) of FIG.","4, in the display device 100 according to the embodiment of the invention, the front cover 105 may not cover the front surface of the display panel 110.Namely, one end of the front cover 105 may be positioned on the side of the display panel 110.Referring to FIGS.","5 and 6, the backlight unit 120 may include the optical layer 123 including substrates 122, at least one light assembly 124, a reflecting sheet 126 and the diffusion plate 129, and the optical sheet 125 positioned on a front surface of the optical layer 123.The substrates 122 may include a plurality of straps, which extend in a first direction and are separated from one another by a predetermined distance in a second direction perpendicular to the first direction.","At least one light assembly 124 may be mounted on the substrate 122.The substrate 122 may have an electrode pattern for connecting an adaptor to the light assembly 124.For example, a carbon nanotube electrode pattern for connecting the adaptor to the light assembly 124 may be formed on the substrate 122.The substrate 122 maybe formed of at least one of polyethylene terephthalate (PET), glass, polycarbonate (PC), and silicon.","The substrate 122 maybe a printed circuit board (PCB), on which at least one light assembly 124 is mounted.","The light assemblies 124 may be disposed on the substrate 122 at predetermined intervals in the first direction.","A diameter of the light assembly 124 may be greater than a width of the substrate 122.Namely, the diameter of the light assembly 124 may be greater than a length of the substrate 122 in the second direction.","The light assembly 124 may be one of a light emitting diode (LED) chip and a LED package having at least one LED chip.","The light assembly 124 may be configured as a colored LED emitting at least one of red, green, and blue light or a white LED.","The colored LED may include at least one of a red LED, a green LED, and a blue LED.","The light source included in the light assembly 124 may be a COB (Chip-On-Board) type.","The COB light source may have a configuration, in which the LED chip as the light source is directly coupled to the substrate 122.Thus, the process may be simplified.","Further, a resistance may be reduced, and a loss of energy resulting from heat may be reduced.","Namely, power efficiency of the light assembly 124 may increase.","The COB light source can provide the brighter lighting and may be implemented to be thinner and lighter than a related art.","The reflecting sheet 126 may be positioned at the front surface of the substrate 122.The reflecting sheet 126 may be positioned in an area excluding a formation area of the light assemblies 124 of the substrates 122.Namely, the reflecting sheet 126 may have a plurality of holes 235.The reflecting sheet 126 may reflect light emitted from the light assembly 124 to a front surface of the reflecting sheet 126.Further, the reflecting sheet 126 may again reflect light reflected from the diffusion plate 129.The reflecting sheet 126 may include at least one of metal and metal oxide which are a reflection material.","The reflecting sheet 126 may include metal and/or metal oxide having a high reflectance, for example, aluminum (Al), silver (Ag), gold (Au), and titanium dioxide (TiO2).","The reflecting sheet 126 may be formed by depositing and/or coating the metal or the metal oxide on the substrate 122.An ink including the metal material may be printed on the reflecting sheet 126.On the reflecting sheet 126, a deposition layer may be formed using a heat deposition method, an evaporation method, or a vacuum deposition method such as a sputtering method.","On the reflecting sheet 126, a coating layer and/or a printing layer may be formed using a printing method, a gravure coating method or a silk screen method.","An air gap may be positioned between the reflecting sheet 126 and the diffusion plate 129.The air gap may serve as a buffer capable of widely spreading light emitted from the light assembly 124.A supporter (or support plate) 200 may be positioned between the reflecting sheet 126 and the diffusion plate 129, so as to maintain the air gap.","A resin may be deposited on the light assembly 124 and/or the reflecting sheet 126.The resin may function to diffuse light emitted from the light assembly 124.The diffusion plate 129 may upwardly diffuse light emitted from the light assembly 124.The optical sheet 125 may be positioned at a front surface of the diffusion plate 129.A back surface of the optical sheet 125 may be adhered to the diffusion plate 129, and a front surface of the optical sheet 125 may be adhered to the back surface of the display panel 110.The optical sheet 125 may include at least one sheet.","More specifically, the optical sheet 125 may include one or more prism sheets and/or one or more diffusion sheets.","The plurality of sheets included in the optical sheet 125 may be attached and/or adhered to one another.","In other words, the optical sheet 125 may include a plurality of sheets having different functions.","For example, the optical sheet 125 may include first to third optical sheets 125a to 125c.","The first optical sheets 125a may function as a diffusion sheet, and the second and third optical sheets 125b and 125c may function as a prism sheet.","A number and/or a position of the diffusion sheets and the prism sheets may be changed.","For example, the optical sheet 125 may include the first optical sheets 125a as the diffusion sheet and the second optical sheet 125b as the prism sheet.","The diffusion sheet may prevent light coming from the diffusion plate from being partially concentrated and may homogenize a luminance of the light.","The prism sheet may concentrate light coming from the diffusion sheet and may make the concentrated light be vertically incident on the display panel 110.The coupling unit 125d may be formed on at least one of corners of the optical sheet 125.The coupling unit 125d may be formed in at least one of the first to third optical sheets 125a to 125c.","The coupling unit 125d may be formed at the corner on the long side of the optical sheet 125.The coupling unit 125d formed on the first long side and the coupling unit 125d formed on the second long side may be asymmetric.","For example, a number and/or a position of the coupling units 125d formed on the first long side may be different from a number and/or a position of the coupling units 125d formed on the second long side.","Referring to FIG.","7, the substrates 122 including the plurality of straps, which extend in the first direction and are separated from one another by a predetermined distance in the second direction perpendicular to the first direction, may be provided on the frame 130.One end of each of the plurality of substrates 122 may be connected to a line electrode 232.The line electrode 232 may extend in the second direction.","The line electrode 232 may be connected to the ends of the substrates 122 at predetermined intervals in the second direction.","The substrates 122 may be electrically connected to the adaptor through the line electrode 232.The light assemblies 124 may be mounted on the substrate 122 at predetermined intervals in the first direction.","A diameter of the light assembly 124 may be greater than a width of the substrate 122 in the second direction.","Hence, an outer area of the light assembly 124 may be positioned beyond a formation area of the substrate 122.FIGS.","8 and 9 show a light source according to the embodiment of the invention.","As shown in FIG.","8, a light source 203 may be a COB light source.","The COB light source 203 may include at least one of an emission layer 135, first and second electrodes 147 and 149, and a fluorescent layer 137.The emission layer 135 may be positioned on the substrate 122.The emission layer 135 may emit one of red, green, and blue light.","The emission layer 135 may include one of Firpic, (CF3ppy) 2Ir(pic), 9,10-di(2-naphthyl)anthracene (AND), perylene, distyrybiphenyl, PVK, OXD-7, UGH-3(Blue), and a combination thereof.","The first and second electrodes 147 and 149 may be positioned on both sides of a lower surface of the emission layer 135.The first and second electrodes 147 and 149 may transmit an external driving signal to the emission layer 135.The fluorescent layer 137 may cover the emission layer 135 and the first and second electrodes 147 and 149.The fluorescent layer 137 may include a fluorescent material converting light of a spectrum generated from the emission layer 135 into white light.","A thickness of the emission layer 135 on the fluorescent layer 137 may be uniform.","The fluorescent layer 137 may have a refractive index of 1.4 to 2.0.The COB light source 203 according to the embodiment of the invention may be directly mounted on the substrate 122.Thus, the size of the light assembly 124 may decrease.","Because heat dissipation of the light sources 203 is excellent by forming the light sources 203 on the substrate 122, the light sources 203 may be driven at a high current.","Hence, a number of light sources 203 required to secure the same light quantity may decrease.","Further, because the light sources 203 are mounted on the substrate 122, a wire bonding process may not be necessary.","Hence, the manufacturing cost may be reduced due to the simplification of the manufacturing process.","As shown in FIG.","9, the light source 203 according to the embodiment of the invention may emit light in a first emission range EA1.Namely, the light source 203 may emit light in the first emission range EA1 including a second emission range EA2 of the front side and third and fourth emission ranges EA3 and EA4 of both sides.","Thus, the light source 203 according to the embodiment of the invention is different from a related art POB light source emitting light in the second emission range EA2.In other words, the light source 203 according to the embodiment of the invention may be the COB light source, and the COB light source 203 may emit light in a wide emission range including the side.","Because the COB light source 203 emits light even in a direction corresponding to the third and fourth emission ranges EA3 and EA4 of the side, the embodiment of the invention needs to efficiently control light of the side direction.","The reflecting sheet according to the embodiment of the invention may control a reflectance of light emitted from the light source 203 in the side direction.","Thus, the embodiment of the invention may reduce the non-uniformity of brightness resulting from light of the side direction.","FIG.","10 illustrates a connection relationship between the reflecting sheet and components around the reflecting sheet according to the embodiment of the invention.","As shown in FG.","10, the reflecting sheet 126 according to the embodiment of the invention may be placed on the frame 130.For example, the reflecting sheet 126 may be coupled to a receiving unit 132 formed inside the frame 130.The reflecting sheet 126 may include a horizontal coupling unit HH and a vertical coupling unit VH.","For example, coupling holes may be formed along a long side and/or a short side of the reflecting sheet 126.The horizontal coupling unit HH and the vertical coupling unit VH may be inserted into a horizontal protrusion 130H and/or a vertical protrusion 130V formed on the frame 130.A guide panel GP may be formed on the reflecting sheet 126.The guide panel GP may be formed of plastic material of injection molding or press processed metal material.","The guide panel GP may be coupled to the horizontal protrusion 130H and/or the vertical protrusion 130V.","When the guide panel GP is coupled to the reflecting sheet 126, the reflecting sheet 126 may be fixed between the frame 30 and the guide panel GP.","FIG.","10 shows that the long sides and the short sides of the guide panel GP are separated from one another, as an example.","The guide panel GP, which the long sides and the short sides are connected to one another, may be used.","The reflecting sheet 126 placed on the frame 130 may be configured as a three-dimensional shape corresponding to a shape of the receiving unit 132.Even when the reflecting sheet 126 according to the embodiment of the invention has the three-dimensional shape, the reflecting sheet 126 can provide an optimum reflection effect.","For example, the reflecting sheet 126 can uniformly reflect light throughout its entire area.","The reflecting sheet 126 may constitute a portion of the backlight unit 120 (refer to FIG.","5).","The substrate 122, on which the light sources 203 are mounted, may be positioned between the reflecting sheet 126 and the frame 130.The plurality of substrates 122 may be arranged in the horizontal direction and/or the vertical direction.","The substrates 122 may be connected to signal lines 121 connected to a controller, etc., of the display device 100.The signal lines 121 may be connected to the substrates 122 through holes formed in the frame 130.The reflecting sheet 126 may include a plurality of lens holes 235.The plurality of lens holes 235 may correspond to the light sources 203 on the substrate 122.For example, the plurality of lens holes 235 may be arranged in the horizontal direction and/or the vertical direction correspondingly to the light sources 203.A lens 124b may be inserted into the lens hole 235.For example, the lens 124b may be coupled to the light source 203 through the lens hole 235.The reflecting sheet 126 may include a plurality of support holes (or support plate holes) 205.A supporter 200 may be coupled to the support hole 205.The supporter 200 may support the optical sheet 125 and/or the diffusion plate 129 positioned in front of the reflecting sheet 126.Namely, the reflecting sheet 126 may be separated from the optical sheet 125 and/or the diffusion plate 129 at a predetermined distance.","The reflecting sheet 126 may include a plurality of fixing pin holes 206.A fixing pin 202 may be coupled to the fixing pin hole 206.Also, the fixing pin 202 may be coupled to a frame hole 204 formed in the frame 130.Thus, the fixing pin 202 may fix the reflecting sheet 126 to the frame 130.FIGS.","11 to 13 illustrate configuration of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","11 to 13, the reflecting sheet 126 according to the embodiment of the invention may be placed in an inner area of the frame 130.The reflecting sheet 126 placed on the frame 130 may have the three-dimensional shape corresponding to a shape of the frame 130.As shown in FIG.","11, the frame 130 may include first to third frame areas 130a to 130c.","The first frame area 130a may be a bottom surface of the frame 130.The second frame area 130b may be substantially flat.","Namely, the second frame area 130b may be a surface positioned on an X-Y plane of the display device 100.The second frame area 130b may be a sidewall surface extended upwardly from the first frame area 130a.","The second frame area 130b may extend in a direction parallel to a Z-axis direction or a direction inclined to the Z-axis direction.","The receiving unit 132 (refer to FIG.","10) may be formed inside the frame 130 by the second frame area 130b serving as a sidewall of the frame 130.The third frame area 130c may be a surface extended from the second frame area 130b in an X-axis direction.","The third frame area 130c may be substantially parallel to the first frame area 130a.","Namely, the third frame area 130c may be a flat surface in the same manner as the first frame area 130a at a height level different from the first frame area 130a by the second frame area 130b.","The third frame area 130c may include a protruding area.","The third frame area 130c may be coupled to a protrusion formed through a separate process.","The protruding area and/or the protrusion of the third frame area 130c may be coupled to the reflecting sheet 126.For example, the protruding area and/or the protrusion of the third frame area 130c may be coupled to a third sheet area 126c of the reflecting sheet 126.The protruding area and/or the protrusion of the third frame area 130c may be coupled to the optical sheet 125 (refer to FIG.","5).","The reflecting sheet 126 may be coupled to an area formed by the first to third frame areas 130a to 130c of the frame 130.For example, the reflecting sheet 126 may be coupled to the first frame area 130a through the fixing pin 202.When a portion of the reflecting sheet 126 is coupled to the first frame area 130a through the fixing pin 202, the portion of the reflecting sheet 126 may naturally contact the frame 130.When the reflecting sheet 126 is coupled to the frame 130 through the fixing pin 202, the shape of the reflecting sheet 126 may be naturally changed depending on the shape of the frame 130.Namely, a naturally rounded second sheet area 126b of the reflecting sheet 126 may be formed.","Thus, a separate process for forming a chamfer of the reflecting sheet 126 may not be necessary, and workability may be improved.","The reflecting sheet 126 may include first to third sheet areas 126a to 126c.","Namely, an area of the reflecting sheet 126 may be divided depending on whether or not the reflecting sheet 126 and the frame 130 contact each other.","For example, the area of the reflecting sheet 126 may be divided into a contact area contacting the frame 130 and a non-contact area not contacting the frame 130.The area of the reflecting sheet 126 may be divided or delineated into the first sheet area 126a and the second sheet area 126b by the fixing pin 202.In other words, the second sheet area 126b may be an area between the fixing pin 202 and a portion contacting the third frame area 130c, Namely, the first sheet area 126a and the second sheet area 126b may be determined depending on whether or not the reflecting sheet 126 contacts the first frame area 130a of the frame 130.The second sheet area 126b may be naturally separated from the frame 130 by properties and elasticity of the reflecting sheet 126.For example, when the first sheet area 126a is coupled to the frame 130 by the fixing pin 202, the second sheet area 126b may naturally form a curved surface by its own weight and may be separated from the frame 130.A separation space 130d may be formed between the second sheet area 126b and the frame 130.An angle formed by the second sheet area 126b of the reflecting sheet 126 and the bottom surface of the frame 130 may gradually increase.","Namely, in the non-contact area of the reflecting sheet 126, the reflecting sheet 126 may have a two-dimensional curve shape.","Thus, the second sheet area 126b may be separated from the frame 130 at a predetermined angle.","The third sheet area 126c may be placed in the third frame area 130c.","The third sheet area 126c may be coupled to the third frame area 130c.","Alternatively, the third sheet area 126c may be naturally positioned on the third frame area 130c.","Namely, the third sheet area 126c may contact the third frame area 130c by elastic force of the Z-axis direction resulting from the rounded second sheet area 126b.","Light L may be emitted through the lens 124b.","Namely, light generated in the light source 203 may be emitted to the outside through the lens 124b.","The light L emitted through the lens 124b may travel through various paths.","For example, a portion of the light L may travel through a path of the side direction of the lens 124b.","The portion of the light L in the path of the side direction may travel toward the second sheet area 126b.","At least a portion of light generated in the light source 203 may be totally reflected inside the lens 124b and may travel toward the second sheet area 126b.","In this instance, an amount of light L upwardly travelling in the second sheet area 126b may be more than an amount of light L downwardly travelling in the second sheet area 126b.","In other words, an amount and/or a density of light L transferred to the reflecting sheet 126 may be non-uniform.","When the amount and/or the density of the light L is not uniform, a viewer watching the display device 100 may perceive non-uniformity of the amount and/or the density of the light L. For example, when an amount of light L incident on an upper portion of the second sheet area 126b is more than an amount of light L incident on a lower portion of the second sheet area 126b, a corresponding area may be recognized as being brighter than other areas because of the light L reflected from the upper portion of the second sheet area 126b.","As shown in FIG.","12, an angle formed by an extension line from a boundary between the first sheet area 126a and the second sheet area 126b to a boundary between the second sheet area 126b and the third sheet area 126c and two straight lines parallel to the X-axis direction may be called “A”.","An inclined angle of the second sheet area 126b using an intersection point P between the second sheet area 126b and a straight line of the angle A as a starting point may increase.","Namely, an angle of the second sheet area 126b passing the intersection point P in the X-axis direction may sharply increase.","Because the angle of the second sheet area 126b passing the intersection point P increases, a density of the light L emitted from the lens 124b (refer to FIG.","11) per unit area may further increase.","Thus, a corresponding portion may be seen as being brighter than other portions.","As a result, the viewer may feel that the light is not uniform.","The display device 100 according to the embodiment of the invention can make light be uniformly reflected from the reflecting sheet 126.Hence, the viewer cannot feel or can feel less the non-uniformity of the light.","As shown in FIG.","13, in the display device 100 according to the embodiment of the invention, dots DT may be formed in at least a portion of the reflecting sheet 126.The dot DT may be an area having a pattern different from other areas.","The dot DT may be an area of uneven portions (or concave-convex portions) formed on the reflecting sheet 126.The dot DT may be an area, in which at least a portion of the reflecting sheet 126 is colored.","For example, the dot DT may be an area of a relatively dark color.","For example, the dot DT may be a black or gray area.","The dot DT may be an area, in which the uneven portion and the colored portion are mixed with each other.","The dot DT may have a geometric shape, in which there is a difference in at least one of a shape, a size, a location, and a color.","For example, the dot DT may be one of various shapes including a circle, an oval, a rectangle, a rod, a triangle, etc., formed on the reflecting sheet 126 and/or a combination of the various shapes.","The dots DT may affect a reflectance of a corresponding area.","Namely, the dots DT may change a reflectance of light.","For example, the reflectance of light may be reduced depending on at least one of a shape, a size, a location, and a color of the dot DT.","The plurality of dots DT may gather (or arranged) and form a dot area DA.","The dot area DA may be a gathering (or arranging) of the dots DT.","Namely, the dot area DA may be a formation area of the plurality of dots DT, which are the same as or different from one another in at least one of a shape, a size, a location, and a color.","For example, the dot area DA may be formed in at least a portion of the second sheet area 126b.","As described above, a density of light per unit area in the second sheet area 126b may be high because of the inclined shape of the second sheet area 126b.","The dot area DA may change a reflectance of light incident on the second sheet area 126b.","In other words, a density of incident light per unit area is high, but a density of reflected light per unit area may decrease.","Thus, a phenomenon, in which a contrast of a portion corresponding to the second sheet area 126b is different from a contrast of other portions, may be prevented.","Namely, light can be uniformly reflected from the entire reflecting sheet 126 because of the dot area DA.","The dots DT constituting the dot area DA may be divided into a plurality of groups having different attributes.","For example, a formation area of dots having a first attribute may be called a first area, and a formation area of dots having a second attribute may be called a second area.","Hereinafter, the dot area DA may be displayed by changing the color, the density, etc., of the reflecting sheet 126, and areas having the different colors, densities, etc., may be formation areas of dots having different attributes even if a separate explanation is not given.","For example, dots having different attributes may be disposed in an area with a first color and an area with a second color.","Namely, dots, which are different from one another in at least one of the size, the density, the color, and the interval, may be disposed in different areas.","The reflecting sheet 126 may further include anon-dot area NDA.","The non-dot area NDA may be an area, in which there is no dot DT.","The non-dot area NDA may be positioned in various areas of the reflecting sheet 126.For example, the non-dot area NDA may include first and second non-dot areas NDA1 and NDA2.A width of the non-dot area NDA may be greater than a distance between adjacent dots.","Namely, the width of the non-dot area NDA in a direction from the first sheet area 126a to the third sheet area 126c may be greater than a distance between two dots adjacent to the non-dot area NDA.","The width of the non-dot area NDA may be equal to or greater than 2 mm.","The second non-dot area NDA2 may be positioned at a boundary between the second sheet area 126b and the third sheet area 126c.","The second non-dot area NDA2 may be positioned in the second sheet area 126b at the boundary between the second sheet area 126b and the third sheet area 126c.","The second non-dot area NDA2 may be an uppermost area of the second sheet area 126b and thus may be close to the optical sheet 125 and/or the diffusion plate 129 positioned in front of the reflecting sheet 126.Hence, if the dot DT exists in the second non-dot area NDA2, the user of the display device 100 may observe the dot DT.","Thus, the dot DT may not exist in the second non-dot area NDA2.FIGS.","14 to 23 illustrate a dot distribution of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","14 to 23, the dots DT of the reflecting sheet 126 according to the embodiment of the invention may be disposed in various shapes.","As shown in (a) of FIG.","14, the dots DT may be disposed in the dot area DA.","The adjacent dots DT may be separated from each other by a first distance O1.Namely, the dots DT may be disposed at regular intervals of the first distance O1.The distance between the dots DT may affect the reflectance of the reflecting sheet 126.For example, when the distance between the dots DT decreases, the reflectance may decrease.","As shown in (b) of FIG.","14, the adjacent dots DT may be separated from each other by the first distance O1, and the adjacent dots DT may be separated from each other by a second distance O2.Namely, a distance between the dots DT may not be uniform As shown in (a) of FIG.","15, the dot area DA may be divided into a plurality of areas.","For example, the dot area DA may be divided into a first area P1 and a second area P2.An attribute of dots DT included in the first area P1 may be different from an attribute of dots DT included in the second area P2.For example, at least one of a size, a density, and a color of a first dot DT1 in the first area P1 may be different from at least one of a size, a density, and a color of a second dot DT2 in the second area P2.The second area P2 may be positioned further outside than the first area P1.Namely, the second area P2 may be an area close to the third sheet area 126c.","The second dot DT2 of the second area P2 may be larger than the first dot DT1 of the first area P1.Thus, a reflectance of the second area P2 may be less than a reflectance of the first area P1.As shown in (b) of FIG.","15, the dot area DA may be divided into a plurality of areas.","For example, the dot area DA may be divided into first to third areas P1 to P3.First to third dots DP1 to DP3 of the first to third areas P1 to P3 may have different attributes.","For example, the second dot DT2 may be larger than the first dot DT1, and the third dot DT3 may be larger than the second dot DT2.Alternatively, the first to third dots DP1 to DP3 have the same size, but a density of the first area P1 may be different from a density of the second area P2, and a density of the second area P2 may be different from a density of the third area P3.For example, the density of the first area P1 may be less than the density of the second area P2, and the density of the second area P2 may be less than the density of the third area P3.As shown in FIG.","16, the dot area DA may not be divided into a plurality of areas.","However, dots DT included in the dot area DA may be different from each other in at least one of a size, a density, and a color.","For example, as the dot DT goes along the X-axis direction, the size of the dot DT may gradually increase.","Namely, an attribute of the dot DT including at least one of the size, the density, and the color may gradually change.","As shown in (a) of FIG.","17, a size of the dot DT may gradually change depending on a location.","As shown in (b) of FIG.","17, a size of the dot DT may sharply change depending on a location.","For example, the size of the dot DT may be changed in a curve shape of a quadratic function.","As shown in FIG.","18, dots DT may be disposed in a horizontal dot area HDA and a vertical dot area VDA in various shapes.","The horizontal dot area HDA may be a dot area DA formed on the long side of the reflecting sheet 126, and a vertical dot area VDA may be a dot area DA formed on the short side of the reflecting sheet 126.Detailed locations of the horizontal dot area HDA and the vertical dot area VDA will be described in corresponding paragraphs.","As shown in (a) of FIG.","18, the horizontal dot area HDA and/or the vertical dot area VDA may be divided into a plurality of areas.","For example, the horizontal dot area HDA and/or the vertical dot area VDA may be divided into an uppermost area A, a leftmost area B, a rightmost area D, a lowermost area E, and/or a an inner area C. The horizontal dot area HDA and/or the vertical dot area VDA may be divided in different manners.","Dots in the plurality of areas of the horizontal dot area HDA and/or the vertical dot area VDA may have different attributes.","For example, a size and/or a density of a dot DT in the uppermost area A may be greater than a size and/or a density of a dot DT in the lowermost area E. A size and/or a density of a dot DT in the inner area C may be greater than a size and/or a density of dots DT in the leftmost area B and the rightmost area D. As shown in (b) of FIG.","18, the horizontal dot area HDA and/or the vertical dot area VDA may not be divided into a plurality of areas.","Namely, the dots DT, of which the attributes gradually change, may be disposed.","For example, a size and/or a density of the dot DT may increase as the dot DT goes to the upper side of the horizontal dot area HDA and/or the vertical dot area VDA.","The size and/or the density of the dot DT may decrease as the dot DT goes to the inner side of the horizontal dot area HDA and/or the vertical dot area VDA.","As shown in (c) of FIG.","18, attributes of dots DT in an inner area and an outer area of the horizontal dot area HDA and/or the vertical dot area VDA may change.","For example, a dot DT having a relatively small size may be disposed at a boundary between the left and right sides and/or the lower side of the horizontal dot area HDA and/or the vertical dot area VDA.","A dot DT having a relatively large size may be disposed at a boundary between the inner side and/or the upper side of the horizontal dot area HDA and/or the vertical dot area VDA.","The attribute of the dot DT including the size may change gradually or non-gradually.","For example, in an area ranging from the outer area to the inner area of the horizontal dot area HDA and/or the vertical dot area VDA, the size of the dot DT may gradually change or may change depending on a location.","For example, the size of the dot DT in a first area including the left and right sides of the horizontal dot area HDA and/or the vertical dot area VDA may be different from the size of the dot DT in a second area including the inner side of the horizontal dot area HDA and/or the vertical dot area VDA.","In other words, there may be a difference in at least one of the size, the color, the interval, and the density of the dots DT disposed in a horizontal direction and/or a vertical direction of the horizontal dot area HDA and/or the vertical dot area VDA.","For example, in the instance of the horizontal dot area HDA, sizes of two dots DT positioned adjacent to each other in the horizontal direction of the horizontal dot area HDA may be different from each other.","The arrangement of the dots DT may be related to the lens hole positioned along the horizontal direction of the horizontal dot area HDA.","Namely, a portion, in which the lens hole is positioned, may be brighter, and other areas may be darker.","The dots DT having different attributes may be arranged along the horizontal direction of the horizontal dot area HDA, so as to prevent a luminance difference, in which a brighter portion and a darker portion are present.","As shown in FIG.","19, dots constituting the horizontal dot area HDA and the vertical dot area VDA may have different attributes.","For example, a size range of the dots constituting the horizontal dot area HDA may be greater than a size range of the dots constituting the vertical dot area VDA.","Namely, the horizontal dot area HDA may include relatively smaller dots and relatively larger dots than the vertical dot area VDA.","In other words, a diversity of the dots constituting the horizontal dot area HDA may be more than a diversity of the dots constituting the vertical dot area VDA.","For example, the smallest dot in the horizontal dot area HDA may be smaller than the smallest dot in the vertical dot area VDA, and the largest dot in the horizontal dot area HDA may be larger than the largest dot in the vertical dot area VDA.","For example, the smallest dot of the horizontal dot area HDA may have the size equal to or less than 0.5 mm, and the largest dot of the horizontal dot area HDA may have the size equal to or greater than 2 mm.","On the other hand, the smallest dot of the vertical dot area VDA may have the size equal to or less than 0.8 mm, and the largest dot of the vertical dot area VDA may have the size equal to or greater than 1.2 mm.","For example, when the sizes of the dots included in the horizontal dot area HDA are divided into “A” groups and the sizes of the dots included in the vertical dot area VDA are divided into “B” groups, A is greater than B.","In other words, a size diversity of the dots included in the horizontal dot area HDA may be more than a size diversity of the dots included in the vertical dot area VDA.","An amount range of the dots constituting the horizontal dot area HDA may be greater than an amount range of the dots constituting the vertical dot area VDA.","For example, when the dots having the same size are used, a number of dots included in the horizontal dot area HDA may be more or less than a number of dots included in the vertical dot area VDA.","As shown in FIG.","20, the dot area DA may exist on the reflecting sheet 126.For example, the dots may be distributed along the short sides of the display device 100.For example, the dots may be distributed in the second area 126b (refer to FIG.","13) of the reflecting sheet 126.As described above, the dot area DA may include a horizontal dot area HDA and a vertical dot area VDA.","A description of one of the horizontal dot area HDA and the vertical dot area VDA is equally applied to the other, except in the instance where the horizontal dot area HDA and the vertical dot area VDA are separately described.","The arrangement of the dots DT in the dot area DA may be related to the arrangement of the lens holes 235.As described above, the lens hole 235 may correspond to the light source 203 (refer to FIG.","10) and the lens 124b (refer to FIG.","10).","The plurality of lens holes 235 may be disposed on the reflecting sheet 126 in accordance with a predetermined rule.","Some of the plurality of lens holes 235 may be disposed adjacent to the dot area DA.","For example, the lens holes 235 may be separated from the dot area DA by a predetermined distance and may be disposed in parallel with each other.","A first area AR1 and a second area AR2 may be formed based on the lens holes 235.For example, the first area AR1 may be an area including the lens hole 235, and the second area AR2 may be an area between the lens holes 235.The dots DT disposed in the first area AR1 and the second area AR2 may have different attributes.","For example, at least one of a size, a density, and a color of the dot DT in the first area AR1 may be different from at least one of a size, a density, and a color of the dot the second area AR2.The difference is because intensities of light beams reaching the first area AR1 and the second area AR2 may be different from each other depending on a distance between the lens hole 235 and the first area AR1 and the second area AR2.As shown in FIG.","21A, attributes of the dots DT constituting the horizontal dot area HDA and/or the vertical dot area VDA may change depending on the area.","The horizontal dot area HDA may include first to third horizontal dot areas HDA1 to HDA3.Namely, the dot area DA may be divided into a plurality of areas.","The first horizontal dot area HDA1 may be an area including both sides of the horizontal dot area HDA and may be a boundary area in an inside direction of the reflecting sheet 126.The second horizontal dot area HDA2 may be an area inside the first horizontal dot area HDA1, and the third horizontal dot area HDA3 may be an area inside the second horizontal dot area HDA2.The dots DT in the first to third horizontal dot areas HDA1 to HDA3 may have different attributes.","Namely, there may be a difference between the dots DT of the first to third horizontal dot areas HDA1 to HDA3 in at least one of a size, a density, and a color of the dot DT.","For example, the dots DT included in the first horizontal dot area HDA1 may be the same as one another in at least one of the size, the distance, the density, and the color.","However, the dot DT of the first horizontal dot area HDA1 may be different from the dot DT of the second horizontal dot area HDA2 in at least one of the size, the distance, the density, and the color.","Considering the above description, each of the first to third horizontal dot areas HDA1 to HDA3 may be regarded as the gathering (or arranging) of the dots DT having the same attribute.","The vertical dot area VDA may include first to third vertical dot areas VDA1 to VDA3.The dots DT constituting the first to third vertical dot areas VDA1 to VDA3 may have different attributes.","The above description of the first to third horizontal dot areas HDA1 to HDA3 of the horizontal dot area HDA may be equally applied to the first to third vertical dot areas VDA1 to VDA3 of the vertical dot area VDA.","The horizontal dot area HDA and the vertical dot area VDA may be adjacent to four corner areas of the reflecting sheet 126.For example, the horizontal dot area HDA may be disposed on one side of a cutting portion S1, and the vertical dot area VDA may be disposed on the other side of the cutting portion S1.The first horizontal dot area HDA1 and the first vertical dot area VDA1 may be positioned in an area including the corner area close to the horizontal dot area HDA and the vertical dot area VDA Because the corner area is relatively far away from the lens hole 235, the corner area may be relatively dark.","Thus, the dot DT may not be disposed in the middle of the corner area.","The dots DT having a relatively high reflectance may be disposed in the first horizontal dot area HDA1 and the first vertical dot area VDA1 close to the corner area.","For example, the relatively small dots DT may be disposed.","For example, the dots DT having the relatively low density may be disposed.","As shown in FIG.","21B, the plurality of lens holes 235 may be divided into a first lens hole group 235a and a second lens hole group 235b depending on a distance between the lens holes 235 and the dot area DA.","For example, the first lens hole group 235a may include the lens holes 235 adjacent to the dot area DA, and the second lens hole group 235b may include the lens holes 235 in the rear of the first lens hole group 235a.","A portion of light emitted from the second lens hole group 235b may be shielded by the first lens hole group 235a.","For example, a shielding area LH may be formed.","The brightness of a corresponding area may be less than the brightness of other area because of the shielding area LH.","Thus, the dots DT of the shielding area LH and the dots DT of other area may be differently configured.","For example, a size of the dot DT in at least a portion of the shielding area LH may be different from that in the other area.","As shown in FIG.","22, a shape of the dot area DA may be changed depending on a location of the lens hole 235.For example, the dot area DA may include a first area AR1 including the lens hole 235 and a second area AR2 except the first area AR1 from the dot area DA.","The first area AR1 may protrude to the lens hole 235 further than the second area AR2.For example, a protrusion area PD may be added to the dot area DA.","A luminance of an area close to the lens hole 235 may be reduced by the protrusion area PD.","The dots DT constituting the protrusion area PD may be different from the dots DT of other area.","As shown in FIG.","23A, the shape of the dot area DA may be changed depending on a relative location between the dot area DA and the lens hole 235.For example, as described above, the first area AR1 corresponding to the lens hole 235 may include the protrusion area PD protruding to the lens hole 235.A first dot DT1 constituting the protrusion area PD may be different from a second dot DT2 in the rear of the first dot DT1.A shape of the horizontal dot area HDA may be different from a shape of the vertical dot area VDA.","For example, the protrusion area PD may be included only in one of the horizontal dot area HDA and the vertical dot area VDA.","This may be related to the fact that a number of lens holes 235 in the horizontal dot area HDA is more than a number of lens holes 235 in the vertical dot area VDA.","As shown in FIG.","23B, each of the horizontal dot area HDA and the vertical dot area VDA disposed on the reflecting sheet 126 may have a specific shape.","For example, a height and/or a width of the horizontal dot area HDA and/or the vertical dot area VDA may be differently set depending on a location.","The horizontal dot area HDA may be divided.","For example, the horizontal dot area HDA may be divided into first to third horizontal areas HA1 to HA3.The second horizontal area HA2 may be a center area of the horizontal dot area HDA.","The first and third horizontal areas HA1 and HA3 may correspond to both sides of the second horizontal area HA2.The first and third horizontal areas HA1 and HA3 may have a shape different from the second horizontal area HA2.For example, the first and third horizontal areas HA1 and HA3 may have a shape protruding to the inside of the reflecting sheet 126 further than the second horizontal area HA2.For example, the second horizontal area HA2 may have a fourth height H4.The fourth height H4 may be less than at least one of first to third heights H1 to H3.The shape difference may be because the first and third horizontal areas HA1 and HA3 are closer to the corner of the reflecting sheet 126 than the second horizontal area HA2.Namely, because the reflecting sheet 126 has the rounded shape in the horizontal and vertical directions at the corner of the reflecting sheet 126, the luminance needs to be more precisely controlled.","In the first and third horizontal areas HA1 and HA3, the horizontal dot area HDA may have the shape protruding in a predetermined pattern along the inside direction of the reflecting sheet 126.For example, the horizontal dot area HDA may have the shape protruding by the first height H1 and the second height H2 and then protruding by the third height H3.The first and third heights H1 and H3 may be greater than the second height H2.The first and third heights H1 and H3 may be different from each other.","For example, the first heights H1 may be greater than the third height H3.The horizontal dot area HDA of the first height H1 and the horizontal dot area HDA of the third height H3 may be formed between the lens holes 235.For example, the horizontal dot area HDA of the first and third heights H1 and H3 may be formed in first and second areas A1 and A2 between the lens holes 235.Because light beams emitted from the plurality of lens holes 235 overlap each other through the above-described shape of the horizontal dot area HDA, the brightness of the first and second areas A1 and A2 may be efficiently controlled.","FIG.","23B shows that the horizontal dot area HDA has the first to fourth heights H1 to H4, as an example.","The vertical dot area VDA having the height/the width different from the horizontal dot area HDA may be configured, so as to achieve the same or similar configuration and effect.","FIGS.","24 and 25 illustrate the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","24 and 25, the reflecting sheet 126 according to the embodiment of the invention may include the dot area DA.","The dot area DA may be formed along the long side and/or the short side of the reflecting sheet 126.Namely, the dot area DA may be formed in the corner area of the reflecting sheet 126.In other words, the dot area DA may be formed in the second sheet area 126b(refer to FIG.","11) of the reflecting sheet 126 placed in the receiving unit 132 (refer to FIG.","10) of the frame 130 (refer to FIG.","10).","The dot area DA may include first and second horizontal dot areas HDA1 and HDA2 and first and second vertical dot areas VDA1 and VDA2.The first and second horizontal dot areas HDA1 and HDA2 are represented as the horizontal dot area HDA, and the first and second vertical dot areas VDA1 and VDA2 are represented as the vertical dot area VDA, except in the instance where they need to be distinguished from each other.","A shape of the horizontal dot area HDA may be different from a shape of the vertical dot area VDA.","For example, the shape of the horizontal dot area HDA may not be symmetric to the shape of the vertical dot area VDA based on a cutting portion S1 positioned at the corner of the reflecting sheet 126.The reflecting sheet 126 may include lens holes 235 for coupling the lenses 124b (refer to FIG.","11), fixing pin holes 206, supporter holes 205, a horizontal coupling unit HH, and a vertical coupling unit VH.","The lens holes 235 may be disposed in parallel with one another along the horizontal and vertical directions based on the size of the display device 100.The fixing pin hole 206 may be coupled to the fixing pin 202 (refer to FIG.","10) for fixing the reflecting sheet 126 to the frame 130 (refer to FIG.","10).","The fixing pin hole 206 may be positioned adjacent to the outermost lens hole 235.For example, the fixing pin hole 206 may be positioned between the adjacent lens holes 235 or between the lens hole 235 and the dot area DA.","The fixing pin hole 206 may be positioned adjacent to the lens hole 235 disposed on the outermost side.","For example, the fixing pin hole 206 may be positioned closer to the outermost side than the outermost lens hole 235.For example, the fixing pin hole 206 may be positioned at a location overlapping the outermost lens hole 235.When the fixing pin 202 (refer to FIG.","10) is coupled to the frame 130 (refer to FIG.","10) through the fixing pin hole 206, the second sheet area 126b may be naturally formed.","Namely, when the fixing pin 202 (refer to FIG.","10) is coupled to the frame 130 (refer to FIG.","10) through the fixing pin hole 206 formed in the horizontal and vertical directions, a round chamfer may be formed in the outer area of the reflecting sheet 126.A distance between the fixing pin holes 206 may be differently set.","For example, a number of fixing pin holes 206 positioned in a horizontal center area HCA may be more than a number of fixing pin holes 206 positioned in other areas based on the horizontal direction of the reflecting sheet 126.A distance between the fixing pin holes 206 positioned in the horizontal center area HCA may be called a first horizontal distance HD1, and a distance between the fixing pin holes 206 positioned in areas other than the horizontal center area HCA may be called a second horizontal distance HD2.The first horizontal distance HD1 may be less than the second horizontal distance HD2.Namely, the fixing pin holes 206 in the horizontal center area HCA may be more densely disposed.","Thus, a round chamfer may be naturally formed at the four upper, lower, left, and right corners of the reflecting sheet 126 while the reflecting sheet 126 is efficiently fixed.","The fixing pin holes 206 disposed in the vertical direction may exist.","For example, the fixing pin holes 206 may be disposed along the left and right short sides of the reflecting sheet 126.The fixing pin holes 206 on the first short side SS1 may be disposed at predetermined intervals of a first vertical distance VD1.The fixing pin holes 206 on the second short side SS2 may be disposed at predetermined intervals of a second vertical distance VD2.The first vertical distance VD1 and the second vertical distance VD2 may be different from each other.","The second vertical distance VD2 may be greater than the first vertical distance VD1.A difference between the first vertical distance VD1 and the second vertical distance VD2 may be generated by a shape of the frame 130 coupled to the reflecting sheet 126.For example, the difference between the first vertical distance VD1 and the second vertical distance VD2 may be generated by a coupling space of a rib for assisting rigidity of the frame 130 and/or various electronic parts coupled to the frame 130.The supporter holes 205 may be coupled to the supporters 200.The supporter holes 205 may support the diffusion plate 129 (refer to FIG.","5) and/or the optical sheet 125 (refer to FIG.","5) on the reflecting sheet 126.The supporter holes 205 may be positioned in the middle of the reflecting sheet 126 for the efficient support.","Namely, the supporter hole 205 may be positioned further inside than the outermost lens hole 235.The horizontal coupling unit HH and the vertical coupling unit VH may be disposed along the corner area of the reflecting sheet 126.The horizontal coupling unit HH and the vertical coupling unit VH may be inserted into the protrusions of the frame 130 (refer to FIG.","10).","FIG.","25 shows one edge area of the reflecting sheet 126.Outermost lens holes 235a to 235c may mean the lens hole 235 positioned on the outermost side.","Among the outermost lens holes 235a to 235c, the first and second outermost lens holes 235a and 235b positioned on the upper side may be separated from the lower side of the horizontal dot area HDA by a first distance HDS and may be separated from the upper side of the horizontal dot area HDA by a second distance HDE.","Among the outermost lens holes 235a to 235c, the first and third lens holes 235a and 235c positioned on the side may be separated from the lower side of the vertical dot area VDA by a third distance VDS and may be separated from the upper side of the vertical dot area VDA by a fourth distance VDE.","The first distance HDS may be different from the third distance VDS, and the second distance HDE may be different from the fourth distance VDE.","This means that a width, a length, etc., of the horizontal dot area HDA may be different from a width, a length, etc., of the vertical dot area VDA.","The first distance HDS may be greater than the third distance VDS.","Namely, a distance between the horizontal dot area HDA and the lens hole 235 is greater than a distance between the vertical dot area VDA and the lens hole 235.The second sheet area 126b (refer to FIG.","11) corresponding to the horizontal dot area HDA may be shorter than the second sheet area 126b (refer to FIG.","11) corresponding to the vertical dot area VDA.","Because lengths of the long side and the short side of the second sheet area 126b are different from each other, a slope of the round chamfer of the vertical dot area VDA on the short side may be greater than a slope of the round chamfer of the horizontal dot area HDA on the long side.","An increase in the slope may increase a reflectance.","When the reflectance increases, a corresponding portion may look brighter.","In the reflecting sheet 126 according to the embodiment of the invention, because the vertical dot area VDA is positioned closer to the lens hole 235 than the horizontal dot area HDA, the reflectance may be controlled in spite of the high slope of the vertical dot area VDA on the short side of the reflecting sheet 126.The non-dot area NDA may be positioned between the horizontal/vertical dot area HDA or VDA and a horizontal/vertical margin area HM or VM.","Namely, the non-dot area NDA not including the dot DT may be positioned on the horizontal/vertical dot area HDA or VDA, so that the user watching the display device 100 cannot recognize the dots DT.","The non-dot area NDA is formed considering that the dots DT may be recognized from the outside when the dots DT exist in a corresponding area.","The horizontal and vertical margin areas HM and VM may correspond to the third sheet area 126c.","Namely, the horizontal and vertical margin areas HM and VM may be an outermost area of the reflecting sheet 126.In other words, the horizontal and vertical margin areas HM and VM may be an area of the reflecting sheet 126 contacting the third frame area 130c of the frame 130 (refer to FIG.","11).","The dots DT may not exist in the horizontal/vertical margin area HM or VM.","A gap CR may exist between the horizontal margin area HM and the vertical margin area VM.","The reflecting sheet 126 may be a plane.","Namely, the reflecting sheet 126 may be a two-dimensional plane.","When the reflecting sheet 126 of the two-dimensional shape is coupled to the receiving unit 132 (refer to FIG.","10) of the three-dimensional shape, the reflecting sheet 126 may be changed into the three-dimensional shape.","The shape of the reflecting sheet 126 may be changed by overlapping at least a portion of the reflecting sheet 126 along the cutting portion S1.A shadow may be generated by the overlap of the reflecting sheet 126.The gap CR may prevent the overlap of the reflecting sheet 126 and thus suppress the generation of the shadow.","A folded portion S2 may extend from an end of the cutting portion S1.The folded portion S2 may not be cut, unlike the cutting portion S1.The folded portion S2 may be formed by previously folding a corresponding area along the cutting portion S1.Thus, when the reflecting sheet 126 is changed into the three-dimensional shape in the receiving unit 132 (refer to FIG.","10), the reflecting sheet 126 may be guided by the folded portion S2 and may be changed into a previously designed shape.","FIGS.","26 to 28 illustrate configuration of the cutting portion of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","26 to 28, the reflecting sheet 126 according to the embodiment of the invention may be naturally changed into the three-dimensional shape by the cutting portion S1.As shown in (a) of FIG.","26, the reflecting sheet 126 may have originally the two-dimensional shape.","Namely, the reflecting sheet 126 may be configured as a thin sheet.","The thin sheet may be processed into the shape of the reflecting sheet 126.A cutting surface CA may be formed on the reflecting sheet 126.The cutting surface CA may be a triangular surface.","For example, the triangular cutting surface CA may exist at each corner of the reflecting sheet 126.Namely, the cutting surface CA may be positioned between the long side LS and the short side SS of the reflecting sheet 126.The folded portion S2 may be provided in an end portion of the cutting surface CA.","The reflecting sheet 126 having the cutting surface CA may be folded in a direction, in which both sides of the triangular cutting surface CA approach each other.","The reflecting sheet 126 may be naturally folded by the folded portion S2.As shown in (b) of FIG.","26, the cutting portion S1 may be formed as both sides of the triangular cutting surface CA approach each other.","The folded portion S2 may be formed at an end of the cutting portion S1.The reflecting sheet 126 may be naturally changed into the three-dimensional shape by the cutting portion S1 and the folded portion S2.The cutting portion S1 may be formed at a vertex of the reflecting sheet 126 in a diagonal direction.","As shown in FIG.","27A, the cutting surface CA may be positioned on the long side LS of the reflecting sheet 126.This is different from the above description, in which the cutting surface CA is positioned between the long side LS and the short side SS of the reflecting sheet 126.The horizontal dot area HDA positioned on the long side LS may be regarded as being divided into a first horizontal dot area HDA1 and a second horizontal dot area HDA2 because of the cutting surface CA on the long side LS.","When the reflecting sheet 126 is placed on the frame 130 (refer to FIG.","10), both sides of the triangular cutting surface CA may naturally approach each other.","When both sides of the triangular cutting surface CA approach each other, the reflecting sheet 126 may be naturally changed into the three-dimensional shape.","Thus, a separate process for forming the chamfer may not be necessary.","In other words, workability may be improved.","The gap CR may be formed so that a first horizontal margin area HM1 and a second horizontal margin area HM2 do not overlap each other.","Namely, when both sides of the triangular cutting surface CA approach each other, the first and second horizontal margin areas HM1 and HM2 may not overlap each other by the gap CR even if a portion of the reflecting sheet 126 overlaps.","Thus, even when the guide panel GP (refer to FIG.","10) is coupled on the horizontal margin area HM, a floating problem resulting from the overlap of the horizontal margin area HM can be prevented.","When both sides of the triangular cutting surface CA approach each other, the first and second horizontal margin areas HM1 and HM2 may be close to each other within the range where they do not overlap each other.","Thus, the gap CR may be observed as being very small in the reflecting sheet 126 placed on the frame 130 (refer to FIG.","10).","As shown in (a) of FIG.","27B, a first gap CR1 may exist in the reflecting sheet 126 of the two-dimensional shape.","The reflecting sheet 126 of the two-dimensional shape may indicate the reflecting sheet 126 before being coupled to the frame 130 (refer to FIG.","10).","In this instance, the second horizontal margin area HM2 may not be parallel.","Namely, a slope area IA may be formed in at least a portion of the second horizontal margin area HM2.The slope area IA may be inclined downwardly by an inclined distance IM.","As shown in (b) of FIG.","27B, when the reflecting sheet 126 is placed on the frame 130 (refer to FIG.","10), a portion of the reflecting sheet 126 may overlap.","For example, a portion of the first horizontal margin area HM1 may be overlappingly positioned under the second horizontal margin area HM2 based on the cutting portion S1.When the reflecting sheet 126 is changed into the three-dimensional shape by overlapping a portion of the reflecting sheet 126, the slope area IA may rotate counterclockwise by the inclined distance IM.","Hence, the first and second horizontal margin areas HM1 and HM2 may be positioned on the same line T. A second gap CR2 of the reflecting sheet 126 changed into the three-dimensional shape may be smaller than the first gap CR1 of the reflecting sheet 126 of the two-dimensional shape.","The second gap CR2 may be very small and may be similar to a width of the cutting portion S1.Even if portions of the reflecting sheet 126 overlap each other based on the cutting portion S1, the first and second horizontal margin areas HM1 and HM2 may not overlap each other.","The cutting portion S1 may have the shape extending downwardly from the long side LS due to a location of the cutting surface CA.","The shape of the cutting portion S1 may be advantageous in causing light to reach the end of the reflecting sheet 126.When the cutting surface CA is changed into the shape of the cutting portion S1, the first and second horizontal margin areas HM1 and HM2 may form one horizontal dot area HDA.","FIG.","27C shows the reflecting sheet 126 placed in the third frame area 130c of the frame 130 (refer to FIG.","10) when viewed from the side.","Even if an overlap area OA is generated in a portion of the reflecting sheet 126, the first and second horizontal margin areas HM1 and HM2 may not overlap each other.","Thus, even if the guide panel GP is coupled on the first and second horizontal margin areas HM1 and HM2, it may be prevented from an arm portion from being formed due to the overlap of the first and second horizontal margin areas HM1 and HM2.As shown in (a) of FIG.","28, the cutting portion S1 may start from the short side SS.","The gap CR may exist at a starting position of the cutting portion S1.As shown in (b) of FIG.","28, even when the cutting portion S1 exists on the short side SS and/or the long side LS, the folded portion S2 may be formed.","The folded portion S2 may be formed in the diagonal direction, unlike the cutting portion S1.Thus, the folded portion S2 may guide the folding of the reflecting sheet 126.FIGS.","29 and 30 illustrate a dot area according to the embodiment of the invention.","As shown in FIGS.","29 and 30, the dot area DA according to the embodiment of the invention may have various shapes so as to optimally reflect light.","As shown in (a) of FIG.","29, the horizontal dot area HDA and the vertical dot area VDA may have different shapes.","For example, the horizontal dot area HDA may be separated from the cutting portion S1 and/or the folded portion S2 by a first angle DA1, and the vertical dot area VDA may be separated from the cutting portion S1 and/or the folded portion S2 by a second angle DA2.The first angle DA1 may be different from the second angle DA2.For example, the first angle DA1 may be greater than the second angle DA2.A difference between the location and/or the shape of the horizontal dot area HDA and the location and/or the shape of the vertical dot area VDA may be related to an amount of incident light.","For example, the lens coupled to the second lens hole 235b may shield light emitted from other lens.","Namely, a shade area GA may be formed by the lens coupled to the second lens hole 235b.","Thus, the horizontal dot area HDA may be separated from the cutting portion S1 and/or the folded portion S2 by the first angle DA1, so that the horizontal dot area HDA does not overlap the shade area GA. Also, the location and/or the width of the vertical dot area VDA may be determined in consideration of the shade between the lens holes 235.The cutting portion S1 and/or the folded portion S2 may be a direction toward a center point CH of the first lens hole 235a.","Namely, the cutting portion S1 and/or the folded portion S2 may be positioned on an imaginary extension line HDR connecting the center point CH to the cutting portion S1 and/or the folded portion S2 and may be positioned on the line parallel to and/or the same line as the cutting portion S1 and/or the folded portion S2.Thus, light emitted from the lens 124b (refer to FIG.","11) coupled to the first lens hole 235a may be efficiently transferred up to end of the corner area of the reflecting sheet 126.As shown in (b) of FIG.","29, the first and second angles DA1 and DA2 between the cutting portion S1 and/or the folded portion S2 and the horizontal dot area HDA and the vertical dot area VDA may be the same as each other.","For example, when the shade is not generated or slightly generated by the size of the display device 100 and/or the location of the lens hole 235, the first and second angles DA1 and DA2 may be substantially equally configured.","As shown in FIG.","30, the first and second angles DA1 and DA2 may be asymmetric.","The shape of the horizontal dot area HDA at the first angle DA1 may be different from the shape of the vertical dot area VDA at the second angle DA2.As described above, the shape of the horizontal dot area HDA and/or the vertical dot area VDA may be determined depending on the generation of the shade based on the disposition of the lens hole 235 and the lens 124b (refer to FIG.","11) coupled to the lens hole 235.The horizontal dot area HDA and/or the vertical dot area VDA may have a bending shape.","For example, a distance between the horizontal dot area HDA and the cutting portion S1 and a distance between the vertical dot area VDA and the cutting portion S1 may be changed.","FIGS.","31 to 38 illustrate configuration related to the lens hole of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","31 to 38, the reflecting sheet 126 according to the embodiment of the invention may include the lens hole 235 of various shapes and/or various dispositions capable of controlling a reflection amount of light.","As shown in FIG.","31, at least one of the lens holes 235 may include a first lens hole 235a.","The first lens hole 235a may not have a circular shape (or a perfectly circular shape).","The first lens hole 235a may have a shape, in which a radius is changed.","The first lens hole 235a may have a shape, in which a radius is successively changed.","For example, the first lens hole 235a of an oval shape may be used.","The first lens hole 235a may have a shape, in which a radius is non-successively changed.","For example, the first lens hole 235a may have a combination shape of a circle of a first radius R1 and a circle of a second radius R2.The second radius R2 may be an area corresponding to an angle AA.","The angle AA may be less than 180 degrees.","Namely, the area corresponding to the angle AA may have a fan shape of the second radius R2.In other words, a width of the area corresponding to the angle AA may be less than widths of other areas.","As described above, the second radius R2 may be greater than the first radius R1.Thus, a portion of light emitted through the first lens hole 235a may be emitted from the area corresponding to the angle AA to the rear of the reflecting sheet 126.A total amount of light reflected onto the front of the reflecting sheet 126 by the reflecting sheet 126 may decrease by an amount of light emitted to the rear of the reflecting sheet 126.An area corresponding to the second radius R2 of the first lens hole 235a may face a chamber area CSA.","Namely, the area corresponding to the second radius R2 of the first lens hole 235a may face an outer peripheral of the reflecting sheet 126.In other words, the area corresponding to the second radius R2 of the first lens hole 235a may face the second sheet area 126b (refer to FIG.","13).","As described above, because a portion of light is emitted to the rear of the reflecting sheet 126 by the second radius R2, an influence of the first lens hole 235a on the chamber area CSA may be less than an influence of the general lens hole 235.Thus, the chamber area CSA may be prevented from being brighter than other area.","As shown in FIG.","32, the lens hole 235 may include a first lens hole 235a, of which a radius is changed, and a circular second lens hole 235b.","The first lens hole 235a may be positioned on the upper, left, right, and lower sides of the disposed lens holes 235.As described above, the disposition of the first lens hole 235a may prevent the upper, left, right, and lower sides of the lens hole 235 from being brighter than other area.","As shown in FIG.","33, the dot area DA may be formed in various shapes.","Namely, the dot area DA of the various shapes may be configured so that the reflecting sheet 126 uniformly reflects light.","For example, the dot area DA may be formed around the lens hole 235.For example, the dot area DA may be formed in at least a partial area around the lens hole 235.For example, the dot area DA may have the shape surrounding the lens hole 235.Namely, a first circular dot area CDT1 may be formed.","The first ring-shaped dot area CDT1 may have the shape surrounding the lens hole 235.For example, the first ring-shaped dot area CDT1 may have the shape, in which the dots DT of the same size and/or the same shape surround the lens hole 235.For example, the first ring-shaped dot area CDT1 may have the shape, in which the dots DT, of which at least a partial size and/or shape is different, surround the lens hole 235.A reflectance of a corresponding area may be changed by the first ring-shaped dot area CDT1.For example, a reflectance of a formation area of the first ring-shaped dot area CDT1 may be reduced.","Thus, the first ring-shaped dot area CDT1 may be formed around a specific lens hole 235, which needs to reduce the reflectance.","The horizontal dot area HDA and/or the vertical dot area VDA may include a plurality of areas, in which attributes of the dots are different from one another.","For example, the horizontal dot area HDA may include first to third horizontal dot areas HDA1 to HDA3, and the vertical dot area VDA may include first to third vertical dot areas VDA1 to VDA3.There may be a difference between the dots of the areas in at least one of a size, an interval, a density, and a color of the dot.","For example, the size of the dot in the first horizontal dot area HDA1 may be less than the size of the dot in the second horizontal dot area HDA2, and the size of the dot in the second horizontal dot area HDA2 may be less than the size of the dot in the third horizontal dot area HDA3, or vice versa.","The configuration of the first to third horizontal dot areas HDA1 to HDA3 may be equally applied to the first to third vertical dot areas VDA1 to VDA3.As shown in FIG.","34, the reflecting sheet 126 may include a plurality of lens holes 235.The first ring-shaped dot area CDT1 may be formed in a specific lens hole 235 among the plurality of lens holes 235.For example, the plurality of lens holes 235 may include a first lens hole 235a, in which the first ring-shaped dot area CDT1 is formed, and a second lens hole 235b, in which the first ring-shaped dot area CDT1 is not formed.","The first lens hole 235a having the first ring-shaped dot area CDT1 may be the lens hole 235 positioned on the outside among the plurality of lens holes 235a.","Namely, the first ring-shaped dot area CDT1 may be formed in the outermost lens hole 235.This may be because the first lens hole 235a positioned on the outside is close to the bending second sheet area 126b (refer to FIG.","13) of the reflecting sheet 126.Namely, the first ring-shaped dot area CDT1 may be formed in the first lens hole 235a, so as to prevent an excessively large amount of light from being reflected from the second sheet area 126b.","As shown in (a) of FIG.","35A, a first ring-shaped dot area CDT1 may be formed around the lens hole 235.The first ring-shaped dot area CDT1 may be dots DT surrounding the lens hole 235.The first ring-shaped dot area CDT1 may be dots DT surrounding the lens hole 235 one time.","The dots DT constituting the first ring-shaped dot area CDT1 may have the same size and/or the same shape.","Alternatively, at least a portion of the dots DT constituting the first ring-shaped dot area CDT1 may have different sizes and different shapes.","For example, a size of the dot DT positioned in the outside direction of the reflecting sheet 126 may be greater than a size of the dot DT positioned in the inside direction of the reflecting sheet 126.As shown in (b) of FIG.","35A, a second ring-shaped dot area CDT2 may be formed around the lens hole 235.The second ring-shaped dot area CDT2 may be dots DT surrounding the lens hole 235 several times (several loops or nested).","This is a difference between the first ring-shaped dot area CDT1 surrounding the lens hole 235 one time and the second ring-shaped dot area CDT2.As shown in (c) of FIG.","35A, a third ring-shaped dot area CDT3 may be formed around the lens hole 235.The third ring-shaped dot area CDT3 may be formed around a predetermined portion of the lens hole 235.For example, the third ring-shaped dot area CDT3 may be formed in a portion corresponding to an angle AC in the lens hole 235.The third ring-shaped dot area CDT3 may surround the portion corresponding to the angle AC one time or several times.","As shown in (d) of FIG.","35A, a fourth ring-shaped dot area CDT4 may be formed around the lens hole 235.A density of dots of the fourth ring-shaped dot area CDT4 may vary depending on a location.","For example, the dots may have the same size, but a distance between the dots may be changed.","For example, a distance between the dots positioned close to the lens hole 235 may be relatively short, and a distance between the dots positioned far away from the lens hole 235 may be relatively long.","As shown in (a) of FIG.","35B, a fourth ring-shaped dot area CDT4 may be formed around at least a portion of the lens hole 235.The fourth ring-shaped dot area CDT4 may be dots DT positioned in a portion corresponding to an angle AC in the lens hole 235.The fourth ring-shaped dot area CDT4 may be separated from the lens hole 235.Namely, the fourth ring-shaped dot area CDT4 may be formed at a location which is separated from a boundary of the lens hole 235 by a predetermined distance.","As shown in (b) of FIG.","35B, a fifth ring-shaped dot area CDT5 may be formed around at least a portion of the lens hole 235.The fifth ring-shaped dot area CDT5 may include a first dot area DT1 and a second dot area DT2.An attribute of a dot constituting the first dot area DT1 may be different from an attribute of a dot constituting the second dot area DT2.For example, sizes of the dots constituting the first and second dot areas DT1 and DT2 may be different from each other.","For example, a size of the dot constituting the second dot area DT2 may be greater than a size of the dot constituting the first dot area DT1.An area corresponding to the second dot area DT2 may be an area which can emit a larger amount of light than the lens positioned in the lens hole 235.Thus, the second dot area DT2 may be formed, so as to further reduce a reflectance of the fifth ring-shaped dot area CDT5 than other areas.","As shown in (c) of FIG.","35B, the lens hole 235 may be a first lens hole 235a, which is not circular.","As described above, a radius of at least a portion of the first lens hole 235a may be different from a radius of at least another portion of the first lens hole 235a.","The first lens hole 235a may cause a portion of light to be emitted downwardly from the reflecting sheet 126, thereby controlling an amount of the light.","A sixth ring-shaped dot area CDT6 may be formed in an area AC.","The area AC may be an area having a relatively large radius in the first lens hole 235a.","For example, the sixth ring-shaped dot area CDT6 may be formed in an area having a radius R2.An amount of light emitted and/or reflected in a specific direction may be efficiently controlled by the area having the radius R2 and the sixth ring-shaped dot area CDT6.As shown in (d) of FIG.","35B, the lens hole 235 may be a first lens hole 235a, which is not circular.","A sixth ring-shaped dot area CDT6 and a seventh ring-shaped dot area CDT7 may be formed around the first lens hole 235a.","The sixth ring-shaped dot area CDT6 and the seventh ring-shaped dot area CDT7 may surround the first lens hole 235a.","As shown in FIG.","36, the lens hole 235 may include first lens holes 235a and second lens holes 235b.","As shown in (a) of FIG.","36, the first lens hole 235a may be a lens hole 235 having a ring-shaped dot area.","A location of the first lens hole 235a having the ring-shaped dot area may be different from a location of the second lens hole 235b not having the ring-shaped dot area.","For example, the first lens holes 235a may be positioned in the inner area of the reflecting sheet 126, and the second lens holes 235b may be positioned in the outer area of the reflecting sheet 126.The locations of the first and second lens holes 235a and 235b may be changed.","The lens holes 235 may be arranged in the horizontal direction and/or the vertical direction.","The lens holes 235 arranged in the horizontal direction and/or the vertical direction may be disposed in parallel with one another.","Such a disposition or arrangement can achieve the common design and the common manufacturing process and can obtain an effect capable of reducing the cost.","The lens holes 235 arranged in the horizontal direction and/or the vertical direction may not be disposed in parallel with one another.","For example, the lens holes 235 may be disposed in a zigzag pattern in the vertical direction.","Such a disposition or arrangement can obtain an effect reducing a light overlap and/or a light shade between the lens holes 235.Because the first lens hole 235a is positioned in the inner area of the reflecting sheet 126, a luminance of the first sheet area 126a (refer to FIG.","11) of the reflecting sheet 126 may be more unifoimly controlled.","This can be clearly understood considering that light emitted from the lens holes 235 is relatively bright around the lens holes 235 and becomes darker as it is far away from the lens holes 235.The first lens hole 235a, in which dots are formed, may control a brightness and/or a reflectance around the lens hole 235 and may homogenize an entire luminance.","As shown in (b) of FIG.","36, the first lens holes 235a may be disposed in accordance with a predetermined rule.","For example, the lens hole positioned in one of the left and right directions or one of the plurality of lens holes 235 may be the first lens hole 235a.","The first lens holes 235a may be disposed in the zigzag pattern in the vertical direction.","Namely, the first lens holes 235a may not be in parallel with one another in the vertical direction.","Such a disposition may minimize a reduction in the entire brightness by the first lens hole 235a and may homogenize the luminance.","As shown in (a) of FIG.","37, a third ring-shaped dot area CDT3 may be formed in a first lens hole 235 having an overlap shape of circles each having a different radius.","For example, the third ring-shaped dot area CDT3 may be formed in a circle having a large second radius R2.For example, the third ring-shaped dot area CDT3 may be formed in at least a portion of the circle having the second radius R2.As shown in (b) of FIG.","37, when the shape of the first lens hole 235 is changed, a location of the third ring-shaped dot area CDT3 may be changed in accordance with the first lens hole 235.As shown in FIG.","38, the plurality of lens holes 235 may include first lens holes 235a and second lens holes 235b.","A third ring-shaped dot area CDT3 may be formed in the first lens hole 235a.","A radius of the first lens hole 235a may be changed.","The first lens hole 235a may be positioned on the outside of the plurality of lens holes 235.For example, the first lens hole 235a may be a lens hole 235 positioned in an area close to the long side and/or the short side.","For example, the first lens hole 235a may be a lens hole 235 positioned adjacent to a horizontal dot area HDA and/or a vertical dot area VDA.","Namely, the third ring-shaped dot area CDT3 may be positioned between the first lens hole 235a and the horizontal dot area HDA and/or the vertical dot area VDA.","Thus, an excessively large amount of light may be prevented from being reflected from the second sheet area 126b (refer to FIG.","11) of the reflecting sheet 126.FIGS.","39 to 43 illustrate configuration related to a lens hole reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","39 to 43, the display device 100 according to the embodiment of the invention may further include a lens hole reflecting sheet 126d.","As shown in FIG.","39, the lens hole reflecting sheet 126d may be inserted into a lens hole 235 of the reflecting sheet 126.The lens hole reflecting sheet 126d may be positioned between the lens 124b and the light source 203.The lens 124b may be a refractive lens or a reflective lens.","The refractive or reflective lens 124b may emit light provided by the light source 203 at various angles.","The lens hole reflecting sheet 126d may reflect light emitted downwardly from the lens 124b to the upward side of the lens 124b, thereby increasing light efficiency.","As shown in FIG.","40, the lens hole reflecting sheet 126d may include a hole 126bh and a ring unit 126bb.","The hole 126bh may be positioned in the middle of the lens hole reflecting sheet 126d.","The light source 203 may be inserted into the hole 126bh.","The ring unit 126bb may be an outer peripheral area of the hole 126bh.","The ring unit 126bb may include at least one lens coupling unit 126bc.","For example, at least one lens leg 124d formed on the lower side of the lens 124b (refer to FIG.","39) may pass through the lens coupling unit 126bc.","As shown in FIG.","41, dots DT may be formed in at least a portion of the ring unit 126bb.","The dots DT may be separated from one another by a vertical distance vd and/or a horizontal distance hd.","The vertical distance vd and/or the horizontal may be uniform.","For example, the dots DT may be formed on the ring unit 126bb at regular intervals.","The vertical distance vd and/or the horizontal may not be uniform.","For example, the dots DT may be non-uniformly distributed on the ring unit 126bb.","FIG.","42 shows that the lens 124b (refer to FIG.","39) and the lens hole reflecting sheet 126d (refer to FIG.","39) are not coupled.","As shown in FIG.","42, one light source 203 may be configured as a plurality of LEDS.","Namely, a plurality of LED chips may be used in one light package, and thus an intensity of light with respect to one light package may increase.","The light source 203 may include first and second light sources 203a and 203b.","The first and second light sources 203a and 203b may be positioned adjacent to each other.","For example, the rectangular first and second light sources 203a and 203b may be positioned in parallel with each other.","The first and second light sources 203a and 203b may emit light having a predetermined directivity.","For example, each of the first and second light sources 203a and 203b may mainly emit light in a radial direction HA of the outside direction.","As shown in (a) of FIG.","43, dots DT may be formed in a predetermined area of the lens hole reflecting sheet 126d.","The dots DT may have a configuration corresponding to radial characteristics of the first and second light sources 203a and 203b (refer to FIG.","42).","For example, first and second dot areas DTA1 and DTA2 corresponding to the radial direction HA (refer to FIG.","42) may be formed.","The first and second dot areas DTA1 and DTA2 may be dots positioned on a path of the radial direction HA (refer to FIG.","42).","For example, the first and second dot areas DTA1 and DTA2 may be formed at a predetermined width.","The first and second dot areas DTA1 and DTA2 may be separated from each other.","The second dot area DTA2 may be positioned further inside than the first dot area DTA1.A size of the first dot area DTA1 may be greater than a size of the second dot area DTA2 considering that light emitted from the first and second light sources 203a and 203b(refer to FIG.","42) is radiated in a fan shape.","Only one of the first and second dot areas DTA1 and DTA2 may be formed, if necessary or desired.","As shown in (b) of FIG.","43, at least one of the first and second dot areas DTA1 and DTA2 may be formed in the reflecting sheet 126.For example, the first dot area DTA1 may be formed in the reflecting sheet 126, and the second dot area DTA2 may be formed in the lens hole reflecting sheet 126d.","The first dot area DTA1 formed in the reflecting sheet 126 may be advantageous to control a reflection amount of light than when the first dot area DTA1 is formed in the lens hole reflecting sheet 126d having the relatively small area.","FIGS.","44 and 45 illustrate configuration related to horizontal and vertical coupling units of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","44 and 45, the reflecting sheet 126 of the display device 100 according to the embodiment of the invention may include a horizontal coupling unit HH and a vertical coupling unit VH.","As shown in FIG.","44, the horizontal coupling unit HH and/or the vertical coupling unit VH may be formed in a corner area of the reflecting sheet 126.The horizontal coupling unit HH and/or the vertical coupling unit VH may be formed in a horizontal margin area HM and/or a vertical margin area VM of the reflecting sheet 126.The dots DT may not be formed in the horizontal margin area/or the vertical margin area VM.","The reflecting sheet 126 may be coupled to the frame 130 (refer to FIG.","10).","For example, the reflecting sheet 126 may be coupled to the frame 130 in such a manner that the horizontal coupling unit HH and/or the vertical coupling unit VH are inserted into a structure of the frame 130.The reflecting sheet 126 may be modified.","For example, the reflecting sheet 126 may contract or expand because of heat generated by an operation of the display device 100.The reflecting sheet 126 may be modified in the horizontal direction and/or the vertical direction.","A modification amount of the reflecting sheet 126 in the horizontal direction may be greater than a modification amount of the reflecting sheet 126 in the vertical direction.","Namely, because the horizontal direction corresponds to the long side and the vertical direction corresponds to the short side, a total modification amount in the horizontal direction may be greater than a total modification amount in the vertical direction although a modification amount per unit distance in the horizontal direction and the vertical direction is similar.","The horizontal coupling unit HH and/or the vertical coupling unit VH may be configured in consideration of the coupling and/or the modification of the reflecting sheet 126.For example, the plurality of horizontal coupling units HH and/or the plurality of vertical coupling units VH may be formed for the coupling of the reflecting sheet 126.For example, first to third horizontal coupling units HH1 to HH3 may be separated from one another by a predetermined distance and may be formed in the horizontal margin area HM.","First and second vertical coupling units VH1 and VH2 may be separated from one another by a predetermined distance and may be formed in the vertical margin area VM.","As shown in FIG.","45, the horizontal coupling unit HH and/or the vertical coupling unit VH may have a shape in consideration of the modification of the reflecting sheet 126.The horizontal coupling unit HH may be inserted into a horizontal protrusion 130H formed in and/or coupled to the third frame area 130c of the frame 130.A first width W1 of the horizontal coupling unit HH may be greater than a width of the horizontal protrusion 130H.","The first width W1 of the horizontal coupling unit HH may be greater than a second width W2 of the vertical coupling unit VH.","Namely, the first width W1 of the reflecting sheet 126 may be greater than the width of the horizontal protrusion 130H in consideration of the modification of the reflecting sheet 126 in the horizontal direction.","The vertical coupling unit VH may be inserted into a vertical protrusion 130V formed in and/or coupled to the third frame area 130c of the frame 130.A second height H2 of the vertical coupling unit VH may be greater than a first height H1 of the horizontal protrusion 130H.","Namely, the second height H2 of the vertical coupling unit VH may be relatively large in consideration of the modification of the reflecting sheet 126 in the horizontal direction.","The vertical coupling unit VH may not include a detachment prevention unit HHU positioned on the horizontal coupling unit HH.","This may be because the modification of the reflecting sheet 126 in the horizontal direction is greater than the modification of the reflecting sheet 126 in the vertical direction.","Namely, if the vertical coupling unit VH includes the detachment prevention unit HHU, the detachment prevention unit HHU may contact the vertical protrusion 130V in the modification of the horizontal direction (i.e., the X-axis direction).","Hence, a wrinkle may be generated in the reflecting sheet 126.Anon-dot area NDA may exist between horizontal and vertical dot areas HDA and VDA and horizontal and vertical margin areas HM and VM.","Namely, the non-dot area NDA not including the dot may be formed in a strap shape along the horizontal and vertical directions.","If the dots are formed in the non-dot area NDA, a corresponding area may be observed from the outside of the display device 100.Hence, the dots may not be formed in the non-dot area NDA.","Further, the non-dot area NDA may serve as a buffer when the reflecting sheet 126 contracts or expands.","FIGS.","46 to 48 illustrate configuration related to a cutting portion of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","46 to 48, the reflecting sheet 126 of the display device 100 according to the embodiment of the invention may include a cutting portion HC uniformly reflecting light.","As shown in FIG.","46, a lens hole 235 may include a first lens hole 235a and a second lens hole 235b.","As shown in (a) of FIG.","46, the first lens hole 235a may be a lens hole 235 including ring-shaped dots DT.","A location of the first lens hole 235a including the dots DT may be different from a location of the second lens hole 235b not including the dot DT.","For example, the first lens hole 235a may be positioned in the inner area of the reflecting sheet 126, and the second lens hole 235b may be positioned in the outer area of the reflecting sheet 126.The locations of the first and second lens holes 235a and 235b may be changed.","Because the first lens hole 235a is positioned in the inner area of the reflecting sheet 126, an effect capable of more uniformly controlling a luminance of the first sheet area 126a (refer to FIG.","11) of the reflecting sheet 126 may be expected.","This can be clearly understood considering that light emitted from the lens hole 235 is relatively bright around the lens hole 235 and becomes darker as it is far away from the lens hole 235.The first lens hole 235a, in which the dots DT are formed, may control a brightness and/or a reflectance around the lens hole 235 and may homogenizes an entire luminance.","As shown in (b) of FIG.","46, the first lens holes 235a may be disposed in accordance with a predetermined rule.","For example, the lens hole positioned in one of the left and right directions or one of the plurality of lens holes 235 may be the first lens hole 235a.","The first lens holes 235a may be disposed in the zigzag pattern in the vertical direction.","Namely, the first lens holes 235a may not be in parallel with one another in the vertical direction.","Such a disposition may minimize a reduction in the entire brightness by the first lens hole 235a and may homogenizes the luminance.","As shown in FIG.","47, the substrate 122 may have a shape, in which a first substrate 122a and a second substrate 122b are connected.","Namely, the substrate 122, on which the light source 203 is mounted in the rear of the reflecting sheet 126, may be divided into a plurality of substrates.","A first light source 203a may be positioned at the first substrate 122a, and a second light source 203b may be positioned at the second substrate 122b.","The first and second substrates 122a and 122b may be connected through a connector CT.","The connector CT may be positioned between the first and second substrates 122a and 122b.","The connector CT may be a structure electrically and/or physically connected to the first and second substrates 122a and 122b.","For example, the connector CT may be a soldering area.","The connector CT may protrude in the direction of the reflecting sheet 126 by a distance CTH further than the substrate 122.The cutting portion HC may correspond to the connector CT. For example, the cutting portion HC may be positioned on the connector CT. As shown in FIG.","48A, when the reflecting sheet 126 is coupled to the substrate 122, cutting surfaces HCS of the cutting portion HC may be separated from each other.","Namely, a gap may be naturally generated between the cutting surfaces HCS by the connector CT, which upwardly protrudes.","When the cutting surfaces HCS are coupled to the connector CT, a wrinkle of the reflecting sheet 126 resulting from the connector CT may be prevented.","Thus, the non-uniformity of light resulting from the wrinkle of the reflecting sheet 126 may be prevented.","The dots DT may be formed in the cutting surface HCS.","Namely, the dots DT may be formed in a corresponding area, so as to control an amount of light reflected from the cutting surface HCS, which relatively upwardly protrudes.","As shown in FIG.","48B, the dots DT may be formed in the cutting portion HC.","The dots DT may be positioned about the cutting surface HCS of the cutting portion HC.","For example, the dots DT may be positioned in the left and right cutting of the cutting portion HC.","Thus, the non-uniformity of the luminance resulting from the cutting may be minimized.","FIGS.","49 and 50 illustrate configuration related to a supporter hole of the reflecting sheet according to the embodiment of the invention.","As shown in FIGS.","49 and 50, the reflecting sheet 126 of the display device 100 according to the embodiment of the invention may uniformly reflect light through a dot area DTA formed around a supporter hole 205.As shown in FIG.","49, a plurality of lens holes 235 may be formed on the reflecting sheet 126.Each of the light sources 203 coupled to the plurality of lens holes 235 may emit light.","The supporter hole 205 may be formed on the reflecting sheet 126.As described above, the supporter hole 205 may have a configuration for the coupling of the supporter 200 (refer to FIG.","10).","The supporter hole 205 may be positioned further inside than the lens hole 235, which is positioned on the outermost side.","For example, the supporter hole 205 may be positioned between the lens holes 235.The supporter hole 205 may be affected by the plurality of light sources 203 coupled to the plurality of lens holes 235.For example, light emitted from the plurality of light sources 203 may affect the specific supporter hole 205 considering a light path LP with respect to the specific supporter hole 205.As described above, the supporter hole 205 maybe coupled to the supporter 200 (refer to FIG.","10).","The supporter 200 may be formed of plastic and/or rubber material.","The supporter 200 may reflect at least a portion of light.","The reflecting sheet 126 according to the embodiment of the invention may have a dot area DTA in consideration of the reflection of the supporter 200, on which light can be overlappingly concentrated.","Namely, the dot area DTA may be formed around the supporter hole 205, so as to reduce an influence of the supporter 200 on the reflection of the reflecting sheet 126.As shown in FIG.","50, the dot area DTA around the supporter hole 205 may be formed toward an inner area EA of the reflecting sheet 126.Namely, the dot area DTA may be positioned further inside than the supporter hole 205.The plurality of dot areas DTA around the supporter holes 205 may be positioned opposite each other.","For example, when first and second supporter holes 205a and 205b exist, first and second dot areas DTA1 and DTA2 may be positioned adjacent to the first and second supporter holes 205a and 205b further inside than the first and second supporter holes 205a and 205b.","The dot area DTA around the supporter hole 205 may have a semicircular shape centering around the supporter hole 205.Namely, a center area of the dot area DTA, which is relatively greatly affected by the supporter 200 (refer to FIG.","10), may be protrudingly configured.","FIG.","51 shows a light assembly including the light source shown in FIG.","19.As shown in FIG.","51, a plurality of light assemblies 124 according to the embodiment of the invention may be disposed along the substrate 122 and separated from one another.","The light assembly 124 may include a light source 203 and a lens 300 positioned on one side of the light source 203.The light source 203 may be various sources emitting light.","For example, the light source 203 may be a COB type LED as described above.","The lens 300 may be positioned on the light source 203.At least a partial area of the light source 203 may overlap the lens 300.For example, the light source 203 may be inserted into a groove inside the lens 300.Alternatively, an area of the light source 203, from which light is substantially emitted, may be inserted into the lower side of the lens 300.For example, when the lens 300 has a leg structure, a portion of the upper side of the light source 203 may be inserted into the lower side of the lens 300.The lens 300 may reflect a portion of light emitted from the light source 203 and may refract a portion of the light.","For example, the lens 300 may be a refractive lens or a reflective lens.","The light emitted from the light source 203 may be uniformly and entirely spread through the reflection in a portion of the lens 300 and/or the refraction in a portion of the lens 300.The light source 203 inserted into the lens 300 may be adhered to the lens 300.For example, the lens 300 and the light source 203 may be attached to each other using an adhesive.","The lens 300 may correspond to each light source 203.For example, first to third lenses 300a to 300c may be respectively positioned on first to third light sources 203a to 203c.","The lens 300 may control a path of light emitted from the light source 203.Namely, the lens 300 may control the light source 203 so that the light of the light source 203 is not concentrated on a specific location.","In other words, the lens 300 may cause the light of the light source 203 to be uniformly diffused.","The lens 300 according to the embodiment of the invention may efficiently control the path of the light of the light source 203.The lens 300 according to the embodiment of the invention may efficiently control light emitted from the side of the light source 203.FIGS.","52 and 53 show a lens according to the embodiment of the invention.","As shown in FIGS.","52 and 53, a lens 300 according to the embodiment of the invention may have a specific shape.","The lens 300 may include a first surface S1, a second surface S2 opposite the first surface S1, and a third surface S3 connecting the first surface S1 and the second surface S2.The first surface S1 may be an upper surface of the lens 300.At least a portion of the first surface S1 of the lens 300 according to the embodiment of the invention may be depressed.","A depressed portion of the first surface S1 may have a shape curved from the center of the lens 300 to the outside of the lens 300.For example, a first concave portion A1 may be formed on the first surface S1.An uppermost area of the first surface S1 may be a top surface TS.","The first surface S1 may have a circular cross-section.","Light emitted from the upper side of the light source 203 may be upwardly emitted through the first surface S1 of the lens 300.The second surface S2 may be a lower surface of the lens 300.Namely, the second surface S2 may be a surface opposite the first surface S1 corresponding to the upper surface of the lens 300.At least a portion of the second surface S2 of the lens 300 according to the embodiment of the invention may be depressed.","For example, a second concave portion A2 may be formed on the second surface S2.A radius of the second concave portion A2 on the second surface S2 may be denoted as R2.The radius R2 of the second concave portion A2 may be 1.5 to 4 times a radius of the light source 203 coupled to the lens 300.A lowermost area of the second surface S2 may be a bottom surface BS.","The second surface S2 may have a circular cross-section.","The light source 203 may be coupled to the second surface S2.As described above, a portion of the light source 203 may be inserted into the second surface S2.A radius of the second surface S2 may be “R2+R3”.","A radius R1 of the first surface S1 may be 1 to 3 times the radius (R2+R3) of the second surface S2.Namely, a width of the top surface TS may be greater than a width of the bottom surface BS.","The radius (R2+R3) of the second surface S2 may be 2 to 4 times a radius R2 of the second concave portion A2.The third surface S3 may be a surface connecting the first surface S1 and the second surface S2.Namely, the third surface S3 may be a side surface connecting the upper surface and the lower surface of the lens 300.The first surface S1 and the second surface S2 each have the circular cross section, and the third surface S3 forms an outer surface connecting the first surface S1 and the second surface S2.Therefore, the lens 300 may have an outline of a cylindrical shape having a height H. In the cylindrical shape of the lens 300, at least a portion of the first to third surfaces S1 to S3 may be changed.","FIG.","54 shows an example of a light path of a lens shown in FIG.","52.As shown in FIG.","54, the lens 300 according to the embodiment of the invention may control a path LP of light and may cause the light to be uniformly transferred to the optical sheet 125.In particular, the lens 300 according to the embodiment of the invention may change the path LP of light emitted from the side of the light source 203.The light emitted from the side of the light source 203 may be firstly diffused from the second concave portion A2.Namely, as described above, the light path LP may be radiated due to a shape of a third area A2R of the second concave portion A2.The light path LP distributed from the side of the second concave portion A2 may be again radiated via a curved surface S32 of the third surface S3.At least a portion of the light path LP passing through the second concave portion A2, etc., may be refracted and/or reflected from the first concave portion A1.Thus, the light path LP may be prevented from being concentrated on a specific location.","As a result, light may be uniformly distributed on the optical sheet 125.FIGS.","55 to 60 show a lens according to another example embodiment of the invention.","As shown in FIGS.","55 to 60, the lens 300 according to the embodiment of the invention may be variously configured.","As shown in FIG.","55, a curved surface S33 of the third surface S3 may have a shape protruding to the outside of the lens 300.For example, the curved surface S33 may form a curved surface S32 corresponding to an imaginary fourth circle C4 adjoining an external surface of the third surface S3.The curved surface S33 may have the shape extending from the second surface S2 by a distance EA1.As shown in FIG.","56, the plurality of light sources 203 may correspond to one lens 300.For example, first and second light sources 203a and 203b may be positioned inside the second concave portion A2.The light source 203 may have the relatively small size.","The light source 203 may have a performance of high power.","Thus, the first and second light sources 203a and 203b may correspond to one lens 300.The second concave portion A2 may have an oval shape.","For example, the second concave portion A2 may have the shape, in which a width A2W of the second concave portion A2 is greater than a height A2H of the second concave portion A2.The plurality of light sources 203a and 203b may be positioned in a space obtained by configuring the second concave portion A2 in the oval shape.","When the plurality of light sources 203 are positioned inside the second concave portion A2, the shape of the second concave portion A2 and/or the curved surface S32 of the third surface S3 may importantly operate in the embodiment of the invention.","Namely, because a large amount of light may be generated from the sides of the first and second light sources 203a and 203b, it is necessary to more efficiently control the light emitted from the sides of the first and second light sources 203a and 203b.","The embodiment of the invention may efficiently distribute the light emitted from the sides of the light sources through the curved third area A2R on the side of the second concave portion A2 and/or the curved surface S32 on the lower side of the third surface S3.As shown in FIG.","57, the third area A2R of the second concave portion A2 may have the shape of a curved surface protruding to the outside of the lens 300.For example, the third area A2R may have the shape of the curved surface corresponding to an imaginary fifth circle C5 adjoining the third area A2R of the second concave portion A2 outside the second concave portion A2.In this instance, a length of the second concave portion A2 may extend by a distance EA2.As shown in FIGS.","34 to 58, the embodiment of the invention may be applied to the lens 300, which may be configured in the various shapes.","As shown in FIG.","58, the third surface S3 may have a shape inclined at a predetermined angle.","For example, the third surface S3 may have the shape inclined to the inside by an angle S3D based on the vertical line.","The third surface S3 may include a straight surface S31 and a curved surface S32.The curved surface S32 may be connected to the second surface S2.The third area A2R may be formed on the second concave portion A2.Namely, a curved surface may be formed in an area extending from the lower side of the second concave portion A2 to the bottom surface BS.","The light emitted from the light source may be distributed due to the third area A2R.","In particular, the third area A2R may improve the uniformity of the light emitted from the side of the light source.","As shown in FIG.","59, a predetermined curved surface S32 may be formed in an area where the third surface S3 of the lens 300 and the bottom surface BS meet.","Third areas A2R1 and A2R2 may be formed on the second concave portion A2.Namely, a curved surface may be formed in a portion of an area where the second concave portion A2 and the bottom surface BS meet.","The third areas A2R1 and A2R2 may include a 3a area A2R1 and a 3b area A2R2.Namely, a plurality of curved surfaces may be formed in a plurality of areas where the second concave portion A2 and the bottom surface BS meet.","As shown in FIG.","60, a curved surface S32 may be formed in an area where the third surface S3 of the lens 300 and the bottom surface BS meet.","The third area A2R of the curved surface may be formed on the second concave portion A2.FIGS.","61 and 62 show a disposition of a light assembly according to another example embodiment of the invention.","As shown in FIGS.","61 and 62, the light assembly 124 may be positioned on the frame 130.The light assembly 124 may be configured in various shapes depending on a location.","The light assembly 124 may include at least one of the lenses 300 having the above-described shapes.","Thus, a contrast or a hot spot resulting from the lens 300 may be prevented from being generated.","As shown in (a) of FIG.","61, the light assembly 124 may be positioned on the frame 130.In FIGS.","61 and 62, alphabets “A” and “B” indicate the light assembly 124.Namely, the light assemblies 124 may be arranged in the horizontal and vertical directions.","The light assemblies 124 shown in (a) of FIG.","61 may the “A” type light assemblies 124.For example, the light assembly 124 including the lens 300 of the specific shape may be positioned.","As shown in (b) of FIG.","61, the “A” type light assemblies 124 and the “B” type light assemblies 124 may be arranged.","For example, the light assemblies 124 including the lenses 300 of two types may be arranged.","In this instance, the “B” type light assemblies 124 may be arranged on the outermost side of an array of the light assemblies 124, and the “A” type light assemblies 124 may be arranged in an inner area of the array.","The light assemblies 124 different from the light assemblies 124 arranged in the inner area of the array may be arranged on the outermost side of the array.","Thus, the light assembly 124 positioned on the outermost side of the array may include the lens 300 different from the light assembly 124 positioned in the inner area of the array, so as to uniformly distribute light.","As shown in (a) and (b) of FIG.","62, the light assemblies 124 of at least two types may be alternately arranged.","For example, the light assemblies 124 each including the “A” type lens 300 and the light assemblies 124 each including the “B” type lens 300 may be alternately arranged in the horizontal direction or the vertical direction.","The embodiments and/or the configurations of the invention may be combined with each other.","For example, a configuration “A” described in one embodiment of the invention and the drawings and a configuration “B” described in another embodiment of the invention and the drawings may be combined with each other.","Namely, although the combination between the configurations is not directly described, the combination is possible except in the instance where it is described that the combination is impossible.","This is certain considering that the embodiment of the invention relates to the display device.","Any reference in this specification to “one embodiment,” “an embodiment,” “exemplary embodiment,” etc., means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention.","The appearances of such phrases in various places in the specification are not necessarily all referring to the same embodiment.","Further, when a particular feature, structure, or characteristic is described in connection with any embodiment, it is submitted that it is within the purview of one skilled in the art to effect such feature, structure, or characteristic in connection with other ones of the embodiments.","Although embodiments have been described with reference to a number of illustrative embodiments thereof, it should be understood that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the scope of the principles of this disclosure.","More particularly, various variations and modifications are possible in the component parts and/or arrangements of the subject combination arrangement within the scope of the disclosure, the drawings and the appended claims.","In addition to variations and modifications in the component parts and/or arrangements, alternative uses will also be apparent to those skilled in the art."]],"string":"[\n [\n \"BACKLIGHT UNIT AND DISPLAY DEVICE HAVING BACKLIGHT UNIT\",\n \"A display device including a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a reflecting sheet on the substrate.\",\n \"The reflecting sheet includes a first sheet part on the bottom and having a rectangular shape with a first long side, a second long side opposite the first long side, a first short side adjacent to the first long side and the second long side, and a second short side opposite the first short side, the first sheet part comprising a plurality of holes corresponding to the plurality of light sources; a second sheet part extended from the first sheet part toward the side wall of the frame; and a plurality of dots on the second sheet part, wherein the plurality of dots reduces a reflectance of light, and wherein a size of the plurality of dots increases from a corner of the second sheet part in a first direction parallel to the long sides and a second direction parallel to the short sides.\"\n ],\n [\n \"1.A display device comprising: a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a reflecting sheet on the substrate, wherein the reflecting sheet includes: a first sheet part on the bottom and having a rectangular shape with a first long side, a second long side opposite the first long side, a first short side adjacent to the first long side and the second long side, and a second short side opposite the first short side, the first sheet part comprising a plurality of holes corresponding to the plurality of light sources; a second sheet part extended from the first sheet part toward the side wall of the frame; and a plurality of dots on the second sheet part, wherein the plurality of dots reduces a reflectance of light, and wherein a size of the plurality of dots increases from a corner of the second sheet part in a first direction parallel to the long sides and a second direction parallel to the short sides.\",\n \"2.The display device of claim 1, wherein the size of the plurality of dots gradually changes along an outer side of the second sheet part from each corner of the second sheet part in the first direction and the second direction.\",\n \"3.The display device of claim 1, wherein the second sheet part comprises a cut line between a horizontal portion of the second sheet part arranged along the first direction and a vertical portion of the second sheet part arranged along the second direction.\",\n \"4.The display device of claim 3, wherein the second sheet part comprises a first dot area, and a second dot area next to the first dot area, wherein the first dot area is a closest area to the corner of the second sheet part and the second dot area is farther from the corner of the second sheet part than the first dot area.\",\n \"5.The display device of claim 4, wherein a first border line between the first dot area and the second dot area is not straight.\",\n \"6.The display device of claim 4, wherein the second sheet part further comprises a third dot area next to the second dot area, the third dot area is the farthest area from the corner of the second sheet part among the first dot area, the second dot area and the third dot area.\",\n \"7.The display device of claim 6, wherein a second border line between the second dot area and the third dot area is not straight.\",\n \"8.The display device of claim 6, wherein a size of the dots in the first dot area is the same and is smaller than a size of the dots in the second dot area, and the size of the dots in the second dot area is the same and is smaller than a size of the dots in the third dot area, the size of the dots in the third dot area being the same.\",\n \"9.The display device of claim 6, wherein the first dot area, the second dot area, and the third dot area on the second sheet part along the long side form a horizontal dot area, and wherein the first dot area, the second dot area, and the third dot area on the second sheet part along the short side form a vertical dot area, and wherein a width of the vertical dot area is different from a width of the horizontal dot area.\",\n \"10.The display device of claim 9, wherein the second dot area of the horizontal dot area is separated from the cutting portion by a first angle and the second dot area of the vertical dot area is separated from the cutting portion by a second angle, and wherein the first angle is different from the second angle.\",\n \"11.The display device of claim 9, wherein the first vertical dot area is the closest to the cut line among the first to third vertical dot areas, wherein the first horizontal dot area is the closest to the cut line among the first to third horizontal dot areas, and wherein an empty area without dots is positioned between the first vertical dot area and the first horizontal dot area around the cut line.\",\n \"12.The display device of claim 9, wherein the vertical dot area has a different shape than the horizontal dot area.\",\n \"13.The display device of claim 12, the width of the vertical dot area is greater than the width of the horizontal dot area.\",\n \"14.The display device of claim 9, wherein an outline of the vertical dot area or the horizontal dot area adjacent to the cut line is inclined with respect to the cut line.\",\n \"15.The display device of claim 7, wherein the first border line is substantially parallel with the second border line.\",\n \"16.The display device of claim 1, further comprising a separation space between the second sheet part of the reflecting sheet and the frame.\",\n \"17.The display device of claim 1, further comprising a signal line electrically connected to the substrate, wherein the frame includes a hole on the bottom of the frame, and wherein the signal line passes through the hole.\",\n \"18.A display device comprising: a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a reflecting sheet on the substrate, wherein the reflecting sheet includes: a first sheet part on the bottom and being a rectangular shape, the first sheet part comprising a plurality of holes corresponding to the plurality of light sources; a second sheet part extended from the first sheet part toward the side wall of the frame; and a plurality of dot areas on the second sheet part, the plurality of dot areas forming a gradation in a direction along a side of the first sheet part, wherein the gradation of the plurality of dot areas becomes darker as the dot areas go farther from a corner of the first sheet part and the gradation of the plurality of dot areas becomes brighter as the dot areas go closer to another corner of the first sheet part.\",\n \"19.The display device of claim 18, wherein a size of dots in the plurality of dot areas becomes greater as the dot areas go farther from a corner of the first sheet part and the size of dots in the plurality of dot areas becomes smaller as the dot areas go closer to another corner of the first sheet part.\",\n \"20.The display device of claim 18, wherein the frame is a rectangular plate having a short side and a long side, the second sheet part includes a vertical sheet part adjacent to the short side of the frame and a horizontal sheet part adjacent to the long side of the frame, and wherein the plurality of dot areas includes a vertical dot area and a horizontal dot area, the vertical dot area is positioned on the vertical sheet part and the horizontal dot area is positioned on the horizontal sheet part.\",\n \"21.The display device of claim 20, further comprising a cut line between the vertical sheet part and the horizontal sheet part of the second sheet part, wherein the vertical dot area includes a plurality of vertical dot areas forming a gradation in a vertical direction along the short side of the frame, wherein the horizontal dot area includes a plurality of horizontal dot areas forming a gradation in a horizontal direction along the long side of the frame, and wherein a shape of the vertical dot area and a shape of the horizontal dot area are asymmetric with respect to the cut line.\",\n \"22.The display device of claim 21, wherein the plurality of vertical dot areas comprises a first vertical area, a second vertical area next to the first vertical area, the first vertical area is the closest area to the cut line among the plurality of vertical dot areas and the second vertical area is farther from the cut line than the first vertical area, wherein the plurality of horizontal dot areas comprises a first horizontal area, a second horizontal area next to the first horizontal area, the first horizontal area is the closest area to the cut line among the plurality of horizontal dot areas and the second horizontal area is farther from the cut line than the first horizontal area, and wherein an empty area without dots is positioned between the first vertical area and the first horizontal area around the cut line.\",\n \"23.The display device of claim 22, wherein the empty area without dots is gradually narrower as the empty area goes closer to a corner of the second sheet part.\",\n \"24.The display device of claim 18, wherein the gradation of the plurality of dot areas darker as the dot areas go from a border between the first sheet part and the second sheet part toward the side wall of the frame.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>The present disclosure provides a backlight unit including a reflecting sheet having a dot area.\",\n \"In one aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, and wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.\",\n \"The backlight unit may further include at least one of a diffusion plate and an optical sheet positioned on the reflecting sheet.\",\n \"The backlight unit may further include a plurality of lenses positioned on the plurality of light sources.\",\n \"The backlight unit may further include a plurality of pins fixing the reflecting sheet to the frame.\",\n \"The plurality of pins maybe arranged outside the plurality of holes.\",\n \"The plurality of pins maybe arranged in a row.\",\n \"The first sheet part and the second sheet part may be delineated by the plurality of pins.\",\n \"At least one of the plurality of pins maybe positioned between at least two outermost holes among the plurality of holes positioned on a short side of the reflecting sheet.\",\n \"A distance between a dot area on a long side of the reflecting sheet and an outermost hole of the plurality of holes on the long side maybe greater than a distance between a dot area on a short side of the reflecting sheet and an outermost hole of the plurality of holes on the short side.\",\n \"A bent area maybe positioned at a boundary between the first sheet part and the second sheet part and a boundary between the second sheet part and third sheet part.\",\n \"The second sheet part may be rounded.\",\n \"A slope of the second sheet part may increase as the slope goes towards the third sheet part.\",\n \"Sizes of the plurality of dots in the second sheet area may vary depending on an increase in the slope.\",\n \"The sizes of the plurality of dots in the second sheet area may increase as the slope increases.\",\n \"In a corner of the reflecting sheet, a shape of a dot area on a long side of the reflecting sheet and a shape of a dot area on a short side of the reflecting sheet maybe asymmetric.\",\n \"The backlight unit may further include a cutting line on a corner of the reflecting sheet.\",\n \"A distance between a specific point on the cutting line and a dot nearest to the cutting line in a direction parallel to a long side of the reflecting sheet maybe different from a distance between the specific point and a dot nearest to the cutting line in a direction parallel to a short side of the reflecting sheet.\",\n \"The second sheet area may include a non-dot area adjacent to the third sheet part.\",\n \"A width of the non-dot area maybe greater than a distance between adjacent dots of the plurality of dots.\",\n \"The first sheet part and the third sheet part may contact the frame, and the second sheet part may be separated from the frame.\",\n \"A distance between adjacent dots of the plurality of dots in the first dot area maybe different from a distance between adjacent dots of the plurality of dots in the second dot area.\",\n \"The first dot area may be located closer to the first sheet part than the second dot area.\",\n \"In another aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas include a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a distance of adjacent dots of the plurality of dots in the first dot area is different from a distance of adjacent dots of the plurality of dots in the second dot area.\",\n \"In another aspect, there is a display device including: a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; a reflecting sheet located on the at least one substrate; an optical sheet located on the reflecting sheet; and a display panel located on the optical sheet, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.\"\n ],\n [\n \"This application is a Continuation of co-pending application Ser.\",\n \"No.\",\n \"14/929,828, filed on Nov. 2, 2015, which claims priority under 35 U.S.C.\",\n \"§ 119(e) to U.S.\",\n \"Provisional Application No.\",\n \"62/073,509, filed on Oct. 31, 2014, and under 35 U.S.C.\",\n \"§ 119(a) to Application Nos.\",\n \"10-2015-0109165 and 10-2015-0109155, both filed in Republic of Korea on Jul.\",\n \"31, 2015, all of which are hereby expressly incorporated by reference into the present application.\",\n \"BACKGROUND OF THE INVENTION Field of the Invention The present disclosure relates to a backlight unit and a display device including the backlight unit.\",\n \"Discussion of the Related Art With the development of the information society, various demands for display devices have been increasing.\",\n \"Various display devices, such as liquid crystal displays (LCDs), plasma display panels (PDPs), electroluminescent displays (ELDs), and vacuum fluorescent displays (VFDs), have been recently studied and used to meet various demands for the display devices.\",\n \"Among the display devices, a liquid crystal display panel of the liquid crystal display includes a liquid crystal layer, and a thin film transistor (TFT) substrate and a color filter substrate which are positioned opposite each other with the liquid crystal layer interposed there between.\",\n \"The liquid crystal display panel displays an image using light provided by a backlight unit of the liquid crystal display.\",\n \"SUMMARY OF THE INVENTION The present disclosure provides a backlight unit including a reflecting sheet having a dot area.\",\n \"In one aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, and wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.\",\n \"The backlight unit may further include at least one of a diffusion plate and an optical sheet positioned on the reflecting sheet.\",\n \"The backlight unit may further include a plurality of lenses positioned on the plurality of light sources.\",\n \"The backlight unit may further include a plurality of pins fixing the reflecting sheet to the frame.\",\n \"The plurality of pins maybe arranged outside the plurality of holes.\",\n \"The plurality of pins maybe arranged in a row.\",\n \"The first sheet part and the second sheet part may be delineated by the plurality of pins.\",\n \"At least one of the plurality of pins maybe positioned between at least two outermost holes among the plurality of holes positioned on a short side of the reflecting sheet.\",\n \"A distance between a dot area on a long side of the reflecting sheet and an outermost hole of the plurality of holes on the long side maybe greater than a distance between a dot area on a short side of the reflecting sheet and an outermost hole of the plurality of holes on the short side.\",\n \"A bent area maybe positioned at a boundary between the first sheet part and the second sheet part and a boundary between the second sheet part and third sheet part.\",\n \"The second sheet part may be rounded.\",\n \"A slope of the second sheet part may increase as the slope goes towards the third sheet part.\",\n \"Sizes of the plurality of dots in the second sheet area may vary depending on an increase in the slope.\",\n \"The sizes of the plurality of dots in the second sheet area may increase as the slope increases.\",\n \"In a corner of the reflecting sheet, a shape of a dot area on a long side of the reflecting sheet and a shape of a dot area on a short side of the reflecting sheet maybe asymmetric.\",\n \"The backlight unit may further include a cutting line on a corner of the reflecting sheet.\",\n \"A distance between a specific point on the cutting line and a dot nearest to the cutting line in a direction parallel to a long side of the reflecting sheet maybe different from a distance between the specific point and a dot nearest to the cutting line in a direction parallel to a short side of the reflecting sheet.\",\n \"The second sheet area may include a non-dot area adjacent to the third sheet part.\",\n \"A width of the non-dot area maybe greater than a distance between adjacent dots of the plurality of dots.\",\n \"The first sheet part and the third sheet part may contact the frame, and the second sheet part may be separated from the frame.\",\n \"A distance between adjacent dots of the plurality of dots in the first dot area maybe different from a distance between adjacent dots of the plurality of dots in the second dot area.\",\n \"The first dot area may be located closer to the first sheet part than the second dot area.\",\n \"In another aspect, there is a backlight unit including a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; and a reflecting sheet located on the at least one substrate, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas include a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a distance of adjacent dots of the plurality of dots in the first dot area is different from a distance of adjacent dots of the plurality of dots in the second dot area.\",\n \"In another aspect, there is a display device including: a frame including a bottom and a sidewall extending from the bottom; at least one substrate located on the frame, and a plurality of light sources mounted on the at least one substrate; a reflecting sheet located on the at least one substrate; an optical sheet located on the reflecting sheet; and a display panel located on the optical sheet, wherein the reflecting sheet including: a first sheet part located on the bottom, the first sheet part including a plurality of holes corresponding to the plurality of the light sources; a second sheet part extended from the first sheet; and a third sheet part extended from the second sheet part and located on the sidewall; wherein the second sheet part includes a plurality of dot areas positioned sequentially in a direction from the first sheet part to the third sheet part and the plurality of dot areas including a first dot area and a second dot area, the first dot area including a plurality of dots having the same size and the second dot area including a plurality of dots having the same size, wherein a size of the plurality of dots in the first dot area is different from a size of the plurality of dots in the second dot area.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention.\",\n \"In the drawings: FIGS.\",\n \"1 and 2 illustrate a display device according to an example embodiment of the invention; FIGS.\",\n \"3 to 7 illustrate configuration of a display device related to an example embodiment of the invention; FIGS.\",\n \"8 and 9 illustrate a light source according to an example embodiment of the invention; FIG.\",\n \"10 illustrates a connection relationship between a reflecting sheet and components around the reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"11 to 13 illustrate configuration of a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"14 to 23B illustrate a dot distribution of a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"24 and 25 illustrate a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"26 to 28 illustrate configuration of a cutting portion of a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"29 and 30 illustrate a dot area according to an example embodiment of the invention; FIGS.\",\n \"31 to 38 illustrate configuration related to a lens hole of a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"39 to 43 illustrate configuration related to a lens hole reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"44 and 45 illustrate configuration related to horizontal and vertical coupling units of a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"46 to 48B illustrate configuration related to a cutting portion of a reflecting sheet according to an example embodiment of the invention; FIGS.\",\n \"49 and 50 illustrate configuration related to a supporter hole of a reflecting sheet according to an example embodiment of the invention; FIG.\",\n \"51 shows a light assembly including a light source shown in FIG.\",\n \"19; FIGS.\",\n \"52 and 53 show a lens according to an example embodiment of the invention; FIG.\",\n \"54 shows an example of a light path of a lens shown in FIG.\",\n \"52; FIGS.\",\n \"55 to 60 show a lens according to another example embodiment of the invention; and FIGS.\",\n \"61 and 62 show a disposition of a light assembly according to another example embodiment of the invention.\",\n \"DETAILED DESCRIPTION OF THE EMBODIMENTS Reference will now be made in detail to embodiments of the invention, examples of which are illustrated in the accompanying drawings.\",\n \"Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.\",\n \"A suffix such as “module” and “unit” may be assigned or used interchangeably to refer to elements or components.\",\n \"Use of such a suffix herein is merely intended to facilitate the description of the embodiments of the invention, and the suffix itself is not intended to give any special meaning or function.\",\n \"It will be paid attention that detailed description of known arts will be omitted if it is determined that the detailed description of the know arts can obscure the embodiments of the invention.\",\n \"The accompanying drawings are merely intended to easily describe the embodiments of the invention, and the spirit and technical scope of the present invention is not limited by the accompanying drawings.\",\n \"It should be understood that the present invention is not limited to specific disclosed embodiments, but includes all modifications, equivalents and substitutes included within the spirit and technical scope of the present invention.\",\n \"Hereinafter, the embodiments of the invention are described using a liquid crystal display panel as an example of a display panel.\",\n \"Other display panels may be used.\",\n \"For example, a plasma display panel (PDP), a field emission display (FED) panel, and an organic light emitting diode (OLED) display panel may be used.\",\n \"In what follows, a display panel may include a first long side LS1, a second long side LS2 opposite the first long side LS1, a first short side SS1 adjacent to the first long side LS1 and the second long side LS2, and a second short side SS2 opposite the first short side SS1.In the embodiment disclosed herein, the first short side SS1 may be referred to as a first side area; the second short side SS2 may be referred to as a second side area opposite the first side area; the first long side LS1 may be referred to as a third side area which is adjacent to the first side area and the second side area and is positioned between the first side area and the second side area; and the second long side LS2 may be referred to as a fourth side area which is adjacent to the first side area and the second side area, is positioned between the first side area and the second side area, and is opposite to the third side area.\",\n \"The embodiment of the invention describes that lengths of the first and second long sides LS1 and LS2 are longer than lengths of the first and second short sides SS1 and SS2 for the sake of brevity and ease of reading.\",\n \"However, the lengths of the first and second long sides LS1 and LS2 may be almost equal to the lengths of the first and second short sides SS1 and SS2.In the following description, a first direction DR1 may be a direction parallel to the long sides LS1 and LS2 of the display panel, and a second direction DR2 may be a direction parallel to the short sides SS1 and SS2 of the display panel.\",\n \"Further, a third direction DR3 may be a direction vertical to the first direction DR1 and/or the second direction DR2.In the embodiment disclosed herein, the first direction DR1 and the second direction DR2 may be commonly referred to as a horizontal direction.\",\n \"Further, the third direction DR3 may be referred to as a vertical direction.\",\n \"FIGS.\",\n \"1 and 2 illustrate a display device according to an example embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"1 and 2, a display device 100 according to the embodiment of the invention may include a display panel 110 and a back cover 150 positioned in the rear of the display panel 110.The back cover 150 may be connected to the display panel 110 in a sliding manner in a direction (i.e., the second direction DR2) from the first long side LS1 to the second long side LS2.In other words, the back cover 150 may be inserted into the first short side SS1, the second short side SS2 opposite the first short side SS1, and the first long side LS1 which is adjacent to the first and second short sides SS1 and SS2 and is positioned between the first short side SS1 and the second short side SS2, of the display panel 110 in the sliding manner.\",\n \"The back cover 150 and/or other components adjacent to the back cover 150 may include a protrusion, a sliding unit, a connection unit, etc., so that the back cover 150 is connected to the display panel 110 in the sliding manner.\",\n \"FIGS.\",\n \"3 to 7 illustrate configuration of a display device related to the embodiment of the invention.\",\n \"As shown in FIG.\",\n \"3, the display device 100 according to the embodiment of the invention may include a front cover 105, the display panel 110, a backlight unit 120, a frame 130, and the back cover 150.The front cover 105 may cover at least a portion of a front surface and a side surface of the display panel 110.The front cover 105 may have a rectangular fame shape, in which a center portion is empty.\",\n \"Because the center portion of the front cover 105 is empty, an image displayed on the display panel 110 may be seen to the outside.\",\n \"The front cover 105 may include a front cover and a side cover.\",\n \"Namely, the front cover 105 may include the front cover positioned at the front surface of the display panel 110 and the side cover at the side surface of the display panel 110.The front cover and the side cover may be separately configured.\",\n \"One of the front cover and the side cover may be omitted.\",\n \"For example, the front cover may be omitted, and only the side cover may be absent in terms of a beautiful appearance of the display device 100.The display panel 110 may be positioned in front of the display device 100 and may display an image.\",\n \"The display panel 110 may divide the image into a plurality of pixels and may output the image while controlling color, brightness, and chroma of each pixel.\",\n \"The display panel 110 may include an active area, on which the image is displayed, and an inactive area, on which the image is not displayed.\",\n \"The display panel 110 may include a front substrate and a back substrate which are positioned opposite each other with a liquid crystal layer interposed there between.\",\n \"The front substrate may include a plurality of pixels each including red, green, and blue subpixels.\",\n \"The front substrate may generate an image corresponding to the red, green, or blue color in response to a control signal.\",\n \"The back substrate may include switching elements.\",\n \"The back substrate may turn on pixel electrodes.\",\n \"For example, the pixel electrode may change a molecule arrangement of the liquid crystal layer in response to a control signal received from the outside.\",\n \"The liquid crystal layer may include a plurality of liquid crystal molecules.\",\n \"The arrangement of the liquid crystal molecules may change depending on a voltage difference between the pixel electrode and a common electrode.\",\n \"The liquid crystal layer may transmit light provided by the backlight unit 120 to the front substrate.\",\n \"The backlight unit 120 may be positioned at a back surface of the display panel 110.The backlight unit 120 may include a plurality of light sources.\",\n \"The light sources of the backlight unit 120 may be arranged in an edge type or a direct type.\",\n \"In the instance of the edge type backlight unit 120, a light guide plate may be added.\",\n \"The backlight unit 120 may be coupled to a front surface of the frame 130.For example, the plurality of light sources may be disposed at the front surface of the frame 130.In this instance, the backlight unit 120 may be commonly called the direct type backlight unit 120.The backlight unit 120 may be driven in an entire driving method or a partial driving method such as a local dimming method and an impulsive driving method.\",\n \"The backlight unit 120 may include an optical sheet 125 and an optical layer 123.The optical sheet 125 can cause light of the light sources to be uniformly transferred to the display panel 110.The optical sheet 125 may include a plurality of layers.\",\n \"For example, the optical sheet 125 may include at least one prism sheet and/or at least one diffusion sheet.\",\n \"The optical sheet 125 may further include at least one coupling unit 125d.\",\n \"The coupling unit 125d may be coupled to the front cover 105 and/or the back cover 150.Namely, the coupling unit 125d may be directly coupled to the front cover 105 and/or the back cover 150.Alternatively, the coupling unit 125d may be coupled to a structure formed on the front cover 105 and/or the back cover 150.Namely, the coupling unit 125d may be indirectly coupled to the front cover 105 and/or the back cover 150.The optical layer 123 may include the light source, etc.\",\n \"The detailed configuration of the optical layer 123 will be described in the corresponding paragraphs.\",\n \"The frame 130 may support components constituting the display device 100.For example, the frame 130 may be coupled to the backlight unit 120.The frame 130 may be formed of a metal material, for example, an aluminum alloy.\",\n \"The back cover 150 may be positioned at a back surface of the display device 100.The back cover 150 may protect inner configuration of the display device 100 from the outside.\",\n \"At least a portion of the back cover 150 may be coupled to the frame 130 and/or the front cover 105.The back cover 150 may be an injection production (or injection molded) formed of a resin material.\",\n \"FIG.\",\n \"4 shows the configuration of the optical sheet 125.As shown in (a) of FIG.\",\n \"4, the optical sheet 125 and/or a diffusion plate 129 may be positioned on the frame 130.The optical sheet 125 and/or the diffusion plate 129 may be coupled to the frame 130 at an edge of the frame 130.The optical sheet 125 and/or the diffusion plate 129 may be directly placed at the edge of the frame 130.Namely, an outer perimeter of the optical sheet 125 and/or the diffusion plate 129 may be supported by the frame 130.An upper surface of an edge of the optical sheet 125 and/or the diffusion plate 129 may be surrounded by a first guide panel 117.For example, the optical sheet 125 and/or the diffusion plate 129 may be positioned between the edge of the frame 130 and a flange 117a of the first guide panel 117.The display panel 110 may be positioned at a front surface of the optical sheet 125.An edge of the display panel 110 may be coupled to the first guide panel 117.Namely, the display panel 110 may be supported by the first guide panel 117.An edge area of the front surface of the display panel 110 may be surrounded by the front cover 105.For example, the display panel 110 may be positioned between the first guide panel 117 and the front cover 105.As shown in (b) of FIG.\",\n \"4, the display device 100 according to the embodiment of the invention may further include a second guide panel 113.The optical sheet 125 and/or the diffusion plate 129 may be coupled to the second guide panel 113.Namely, the second guide panel 113 may have a shape, in which the second guide panel 113 is coupled to the frame 130 and the optical sheet 125 and/or the diffusion plate 129 are/is coupled to the second guide panel 113.The second guide panel 113 may be formed of a material different from the frame 130.The frame 130 may have a shape surrounding the first and second guide panels 117 and 113.As shown in (c) of FIG.\",\n \"4, in the display device 100 according to the embodiment of the invention, the front cover 105 may not cover the front surface of the display panel 110.Namely, one end of the front cover 105 may be positioned on the side of the display panel 110.Referring to FIGS.\",\n \"5 and 6, the backlight unit 120 may include the optical layer 123 including substrates 122, at least one light assembly 124, a reflecting sheet 126 and the diffusion plate 129, and the optical sheet 125 positioned on a front surface of the optical layer 123.The substrates 122 may include a plurality of straps, which extend in a first direction and are separated from one another by a predetermined distance in a second direction perpendicular to the first direction.\",\n \"At least one light assembly 124 may be mounted on the substrate 122.The substrate 122 may have an electrode pattern for connecting an adaptor to the light assembly 124.For example, a carbon nanotube electrode pattern for connecting the adaptor to the light assembly 124 may be formed on the substrate 122.The substrate 122 maybe formed of at least one of polyethylene terephthalate (PET), glass, polycarbonate (PC), and silicon.\",\n \"The substrate 122 maybe a printed circuit board (PCB), on which at least one light assembly 124 is mounted.\",\n \"The light assemblies 124 may be disposed on the substrate 122 at predetermined intervals in the first direction.\",\n \"A diameter of the light assembly 124 may be greater than a width of the substrate 122.Namely, the diameter of the light assembly 124 may be greater than a length of the substrate 122 in the second direction.\",\n \"The light assembly 124 may be one of a light emitting diode (LED) chip and a LED package having at least one LED chip.\",\n \"The light assembly 124 may be configured as a colored LED emitting at least one of red, green, and blue light or a white LED.\",\n \"The colored LED may include at least one of a red LED, a green LED, and a blue LED.\",\n \"The light source included in the light assembly 124 may be a COB (Chip-On-Board) type.\",\n \"The COB light source may have a configuration, in which the LED chip as the light source is directly coupled to the substrate 122.Thus, the process may be simplified.\",\n \"Further, a resistance may be reduced, and a loss of energy resulting from heat may be reduced.\",\n \"Namely, power efficiency of the light assembly 124 may increase.\",\n \"The COB light source can provide the brighter lighting and may be implemented to be thinner and lighter than a related art.\",\n \"The reflecting sheet 126 may be positioned at the front surface of the substrate 122.The reflecting sheet 126 may be positioned in an area excluding a formation area of the light assemblies 124 of the substrates 122.Namely, the reflecting sheet 126 may have a plurality of holes 235.The reflecting sheet 126 may reflect light emitted from the light assembly 124 to a front surface of the reflecting sheet 126.Further, the reflecting sheet 126 may again reflect light reflected from the diffusion plate 129.The reflecting sheet 126 may include at least one of metal and metal oxide which are a reflection material.\",\n \"The reflecting sheet 126 may include metal and/or metal oxide having a high reflectance, for example, aluminum (Al), silver (Ag), gold (Au), and titanium dioxide (TiO2).\",\n \"The reflecting sheet 126 may be formed by depositing and/or coating the metal or the metal oxide on the substrate 122.An ink including the metal material may be printed on the reflecting sheet 126.On the reflecting sheet 126, a deposition layer may be formed using a heat deposition method, an evaporation method, or a vacuum deposition method such as a sputtering method.\",\n \"On the reflecting sheet 126, a coating layer and/or a printing layer may be formed using a printing method, a gravure coating method or a silk screen method.\",\n \"An air gap may be positioned between the reflecting sheet 126 and the diffusion plate 129.The air gap may serve as a buffer capable of widely spreading light emitted from the light assembly 124.A supporter (or support plate) 200 may be positioned between the reflecting sheet 126 and the diffusion plate 129, so as to maintain the air gap.\",\n \"A resin may be deposited on the light assembly 124 and/or the reflecting sheet 126.The resin may function to diffuse light emitted from the light assembly 124.The diffusion plate 129 may upwardly diffuse light emitted from the light assembly 124.The optical sheet 125 may be positioned at a front surface of the diffusion plate 129.A back surface of the optical sheet 125 may be adhered to the diffusion plate 129, and a front surface of the optical sheet 125 may be adhered to the back surface of the display panel 110.The optical sheet 125 may include at least one sheet.\",\n \"More specifically, the optical sheet 125 may include one or more prism sheets and/or one or more diffusion sheets.\",\n \"The plurality of sheets included in the optical sheet 125 may be attached and/or adhered to one another.\",\n \"In other words, the optical sheet 125 may include a plurality of sheets having different functions.\",\n \"For example, the optical sheet 125 may include first to third optical sheets 125a to 125c.\",\n \"The first optical sheets 125a may function as a diffusion sheet, and the second and third optical sheets 125b and 125c may function as a prism sheet.\",\n \"A number and/or a position of the diffusion sheets and the prism sheets may be changed.\",\n \"For example, the optical sheet 125 may include the first optical sheets 125a as the diffusion sheet and the second optical sheet 125b as the prism sheet.\",\n \"The diffusion sheet may prevent light coming from the diffusion plate from being partially concentrated and may homogenize a luminance of the light.\",\n \"The prism sheet may concentrate light coming from the diffusion sheet and may make the concentrated light be vertically incident on the display panel 110.The coupling unit 125d may be formed on at least one of corners of the optical sheet 125.The coupling unit 125d may be formed in at least one of the first to third optical sheets 125a to 125c.\",\n \"The coupling unit 125d may be formed at the corner on the long side of the optical sheet 125.The coupling unit 125d formed on the first long side and the coupling unit 125d formed on the second long side may be asymmetric.\",\n \"For example, a number and/or a position of the coupling units 125d formed on the first long side may be different from a number and/or a position of the coupling units 125d formed on the second long side.\",\n \"Referring to FIG.\",\n \"7, the substrates 122 including the plurality of straps, which extend in the first direction and are separated from one another by a predetermined distance in the second direction perpendicular to the first direction, may be provided on the frame 130.One end of each of the plurality of substrates 122 may be connected to a line electrode 232.The line electrode 232 may extend in the second direction.\",\n \"The line electrode 232 may be connected to the ends of the substrates 122 at predetermined intervals in the second direction.\",\n \"The substrates 122 may be electrically connected to the adaptor through the line electrode 232.The light assemblies 124 may be mounted on the substrate 122 at predetermined intervals in the first direction.\",\n \"A diameter of the light assembly 124 may be greater than a width of the substrate 122 in the second direction.\",\n \"Hence, an outer area of the light assembly 124 may be positioned beyond a formation area of the substrate 122.FIGS.\",\n \"8 and 9 show a light source according to the embodiment of the invention.\",\n \"As shown in FIG.\",\n \"8, a light source 203 may be a COB light source.\",\n \"The COB light source 203 may include at least one of an emission layer 135, first and second electrodes 147 and 149, and a fluorescent layer 137.The emission layer 135 may be positioned on the substrate 122.The emission layer 135 may emit one of red, green, and blue light.\",\n \"The emission layer 135 may include one of Firpic, (CF3ppy) 2Ir(pic), 9,10-di(2-naphthyl)anthracene (AND), perylene, distyrybiphenyl, PVK, OXD-7, UGH-3(Blue), and a combination thereof.\",\n \"The first and second electrodes 147 and 149 may be positioned on both sides of a lower surface of the emission layer 135.The first and second electrodes 147 and 149 may transmit an external driving signal to the emission layer 135.The fluorescent layer 137 may cover the emission layer 135 and the first and second electrodes 147 and 149.The fluorescent layer 137 may include a fluorescent material converting light of a spectrum generated from the emission layer 135 into white light.\",\n \"A thickness of the emission layer 135 on the fluorescent layer 137 may be uniform.\",\n \"The fluorescent layer 137 may have a refractive index of 1.4 to 2.0.The COB light source 203 according to the embodiment of the invention may be directly mounted on the substrate 122.Thus, the size of the light assembly 124 may decrease.\",\n \"Because heat dissipation of the light sources 203 is excellent by forming the light sources 203 on the substrate 122, the light sources 203 may be driven at a high current.\",\n \"Hence, a number of light sources 203 required to secure the same light quantity may decrease.\",\n \"Further, because the light sources 203 are mounted on the substrate 122, a wire bonding process may not be necessary.\",\n \"Hence, the manufacturing cost may be reduced due to the simplification of the manufacturing process.\",\n \"As shown in FIG.\",\n \"9, the light source 203 according to the embodiment of the invention may emit light in a first emission range EA1.Namely, the light source 203 may emit light in the first emission range EA1 including a second emission range EA2 of the front side and third and fourth emission ranges EA3 and EA4 of both sides.\",\n \"Thus, the light source 203 according to the embodiment of the invention is different from a related art POB light source emitting light in the second emission range EA2.In other words, the light source 203 according to the embodiment of the invention may be the COB light source, and the COB light source 203 may emit light in a wide emission range including the side.\",\n \"Because the COB light source 203 emits light even in a direction corresponding to the third and fourth emission ranges EA3 and EA4 of the side, the embodiment of the invention needs to efficiently control light of the side direction.\",\n \"The reflecting sheet according to the embodiment of the invention may control a reflectance of light emitted from the light source 203 in the side direction.\",\n \"Thus, the embodiment of the invention may reduce the non-uniformity of brightness resulting from light of the side direction.\",\n \"FIG.\",\n \"10 illustrates a connection relationship between the reflecting sheet and components around the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FG.\",\n \"10, the reflecting sheet 126 according to the embodiment of the invention may be placed on the frame 130.For example, the reflecting sheet 126 may be coupled to a receiving unit 132 formed inside the frame 130.The reflecting sheet 126 may include a horizontal coupling unit HH and a vertical coupling unit VH.\",\n \"For example, coupling holes may be formed along a long side and/or a short side of the reflecting sheet 126.The horizontal coupling unit HH and the vertical coupling unit VH may be inserted into a horizontal protrusion 130H and/or a vertical protrusion 130V formed on the frame 130.A guide panel GP may be formed on the reflecting sheet 126.The guide panel GP may be formed of plastic material of injection molding or press processed metal material.\",\n \"The guide panel GP may be coupled to the horizontal protrusion 130H and/or the vertical protrusion 130V.\",\n \"When the guide panel GP is coupled to the reflecting sheet 126, the reflecting sheet 126 may be fixed between the frame 30 and the guide panel GP.\",\n \"FIG.\",\n \"10 shows that the long sides and the short sides of the guide panel GP are separated from one another, as an example.\",\n \"The guide panel GP, which the long sides and the short sides are connected to one another, may be used.\",\n \"The reflecting sheet 126 placed on the frame 130 may be configured as a three-dimensional shape corresponding to a shape of the receiving unit 132.Even when the reflecting sheet 126 according to the embodiment of the invention has the three-dimensional shape, the reflecting sheet 126 can provide an optimum reflection effect.\",\n \"For example, the reflecting sheet 126 can uniformly reflect light throughout its entire area.\",\n \"The reflecting sheet 126 may constitute a portion of the backlight unit 120 (refer to FIG.\",\n \"5).\",\n \"The substrate 122, on which the light sources 203 are mounted, may be positioned between the reflecting sheet 126 and the frame 130.The plurality of substrates 122 may be arranged in the horizontal direction and/or the vertical direction.\",\n \"The substrates 122 may be connected to signal lines 121 connected to a controller, etc., of the display device 100.The signal lines 121 may be connected to the substrates 122 through holes formed in the frame 130.The reflecting sheet 126 may include a plurality of lens holes 235.The plurality of lens holes 235 may correspond to the light sources 203 on the substrate 122.For example, the plurality of lens holes 235 may be arranged in the horizontal direction and/or the vertical direction correspondingly to the light sources 203.A lens 124b may be inserted into the lens hole 235.For example, the lens 124b may be coupled to the light source 203 through the lens hole 235.The reflecting sheet 126 may include a plurality of support holes (or support plate holes) 205.A supporter 200 may be coupled to the support hole 205.The supporter 200 may support the optical sheet 125 and/or the diffusion plate 129 positioned in front of the reflecting sheet 126.Namely, the reflecting sheet 126 may be separated from the optical sheet 125 and/or the diffusion plate 129 at a predetermined distance.\",\n \"The reflecting sheet 126 may include a plurality of fixing pin holes 206.A fixing pin 202 may be coupled to the fixing pin hole 206.Also, the fixing pin 202 may be coupled to a frame hole 204 formed in the frame 130.Thus, the fixing pin 202 may fix the reflecting sheet 126 to the frame 130.FIGS.\",\n \"11 to 13 illustrate configuration of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"11 to 13, the reflecting sheet 126 according to the embodiment of the invention may be placed in an inner area of the frame 130.The reflecting sheet 126 placed on the frame 130 may have the three-dimensional shape corresponding to a shape of the frame 130.As shown in FIG.\",\n \"11, the frame 130 may include first to third frame areas 130a to 130c.\",\n \"The first frame area 130a may be a bottom surface of the frame 130.The second frame area 130b may be substantially flat.\",\n \"Namely, the second frame area 130b may be a surface positioned on an X-Y plane of the display device 100.The second frame area 130b may be a sidewall surface extended upwardly from the first frame area 130a.\",\n \"The second frame area 130b may extend in a direction parallel to a Z-axis direction or a direction inclined to the Z-axis direction.\",\n \"The receiving unit 132 (refer to FIG.\",\n \"10) may be formed inside the frame 130 by the second frame area 130b serving as a sidewall of the frame 130.The third frame area 130c may be a surface extended from the second frame area 130b in an X-axis direction.\",\n \"The third frame area 130c may be substantially parallel to the first frame area 130a.\",\n \"Namely, the third frame area 130c may be a flat surface in the same manner as the first frame area 130a at a height level different from the first frame area 130a by the second frame area 130b.\",\n \"The third frame area 130c may include a protruding area.\",\n \"The third frame area 130c may be coupled to a protrusion formed through a separate process.\",\n \"The protruding area and/or the protrusion of the third frame area 130c may be coupled to the reflecting sheet 126.For example, the protruding area and/or the protrusion of the third frame area 130c may be coupled to a third sheet area 126c of the reflecting sheet 126.The protruding area and/or the protrusion of the third frame area 130c may be coupled to the optical sheet 125 (refer to FIG.\",\n \"5).\",\n \"The reflecting sheet 126 may be coupled to an area formed by the first to third frame areas 130a to 130c of the frame 130.For example, the reflecting sheet 126 may be coupled to the first frame area 130a through the fixing pin 202.When a portion of the reflecting sheet 126 is coupled to the first frame area 130a through the fixing pin 202, the portion of the reflecting sheet 126 may naturally contact the frame 130.When the reflecting sheet 126 is coupled to the frame 130 through the fixing pin 202, the shape of the reflecting sheet 126 may be naturally changed depending on the shape of the frame 130.Namely, a naturally rounded second sheet area 126b of the reflecting sheet 126 may be formed.\",\n \"Thus, a separate process for forming a chamfer of the reflecting sheet 126 may not be necessary, and workability may be improved.\",\n \"The reflecting sheet 126 may include first to third sheet areas 126a to 126c.\",\n \"Namely, an area of the reflecting sheet 126 may be divided depending on whether or not the reflecting sheet 126 and the frame 130 contact each other.\",\n \"For example, the area of the reflecting sheet 126 may be divided into a contact area contacting the frame 130 and a non-contact area not contacting the frame 130.The area of the reflecting sheet 126 may be divided or delineated into the first sheet area 126a and the second sheet area 126b by the fixing pin 202.In other words, the second sheet area 126b may be an area between the fixing pin 202 and a portion contacting the third frame area 130c, Namely, the first sheet area 126a and the second sheet area 126b may be determined depending on whether or not the reflecting sheet 126 contacts the first frame area 130a of the frame 130.The second sheet area 126b may be naturally separated from the frame 130 by properties and elasticity of the reflecting sheet 126.For example, when the first sheet area 126a is coupled to the frame 130 by the fixing pin 202, the second sheet area 126b may naturally form a curved surface by its own weight and may be separated from the frame 130.A separation space 130d may be formed between the second sheet area 126b and the frame 130.An angle formed by the second sheet area 126b of the reflecting sheet 126 and the bottom surface of the frame 130 may gradually increase.\",\n \"Namely, in the non-contact area of the reflecting sheet 126, the reflecting sheet 126 may have a two-dimensional curve shape.\",\n \"Thus, the second sheet area 126b may be separated from the frame 130 at a predetermined angle.\",\n \"The third sheet area 126c may be placed in the third frame area 130c.\",\n \"The third sheet area 126c may be coupled to the third frame area 130c.\",\n \"Alternatively, the third sheet area 126c may be naturally positioned on the third frame area 130c.\",\n \"Namely, the third sheet area 126c may contact the third frame area 130c by elastic force of the Z-axis direction resulting from the rounded second sheet area 126b.\",\n \"Light L may be emitted through the lens 124b.\",\n \"Namely, light generated in the light source 203 may be emitted to the outside through the lens 124b.\",\n \"The light L emitted through the lens 124b may travel through various paths.\",\n \"For example, a portion of the light L may travel through a path of the side direction of the lens 124b.\",\n \"The portion of the light L in the path of the side direction may travel toward the second sheet area 126b.\",\n \"At least a portion of light generated in the light source 203 may be totally reflected inside the lens 124b and may travel toward the second sheet area 126b.\",\n \"In this instance, an amount of light L upwardly travelling in the second sheet area 126b may be more than an amount of light L downwardly travelling in the second sheet area 126b.\",\n \"In other words, an amount and/or a density of light L transferred to the reflecting sheet 126 may be non-uniform.\",\n \"When the amount and/or the density of the light L is not uniform, a viewer watching the display device 100 may perceive non-uniformity of the amount and/or the density of the light L. For example, when an amount of light L incident on an upper portion of the second sheet area 126b is more than an amount of light L incident on a lower portion of the second sheet area 126b, a corresponding area may be recognized as being brighter than other areas because of the light L reflected from the upper portion of the second sheet area 126b.\",\n \"As shown in FIG.\",\n \"12, an angle formed by an extension line from a boundary between the first sheet area 126a and the second sheet area 126b to a boundary between the second sheet area 126b and the third sheet area 126c and two straight lines parallel to the X-axis direction may be called “A”.\",\n \"An inclined angle of the second sheet area 126b using an intersection point P between the second sheet area 126b and a straight line of the angle A as a starting point may increase.\",\n \"Namely, an angle of the second sheet area 126b passing the intersection point P in the X-axis direction may sharply increase.\",\n \"Because the angle of the second sheet area 126b passing the intersection point P increases, a density of the light L emitted from the lens 124b (refer to FIG.\",\n \"11) per unit area may further increase.\",\n \"Thus, a corresponding portion may be seen as being brighter than other portions.\",\n \"As a result, the viewer may feel that the light is not uniform.\",\n \"The display device 100 according to the embodiment of the invention can make light be uniformly reflected from the reflecting sheet 126.Hence, the viewer cannot feel or can feel less the non-uniformity of the light.\",\n \"As shown in FIG.\",\n \"13, in the display device 100 according to the embodiment of the invention, dots DT may be formed in at least a portion of the reflecting sheet 126.The dot DT may be an area having a pattern different from other areas.\",\n \"The dot DT may be an area of uneven portions (or concave-convex portions) formed on the reflecting sheet 126.The dot DT may be an area, in which at least a portion of the reflecting sheet 126 is colored.\",\n \"For example, the dot DT may be an area of a relatively dark color.\",\n \"For example, the dot DT may be a black or gray area.\",\n \"The dot DT may be an area, in which the uneven portion and the colored portion are mixed with each other.\",\n \"The dot DT may have a geometric shape, in which there is a difference in at least one of a shape, a size, a location, and a color.\",\n \"For example, the dot DT may be one of various shapes including a circle, an oval, a rectangle, a rod, a triangle, etc., formed on the reflecting sheet 126 and/or a combination of the various shapes.\",\n \"The dots DT may affect a reflectance of a corresponding area.\",\n \"Namely, the dots DT may change a reflectance of light.\",\n \"For example, the reflectance of light may be reduced depending on at least one of a shape, a size, a location, and a color of the dot DT.\",\n \"The plurality of dots DT may gather (or arranged) and form a dot area DA.\",\n \"The dot area DA may be a gathering (or arranging) of the dots DT.\",\n \"Namely, the dot area DA may be a formation area of the plurality of dots DT, which are the same as or different from one another in at least one of a shape, a size, a location, and a color.\",\n \"For example, the dot area DA may be formed in at least a portion of the second sheet area 126b.\",\n \"As described above, a density of light per unit area in the second sheet area 126b may be high because of the inclined shape of the second sheet area 126b.\",\n \"The dot area DA may change a reflectance of light incident on the second sheet area 126b.\",\n \"In other words, a density of incident light per unit area is high, but a density of reflected light per unit area may decrease.\",\n \"Thus, a phenomenon, in which a contrast of a portion corresponding to the second sheet area 126b is different from a contrast of other portions, may be prevented.\",\n \"Namely, light can be uniformly reflected from the entire reflecting sheet 126 because of the dot area DA.\",\n \"The dots DT constituting the dot area DA may be divided into a plurality of groups having different attributes.\",\n \"For example, a formation area of dots having a first attribute may be called a first area, and a formation area of dots having a second attribute may be called a second area.\",\n \"Hereinafter, the dot area DA may be displayed by changing the color, the density, etc., of the reflecting sheet 126, and areas having the different colors, densities, etc., may be formation areas of dots having different attributes even if a separate explanation is not given.\",\n \"For example, dots having different attributes may be disposed in an area with a first color and an area with a second color.\",\n \"Namely, dots, which are different from one another in at least one of the size, the density, the color, and the interval, may be disposed in different areas.\",\n \"The reflecting sheet 126 may further include anon-dot area NDA.\",\n \"The non-dot area NDA may be an area, in which there is no dot DT.\",\n \"The non-dot area NDA may be positioned in various areas of the reflecting sheet 126.For example, the non-dot area NDA may include first and second non-dot areas NDA1 and NDA2.A width of the non-dot area NDA may be greater than a distance between adjacent dots.\",\n \"Namely, the width of the non-dot area NDA in a direction from the first sheet area 126a to the third sheet area 126c may be greater than a distance between two dots adjacent to the non-dot area NDA.\",\n \"The width of the non-dot area NDA may be equal to or greater than 2 mm.\",\n \"The second non-dot area NDA2 may be positioned at a boundary between the second sheet area 126b and the third sheet area 126c.\",\n \"The second non-dot area NDA2 may be positioned in the second sheet area 126b at the boundary between the second sheet area 126b and the third sheet area 126c.\",\n \"The second non-dot area NDA2 may be an uppermost area of the second sheet area 126b and thus may be close to the optical sheet 125 and/or the diffusion plate 129 positioned in front of the reflecting sheet 126.Hence, if the dot DT exists in the second non-dot area NDA2, the user of the display device 100 may observe the dot DT.\",\n \"Thus, the dot DT may not exist in the second non-dot area NDA2.FIGS.\",\n \"14 to 23 illustrate a dot distribution of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"14 to 23, the dots DT of the reflecting sheet 126 according to the embodiment of the invention may be disposed in various shapes.\",\n \"As shown in (a) of FIG.\",\n \"14, the dots DT may be disposed in the dot area DA.\",\n \"The adjacent dots DT may be separated from each other by a first distance O1.Namely, the dots DT may be disposed at regular intervals of the first distance O1.The distance between the dots DT may affect the reflectance of the reflecting sheet 126.For example, when the distance between the dots DT decreases, the reflectance may decrease.\",\n \"As shown in (b) of FIG.\",\n \"14, the adjacent dots DT may be separated from each other by the first distance O1, and the adjacent dots DT may be separated from each other by a second distance O2.Namely, a distance between the dots DT may not be uniform As shown in (a) of FIG.\",\n \"15, the dot area DA may be divided into a plurality of areas.\",\n \"For example, the dot area DA may be divided into a first area P1 and a second area P2.An attribute of dots DT included in the first area P1 may be different from an attribute of dots DT included in the second area P2.For example, at least one of a size, a density, and a color of a first dot DT1 in the first area P1 may be different from at least one of a size, a density, and a color of a second dot DT2 in the second area P2.The second area P2 may be positioned further outside than the first area P1.Namely, the second area P2 may be an area close to the third sheet area 126c.\",\n \"The second dot DT2 of the second area P2 may be larger than the first dot DT1 of the first area P1.Thus, a reflectance of the second area P2 may be less than a reflectance of the first area P1.As shown in (b) of FIG.\",\n \"15, the dot area DA may be divided into a plurality of areas.\",\n \"For example, the dot area DA may be divided into first to third areas P1 to P3.First to third dots DP1 to DP3 of the first to third areas P1 to P3 may have different attributes.\",\n \"For example, the second dot DT2 may be larger than the first dot DT1, and the third dot DT3 may be larger than the second dot DT2.Alternatively, the first to third dots DP1 to DP3 have the same size, but a density of the first area P1 may be different from a density of the second area P2, and a density of the second area P2 may be different from a density of the third area P3.For example, the density of the first area P1 may be less than the density of the second area P2, and the density of the second area P2 may be less than the density of the third area P3.As shown in FIG.\",\n \"16, the dot area DA may not be divided into a plurality of areas.\",\n \"However, dots DT included in the dot area DA may be different from each other in at least one of a size, a density, and a color.\",\n \"For example, as the dot DT goes along the X-axis direction, the size of the dot DT may gradually increase.\",\n \"Namely, an attribute of the dot DT including at least one of the size, the density, and the color may gradually change.\",\n \"As shown in (a) of FIG.\",\n \"17, a size of the dot DT may gradually change depending on a location.\",\n \"As shown in (b) of FIG.\",\n \"17, a size of the dot DT may sharply change depending on a location.\",\n \"For example, the size of the dot DT may be changed in a curve shape of a quadratic function.\",\n \"As shown in FIG.\",\n \"18, dots DT may be disposed in a horizontal dot area HDA and a vertical dot area VDA in various shapes.\",\n \"The horizontal dot area HDA may be a dot area DA formed on the long side of the reflecting sheet 126, and a vertical dot area VDA may be a dot area DA formed on the short side of the reflecting sheet 126.Detailed locations of the horizontal dot area HDA and the vertical dot area VDA will be described in corresponding paragraphs.\",\n \"As shown in (a) of FIG.\",\n \"18, the horizontal dot area HDA and/or the vertical dot area VDA may be divided into a plurality of areas.\",\n \"For example, the horizontal dot area HDA and/or the vertical dot area VDA may be divided into an uppermost area A, a leftmost area B, a rightmost area D, a lowermost area E, and/or a an inner area C. The horizontal dot area HDA and/or the vertical dot area VDA may be divided in different manners.\",\n \"Dots in the plurality of areas of the horizontal dot area HDA and/or the vertical dot area VDA may have different attributes.\",\n \"For example, a size and/or a density of a dot DT in the uppermost area A may be greater than a size and/or a density of a dot DT in the lowermost area E. A size and/or a density of a dot DT in the inner area C may be greater than a size and/or a density of dots DT in the leftmost area B and the rightmost area D. As shown in (b) of FIG.\",\n \"18, the horizontal dot area HDA and/or the vertical dot area VDA may not be divided into a plurality of areas.\",\n \"Namely, the dots DT, of which the attributes gradually change, may be disposed.\",\n \"For example, a size and/or a density of the dot DT may increase as the dot DT goes to the upper side of the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"The size and/or the density of the dot DT may decrease as the dot DT goes to the inner side of the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"As shown in (c) of FIG.\",\n \"18, attributes of dots DT in an inner area and an outer area of the horizontal dot area HDA and/or the vertical dot area VDA may change.\",\n \"For example, a dot DT having a relatively small size may be disposed at a boundary between the left and right sides and/or the lower side of the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"A dot DT having a relatively large size may be disposed at a boundary between the inner side and/or the upper side of the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"The attribute of the dot DT including the size may change gradually or non-gradually.\",\n \"For example, in an area ranging from the outer area to the inner area of the horizontal dot area HDA and/or the vertical dot area VDA, the size of the dot DT may gradually change or may change depending on a location.\",\n \"For example, the size of the dot DT in a first area including the left and right sides of the horizontal dot area HDA and/or the vertical dot area VDA may be different from the size of the dot DT in a second area including the inner side of the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"In other words, there may be a difference in at least one of the size, the color, the interval, and the density of the dots DT disposed in a horizontal direction and/or a vertical direction of the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"For example, in the instance of the horizontal dot area HDA, sizes of two dots DT positioned adjacent to each other in the horizontal direction of the horizontal dot area HDA may be different from each other.\",\n \"The arrangement of the dots DT may be related to the lens hole positioned along the horizontal direction of the horizontal dot area HDA.\",\n \"Namely, a portion, in which the lens hole is positioned, may be brighter, and other areas may be darker.\",\n \"The dots DT having different attributes may be arranged along the horizontal direction of the horizontal dot area HDA, so as to prevent a luminance difference, in which a brighter portion and a darker portion are present.\",\n \"As shown in FIG.\",\n \"19, dots constituting the horizontal dot area HDA and the vertical dot area VDA may have different attributes.\",\n \"For example, a size range of the dots constituting the horizontal dot area HDA may be greater than a size range of the dots constituting the vertical dot area VDA.\",\n \"Namely, the horizontal dot area HDA may include relatively smaller dots and relatively larger dots than the vertical dot area VDA.\",\n \"In other words, a diversity of the dots constituting the horizontal dot area HDA may be more than a diversity of the dots constituting the vertical dot area VDA.\",\n \"For example, the smallest dot in the horizontal dot area HDA may be smaller than the smallest dot in the vertical dot area VDA, and the largest dot in the horizontal dot area HDA may be larger than the largest dot in the vertical dot area VDA.\",\n \"For example, the smallest dot of the horizontal dot area HDA may have the size equal to or less than 0.5 mm, and the largest dot of the horizontal dot area HDA may have the size equal to or greater than 2 mm.\",\n \"On the other hand, the smallest dot of the vertical dot area VDA may have the size equal to or less than 0.8 mm, and the largest dot of the vertical dot area VDA may have the size equal to or greater than 1.2 mm.\",\n \"For example, when the sizes of the dots included in the horizontal dot area HDA are divided into “A” groups and the sizes of the dots included in the vertical dot area VDA are divided into “B” groups, A is greater than B.\",\n \"In other words, a size diversity of the dots included in the horizontal dot area HDA may be more than a size diversity of the dots included in the vertical dot area VDA.\",\n \"An amount range of the dots constituting the horizontal dot area HDA may be greater than an amount range of the dots constituting the vertical dot area VDA.\",\n \"For example, when the dots having the same size are used, a number of dots included in the horizontal dot area HDA may be more or less than a number of dots included in the vertical dot area VDA.\",\n \"As shown in FIG.\",\n \"20, the dot area DA may exist on the reflecting sheet 126.For example, the dots may be distributed along the short sides of the display device 100.For example, the dots may be distributed in the second area 126b (refer to FIG.\",\n \"13) of the reflecting sheet 126.As described above, the dot area DA may include a horizontal dot area HDA and a vertical dot area VDA.\",\n \"A description of one of the horizontal dot area HDA and the vertical dot area VDA is equally applied to the other, except in the instance where the horizontal dot area HDA and the vertical dot area VDA are separately described.\",\n \"The arrangement of the dots DT in the dot area DA may be related to the arrangement of the lens holes 235.As described above, the lens hole 235 may correspond to the light source 203 (refer to FIG.\",\n \"10) and the lens 124b (refer to FIG.\",\n \"10).\",\n \"The plurality of lens holes 235 may be disposed on the reflecting sheet 126 in accordance with a predetermined rule.\",\n \"Some of the plurality of lens holes 235 may be disposed adjacent to the dot area DA.\",\n \"For example, the lens holes 235 may be separated from the dot area DA by a predetermined distance and may be disposed in parallel with each other.\",\n \"A first area AR1 and a second area AR2 may be formed based on the lens holes 235.For example, the first area AR1 may be an area including the lens hole 235, and the second area AR2 may be an area between the lens holes 235.The dots DT disposed in the first area AR1 and the second area AR2 may have different attributes.\",\n \"For example, at least one of a size, a density, and a color of the dot DT in the first area AR1 may be different from at least one of a size, a density, and a color of the dot the second area AR2.The difference is because intensities of light beams reaching the first area AR1 and the second area AR2 may be different from each other depending on a distance between the lens hole 235 and the first area AR1 and the second area AR2.As shown in FIG.\",\n \"21A, attributes of the dots DT constituting the horizontal dot area HDA and/or the vertical dot area VDA may change depending on the area.\",\n \"The horizontal dot area HDA may include first to third horizontal dot areas HDA1 to HDA3.Namely, the dot area DA may be divided into a plurality of areas.\",\n \"The first horizontal dot area HDA1 may be an area including both sides of the horizontal dot area HDA and may be a boundary area in an inside direction of the reflecting sheet 126.The second horizontal dot area HDA2 may be an area inside the first horizontal dot area HDA1, and the third horizontal dot area HDA3 may be an area inside the second horizontal dot area HDA2.The dots DT in the first to third horizontal dot areas HDA1 to HDA3 may have different attributes.\",\n \"Namely, there may be a difference between the dots DT of the first to third horizontal dot areas HDA1 to HDA3 in at least one of a size, a density, and a color of the dot DT.\",\n \"For example, the dots DT included in the first horizontal dot area HDA1 may be the same as one another in at least one of the size, the distance, the density, and the color.\",\n \"However, the dot DT of the first horizontal dot area HDA1 may be different from the dot DT of the second horizontal dot area HDA2 in at least one of the size, the distance, the density, and the color.\",\n \"Considering the above description, each of the first to third horizontal dot areas HDA1 to HDA3 may be regarded as the gathering (or arranging) of the dots DT having the same attribute.\",\n \"The vertical dot area VDA may include first to third vertical dot areas VDA1 to VDA3.The dots DT constituting the first to third vertical dot areas VDA1 to VDA3 may have different attributes.\",\n \"The above description of the first to third horizontal dot areas HDA1 to HDA3 of the horizontal dot area HDA may be equally applied to the first to third vertical dot areas VDA1 to VDA3 of the vertical dot area VDA.\",\n \"The horizontal dot area HDA and the vertical dot area VDA may be adjacent to four corner areas of the reflecting sheet 126.For example, the horizontal dot area HDA may be disposed on one side of a cutting portion S1, and the vertical dot area VDA may be disposed on the other side of the cutting portion S1.The first horizontal dot area HDA1 and the first vertical dot area VDA1 may be positioned in an area including the corner area close to the horizontal dot area HDA and the vertical dot area VDA Because the corner area is relatively far away from the lens hole 235, the corner area may be relatively dark.\",\n \"Thus, the dot DT may not be disposed in the middle of the corner area.\",\n \"The dots DT having a relatively high reflectance may be disposed in the first horizontal dot area HDA1 and the first vertical dot area VDA1 close to the corner area.\",\n \"For example, the relatively small dots DT may be disposed.\",\n \"For example, the dots DT having the relatively low density may be disposed.\",\n \"As shown in FIG.\",\n \"21B, the plurality of lens holes 235 may be divided into a first lens hole group 235a and a second lens hole group 235b depending on a distance between the lens holes 235 and the dot area DA.\",\n \"For example, the first lens hole group 235a may include the lens holes 235 adjacent to the dot area DA, and the second lens hole group 235b may include the lens holes 235 in the rear of the first lens hole group 235a.\",\n \"A portion of light emitted from the second lens hole group 235b may be shielded by the first lens hole group 235a.\",\n \"For example, a shielding area LH may be formed.\",\n \"The brightness of a corresponding area may be less than the brightness of other area because of the shielding area LH.\",\n \"Thus, the dots DT of the shielding area LH and the dots DT of other area may be differently configured.\",\n \"For example, a size of the dot DT in at least a portion of the shielding area LH may be different from that in the other area.\",\n \"As shown in FIG.\",\n \"22, a shape of the dot area DA may be changed depending on a location of the lens hole 235.For example, the dot area DA may include a first area AR1 including the lens hole 235 and a second area AR2 except the first area AR1 from the dot area DA.\",\n \"The first area AR1 may protrude to the lens hole 235 further than the second area AR2.For example, a protrusion area PD may be added to the dot area DA.\",\n \"A luminance of an area close to the lens hole 235 may be reduced by the protrusion area PD.\",\n \"The dots DT constituting the protrusion area PD may be different from the dots DT of other area.\",\n \"As shown in FIG.\",\n \"23A, the shape of the dot area DA may be changed depending on a relative location between the dot area DA and the lens hole 235.For example, as described above, the first area AR1 corresponding to the lens hole 235 may include the protrusion area PD protruding to the lens hole 235.A first dot DT1 constituting the protrusion area PD may be different from a second dot DT2 in the rear of the first dot DT1.A shape of the horizontal dot area HDA may be different from a shape of the vertical dot area VDA.\",\n \"For example, the protrusion area PD may be included only in one of the horizontal dot area HDA and the vertical dot area VDA.\",\n \"This may be related to the fact that a number of lens holes 235 in the horizontal dot area HDA is more than a number of lens holes 235 in the vertical dot area VDA.\",\n \"As shown in FIG.\",\n \"23B, each of the horizontal dot area HDA and the vertical dot area VDA disposed on the reflecting sheet 126 may have a specific shape.\",\n \"For example, a height and/or a width of the horizontal dot area HDA and/or the vertical dot area VDA may be differently set depending on a location.\",\n \"The horizontal dot area HDA may be divided.\",\n \"For example, the horizontal dot area HDA may be divided into first to third horizontal areas HA1 to HA3.The second horizontal area HA2 may be a center area of the horizontal dot area HDA.\",\n \"The first and third horizontal areas HA1 and HA3 may correspond to both sides of the second horizontal area HA2.The first and third horizontal areas HA1 and HA3 may have a shape different from the second horizontal area HA2.For example, the first and third horizontal areas HA1 and HA3 may have a shape protruding to the inside of the reflecting sheet 126 further than the second horizontal area HA2.For example, the second horizontal area HA2 may have a fourth height H4.The fourth height H4 may be less than at least one of first to third heights H1 to H3.The shape difference may be because the first and third horizontal areas HA1 and HA3 are closer to the corner of the reflecting sheet 126 than the second horizontal area HA2.Namely, because the reflecting sheet 126 has the rounded shape in the horizontal and vertical directions at the corner of the reflecting sheet 126, the luminance needs to be more precisely controlled.\",\n \"In the first and third horizontal areas HA1 and HA3, the horizontal dot area HDA may have the shape protruding in a predetermined pattern along the inside direction of the reflecting sheet 126.For example, the horizontal dot area HDA may have the shape protruding by the first height H1 and the second height H2 and then protruding by the third height H3.The first and third heights H1 and H3 may be greater than the second height H2.The first and third heights H1 and H3 may be different from each other.\",\n \"For example, the first heights H1 may be greater than the third height H3.The horizontal dot area HDA of the first height H1 and the horizontal dot area HDA of the third height H3 may be formed between the lens holes 235.For example, the horizontal dot area HDA of the first and third heights H1 and H3 may be formed in first and second areas A1 and A2 between the lens holes 235.Because light beams emitted from the plurality of lens holes 235 overlap each other through the above-described shape of the horizontal dot area HDA, the brightness of the first and second areas A1 and A2 may be efficiently controlled.\",\n \"FIG.\",\n \"23B shows that the horizontal dot area HDA has the first to fourth heights H1 to H4, as an example.\",\n \"The vertical dot area VDA having the height/the width different from the horizontal dot area HDA may be configured, so as to achieve the same or similar configuration and effect.\",\n \"FIGS.\",\n \"24 and 25 illustrate the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"24 and 25, the reflecting sheet 126 according to the embodiment of the invention may include the dot area DA.\",\n \"The dot area DA may be formed along the long side and/or the short side of the reflecting sheet 126.Namely, the dot area DA may be formed in the corner area of the reflecting sheet 126.In other words, the dot area DA may be formed in the second sheet area 126b(refer to FIG.\",\n \"11) of the reflecting sheet 126 placed in the receiving unit 132 (refer to FIG.\",\n \"10) of the frame 130 (refer to FIG.\",\n \"10).\",\n \"The dot area DA may include first and second horizontal dot areas HDA1 and HDA2 and first and second vertical dot areas VDA1 and VDA2.The first and second horizontal dot areas HDA1 and HDA2 are represented as the horizontal dot area HDA, and the first and second vertical dot areas VDA1 and VDA2 are represented as the vertical dot area VDA, except in the instance where they need to be distinguished from each other.\",\n \"A shape of the horizontal dot area HDA may be different from a shape of the vertical dot area VDA.\",\n \"For example, the shape of the horizontal dot area HDA may not be symmetric to the shape of the vertical dot area VDA based on a cutting portion S1 positioned at the corner of the reflecting sheet 126.The reflecting sheet 126 may include lens holes 235 for coupling the lenses 124b (refer to FIG.\",\n \"11), fixing pin holes 206, supporter holes 205, a horizontal coupling unit HH, and a vertical coupling unit VH.\",\n \"The lens holes 235 may be disposed in parallel with one another along the horizontal and vertical directions based on the size of the display device 100.The fixing pin hole 206 may be coupled to the fixing pin 202 (refer to FIG.\",\n \"10) for fixing the reflecting sheet 126 to the frame 130 (refer to FIG.\",\n \"10).\",\n \"The fixing pin hole 206 may be positioned adjacent to the outermost lens hole 235.For example, the fixing pin hole 206 may be positioned between the adjacent lens holes 235 or between the lens hole 235 and the dot area DA.\",\n \"The fixing pin hole 206 may be positioned adjacent to the lens hole 235 disposed on the outermost side.\",\n \"For example, the fixing pin hole 206 may be positioned closer to the outermost side than the outermost lens hole 235.For example, the fixing pin hole 206 may be positioned at a location overlapping the outermost lens hole 235.When the fixing pin 202 (refer to FIG.\",\n \"10) is coupled to the frame 130 (refer to FIG.\",\n \"10) through the fixing pin hole 206, the second sheet area 126b may be naturally formed.\",\n \"Namely, when the fixing pin 202 (refer to FIG.\",\n \"10) is coupled to the frame 130 (refer to FIG.\",\n \"10) through the fixing pin hole 206 formed in the horizontal and vertical directions, a round chamfer may be formed in the outer area of the reflecting sheet 126.A distance between the fixing pin holes 206 may be differently set.\",\n \"For example, a number of fixing pin holes 206 positioned in a horizontal center area HCA may be more than a number of fixing pin holes 206 positioned in other areas based on the horizontal direction of the reflecting sheet 126.A distance between the fixing pin holes 206 positioned in the horizontal center area HCA may be called a first horizontal distance HD1, and a distance between the fixing pin holes 206 positioned in areas other than the horizontal center area HCA may be called a second horizontal distance HD2.The first horizontal distance HD1 may be less than the second horizontal distance HD2.Namely, the fixing pin holes 206 in the horizontal center area HCA may be more densely disposed.\",\n \"Thus, a round chamfer may be naturally formed at the four upper, lower, left, and right corners of the reflecting sheet 126 while the reflecting sheet 126 is efficiently fixed.\",\n \"The fixing pin holes 206 disposed in the vertical direction may exist.\",\n \"For example, the fixing pin holes 206 may be disposed along the left and right short sides of the reflecting sheet 126.The fixing pin holes 206 on the first short side SS1 may be disposed at predetermined intervals of a first vertical distance VD1.The fixing pin holes 206 on the second short side SS2 may be disposed at predetermined intervals of a second vertical distance VD2.The first vertical distance VD1 and the second vertical distance VD2 may be different from each other.\",\n \"The second vertical distance VD2 may be greater than the first vertical distance VD1.A difference between the first vertical distance VD1 and the second vertical distance VD2 may be generated by a shape of the frame 130 coupled to the reflecting sheet 126.For example, the difference between the first vertical distance VD1 and the second vertical distance VD2 may be generated by a coupling space of a rib for assisting rigidity of the frame 130 and/or various electronic parts coupled to the frame 130.The supporter holes 205 may be coupled to the supporters 200.The supporter holes 205 may support the diffusion plate 129 (refer to FIG.\",\n \"5) and/or the optical sheet 125 (refer to FIG.\",\n \"5) on the reflecting sheet 126.The supporter holes 205 may be positioned in the middle of the reflecting sheet 126 for the efficient support.\",\n \"Namely, the supporter hole 205 may be positioned further inside than the outermost lens hole 235.The horizontal coupling unit HH and the vertical coupling unit VH may be disposed along the corner area of the reflecting sheet 126.The horizontal coupling unit HH and the vertical coupling unit VH may be inserted into the protrusions of the frame 130 (refer to FIG.\",\n \"10).\",\n \"FIG.\",\n \"25 shows one edge area of the reflecting sheet 126.Outermost lens holes 235a to 235c may mean the lens hole 235 positioned on the outermost side.\",\n \"Among the outermost lens holes 235a to 235c, the first and second outermost lens holes 235a and 235b positioned on the upper side may be separated from the lower side of the horizontal dot area HDA by a first distance HDS and may be separated from the upper side of the horizontal dot area HDA by a second distance HDE.\",\n \"Among the outermost lens holes 235a to 235c, the first and third lens holes 235a and 235c positioned on the side may be separated from the lower side of the vertical dot area VDA by a third distance VDS and may be separated from the upper side of the vertical dot area VDA by a fourth distance VDE.\",\n \"The first distance HDS may be different from the third distance VDS, and the second distance HDE may be different from the fourth distance VDE.\",\n \"This means that a width, a length, etc., of the horizontal dot area HDA may be different from a width, a length, etc., of the vertical dot area VDA.\",\n \"The first distance HDS may be greater than the third distance VDS.\",\n \"Namely, a distance between the horizontal dot area HDA and the lens hole 235 is greater than a distance between the vertical dot area VDA and the lens hole 235.The second sheet area 126b (refer to FIG.\",\n \"11) corresponding to the horizontal dot area HDA may be shorter than the second sheet area 126b (refer to FIG.\",\n \"11) corresponding to the vertical dot area VDA.\",\n \"Because lengths of the long side and the short side of the second sheet area 126b are different from each other, a slope of the round chamfer of the vertical dot area VDA on the short side may be greater than a slope of the round chamfer of the horizontal dot area HDA on the long side.\",\n \"An increase in the slope may increase a reflectance.\",\n \"When the reflectance increases, a corresponding portion may look brighter.\",\n \"In the reflecting sheet 126 according to the embodiment of the invention, because the vertical dot area VDA is positioned closer to the lens hole 235 than the horizontal dot area HDA, the reflectance may be controlled in spite of the high slope of the vertical dot area VDA on the short side of the reflecting sheet 126.The non-dot area NDA may be positioned between the horizontal/vertical dot area HDA or VDA and a horizontal/vertical margin area HM or VM.\",\n \"Namely, the non-dot area NDA not including the dot DT may be positioned on the horizontal/vertical dot area HDA or VDA, so that the user watching the display device 100 cannot recognize the dots DT.\",\n \"The non-dot area NDA is formed considering that the dots DT may be recognized from the outside when the dots DT exist in a corresponding area.\",\n \"The horizontal and vertical margin areas HM and VM may correspond to the third sheet area 126c.\",\n \"Namely, the horizontal and vertical margin areas HM and VM may be an outermost area of the reflecting sheet 126.In other words, the horizontal and vertical margin areas HM and VM may be an area of the reflecting sheet 126 contacting the third frame area 130c of the frame 130 (refer to FIG.\",\n \"11).\",\n \"The dots DT may not exist in the horizontal/vertical margin area HM or VM.\",\n \"A gap CR may exist between the horizontal margin area HM and the vertical margin area VM.\",\n \"The reflecting sheet 126 may be a plane.\",\n \"Namely, the reflecting sheet 126 may be a two-dimensional plane.\",\n \"When the reflecting sheet 126 of the two-dimensional shape is coupled to the receiving unit 132 (refer to FIG.\",\n \"10) of the three-dimensional shape, the reflecting sheet 126 may be changed into the three-dimensional shape.\",\n \"The shape of the reflecting sheet 126 may be changed by overlapping at least a portion of the reflecting sheet 126 along the cutting portion S1.A shadow may be generated by the overlap of the reflecting sheet 126.The gap CR may prevent the overlap of the reflecting sheet 126 and thus suppress the generation of the shadow.\",\n \"A folded portion S2 may extend from an end of the cutting portion S1.The folded portion S2 may not be cut, unlike the cutting portion S1.The folded portion S2 may be formed by previously folding a corresponding area along the cutting portion S1.Thus, when the reflecting sheet 126 is changed into the three-dimensional shape in the receiving unit 132 (refer to FIG.\",\n \"10), the reflecting sheet 126 may be guided by the folded portion S2 and may be changed into a previously designed shape.\",\n \"FIGS.\",\n \"26 to 28 illustrate configuration of the cutting portion of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"26 to 28, the reflecting sheet 126 according to the embodiment of the invention may be naturally changed into the three-dimensional shape by the cutting portion S1.As shown in (a) of FIG.\",\n \"26, the reflecting sheet 126 may have originally the two-dimensional shape.\",\n \"Namely, the reflecting sheet 126 may be configured as a thin sheet.\",\n \"The thin sheet may be processed into the shape of the reflecting sheet 126.A cutting surface CA may be formed on the reflecting sheet 126.The cutting surface CA may be a triangular surface.\",\n \"For example, the triangular cutting surface CA may exist at each corner of the reflecting sheet 126.Namely, the cutting surface CA may be positioned between the long side LS and the short side SS of the reflecting sheet 126.The folded portion S2 may be provided in an end portion of the cutting surface CA.\",\n \"The reflecting sheet 126 having the cutting surface CA may be folded in a direction, in which both sides of the triangular cutting surface CA approach each other.\",\n \"The reflecting sheet 126 may be naturally folded by the folded portion S2.As shown in (b) of FIG.\",\n \"26, the cutting portion S1 may be formed as both sides of the triangular cutting surface CA approach each other.\",\n \"The folded portion S2 may be formed at an end of the cutting portion S1.The reflecting sheet 126 may be naturally changed into the three-dimensional shape by the cutting portion S1 and the folded portion S2.The cutting portion S1 may be formed at a vertex of the reflecting sheet 126 in a diagonal direction.\",\n \"As shown in FIG.\",\n \"27A, the cutting surface CA may be positioned on the long side LS of the reflecting sheet 126.This is different from the above description, in which the cutting surface CA is positioned between the long side LS and the short side SS of the reflecting sheet 126.The horizontal dot area HDA positioned on the long side LS may be regarded as being divided into a first horizontal dot area HDA1 and a second horizontal dot area HDA2 because of the cutting surface CA on the long side LS.\",\n \"When the reflecting sheet 126 is placed on the frame 130 (refer to FIG.\",\n \"10), both sides of the triangular cutting surface CA may naturally approach each other.\",\n \"When both sides of the triangular cutting surface CA approach each other, the reflecting sheet 126 may be naturally changed into the three-dimensional shape.\",\n \"Thus, a separate process for forming the chamfer may not be necessary.\",\n \"In other words, workability may be improved.\",\n \"The gap CR may be formed so that a first horizontal margin area HM1 and a second horizontal margin area HM2 do not overlap each other.\",\n \"Namely, when both sides of the triangular cutting surface CA approach each other, the first and second horizontal margin areas HM1 and HM2 may not overlap each other by the gap CR even if a portion of the reflecting sheet 126 overlaps.\",\n \"Thus, even when the guide panel GP (refer to FIG.\",\n \"10) is coupled on the horizontal margin area HM, a floating problem resulting from the overlap of the horizontal margin area HM can be prevented.\",\n \"When both sides of the triangular cutting surface CA approach each other, the first and second horizontal margin areas HM1 and HM2 may be close to each other within the range where they do not overlap each other.\",\n \"Thus, the gap CR may be observed as being very small in the reflecting sheet 126 placed on the frame 130 (refer to FIG.\",\n \"10).\",\n \"As shown in (a) of FIG.\",\n \"27B, a first gap CR1 may exist in the reflecting sheet 126 of the two-dimensional shape.\",\n \"The reflecting sheet 126 of the two-dimensional shape may indicate the reflecting sheet 126 before being coupled to the frame 130 (refer to FIG.\",\n \"10).\",\n \"In this instance, the second horizontal margin area HM2 may not be parallel.\",\n \"Namely, a slope area IA may be formed in at least a portion of the second horizontal margin area HM2.The slope area IA may be inclined downwardly by an inclined distance IM.\",\n \"As shown in (b) of FIG.\",\n \"27B, when the reflecting sheet 126 is placed on the frame 130 (refer to FIG.\",\n \"10), a portion of the reflecting sheet 126 may overlap.\",\n \"For example, a portion of the first horizontal margin area HM1 may be overlappingly positioned under the second horizontal margin area HM2 based on the cutting portion S1.When the reflecting sheet 126 is changed into the three-dimensional shape by overlapping a portion of the reflecting sheet 126, the slope area IA may rotate counterclockwise by the inclined distance IM.\",\n \"Hence, the first and second horizontal margin areas HM1 and HM2 may be positioned on the same line T. A second gap CR2 of the reflecting sheet 126 changed into the three-dimensional shape may be smaller than the first gap CR1 of the reflecting sheet 126 of the two-dimensional shape.\",\n \"The second gap CR2 may be very small and may be similar to a width of the cutting portion S1.Even if portions of the reflecting sheet 126 overlap each other based on the cutting portion S1, the first and second horizontal margin areas HM1 and HM2 may not overlap each other.\",\n \"The cutting portion S1 may have the shape extending downwardly from the long side LS due to a location of the cutting surface CA.\",\n \"The shape of the cutting portion S1 may be advantageous in causing light to reach the end of the reflecting sheet 126.When the cutting surface CA is changed into the shape of the cutting portion S1, the first and second horizontal margin areas HM1 and HM2 may form one horizontal dot area HDA.\",\n \"FIG.\",\n \"27C shows the reflecting sheet 126 placed in the third frame area 130c of the frame 130 (refer to FIG.\",\n \"10) when viewed from the side.\",\n \"Even if an overlap area OA is generated in a portion of the reflecting sheet 126, the first and second horizontal margin areas HM1 and HM2 may not overlap each other.\",\n \"Thus, even if the guide panel GP is coupled on the first and second horizontal margin areas HM1 and HM2, it may be prevented from an arm portion from being formed due to the overlap of the first and second horizontal margin areas HM1 and HM2.As shown in (a) of FIG.\",\n \"28, the cutting portion S1 may start from the short side SS.\",\n \"The gap CR may exist at a starting position of the cutting portion S1.As shown in (b) of FIG.\",\n \"28, even when the cutting portion S1 exists on the short side SS and/or the long side LS, the folded portion S2 may be formed.\",\n \"The folded portion S2 may be formed in the diagonal direction, unlike the cutting portion S1.Thus, the folded portion S2 may guide the folding of the reflecting sheet 126.FIGS.\",\n \"29 and 30 illustrate a dot area according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"29 and 30, the dot area DA according to the embodiment of the invention may have various shapes so as to optimally reflect light.\",\n \"As shown in (a) of FIG.\",\n \"29, the horizontal dot area HDA and the vertical dot area VDA may have different shapes.\",\n \"For example, the horizontal dot area HDA may be separated from the cutting portion S1 and/or the folded portion S2 by a first angle DA1, and the vertical dot area VDA may be separated from the cutting portion S1 and/or the folded portion S2 by a second angle DA2.The first angle DA1 may be different from the second angle DA2.For example, the first angle DA1 may be greater than the second angle DA2.A difference between the location and/or the shape of the horizontal dot area HDA and the location and/or the shape of the vertical dot area VDA may be related to an amount of incident light.\",\n \"For example, the lens coupled to the second lens hole 235b may shield light emitted from other lens.\",\n \"Namely, a shade area GA may be formed by the lens coupled to the second lens hole 235b.\",\n \"Thus, the horizontal dot area HDA may be separated from the cutting portion S1 and/or the folded portion S2 by the first angle DA1, so that the horizontal dot area HDA does not overlap the shade area GA. Also, the location and/or the width of the vertical dot area VDA may be determined in consideration of the shade between the lens holes 235.The cutting portion S1 and/or the folded portion S2 may be a direction toward a center point CH of the first lens hole 235a.\",\n \"Namely, the cutting portion S1 and/or the folded portion S2 may be positioned on an imaginary extension line HDR connecting the center point CH to the cutting portion S1 and/or the folded portion S2 and may be positioned on the line parallel to and/or the same line as the cutting portion S1 and/or the folded portion S2.Thus, light emitted from the lens 124b (refer to FIG.\",\n \"11) coupled to the first lens hole 235a may be efficiently transferred up to end of the corner area of the reflecting sheet 126.As shown in (b) of FIG.\",\n \"29, the first and second angles DA1 and DA2 between the cutting portion S1 and/or the folded portion S2 and the horizontal dot area HDA and the vertical dot area VDA may be the same as each other.\",\n \"For example, when the shade is not generated or slightly generated by the size of the display device 100 and/or the location of the lens hole 235, the first and second angles DA1 and DA2 may be substantially equally configured.\",\n \"As shown in FIG.\",\n \"30, the first and second angles DA1 and DA2 may be asymmetric.\",\n \"The shape of the horizontal dot area HDA at the first angle DA1 may be different from the shape of the vertical dot area VDA at the second angle DA2.As described above, the shape of the horizontal dot area HDA and/or the vertical dot area VDA may be determined depending on the generation of the shade based on the disposition of the lens hole 235 and the lens 124b (refer to FIG.\",\n \"11) coupled to the lens hole 235.The horizontal dot area HDA and/or the vertical dot area VDA may have a bending shape.\",\n \"For example, a distance between the horizontal dot area HDA and the cutting portion S1 and a distance between the vertical dot area VDA and the cutting portion S1 may be changed.\",\n \"FIGS.\",\n \"31 to 38 illustrate configuration related to the lens hole of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"31 to 38, the reflecting sheet 126 according to the embodiment of the invention may include the lens hole 235 of various shapes and/or various dispositions capable of controlling a reflection amount of light.\",\n \"As shown in FIG.\",\n \"31, at least one of the lens holes 235 may include a first lens hole 235a.\",\n \"The first lens hole 235a may not have a circular shape (or a perfectly circular shape).\",\n \"The first lens hole 235a may have a shape, in which a radius is changed.\",\n \"The first lens hole 235a may have a shape, in which a radius is successively changed.\",\n \"For example, the first lens hole 235a of an oval shape may be used.\",\n \"The first lens hole 235a may have a shape, in which a radius is non-successively changed.\",\n \"For example, the first lens hole 235a may have a combination shape of a circle of a first radius R1 and a circle of a second radius R2.The second radius R2 may be an area corresponding to an angle AA.\",\n \"The angle AA may be less than 180 degrees.\",\n \"Namely, the area corresponding to the angle AA may have a fan shape of the second radius R2.In other words, a width of the area corresponding to the angle AA may be less than widths of other areas.\",\n \"As described above, the second radius R2 may be greater than the first radius R1.Thus, a portion of light emitted through the first lens hole 235a may be emitted from the area corresponding to the angle AA to the rear of the reflecting sheet 126.A total amount of light reflected onto the front of the reflecting sheet 126 by the reflecting sheet 126 may decrease by an amount of light emitted to the rear of the reflecting sheet 126.An area corresponding to the second radius R2 of the first lens hole 235a may face a chamber area CSA.\",\n \"Namely, the area corresponding to the second radius R2 of the first lens hole 235a may face an outer peripheral of the reflecting sheet 126.In other words, the area corresponding to the second radius R2 of the first lens hole 235a may face the second sheet area 126b (refer to FIG.\",\n \"13).\",\n \"As described above, because a portion of light is emitted to the rear of the reflecting sheet 126 by the second radius R2, an influence of the first lens hole 235a on the chamber area CSA may be less than an influence of the general lens hole 235.Thus, the chamber area CSA may be prevented from being brighter than other area.\",\n \"As shown in FIG.\",\n \"32, the lens hole 235 may include a first lens hole 235a, of which a radius is changed, and a circular second lens hole 235b.\",\n \"The first lens hole 235a may be positioned on the upper, left, right, and lower sides of the disposed lens holes 235.As described above, the disposition of the first lens hole 235a may prevent the upper, left, right, and lower sides of the lens hole 235 from being brighter than other area.\",\n \"As shown in FIG.\",\n \"33, the dot area DA may be formed in various shapes.\",\n \"Namely, the dot area DA of the various shapes may be configured so that the reflecting sheet 126 uniformly reflects light.\",\n \"For example, the dot area DA may be formed around the lens hole 235.For example, the dot area DA may be formed in at least a partial area around the lens hole 235.For example, the dot area DA may have the shape surrounding the lens hole 235.Namely, a first circular dot area CDT1 may be formed.\",\n \"The first ring-shaped dot area CDT1 may have the shape surrounding the lens hole 235.For example, the first ring-shaped dot area CDT1 may have the shape, in which the dots DT of the same size and/or the same shape surround the lens hole 235.For example, the first ring-shaped dot area CDT1 may have the shape, in which the dots DT, of which at least a partial size and/or shape is different, surround the lens hole 235.A reflectance of a corresponding area may be changed by the first ring-shaped dot area CDT1.For example, a reflectance of a formation area of the first ring-shaped dot area CDT1 may be reduced.\",\n \"Thus, the first ring-shaped dot area CDT1 may be formed around a specific lens hole 235, which needs to reduce the reflectance.\",\n \"The horizontal dot area HDA and/or the vertical dot area VDA may include a plurality of areas, in which attributes of the dots are different from one another.\",\n \"For example, the horizontal dot area HDA may include first to third horizontal dot areas HDA1 to HDA3, and the vertical dot area VDA may include first to third vertical dot areas VDA1 to VDA3.There may be a difference between the dots of the areas in at least one of a size, an interval, a density, and a color of the dot.\",\n \"For example, the size of the dot in the first horizontal dot area HDA1 may be less than the size of the dot in the second horizontal dot area HDA2, and the size of the dot in the second horizontal dot area HDA2 may be less than the size of the dot in the third horizontal dot area HDA3, or vice versa.\",\n \"The configuration of the first to third horizontal dot areas HDA1 to HDA3 may be equally applied to the first to third vertical dot areas VDA1 to VDA3.As shown in FIG.\",\n \"34, the reflecting sheet 126 may include a plurality of lens holes 235.The first ring-shaped dot area CDT1 may be formed in a specific lens hole 235 among the plurality of lens holes 235.For example, the plurality of lens holes 235 may include a first lens hole 235a, in which the first ring-shaped dot area CDT1 is formed, and a second lens hole 235b, in which the first ring-shaped dot area CDT1 is not formed.\",\n \"The first lens hole 235a having the first ring-shaped dot area CDT1 may be the lens hole 235 positioned on the outside among the plurality of lens holes 235a.\",\n \"Namely, the first ring-shaped dot area CDT1 may be formed in the outermost lens hole 235.This may be because the first lens hole 235a positioned on the outside is close to the bending second sheet area 126b (refer to FIG.\",\n \"13) of the reflecting sheet 126.Namely, the first ring-shaped dot area CDT1 may be formed in the first lens hole 235a, so as to prevent an excessively large amount of light from being reflected from the second sheet area 126b.\",\n \"As shown in (a) of FIG.\",\n \"35A, a first ring-shaped dot area CDT1 may be formed around the lens hole 235.The first ring-shaped dot area CDT1 may be dots DT surrounding the lens hole 235.The first ring-shaped dot area CDT1 may be dots DT surrounding the lens hole 235 one time.\",\n \"The dots DT constituting the first ring-shaped dot area CDT1 may have the same size and/or the same shape.\",\n \"Alternatively, at least a portion of the dots DT constituting the first ring-shaped dot area CDT1 may have different sizes and different shapes.\",\n \"For example, a size of the dot DT positioned in the outside direction of the reflecting sheet 126 may be greater than a size of the dot DT positioned in the inside direction of the reflecting sheet 126.As shown in (b) of FIG.\",\n \"35A, a second ring-shaped dot area CDT2 may be formed around the lens hole 235.The second ring-shaped dot area CDT2 may be dots DT surrounding the lens hole 235 several times (several loops or nested).\",\n \"This is a difference between the first ring-shaped dot area CDT1 surrounding the lens hole 235 one time and the second ring-shaped dot area CDT2.As shown in (c) of FIG.\",\n \"35A, a third ring-shaped dot area CDT3 may be formed around the lens hole 235.The third ring-shaped dot area CDT3 may be formed around a predetermined portion of the lens hole 235.For example, the third ring-shaped dot area CDT3 may be formed in a portion corresponding to an angle AC in the lens hole 235.The third ring-shaped dot area CDT3 may surround the portion corresponding to the angle AC one time or several times.\",\n \"As shown in (d) of FIG.\",\n \"35A, a fourth ring-shaped dot area CDT4 may be formed around the lens hole 235.A density of dots of the fourth ring-shaped dot area CDT4 may vary depending on a location.\",\n \"For example, the dots may have the same size, but a distance between the dots may be changed.\",\n \"For example, a distance between the dots positioned close to the lens hole 235 may be relatively short, and a distance between the dots positioned far away from the lens hole 235 may be relatively long.\",\n \"As shown in (a) of FIG.\",\n \"35B, a fourth ring-shaped dot area CDT4 may be formed around at least a portion of the lens hole 235.The fourth ring-shaped dot area CDT4 may be dots DT positioned in a portion corresponding to an angle AC in the lens hole 235.The fourth ring-shaped dot area CDT4 may be separated from the lens hole 235.Namely, the fourth ring-shaped dot area CDT4 may be formed at a location which is separated from a boundary of the lens hole 235 by a predetermined distance.\",\n \"As shown in (b) of FIG.\",\n \"35B, a fifth ring-shaped dot area CDT5 may be formed around at least a portion of the lens hole 235.The fifth ring-shaped dot area CDT5 may include a first dot area DT1 and a second dot area DT2.An attribute of a dot constituting the first dot area DT1 may be different from an attribute of a dot constituting the second dot area DT2.For example, sizes of the dots constituting the first and second dot areas DT1 and DT2 may be different from each other.\",\n \"For example, a size of the dot constituting the second dot area DT2 may be greater than a size of the dot constituting the first dot area DT1.An area corresponding to the second dot area DT2 may be an area which can emit a larger amount of light than the lens positioned in the lens hole 235.Thus, the second dot area DT2 may be formed, so as to further reduce a reflectance of the fifth ring-shaped dot area CDT5 than other areas.\",\n \"As shown in (c) of FIG.\",\n \"35B, the lens hole 235 may be a first lens hole 235a, which is not circular.\",\n \"As described above, a radius of at least a portion of the first lens hole 235a may be different from a radius of at least another portion of the first lens hole 235a.\",\n \"The first lens hole 235a may cause a portion of light to be emitted downwardly from the reflecting sheet 126, thereby controlling an amount of the light.\",\n \"A sixth ring-shaped dot area CDT6 may be formed in an area AC.\",\n \"The area AC may be an area having a relatively large radius in the first lens hole 235a.\",\n \"For example, the sixth ring-shaped dot area CDT6 may be formed in an area having a radius R2.An amount of light emitted and/or reflected in a specific direction may be efficiently controlled by the area having the radius R2 and the sixth ring-shaped dot area CDT6.As shown in (d) of FIG.\",\n \"35B, the lens hole 235 may be a first lens hole 235a, which is not circular.\",\n \"A sixth ring-shaped dot area CDT6 and a seventh ring-shaped dot area CDT7 may be formed around the first lens hole 235a.\",\n \"The sixth ring-shaped dot area CDT6 and the seventh ring-shaped dot area CDT7 may surround the first lens hole 235a.\",\n \"As shown in FIG.\",\n \"36, the lens hole 235 may include first lens holes 235a and second lens holes 235b.\",\n \"As shown in (a) of FIG.\",\n \"36, the first lens hole 235a may be a lens hole 235 having a ring-shaped dot area.\",\n \"A location of the first lens hole 235a having the ring-shaped dot area may be different from a location of the second lens hole 235b not having the ring-shaped dot area.\",\n \"For example, the first lens holes 235a may be positioned in the inner area of the reflecting sheet 126, and the second lens holes 235b may be positioned in the outer area of the reflecting sheet 126.The locations of the first and second lens holes 235a and 235b may be changed.\",\n \"The lens holes 235 may be arranged in the horizontal direction and/or the vertical direction.\",\n \"The lens holes 235 arranged in the horizontal direction and/or the vertical direction may be disposed in parallel with one another.\",\n \"Such a disposition or arrangement can achieve the common design and the common manufacturing process and can obtain an effect capable of reducing the cost.\",\n \"The lens holes 235 arranged in the horizontal direction and/or the vertical direction may not be disposed in parallel with one another.\",\n \"For example, the lens holes 235 may be disposed in a zigzag pattern in the vertical direction.\",\n \"Such a disposition or arrangement can obtain an effect reducing a light overlap and/or a light shade between the lens holes 235.Because the first lens hole 235a is positioned in the inner area of the reflecting sheet 126, a luminance of the first sheet area 126a (refer to FIG.\",\n \"11) of the reflecting sheet 126 may be more unifoimly controlled.\",\n \"This can be clearly understood considering that light emitted from the lens holes 235 is relatively bright around the lens holes 235 and becomes darker as it is far away from the lens holes 235.The first lens hole 235a, in which dots are formed, may control a brightness and/or a reflectance around the lens hole 235 and may homogenize an entire luminance.\",\n \"As shown in (b) of FIG.\",\n \"36, the first lens holes 235a may be disposed in accordance with a predetermined rule.\",\n \"For example, the lens hole positioned in one of the left and right directions or one of the plurality of lens holes 235 may be the first lens hole 235a.\",\n \"The first lens holes 235a may be disposed in the zigzag pattern in the vertical direction.\",\n \"Namely, the first lens holes 235a may not be in parallel with one another in the vertical direction.\",\n \"Such a disposition may minimize a reduction in the entire brightness by the first lens hole 235a and may homogenize the luminance.\",\n \"As shown in (a) of FIG.\",\n \"37, a third ring-shaped dot area CDT3 may be formed in a first lens hole 235 having an overlap shape of circles each having a different radius.\",\n \"For example, the third ring-shaped dot area CDT3 may be formed in a circle having a large second radius R2.For example, the third ring-shaped dot area CDT3 may be formed in at least a portion of the circle having the second radius R2.As shown in (b) of FIG.\",\n \"37, when the shape of the first lens hole 235 is changed, a location of the third ring-shaped dot area CDT3 may be changed in accordance with the first lens hole 235.As shown in FIG.\",\n \"38, the plurality of lens holes 235 may include first lens holes 235a and second lens holes 235b.\",\n \"A third ring-shaped dot area CDT3 may be formed in the first lens hole 235a.\",\n \"A radius of the first lens hole 235a may be changed.\",\n \"The first lens hole 235a may be positioned on the outside of the plurality of lens holes 235.For example, the first lens hole 235a may be a lens hole 235 positioned in an area close to the long side and/or the short side.\",\n \"For example, the first lens hole 235a may be a lens hole 235 positioned adjacent to a horizontal dot area HDA and/or a vertical dot area VDA.\",\n \"Namely, the third ring-shaped dot area CDT3 may be positioned between the first lens hole 235a and the horizontal dot area HDA and/or the vertical dot area VDA.\",\n \"Thus, an excessively large amount of light may be prevented from being reflected from the second sheet area 126b (refer to FIG.\",\n \"11) of the reflecting sheet 126.FIGS.\",\n \"39 to 43 illustrate configuration related to a lens hole reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"39 to 43, the display device 100 according to the embodiment of the invention may further include a lens hole reflecting sheet 126d.\",\n \"As shown in FIG.\",\n \"39, the lens hole reflecting sheet 126d may be inserted into a lens hole 235 of the reflecting sheet 126.The lens hole reflecting sheet 126d may be positioned between the lens 124b and the light source 203.The lens 124b may be a refractive lens or a reflective lens.\",\n \"The refractive or reflective lens 124b may emit light provided by the light source 203 at various angles.\",\n \"The lens hole reflecting sheet 126d may reflect light emitted downwardly from the lens 124b to the upward side of the lens 124b, thereby increasing light efficiency.\",\n \"As shown in FIG.\",\n \"40, the lens hole reflecting sheet 126d may include a hole 126bh and a ring unit 126bb.\",\n \"The hole 126bh may be positioned in the middle of the lens hole reflecting sheet 126d.\",\n \"The light source 203 may be inserted into the hole 126bh.\",\n \"The ring unit 126bb may be an outer peripheral area of the hole 126bh.\",\n \"The ring unit 126bb may include at least one lens coupling unit 126bc.\",\n \"For example, at least one lens leg 124d formed on the lower side of the lens 124b (refer to FIG.\",\n \"39) may pass through the lens coupling unit 126bc.\",\n \"As shown in FIG.\",\n \"41, dots DT may be formed in at least a portion of the ring unit 126bb.\",\n \"The dots DT may be separated from one another by a vertical distance vd and/or a horizontal distance hd.\",\n \"The vertical distance vd and/or the horizontal may be uniform.\",\n \"For example, the dots DT may be formed on the ring unit 126bb at regular intervals.\",\n \"The vertical distance vd and/or the horizontal may not be uniform.\",\n \"For example, the dots DT may be non-uniformly distributed on the ring unit 126bb.\",\n \"FIG.\",\n \"42 shows that the lens 124b (refer to FIG.\",\n \"39) and the lens hole reflecting sheet 126d (refer to FIG.\",\n \"39) are not coupled.\",\n \"As shown in FIG.\",\n \"42, one light source 203 may be configured as a plurality of LEDS.\",\n \"Namely, a plurality of LED chips may be used in one light package, and thus an intensity of light with respect to one light package may increase.\",\n \"The light source 203 may include first and second light sources 203a and 203b.\",\n \"The first and second light sources 203a and 203b may be positioned adjacent to each other.\",\n \"For example, the rectangular first and second light sources 203a and 203b may be positioned in parallel with each other.\",\n \"The first and second light sources 203a and 203b may emit light having a predetermined directivity.\",\n \"For example, each of the first and second light sources 203a and 203b may mainly emit light in a radial direction HA of the outside direction.\",\n \"As shown in (a) of FIG.\",\n \"43, dots DT may be formed in a predetermined area of the lens hole reflecting sheet 126d.\",\n \"The dots DT may have a configuration corresponding to radial characteristics of the first and second light sources 203a and 203b (refer to FIG.\",\n \"42).\",\n \"For example, first and second dot areas DTA1 and DTA2 corresponding to the radial direction HA (refer to FIG.\",\n \"42) may be formed.\",\n \"The first and second dot areas DTA1 and DTA2 may be dots positioned on a path of the radial direction HA (refer to FIG.\",\n \"42).\",\n \"For example, the first and second dot areas DTA1 and DTA2 may be formed at a predetermined width.\",\n \"The first and second dot areas DTA1 and DTA2 may be separated from each other.\",\n \"The second dot area DTA2 may be positioned further inside than the first dot area DTA1.A size of the first dot area DTA1 may be greater than a size of the second dot area DTA2 considering that light emitted from the first and second light sources 203a and 203b(refer to FIG.\",\n \"42) is radiated in a fan shape.\",\n \"Only one of the first and second dot areas DTA1 and DTA2 may be formed, if necessary or desired.\",\n \"As shown in (b) of FIG.\",\n \"43, at least one of the first and second dot areas DTA1 and DTA2 may be formed in the reflecting sheet 126.For example, the first dot area DTA1 may be formed in the reflecting sheet 126, and the second dot area DTA2 may be formed in the lens hole reflecting sheet 126d.\",\n \"The first dot area DTA1 formed in the reflecting sheet 126 may be advantageous to control a reflection amount of light than when the first dot area DTA1 is formed in the lens hole reflecting sheet 126d having the relatively small area.\",\n \"FIGS.\",\n \"44 and 45 illustrate configuration related to horizontal and vertical coupling units of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"44 and 45, the reflecting sheet 126 of the display device 100 according to the embodiment of the invention may include a horizontal coupling unit HH and a vertical coupling unit VH.\",\n \"As shown in FIG.\",\n \"44, the horizontal coupling unit HH and/or the vertical coupling unit VH may be formed in a corner area of the reflecting sheet 126.The horizontal coupling unit HH and/or the vertical coupling unit VH may be formed in a horizontal margin area HM and/or a vertical margin area VM of the reflecting sheet 126.The dots DT may not be formed in the horizontal margin area/or the vertical margin area VM.\",\n \"The reflecting sheet 126 may be coupled to the frame 130 (refer to FIG.\",\n \"10).\",\n \"For example, the reflecting sheet 126 may be coupled to the frame 130 in such a manner that the horizontal coupling unit HH and/or the vertical coupling unit VH are inserted into a structure of the frame 130.The reflecting sheet 126 may be modified.\",\n \"For example, the reflecting sheet 126 may contract or expand because of heat generated by an operation of the display device 100.The reflecting sheet 126 may be modified in the horizontal direction and/or the vertical direction.\",\n \"A modification amount of the reflecting sheet 126 in the horizontal direction may be greater than a modification amount of the reflecting sheet 126 in the vertical direction.\",\n \"Namely, because the horizontal direction corresponds to the long side and the vertical direction corresponds to the short side, a total modification amount in the horizontal direction may be greater than a total modification amount in the vertical direction although a modification amount per unit distance in the horizontal direction and the vertical direction is similar.\",\n \"The horizontal coupling unit HH and/or the vertical coupling unit VH may be configured in consideration of the coupling and/or the modification of the reflecting sheet 126.For example, the plurality of horizontal coupling units HH and/or the plurality of vertical coupling units VH may be formed for the coupling of the reflecting sheet 126.For example, first to third horizontal coupling units HH1 to HH3 may be separated from one another by a predetermined distance and may be formed in the horizontal margin area HM.\",\n \"First and second vertical coupling units VH1 and VH2 may be separated from one another by a predetermined distance and may be formed in the vertical margin area VM.\",\n \"As shown in FIG.\",\n \"45, the horizontal coupling unit HH and/or the vertical coupling unit VH may have a shape in consideration of the modification of the reflecting sheet 126.The horizontal coupling unit HH may be inserted into a horizontal protrusion 130H formed in and/or coupled to the third frame area 130c of the frame 130.A first width W1 of the horizontal coupling unit HH may be greater than a width of the horizontal protrusion 130H.\",\n \"The first width W1 of the horizontal coupling unit HH may be greater than a second width W2 of the vertical coupling unit VH.\",\n \"Namely, the first width W1 of the reflecting sheet 126 may be greater than the width of the horizontal protrusion 130H in consideration of the modification of the reflecting sheet 126 in the horizontal direction.\",\n \"The vertical coupling unit VH may be inserted into a vertical protrusion 130V formed in and/or coupled to the third frame area 130c of the frame 130.A second height H2 of the vertical coupling unit VH may be greater than a first height H1 of the horizontal protrusion 130H.\",\n \"Namely, the second height H2 of the vertical coupling unit VH may be relatively large in consideration of the modification of the reflecting sheet 126 in the horizontal direction.\",\n \"The vertical coupling unit VH may not include a detachment prevention unit HHU positioned on the horizontal coupling unit HH.\",\n \"This may be because the modification of the reflecting sheet 126 in the horizontal direction is greater than the modification of the reflecting sheet 126 in the vertical direction.\",\n \"Namely, if the vertical coupling unit VH includes the detachment prevention unit HHU, the detachment prevention unit HHU may contact the vertical protrusion 130V in the modification of the horizontal direction (i.e., the X-axis direction).\",\n \"Hence, a wrinkle may be generated in the reflecting sheet 126.Anon-dot area NDA may exist between horizontal and vertical dot areas HDA and VDA and horizontal and vertical margin areas HM and VM.\",\n \"Namely, the non-dot area NDA not including the dot may be formed in a strap shape along the horizontal and vertical directions.\",\n \"If the dots are formed in the non-dot area NDA, a corresponding area may be observed from the outside of the display device 100.Hence, the dots may not be formed in the non-dot area NDA.\",\n \"Further, the non-dot area NDA may serve as a buffer when the reflecting sheet 126 contracts or expands.\",\n \"FIGS.\",\n \"46 to 48 illustrate configuration related to a cutting portion of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"46 to 48, the reflecting sheet 126 of the display device 100 according to the embodiment of the invention may include a cutting portion HC uniformly reflecting light.\",\n \"As shown in FIG.\",\n \"46, a lens hole 235 may include a first lens hole 235a and a second lens hole 235b.\",\n \"As shown in (a) of FIG.\",\n \"46, the first lens hole 235a may be a lens hole 235 including ring-shaped dots DT.\",\n \"A location of the first lens hole 235a including the dots DT may be different from a location of the second lens hole 235b not including the dot DT.\",\n \"For example, the first lens hole 235a may be positioned in the inner area of the reflecting sheet 126, and the second lens hole 235b may be positioned in the outer area of the reflecting sheet 126.The locations of the first and second lens holes 235a and 235b may be changed.\",\n \"Because the first lens hole 235a is positioned in the inner area of the reflecting sheet 126, an effect capable of more uniformly controlling a luminance of the first sheet area 126a (refer to FIG.\",\n \"11) of the reflecting sheet 126 may be expected.\",\n \"This can be clearly understood considering that light emitted from the lens hole 235 is relatively bright around the lens hole 235 and becomes darker as it is far away from the lens hole 235.The first lens hole 235a, in which the dots DT are formed, may control a brightness and/or a reflectance around the lens hole 235 and may homogenizes an entire luminance.\",\n \"As shown in (b) of FIG.\",\n \"46, the first lens holes 235a may be disposed in accordance with a predetermined rule.\",\n \"For example, the lens hole positioned in one of the left and right directions or one of the plurality of lens holes 235 may be the first lens hole 235a.\",\n \"The first lens holes 235a may be disposed in the zigzag pattern in the vertical direction.\",\n \"Namely, the first lens holes 235a may not be in parallel with one another in the vertical direction.\",\n \"Such a disposition may minimize a reduction in the entire brightness by the first lens hole 235a and may homogenizes the luminance.\",\n \"As shown in FIG.\",\n \"47, the substrate 122 may have a shape, in which a first substrate 122a and a second substrate 122b are connected.\",\n \"Namely, the substrate 122, on which the light source 203 is mounted in the rear of the reflecting sheet 126, may be divided into a plurality of substrates.\",\n \"A first light source 203a may be positioned at the first substrate 122a, and a second light source 203b may be positioned at the second substrate 122b.\",\n \"The first and second substrates 122a and 122b may be connected through a connector CT.\",\n \"The connector CT may be positioned between the first and second substrates 122a and 122b.\",\n \"The connector CT may be a structure electrically and/or physically connected to the first and second substrates 122a and 122b.\",\n \"For example, the connector CT may be a soldering area.\",\n \"The connector CT may protrude in the direction of the reflecting sheet 126 by a distance CTH further than the substrate 122.The cutting portion HC may correspond to the connector CT. For example, the cutting portion HC may be positioned on the connector CT. As shown in FIG.\",\n \"48A, when the reflecting sheet 126 is coupled to the substrate 122, cutting surfaces HCS of the cutting portion HC may be separated from each other.\",\n \"Namely, a gap may be naturally generated between the cutting surfaces HCS by the connector CT, which upwardly protrudes.\",\n \"When the cutting surfaces HCS are coupled to the connector CT, a wrinkle of the reflecting sheet 126 resulting from the connector CT may be prevented.\",\n \"Thus, the non-uniformity of light resulting from the wrinkle of the reflecting sheet 126 may be prevented.\",\n \"The dots DT may be formed in the cutting surface HCS.\",\n \"Namely, the dots DT may be formed in a corresponding area, so as to control an amount of light reflected from the cutting surface HCS, which relatively upwardly protrudes.\",\n \"As shown in FIG.\",\n \"48B, the dots DT may be formed in the cutting portion HC.\",\n \"The dots DT may be positioned about the cutting surface HCS of the cutting portion HC.\",\n \"For example, the dots DT may be positioned in the left and right cutting of the cutting portion HC.\",\n \"Thus, the non-uniformity of the luminance resulting from the cutting may be minimized.\",\n \"FIGS.\",\n \"49 and 50 illustrate configuration related to a supporter hole of the reflecting sheet according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"49 and 50, the reflecting sheet 126 of the display device 100 according to the embodiment of the invention may uniformly reflect light through a dot area DTA formed around a supporter hole 205.As shown in FIG.\",\n \"49, a plurality of lens holes 235 may be formed on the reflecting sheet 126.Each of the light sources 203 coupled to the plurality of lens holes 235 may emit light.\",\n \"The supporter hole 205 may be formed on the reflecting sheet 126.As described above, the supporter hole 205 may have a configuration for the coupling of the supporter 200 (refer to FIG.\",\n \"10).\",\n \"The supporter hole 205 may be positioned further inside than the lens hole 235, which is positioned on the outermost side.\",\n \"For example, the supporter hole 205 may be positioned between the lens holes 235.The supporter hole 205 may be affected by the plurality of light sources 203 coupled to the plurality of lens holes 235.For example, light emitted from the plurality of light sources 203 may affect the specific supporter hole 205 considering a light path LP with respect to the specific supporter hole 205.As described above, the supporter hole 205 maybe coupled to the supporter 200 (refer to FIG.\",\n \"10).\",\n \"The supporter 200 may be formed of plastic and/or rubber material.\",\n \"The supporter 200 may reflect at least a portion of light.\",\n \"The reflecting sheet 126 according to the embodiment of the invention may have a dot area DTA in consideration of the reflection of the supporter 200, on which light can be overlappingly concentrated.\",\n \"Namely, the dot area DTA may be formed around the supporter hole 205, so as to reduce an influence of the supporter 200 on the reflection of the reflecting sheet 126.As shown in FIG.\",\n \"50, the dot area DTA around the supporter hole 205 may be formed toward an inner area EA of the reflecting sheet 126.Namely, the dot area DTA may be positioned further inside than the supporter hole 205.The plurality of dot areas DTA around the supporter holes 205 may be positioned opposite each other.\",\n \"For example, when first and second supporter holes 205a and 205b exist, first and second dot areas DTA1 and DTA2 may be positioned adjacent to the first and second supporter holes 205a and 205b further inside than the first and second supporter holes 205a and 205b.\",\n \"The dot area DTA around the supporter hole 205 may have a semicircular shape centering around the supporter hole 205.Namely, a center area of the dot area DTA, which is relatively greatly affected by the supporter 200 (refer to FIG.\",\n \"10), may be protrudingly configured.\",\n \"FIG.\",\n \"51 shows a light assembly including the light source shown in FIG.\",\n \"19.As shown in FIG.\",\n \"51, a plurality of light assemblies 124 according to the embodiment of the invention may be disposed along the substrate 122 and separated from one another.\",\n \"The light assembly 124 may include a light source 203 and a lens 300 positioned on one side of the light source 203.The light source 203 may be various sources emitting light.\",\n \"For example, the light source 203 may be a COB type LED as described above.\",\n \"The lens 300 may be positioned on the light source 203.At least a partial area of the light source 203 may overlap the lens 300.For example, the light source 203 may be inserted into a groove inside the lens 300.Alternatively, an area of the light source 203, from which light is substantially emitted, may be inserted into the lower side of the lens 300.For example, when the lens 300 has a leg structure, a portion of the upper side of the light source 203 may be inserted into the lower side of the lens 300.The lens 300 may reflect a portion of light emitted from the light source 203 and may refract a portion of the light.\",\n \"For example, the lens 300 may be a refractive lens or a reflective lens.\",\n \"The light emitted from the light source 203 may be uniformly and entirely spread through the reflection in a portion of the lens 300 and/or the refraction in a portion of the lens 300.The light source 203 inserted into the lens 300 may be adhered to the lens 300.For example, the lens 300 and the light source 203 may be attached to each other using an adhesive.\",\n \"The lens 300 may correspond to each light source 203.For example, first to third lenses 300a to 300c may be respectively positioned on first to third light sources 203a to 203c.\",\n \"The lens 300 may control a path of light emitted from the light source 203.Namely, the lens 300 may control the light source 203 so that the light of the light source 203 is not concentrated on a specific location.\",\n \"In other words, the lens 300 may cause the light of the light source 203 to be uniformly diffused.\",\n \"The lens 300 according to the embodiment of the invention may efficiently control the path of the light of the light source 203.The lens 300 according to the embodiment of the invention may efficiently control light emitted from the side of the light source 203.FIGS.\",\n \"52 and 53 show a lens according to the embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"52 and 53, a lens 300 according to the embodiment of the invention may have a specific shape.\",\n \"The lens 300 may include a first surface S1, a second surface S2 opposite the first surface S1, and a third surface S3 connecting the first surface S1 and the second surface S2.The first surface S1 may be an upper surface of the lens 300.At least a portion of the first surface S1 of the lens 300 according to the embodiment of the invention may be depressed.\",\n \"A depressed portion of the first surface S1 may have a shape curved from the center of the lens 300 to the outside of the lens 300.For example, a first concave portion A1 may be formed on the first surface S1.An uppermost area of the first surface S1 may be a top surface TS.\",\n \"The first surface S1 may have a circular cross-section.\",\n \"Light emitted from the upper side of the light source 203 may be upwardly emitted through the first surface S1 of the lens 300.The second surface S2 may be a lower surface of the lens 300.Namely, the second surface S2 may be a surface opposite the first surface S1 corresponding to the upper surface of the lens 300.At least a portion of the second surface S2 of the lens 300 according to the embodiment of the invention may be depressed.\",\n \"For example, a second concave portion A2 may be formed on the second surface S2.A radius of the second concave portion A2 on the second surface S2 may be denoted as R2.The radius R2 of the second concave portion A2 may be 1.5 to 4 times a radius of the light source 203 coupled to the lens 300.A lowermost area of the second surface S2 may be a bottom surface BS.\",\n \"The second surface S2 may have a circular cross-section.\",\n \"The light source 203 may be coupled to the second surface S2.As described above, a portion of the light source 203 may be inserted into the second surface S2.A radius of the second surface S2 may be “R2+R3”.\",\n \"A radius R1 of the first surface S1 may be 1 to 3 times the radius (R2+R3) of the second surface S2.Namely, a width of the top surface TS may be greater than a width of the bottom surface BS.\",\n \"The radius (R2+R3) of the second surface S2 may be 2 to 4 times a radius R2 of the second concave portion A2.The third surface S3 may be a surface connecting the first surface S1 and the second surface S2.Namely, the third surface S3 may be a side surface connecting the upper surface and the lower surface of the lens 300.The first surface S1 and the second surface S2 each have the circular cross section, and the third surface S3 forms an outer surface connecting the first surface S1 and the second surface S2.Therefore, the lens 300 may have an outline of a cylindrical shape having a height H. In the cylindrical shape of the lens 300, at least a portion of the first to third surfaces S1 to S3 may be changed.\",\n \"FIG.\",\n \"54 shows an example of a light path of a lens shown in FIG.\",\n \"52.As shown in FIG.\",\n \"54, the lens 300 according to the embodiment of the invention may control a path LP of light and may cause the light to be uniformly transferred to the optical sheet 125.In particular, the lens 300 according to the embodiment of the invention may change the path LP of light emitted from the side of the light source 203.The light emitted from the side of the light source 203 may be firstly diffused from the second concave portion A2.Namely, as described above, the light path LP may be radiated due to a shape of a third area A2R of the second concave portion A2.The light path LP distributed from the side of the second concave portion A2 may be again radiated via a curved surface S32 of the third surface S3.At least a portion of the light path LP passing through the second concave portion A2, etc., may be refracted and/or reflected from the first concave portion A1.Thus, the light path LP may be prevented from being concentrated on a specific location.\",\n \"As a result, light may be uniformly distributed on the optical sheet 125.FIGS.\",\n \"55 to 60 show a lens according to another example embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"55 to 60, the lens 300 according to the embodiment of the invention may be variously configured.\",\n \"As shown in FIG.\",\n \"55, a curved surface S33 of the third surface S3 may have a shape protruding to the outside of the lens 300.For example, the curved surface S33 may form a curved surface S32 corresponding to an imaginary fourth circle C4 adjoining an external surface of the third surface S3.The curved surface S33 may have the shape extending from the second surface S2 by a distance EA1.As shown in FIG.\",\n \"56, the plurality of light sources 203 may correspond to one lens 300.For example, first and second light sources 203a and 203b may be positioned inside the second concave portion A2.The light source 203 may have the relatively small size.\",\n \"The light source 203 may have a performance of high power.\",\n \"Thus, the first and second light sources 203a and 203b may correspond to one lens 300.The second concave portion A2 may have an oval shape.\",\n \"For example, the second concave portion A2 may have the shape, in which a width A2W of the second concave portion A2 is greater than a height A2H of the second concave portion A2.The plurality of light sources 203a and 203b may be positioned in a space obtained by configuring the second concave portion A2 in the oval shape.\",\n \"When the plurality of light sources 203 are positioned inside the second concave portion A2, the shape of the second concave portion A2 and/or the curved surface S32 of the third surface S3 may importantly operate in the embodiment of the invention.\",\n \"Namely, because a large amount of light may be generated from the sides of the first and second light sources 203a and 203b, it is necessary to more efficiently control the light emitted from the sides of the first and second light sources 203a and 203b.\",\n \"The embodiment of the invention may efficiently distribute the light emitted from the sides of the light sources through the curved third area A2R on the side of the second concave portion A2 and/or the curved surface S32 on the lower side of the third surface S3.As shown in FIG.\",\n \"57, the third area A2R of the second concave portion A2 may have the shape of a curved surface protruding to the outside of the lens 300.For example, the third area A2R may have the shape of the curved surface corresponding to an imaginary fifth circle C5 adjoining the third area A2R of the second concave portion A2 outside the second concave portion A2.In this instance, a length of the second concave portion A2 may extend by a distance EA2.As shown in FIGS.\",\n \"34 to 58, the embodiment of the invention may be applied to the lens 300, which may be configured in the various shapes.\",\n \"As shown in FIG.\",\n \"58, the third surface S3 may have a shape inclined at a predetermined angle.\",\n \"For example, the third surface S3 may have the shape inclined to the inside by an angle S3D based on the vertical line.\",\n \"The third surface S3 may include a straight surface S31 and a curved surface S32.The curved surface S32 may be connected to the second surface S2.The third area A2R may be formed on the second concave portion A2.Namely, a curved surface may be formed in an area extending from the lower side of the second concave portion A2 to the bottom surface BS.\",\n \"The light emitted from the light source may be distributed due to the third area A2R.\",\n \"In particular, the third area A2R may improve the uniformity of the light emitted from the side of the light source.\",\n \"As shown in FIG.\",\n \"59, a predetermined curved surface S32 may be formed in an area where the third surface S3 of the lens 300 and the bottom surface BS meet.\",\n \"Third areas A2R1 and A2R2 may be formed on the second concave portion A2.Namely, a curved surface may be formed in a portion of an area where the second concave portion A2 and the bottom surface BS meet.\",\n \"The third areas A2R1 and A2R2 may include a 3a area A2R1 and a 3b area A2R2.Namely, a plurality of curved surfaces may be formed in a plurality of areas where the second concave portion A2 and the bottom surface BS meet.\",\n \"As shown in FIG.\",\n \"60, a curved surface S32 may be formed in an area where the third surface S3 of the lens 300 and the bottom surface BS meet.\",\n \"The third area A2R of the curved surface may be formed on the second concave portion A2.FIGS.\",\n \"61 and 62 show a disposition of a light assembly according to another example embodiment of the invention.\",\n \"As shown in FIGS.\",\n \"61 and 62, the light assembly 124 may be positioned on the frame 130.The light assembly 124 may be configured in various shapes depending on a location.\",\n \"The light assembly 124 may include at least one of the lenses 300 having the above-described shapes.\",\n \"Thus, a contrast or a hot spot resulting from the lens 300 may be prevented from being generated.\",\n \"As shown in (a) of FIG.\",\n \"61, the light assembly 124 may be positioned on the frame 130.In FIGS.\",\n \"61 and 62, alphabets “A” and “B” indicate the light assembly 124.Namely, the light assemblies 124 may be arranged in the horizontal and vertical directions.\",\n \"The light assemblies 124 shown in (a) of FIG.\",\n \"61 may the “A” type light assemblies 124.For example, the light assembly 124 including the lens 300 of the specific shape may be positioned.\",\n \"As shown in (b) of FIG.\",\n \"61, the “A” type light assemblies 124 and the “B” type light assemblies 124 may be arranged.\",\n \"For example, the light assemblies 124 including the lenses 300 of two types may be arranged.\",\n \"In this instance, the “B” type light assemblies 124 may be arranged on the outermost side of an array of the light assemblies 124, and the “A” type light assemblies 124 may be arranged in an inner area of the array.\",\n \"The light assemblies 124 different from the light assemblies 124 arranged in the inner area of the array may be arranged on the outermost side of the array.\",\n \"Thus, the light assembly 124 positioned on the outermost side of the array may include the lens 300 different from the light assembly 124 positioned in the inner area of the array, so as to uniformly distribute light.\",\n \"As shown in (a) and (b) of FIG.\",\n \"62, the light assemblies 124 of at least two types may be alternately arranged.\",\n \"For example, the light assemblies 124 each including the “A” type lens 300 and the light assemblies 124 each including the “B” type lens 300 may be alternately arranged in the horizontal direction or the vertical direction.\",\n \"The embodiments and/or the configurations of the invention may be combined with each other.\",\n \"For example, a configuration “A” described in one embodiment of the invention and the drawings and a configuration “B” described in another embodiment of the invention and the drawings may be combined with each other.\",\n \"Namely, although the combination between the configurations is not directly described, the combination is possible except in the instance where it is described that the combination is impossible.\",\n \"This is certain considering that the embodiment of the invention relates to the display device.\",\n \"Any reference in this specification to “one embodiment,” “an embodiment,” “exemplary embodiment,” etc., means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention.\",\n \"The appearances of such phrases in various places in the specification are not necessarily all referring to the same embodiment.\",\n \"Further, when a particular feature, structure, or characteristic is described in connection with any embodiment, it is submitted that it is within the purview of one skilled in the art to effect such feature, structure, or characteristic in connection with other ones of the embodiments.\",\n \"Although embodiments have been described with reference to a number of illustrative embodiments thereof, it should be understood that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the scope of the principles of this disclosure.\",\n \"More particularly, various variations and modifications are possible in the component parts and/or arrangements of the subject combination arrangement within the scope of the disclosure, the drawings and the appended claims.\",\n \"In addition to variations and modifications in the component parts and/or arrangements, alternative uses will also be apparent to those skilled in the art.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874682"}}},{"rowIdx":4494670,"cells":{"text":{"kind":"list like","value":[["IDENTIFICATION OF AREAS OF INTEREST DURING INTRAORAL SCANS","A processing device receives a first virtual 3D model and a second virtual 3D model, each comprising one or more teeth of a patient.","The processing device compares the first virtual 3D model to the second virtual 3D model and determines, as a result of the comparing, a difference between the first virtual 3D model and the second virtual 3D model at a dental site comprising a tooth of the one or more teeth.","The processing device determines whether the difference comprises a first type of change to the tooth that is indicative of tooth wear or a second type of change to the tooth that is indicative of tooth movement associated with orthodontic treatment.","Responsive to determining that the first difference comprises the first type of change to the first tooth, the processing device generates a first indicator of the tooth wear for the tooth."],["1.A method of detecting tooth wear during orthodontic treatment, comprising: receiving a first virtual three-dimensional (3D) model comprising one or more teeth of a patient, wherein the first virtual 3D model is based on a first intraoral scan of the patient taken at a first time; receiving a second virtual 3D model comprising the one or more teeth of the patient, wherein the second virtual 3D model is based on a second intraoral scan of the patient taken at a second time; comparing, by a processing device, the first virtual 3D model to the second virtual 3D model; determining, as a result of the comparing, a first difference between the first virtual 3D model and the second virtual 3D model at a first dental site comprising a first tooth of the one or more teeth; determining whether the first difference comprises a first type of change to the first tooth that is indicative of tooth wear or a second type of change to the first tooth that is indicative of tooth movement; and responsive to determining that the first difference comprises the first type of change to the first tooth that is indicative of tooth wear, generating a first indicator of the tooth wear for the first tooth.","2.The method of claim 1, further comprising: determining a path of a missing portion of the first tooth; and generating a contour comprising the path of the missing portion of the first tooth, wherein the indicator comprises the contour.","3.The method of claim 1, wherein comparing the first virtual 3D model to the second virtual 3D model comprises determining an alignment between the first virtual 3D model and the second virtual 3D model based on geometric features shared by the first virtual 3D model and the second virtual 3D model.","4.The method of claim 1, further comprising determining a first intraoral area of interest comprising the first dental site, wherein determining the first intraoral area of interest comprises: identifying a plurality of voxels in the second virtual 3D model that satisfy a first criterion; determining a subset of the plurality of voxels that are proximate to one another; and grouping the subset of the plurality of voxels into a volume.","5.The method of claim 4, wherein the indicator comprises a flag that points to the first intraoral area of interest, wherein the first intraoral area of interest is hidden in one or more views of the one or more teeth, and wherein the flag is visible in the one or more views.","6.The method of claim 1, further comprising: determining a first intraoral area of interest comprising the first dental site; and determining an importance rank for the first intraoral area of interest based on the tooth wear.","7.The method of claim 1, further comprising: responsive to determining that the first difference comprises the second type of change to the first tooth that is indicative of tooth movement, generating a second indicator.","8.The method of claim 1, further comprising: determining that the first difference satisfies a first criterion; determining that the first difference comprises a change to the first tooth that is indicative of tooth wear based on the first difference satisfying the first criterion; and generating the first indicator for the first tooth.","9.The method of claim 8, further comprising: determining, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site comprising a second tooth of the one or more teeth; determining that the second difference satisfies a second criterion; determining that the second difference comprises the second type of change to the second tooth that is indicative of tooth movement; and generating a second indicator for the second tooth.","10.The method of claim 1, further comprising: determining, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site; determining that the second difference satisfies a gum recession criterion; determining that the second difference is indicative of gum recession; and generating a second indicator associated with the gum recession.","11.A system comprising: a memory; and a processing device operatively coupled to the memory, the processing device to: receive a first virtual three-dimensional (3D) model comprising one or more teeth of a patient, wherein the first virtual 3D model is based on a first intraoral scan of the patient taken at a first time; receive a second virtual 3D model comprising the one or more teeth of the patient, wherein the second virtual 3D model is based on a second intraoral scan of the patient taken at a second time; compare the first virtual 3D model to the second virtual 3D model; determine, as a result of the comparing, a first difference between the first virtual 3D model and the second virtual 3D model at a first dental site comprising a first tooth of the one or more teeth; determine whether the first difference comprises a first type of change to the first tooth that is indicative of tooth wear or a second type of change to the first tooth that is indicative of tooth movement; and responsive to determining that the first difference comprises the first type of change to first the tooth that is indicative of tooth wear, generate a first indicator of the tooth wear for the first tooth.","12.The system of claim 11, wherein the processing device is further to: determine a path of a missing portion of the first tooth; and generate a contour comprising the path of the missing portion of the first tooth, wherein the indicator comprises the contour.","13.The system of claim 11, wherein comparing the first virtual 3D model to the second virtual 3D model comprises determining an alignment between the first virtual 3D model and the second virtual 3D model based on geometric features shared by the first virtual 3D model and the second virtual 3D model.","14.The system of claim 11, wherein the processing device is further to determine a first intraoral area of interest comprising the first dental site, wherein determining the first intraoral area of interest comprises: identifying a plurality of voxels in the second virtual 3D model that satisfy a criterion; determining a subset of the plurality of voxels that are proximate to one another; and grouping the subset of the plurality of voxels into a volume.","15.The system of claim 14, wherein the indicator comprises a flag that points to the first intraoral area of interest, wherein the first intraoral area of interest is hidden in one or more views of the one or more teeth, and wherein the flag is visible in the one or more views.","16.The system of claim 11, wherein the processing device is further to: determine a first intraoral area of interest comprising the first dental site; and determine an importance rank for the first intraoral area of interest based on the tooth wear.","17.The system of claim 11, wherein the processing device is further to: generate a second indicator responsive to determining that the first difference comprises the second type of change to the first tooth that is indicative of tooth movement.","18.The system of claim 11, wherein the processing device is further to: determine that the first difference satisfies a first criterion; determine that the first difference comprises a change to the first tooth that is indicative of tooth wear based on the first difference satisfying the first criterion; and generate the first indicator for the first tooth.","19.The system of claim 18, wherein the processing device is further to: determine, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site comprising a second tooth of the one or more teeth; determine that the second difference satisfies a second criterion; determine that the second difference comprises the second type of change to the second tooth that is indicative of tooth movement; and generate a second indicator for the second tooth.","20.The system of claim 11, wherein the processing device is further to: determine, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site; determine that the second difference satisfies a gum recession criterion; determine that the second difference is indicative of gum recession; and generate a second indicator associated with the gum recession."],["<SOH> BACKGROUND <EOH>In prosthodontic procedures designed to implant a dental prosthesis in the oral cavity, the dental site at which the prosthesis is to be implanted in many cases should be measured accurately and studied carefully, so that a prosthesis such as a crown, denture or bridge, for example, can be properly designed and dimensioned to fit in place.","A good fit enables mechanical stresses to be properly transmitted between the prosthesis and the jaw, and to prevent infection of the gums via the interface between the prosthesis and the dental site, for example.","Some procedures also call for removable prosthetics to be fabricated to replace one or more missing teeth, such as a partial or full denture, in which case the surface contours of the areas where the teeth are missing need to be reproduced accurately so that the resulting prosthetic fits over the edentulous region with even pressure on the soft tissues.","In some practices, the dental site is prepared by a dental practitioner, and a positive physical model of the dental site is constructed using known methods.","Alternatively, the dental site may be scanned to provide 3D data of the dental site.","In either case, the virtual or real model of the dental site is sent to the dental lab, which manufactures the prosthesis based on the model.","However, if the model is deficient or undefined in certain areas, or if the preparation was not optimally configured for receiving the prosthesis, the design of the prosthesis may be less than optimal.","For example, if the insertion path implied by the preparation for a closely-fitting coping would result in the prosthesis colliding with adjacent teeth, the coping geometry has to be altered to avoid the collision, which may result in the coping design being less optimal.","Further, it the area of the preparation containing a finish line lacks definition, it may not be possible to properly determine the finish line and thus the lower edge of the coping may not be properly designed.","Indeed, in some circumstances, the model is rejected and the dental practitioner then re-scans the dental site, or reworks the preparation, so that a suitable prosthesis may be produced.","In orthodontic procedures it can be important to provide a model of one or both jaws.","Where such orthodontic procedures are designed virtually, a virtual model of the oral cavity is also beneficial.","Such a virtual model may be obtained by scanning the oral cavity directly, or by producing a physical model of the dentition, and then scanning the model with a suitable scanner.","Thus, in both prosthodontic and orthodontic procedures, obtaining a three-dimensional (3D) model of a dental site in the oral cavity is an initial procedure that is performed.","When the 3D model is a virtual model, the more complete and accurate the scans of the dental site are, the higher the quality of the virtual model, and thus the greater the ability to design an optimal prosthesis or orthodontic treatment appliance(s)."],["<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings.","FIG.","1 illustrates one embodiment of a system for performing intraoral scanning and generating a virtual three dimensional model of a dental site.","FIG.","2A illustrates a flow diagram for a method of determining intraoral areas of interest during an intraoral scan session, in accordance with embodiments of the present invention.","FIG.","2B illustrates a flow diagram for a method of providing indications for intraoral areas of interest, in accordance with embodiments of the present invention.","FIG.","3A illustrates a flow diagram for a method of providing data indications of flawed scan data from an intraoral scan session, in accordance with embodiments of the present invention.","FIG.","3B illustrates a flow diagram for a method of providing data indications of intraoral areas of interest, in accordance with embodiments of the present invention.","FIG.","3C illustrates a flow diagram for a method of performing intraoral scanning, in accordance with embodiments of the present invention.","FIG.","4A illustrates a portion of an example dental arch during an intraoral scan session.","FIG.","4B illustrates the example dental arch of FIG.","4A during the intraoral scan session after the generation of further intraoral images.","FIG.","5A illustrates an example dental arch showing intraoral areas of interest.","FIG.","5B illustrates an example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.","FIG.","5C illustrates another example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.","FIG.","6 illustrates a screen shot of an intraoral scan application, in accordance with embodiments of the present invention.","FIG.","7 illustrates a block diagram of an example computing device, in accordance with embodiments of the present invention.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["RELATED APPLICATIONS This patent application is a continuation of U.S. patent application Ser.","No.","15/347,620, filed Nov. 9, 2016, which is a continuation of U.S. patent application Ser.","No.","14/705,788 filed May 6, 2015, now issued as U.S. Pat.","No.","9,510,757, which claims the benefit under 35 U.S.C.","§ 119(e) of U.S.","Provisional Application No.","61/990,004 filed May 7, 2014, all of which are herein incorporated by reference.","TECHNICAL FIELD Embodiments of the present invention relate to the field of intraoral scanning and, in particular, to a system and method for improving the results of intraoral scanning.","BACKGROUND In prosthodontic procedures designed to implant a dental prosthesis in the oral cavity, the dental site at which the prosthesis is to be implanted in many cases should be measured accurately and studied carefully, so that a prosthesis such as a crown, denture or bridge, for example, can be properly designed and dimensioned to fit in place.","A good fit enables mechanical stresses to be properly transmitted between the prosthesis and the jaw, and to prevent infection of the gums via the interface between the prosthesis and the dental site, for example.","Some procedures also call for removable prosthetics to be fabricated to replace one or more missing teeth, such as a partial or full denture, in which case the surface contours of the areas where the teeth are missing need to be reproduced accurately so that the resulting prosthetic fits over the edentulous region with even pressure on the soft tissues.","In some practices, the dental site is prepared by a dental practitioner, and a positive physical model of the dental site is constructed using known methods.","Alternatively, the dental site may be scanned to provide 3D data of the dental site.","In either case, the virtual or real model of the dental site is sent to the dental lab, which manufactures the prosthesis based on the model.","However, if the model is deficient or undefined in certain areas, or if the preparation was not optimally configured for receiving the prosthesis, the design of the prosthesis may be less than optimal.","For example, if the insertion path implied by the preparation for a closely-fitting coping would result in the prosthesis colliding with adjacent teeth, the coping geometry has to be altered to avoid the collision, which may result in the coping design being less optimal.","Further, it the area of the preparation containing a finish line lacks definition, it may not be possible to properly determine the finish line and thus the lower edge of the coping may not be properly designed.","Indeed, in some circumstances, the model is rejected and the dental practitioner then re-scans the dental site, or reworks the preparation, so that a suitable prosthesis may be produced.","In orthodontic procedures it can be important to provide a model of one or both jaws.","Where such orthodontic procedures are designed virtually, a virtual model of the oral cavity is also beneficial.","Such a virtual model may be obtained by scanning the oral cavity directly, or by producing a physical model of the dentition, and then scanning the model with a suitable scanner.","Thus, in both prosthodontic and orthodontic procedures, obtaining a three-dimensional (3D) model of a dental site in the oral cavity is an initial procedure that is performed.","When the 3D model is a virtual model, the more complete and accurate the scans of the dental site are, the higher the quality of the virtual model, and thus the greater the ability to design an optimal prosthesis or orthodontic treatment appliance(s).","BRIEF DESCRIPTION OF THE DRAWINGS The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings.","FIG.","1 illustrates one embodiment of a system for performing intraoral scanning and generating a virtual three dimensional model of a dental site.","FIG.","2A illustrates a flow diagram for a method of determining intraoral areas of interest during an intraoral scan session, in accordance with embodiments of the present invention.","FIG.","2B illustrates a flow diagram for a method of providing indications for intraoral areas of interest, in accordance with embodiments of the present invention.","FIG.","3A illustrates a flow diagram for a method of providing data indications of flawed scan data from an intraoral scan session, in accordance with embodiments of the present invention.","FIG.","3B illustrates a flow diagram for a method of providing data indications of intraoral areas of interest, in accordance with embodiments of the present invention.","FIG.","3C illustrates a flow diagram for a method of performing intraoral scanning, in accordance with embodiments of the present invention.","FIG.","4A illustrates a portion of an example dental arch during an intraoral scan session.","FIG.","4B illustrates the example dental arch of FIG.","4A during the intraoral scan session after the generation of further intraoral images.","FIG.","5A illustrates an example dental arch showing intraoral areas of interest.","FIG.","5B illustrates an example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.","FIG.","5C illustrates another example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.","FIG.","6 illustrates a screen shot of an intraoral scan application, in accordance with embodiments of the present invention.","FIG.","7 illustrates a block diagram of an example computing device, in accordance with embodiments of the present invention.","DETAILED DESCRIPTION Described herein is a method and apparatus for improving the quality of scans, such as intraoral scans taken of dental sites for patients.","During a scan session, a user (e.g., a dental practitioner) of a scanner may generate multiple different images (also referred to as scans) of a dental site, model of a dental site, or other object.","The images may be discrete images (e.g., point-and-shoot images) or frames from a video (e.g., a continuous scan).","These images may not capture all of the areas of the dental site and/or there may be areas for which there is conflicting data between images.","In embodiments described herein, such missing areas and/or conflicting areas may be identified as areas of interest.","This identification may be performed during a scan session.","Accordingly, shortly after the user of the scanner has generated one or more images, the user may be notified of areas of interest that should be rescanned.","The user may then rescan the areas of interest during the scan session.","This can facilitate quick and accurate scan sessions.","Additionally, indications or indicators of areas of interest can be generated during a scan session or after the scan session is complete.","These indications may indicate classifications associated with areas of interest, a severity of the areas of interest, a size of the areas of interest, and additional information.","The indications may be visible in views of the dental site or other scanned object in which the actual areas of interest are hidden.","This can ensure that the user will be made aware of the areas of interest regardless of a current view.","Embodiments described herein are discussed with reference to intraoral scanners, intraoral images, intraoral scan sessions, and so forth.","However, it should be understood that embodiments also apply to other types of scanners than intraoral scanners.","Embodiments may apply to any type of scanner that takes multiple images and stitches these images together to form a combined image or virtual model.","For example, embodiments may apply to desktop model scanners, computed tomography (CT scanners, and so forth.","Additionally, it should be understood that the intraoral scanners or other scanners may be used to scan objects other than dental sites in an oral cavity.","For example, embodiments may apply to scans performed on physical models of a dental site or any other object.","Accordingly, embodiments describing intraoral images should be understood as being generally applicable to any types of images generated by a scanner, embodiments describing intraoral scan sessions should be understood as being applicable to scan sessions for any type of object, and embodiments describing intraoral scanners should be understood as being generally applicable to many types of scanners.","FIG.","1 illustrates one embodiment of a system 100 for performing intraoral scanning and/or generating a virtual three dimensional model of a dental site.","In one embodiment, system 100 carries out one or more operations of below described in methods 200, 250, 300, 340 and/or 370.System 100 includes a computing device 105 that may be coupled to a scanner 150 and/or a data store 110.Computing device 105 may include a processing device, memory, secondary storage, one or more input devices (e.g., such as a keyboard, mouse, tablet, and so on), one or more output devices (e.g., a display, a printer, etc.","), and/or other hardware components.","Computing device 105 may be connected to a data store 110 either directly or via a network.","The network may be a local area network (LAN), a public wide area network (WAN) (e.g., the Internet), a private WAN (e.g., an intranet), or a combination thereof.","The computing device 105 may be integrated into the scanner 150 in some embodiments to improve performance and mobility.","Data store 110 may be an internal data store, or an external data store that is connected to computing device 105 directly or via a network.","Examples of network data stores include a storage area network (SAN), a network attached storage (NAS), and a storage service provided by a cloud computing service provider.","Data store 110 may include a file system, a database, or other data storage arrangement.","In some embodiments, a scanner 150 for obtaining three-dimensional (3D) data of a dental site in a patient's oral cavity is operatively connected to the computing device 105.Scanner 150 may include a probe (e.g., a hand held probe) for optically capturing three dimensional structures (e.g., by confocal focusing of an array of light beams).","One example of such a scanner 150 is the iTero® intraoral digital scanner manufactured by Align Technology, Inc. Other examples of intraoral scanners include the 1M™ True Definition Scanner and the Apollo DI intraoral scanner and CEREC AC intraoral scanner manufactured by Sirona®.","The scanner 150 may be used to perform an intraoral scan of a patient's oral cavity.","An intraoral scan application 108 running on computing device 105 may communicate with the scanner 150 to effectuate the intraoral scan.","A result of the intraoral scan may be a sequence of intraoral images that have been discretely generated (e.g., by pressing on a “generate image” button of the scanner for each image).","Alternatively, a result of the intraoral scan may be one or more videos of the patient's oral cavity.","An operator may start recording the video with the scanner 150 at a first position in the oral cavity, move the scanner 150 within the oral cavity to a second position while the video is being taken, and then stop recording the video.","In some embodiments, recording may start automatically as the scanner identities either teeth.","The scanner 150 may transmit the discrete intraoral images or intraoral video (referred to collectively as intraoral image data 135) to the computing device 105.Computing device 105 may store the image data 135 in data store 110.Alternatively, scanner 150 may be connected to another system that stores the image data in data store 110.In such an embodiment, scanner 150 may not be connected to computing device 105.According to an example, a user (e.g., a practitioner) may subject a patient to intraoral scanning.","In doing so, the user may apply scanner 150 to one or more patient intraoral locations.","The scanning may be divided into one or more segments.","As an example the segments may include a lower buccal region of the patient, a lower lingual region of the patient, a upper buccal region of the patient, an upper lingual region of the patient, one or more preparation teeth of the patient (e.g., teeth of the patient to which a dental device such as a crown or an orthodontic alignment device will be applied), one or more teeth which are contacts of preparation teeth (e.g., teeth not themselves subject to a dental device but which are located next to one or more such teeth or which interface with one or more such teeth upon mouth closure), and/or patient bite (e.g., scanning performed with closure of the patient's mouth with scan being directed towards an interface area of the patient's upper and lower teeth).","Via such scanner application, the scanner 150 may provide image data (also referred to as scan data) 135 to computing device 105.The image data 135 may include 2D intraoral images and/or 3D intraoral images.","Such images may be provided from the scanner to the computing device 105 in the form of one or more points (e.g., one or more pixels and/or groups of pixels).","For instance, the scanner 150 may provide such a 3D image as one or more point clouds.","The manner in which the oral cavity of a patient is to be scanned may depend on the procedure to be applied thereto.","For example, if an upper or lower denture is to be created, then a full scan of the mandibular or maxillary edentulous arches may be performed.","In contrast, if a bridge is to be created, then just a portion of a total arch may be scanned which includes an edentulous region, the neighboring abutment teeth and the opposing arch and dentition.","Thus, the dental practitioner may input the identity of a procedure to be performed into intraoral scan application 108.For this purpose, the dental practitioner may choose the procedure from a number of preset options on a drop-down menu or the like, from icons or via any other suitable graphical input interface.","Alternatively, the identity of the procedure may be input in any other suitable way, for example by means of preset code, notation or any other suitable manner, intraoral scan application 108 having been suitably programmed to recognize the choice made by the user.","By way of non-limiting example, dental procedures may be broadly divided into prosthodontic (restorative) and orthodontic procedures, and then further subdivided into specific forms of these procedures.","Additionally, dental procedures may include identification and treatment of gum disease, sleep apnea, and intraoral conditions.","The term prosthodontic procedure refers, inter alia, to any procedure involving the oral cavity and directed to the design, manufacture or installation of a dental prosthesis at a dental site within the oral cavity, or a real or virtual model thereof, or directed to the design and preparation of the dental site to receive such a prosthesis.","A prosthesis may include any restoration such as crowns, veneers, inlays, onlays, and bridges, for example, and any other artificial partial or complete denture.","The term orthodontic procedure refers, inter alia, to any procedure involving the oral cavity and directed to the design, manufacture or installation of orthodontic elements at a dental site within the oral cavity, or a real or virtual model thereof, or directed to the design and preparation of the dental site to receive such orthodontic elements.","These elements may be appliances including but not limited to brackets and wires, retainers, clear aligners, or functional appliances.","A type of scanner to be used may also be input into intraoral scan application 108, typically by a dental practitioner choosing one among a plurality of options.","If the scanner 150 that is being used is not recognizable by intraoral scan application 108, it may nevertheless be possible to input operating parameters of the scanner thereto instead.","For example, the optimal spacing between a head of the scanner and scanned surface can be provided, as well as the capture area (and shape thereof) of the dental surface capable of being scanned at this distance.","Alternatively, other suitable scanning parameters may be provided.","Intraoral scan application 108 may identify spatial relationships that are suitable for scanning the dental site so that complete and accurate image data may be obtained for the procedure in question.","Intraoral scan application 108 may establish an optimal manner for scanning a target area of the dental site.","Intraoral scan application 108 may identify or determine a scanning protocol by relating the type of scanner, resolution thereof, capture area at an optimal spacing between the scanner head and the dental surface to the target area, etc.","For a point-and-shoot scanning mode, the scanning protocol comprises a series of scanning stations spatially associated with the dental surfaces of the target area.","Preferably, overlapping of the images or scans capable of being obtained at adjacent scanning stations is designed into the scanning protocol to enable accurate image registration, so that intraoral images can be stitched together to provide a composite 3D virtual model.","For a continuous scanning mode (video scan), scanning stations may not be identified.","Instead, a practitioner may activate the scanner and proceed to move the scanner within the oral cavity to capture a video of the target area from multiple different viewpoints.","In one embodiment, intraoral scan application 108 includes an area of interest (AOI) identifying module 115, a flagging module 118 and a model generation module 125.Alternatively, the operations of one or more of the AOI identifying module 115, flagging module 118 and/or model generation module 125 may be combined into a single module and/or divided into multiple modules.","AOI identifying module 115 is responsible for identifying areas of interest (AOIs) from intraoral scan data (e.g., intraoral images) and/or virtual 3D models generated from intraoral scan data.","Such areas of interest may include voids (e.g., areas for which scan data is missing), areas of conflict or flawed scan data (e.g., areas for which overlapping surfaces of multiple intraoral images fail to match), areas indicative of foreign objects (e.g., studs, bridges, etc.","), areas indicative of tooth wear, areas indicative of tooth decay, areas indicative of receding gums, unclear gum line, unclear patient bite, unclear margin line (e.g., margin line of one or more preparation teeth), and so forth.","An identified void may be a void in a surface of an image.","Examples of surface conflict include double incisor edge and/or other physiologically unlikely tooth edge, and/or bite line shift.","The AOI identifying module 115 may, in identifying an AOI, analyze patient image data 135 (e.g., 3D image point clouds) and/or one or more virtual 3D models of the patient alone and/or relative to reference data 138.The analysis may involve direct analysis (e.g., pixel-based and/or other point-based analysis), the application of machine learning, and/or the application of image recognition.","Such reference data 138 may include past data regarding the at-hand patient (e.g., intraoral images and/or virtual 3D models), pooled patient data, and/or pedagogical patient data, some or all of which may be stored in data store 110.The data regarding the at-hand patient may include X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models corresponding to the patient visit during which the scanning occurs.","The data regarding the at-hand patient may additionally include past X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models of the patient (e.g., corresponding to past visits of the patient and/or to dental records of the patient).","The pooled patient data may include X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models regarding a multitude of patients.","Such a multitude of patients may or may not include the at-hand patient.","The pooled patient data may be anonymized and/or employed in compliance with regional medical record privacy regulations (e.g., the Health Insurance Portability and Accountability Act (HIPAA)).","The pooled patient data may include data corresponding to scanning of the sort discussed herein and/or other data.","The pedagogical patient data may include X-rays, 2D intraoral images, 3D intraoral images, 2D models, virtual 3D models, and/or medical illustrations (e.g., medical illustration drawings and/or other images) employed in educational contexts.","The pedagogical patient data may include volunteer data and/or cadaveric data.","AOI identifying module 115 may analyze patient scan data from later in a patient visit during which the scanning occurs (e.g., one or more later-in-the-visit 3D image point clouds and/or one or more later-in-the-visit virtual 3D models of the patient) relative to additional patient scan data in the form of data from earlier in that patient visit (e.g., one or more earlier-in-the-visit 3D image point clouds and/or one or more earlier-in-the-visit virtual 3D models of the patient).","AOI identifying module 115 may additionally or alternatively analyze patient scan data relative to reference data in the form of dental record data of the patient and/or data of the patient from prior to the patient visit (e.g., one or more prior-to-the-visit 3D image point clouds and/or one or more prior-to-the-visit virtual 3D models of the patient).","AOI identifying module 115 may additionally or alternatively analyze patient scan data relative to pooled patient data and/or pedagogical patient data.","In an example, AOI identifying module 115 may generate a first virtual model of a dental site based on a first scan session of the dental site taken at a first time and later generate a second virtual model of the dental site based on a second scan session of the dental site taken at a second time.","The AOI identifying module 115 may then compare the first virtual model to the second virtual model to determine a change in the dental site and identify an AOI to represent the change.","Identifying of areas of interest concerning missing and/or flawed scan data may involve the AOI identifying module 115 performing direct analysis, for instance determining one or more pixels or other points to be missing from patient scan data and/or one or more virtual 3D models of the patient.","Identification of areas of interest concerning missing and/or flawed scan data may additionally or alternatively involve employing pooled patient data and/or pedagogical patient data to ascertain patient scan data and/or virtual 3D models as being incomplete (e.g., possessing discontinuities) relative to that which is indicated by the pooled patient data and/or pedagogical patient data.","Flagging module 118 is responsible for determining how to present and/or call out the identified areas of interest.","Flagging module 118 may provide indications or indicators regarding scan assistance, diagnostic assistance, and/or foreign object recognition assistance.","Areas of interest may be determined, and indicators of the areas of interest may be provided, during and/or after an intraoral scan session.","Such indications may be provided prior to and/or without construction of an intraoral virtual 3D model.","Alternatively, indications may be provided after constructions of an intraoral virtual 3D model of a dental site.","Examples of the flagging module 118 providing indications regarding scan assistance, diagnostic assistance, and/or foreign object recognition assistance will now be discussed.","The flagging module 118 may provide the indications during and/or after an intraoral scan session.","The indications may be presented (e.g., via a user interface) to a user (e.g., a practitioner) in connection with and/or apart from one or more depictions of teeth and/or gingivae of a patient (e.g., in connection with one or more X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models of the patient).","Indication presentation in connection with depictions of patient teeth and/or gingivae may involve the indications being placed so as to correlate an indication with the corresponding portion of the teeth and/or gingivae.","As an illustration, a diagnostic assistance indication regarding a broken tooth might be placed so as to identify the broken tooth.","The indications may be provided in the form of flags, markings, contours, text, images, and/or sounds (e.g., in the form of speech).","Such a contour may be placed (e.g., via contour fitting) so as to follow an extant tooth contour and/or gingival contour.","As an illustration, a contour corresponding to a tooth wear diagnostic assistance indication may be placed so as to follow a contour of the worn tooth.","Such a contour may be placed (e.g., via contour extrapolation) with respect to a missing tooth contour and/or gingival contour so as to follow a projected path of the missing contour.","As an illustration, a contour corresponding to missing tooth scan data may be placed so as to follow the projected path of the tooth portion which is missing, or a contour corresponding to missing gingival scan data may be placed so as to follow the projected path of the gingival portion which is missing.","In presenting indications (e.g., flags), the flagging module 118 may perform one or more operations to pursue proper indication display.","For instance, where indications are displayed in connection with one or more depictions of teeth and/or gingivae (e.g., a corresponding virtual 3D model), such operations may act to display a single indication rather than, say, multiple indications for a single AOI.","Additionally, processing logic may select a location in 3D space for indication placement.","Where indications are displayed in connection with a 3D teeth and/or gingiva depiction (e.g., in connection with a virtual 3D model), the flagging module 118 may divide the 3D space into cubes (e.g., voxels corresponding to one or more pixels of the 3D space).","The flagging module 118 may then consider the voxels relative to the voxels of determined AOIs and tag voxels so as to indicate the indications (e.g., flags) to which they correspond.","As an illustration, suppose that two indications are to be brought to the attention of the user via flagging: a first indication which regards missing scan data and a second indication which regards a caries.","With regard to the missing scan data indication, the flagging module 118 may consider the pixels which correspond to the missing scan data relative to the cubes and tag each cube which encompasses one or more of those pixels.","The flagging module 118 may perform likewise with regard to the caries indication.","Where more than one cube is tagged with respect to a given one of the indications, the flagging module 118 may act such that only one of the tagged voxel receives flag placement.","Moreover, the flagging module 118 may choose a particular voxel which it determines will provide for ease of viewing by the user.","For instance, such choice of a voxel may take into account the totality of indications to be flagged and may endeavor to avoid crowding a single cube with multiple flags where such can be avoided.","In placing indications (e.g., flags) the flagging module 118 may or may not take into account factors other than seeking to avoid crowding.","For instance, the flagging module 118 may take into account available lighting, available angle, available zoom, available axes of rotation, and/or other factors corresponding to user viewing of the teeth and/or gingiva depiction (e.g., the virtual 3D model), and may seek indication (e.g., flag) placement which seeks to optimize user viewing in view of these factors).","The flagging module 118 may key the indications (e.g., via color, symbol, icon, size, text, and/or number).","The keying of an indication may serve to convey information about that indication.","The conveyed information may include classification of an AOI, a size of an AOI and/or an importance rank of an AOI.","Accordingly, different flags or indicators may be used to identify different types of AOIs.","For example, pink indicators may be used to indicate gingival recession and white indicators may be used to indicate tooth wear.","Flagging module 118 may determine a classification, size and/or importance rank of an AOI, and may then determine a color, symbol, icon, text, etc.","for an indicator of that AOI based on the classification, size and/or importance rank.","Turning to keying which conveys indication size, the processing logic may, in implementing such size-oriented keying, employ one or more size thresholds.","The origin of the thresholds may be set (e.g., by a dental expert) during a configuration operation and/or may be preset.","The origin of the thresholds may be set by processing logic which accesses pooled patient data and/or pedagogical patient data correlating size information for foreseeable indications regarding scan assistance (e.g., information regarding sizes of oral-anatomical portions not imaged or poorly imaged due to missing and/or flawed scan data) and degree of success of procedure outcome (e.g., degree of success in orthotic alignment device construction and/or orthotic alignment device patient fit).","Larger size may be indicative of greater clinical importance.","For example, a large void may impair manufacture of an accurate orthodontic aligner, while a large void may not.","As an illustration, three thresholds might be set with respect to areas of missing data and/or caries.","Implementation may be such that indications falling into the largest of the three size thresholds are keyed red and/or with the numeral “1,” that indications falling into the smallest of the three size thresholds are keyed purple and/or with the numeral “3,” and/or that indications falling into the middle-sized of the three thresholds are keyed yellow and/or with the numeral “2.” Turning to keying which conveys AOI classification, indicators may identify classifications assigned to intraoral areas of interest.","For examples, AOIs may be classified as voids, changes, conflicts, foreign objects, or other types of AOI.","AOIs representing changes in patient dentition may represent tooth decay, receding gums, tooth wear, a broken tooth, gum disease, gum color, moles, lesions, tooth shade, tooth color, an improvement in orthodontic alignment, degradation in orthodontic alignment, and so on.","Different criteria may be used for identifying each such class of AOI.","For example, a void may be identified by lack of image data, a conflict may be identified by conflicting surfaces in image data, changes may be identified based on differences in image data, and so on.","In an example of a surface conflict AOI, a first bite line component may correspond to one portion of a patient's teeth (e.g., the upper jaw or to the right side of the jaw).","A second bite line component may correspond to another portion of the patient's teeth (e.g., the lower jaw or to the left side of the jaw).","The AOI identifying module 115 may compare the first bite line component to the second bite line component to check for a deviation.","Such a deviation might be suggestive of the patient having moved his jaw during scanning (e.g., the patient having moved his jaw in an interim between a practitioner's scanning of the lower jaw and the practitioner's scanning of the upper jaw, or in an interim between the practitioner's scanning of the left side of the jaw and the and the practitioner's scanning of right side of the jaw).","In performing a bite line shift surface conflict operation, the AOI identifying module 115 may or may not take into account a deviation threshold (e.g., set during a configuration operation).","The flagging module 118 may or may not then provide indication thereof in the case where the found deviation meets the threshold, and not provide indication otherwise.","The intraoral scan application 108 may or may not apply corrective measures (e.g., averaging) to such found deviations which do not meet the threshold.","Where such a threshold is not taken into account, the flagging module 118 may provide indication of all found deviations.","Although the foregoing is, to facilitate discussion, cast in terms of bite line shift surface conflict, analogous operations may be performed, for instance, with regard to other surface conflict indications.","Keying may also include importance rank, which is discussed in greater detail with reference to FIG.","3B.","When a scan session is complete (e.g., all images for a dental site have been captured), model generation module 125 may generate a virtual 3D model of the scanned dental site.","AOI identifying module 115 and/or flagging module 118 may perform operations to identify AOIs and/or to indicate such AOIs before or after a virtual 3D model has been generated.","To generate the virtual model, model generation module 125 may register (i.e., “stitch” together) the intraoral images generated from the intraoral scan session.","In one embodiment, performing image registration includes capturing 3D data of various points of a surface in multiple images (views from a camera), and registering the images by computing transformations between the images.","The images may then be integrated into a common reference frame by applying appropriate transformations to points of each registered image.","In one embodiment, processing logic performs image registration in a manner discussed in U.S. Pat.","No.","6,542,249, filed Jul.","20, 1999, which is incorporated herein by reference.","In one embodiment, image registration is performed for each pair of adjacent or overlapping intraoral images (e.g., each successive frame of an intraoral video).","Image registration algorithms are carried out to register two adjacent intraoral images, which essentially involves determination of the transformations which align one image with the other.","Each registration between a pair of images may be accurate to within 10-15 microns.","Image registration may involve identifying multiple points in each image (e.g., point clouds) of an image pair, surface fitting to the points of each image, and using local searches around points to match points of the two adjacent images.","For example, model generation module 125 may match points of one image with the closest points interpolated on the surface of the other image, and iteratively minimize the distance between matched points.","Model generation module 125 may also find the best match of curvature features at points of one image with curvature features at points interpolated on the surface of the other image, without iteration.","Model generation module 125 may also find the best match of spin-image point features at points of one image with spin-image point features at points interpolated on the surface of the other image, without iteration.","Other techniques that may be used for image registration include those based on determining point-to-point correspondences using other features and minimization of point-to-surface distances, for example.","Other image registration techniques may also be used.","Many image registration algorithms perform the fitting of a surface to the points in adjacent images, which can be done in numerous ways.","Parametric surfaces such as Bezier and B-Spline surfaces are most common, although others may be used.","A single surface patch may be fit to all points of an image, or alternatively, separate surface patches may be fit to any number of a subset of points of the image.","Separate surface patches may be fit to have common boundaries or they may be fit to overlap.","Surfaces or surface patches may be fit to interpolate multiple points by using a control-point net having the same number of points as a grid of points being fit, or the surface may approximate the points by using a control-point net which has fewer number of control points than the grid of points being fit.","Various matching techniques may also be employed by the image registration algorithms.","In one embodiment, model generation module 125 may determine a point match between images, which may take the form of a two dimensional (2D) curvature array.","A local search for a matching point feature in a corresponding surface patch of an adjacent image is carried out by computing features at points sampled in a region surrounding the parametrically similar point.","Once corresponding point sets are determined between surface patches of the two images, determination of the transformation between the two sets of corresponding points in two coordinate frames can be solved.","Essentially, an image registration algorithm may compute a transformation between two adjacent images that will minimize the distances between points on one surface, and the closest points to them found in the interpolated region on the other image surface used as a reference.","Model generation module 125 repeats image registration for all adjacent image pairs of a sequence of intraoral images to obtain a transformation between each pair of images, to register each image with the previous one.","Model generation module 125 then integrates all images into a single virtual 3D model by applying the appropriate determined transformations to each of the images.","Each transformation may include rotations about one to three axes and translations within one to three planes.","In one embodiment, intraoral scan application 108 includes a training module 120.The training module 120 may provide a user (e.g., a practitioner) with training guidance as to scanning technique, and/or may highlight scan assistance indications of the sort discussed hereinabove (e.g., ones corresponding to missing and/or flawed scan data) which have occurred in the past and/or have been reoccurring for that user.","The training module 120 may consider, relative to a training guidance data pool, scan data (e.g., 3D image point clouds) and/or one or more virtual 3D models arising from scanning performed by that user which led to scan assistance indications.","The training guidance data pool may include, with respect to the scanning performances of multiple users (e.g., multiple practitioners), scan data and/or one or more virtual 3D models (e.g., one which led to scan assistance indications) along with information describing scanning technique changes which might have prevented and/or mitigated the circumstances which led to the scan assistance indications.","The scan data and/or one or more virtual 3D models of the training guidance data pool may be anonymized and/or employed in compliance with regional medical record privacy regulations.","The training module 120 may match the scan data and/or one or more virtual 3D models arising from scanning performed by the user to scan data and/or virtual 3D models of the training guidance data pool, access corresponding information describing scanning technique changes, and present such scanning change technique information to the user (e.g., via a user interface).","As an illustration, the training guidance data pool might, for scan data and/or one or more virtual 3D models which led to double incisor edge scan assistance indications such as ones corresponding to particular angles of scanning, include information indicating that having performed scanning with a specified angular change might have been preventative and/or mitigating.","For instance, such data might, for scan data and/or one or more virtual 3D models which led to double incisor edge scan assistance indications in a fashion indicative of scanning at a 35 degree-to-surface angle—instead of a desired 45 degree-to-surface angle—include information indicating that an angular increase of ten degrees-to-surface might be preventative and/or curative.","Moreover, such data might for scan data and/or one or more virtual 3D models which led to double incisor edge scan assistance indications in a fashion indicative of scanning with a 40 degree-to-surface angle—instead of the desired 45 degree-to-surface angle—include information indicating that an angular increase of five degrees-to-surface might be preventative and/or curative.","As another illustration, the training guidance data pool might, for scan data and/or one or more virtual 3D models which led to missing and/or flawed scan data scan assistance indications (e.g., ones corresponding to particular geometrical areas, width-height dimensions, width-to-height or other dimensional relationships, and/or oral locations), include information indicating that having performed scanning at one or more specified speeds, cadences, angles, and/or distances-from-surface might have been preventative and/or mitigating.","The training module 120 may with respect to particular users (e.g., practitioners) keep historical record (e.g., according to user identifier) of scan assistance indications over time.","The training module 120 may employ this historical record to highlight scan assistance indications which have occurred in the past and/or have been reoccurring for a particular user, to identify improvements and/or declines in user scanning technique over time, and/or to provide scanning technique training guidance which takes into account multiple scanning performances of the user.","The training module 120 may or may not consider the noted training guidance data pool information describing scanning technique changes which may be preventative and/or mitigating.","As one illustration, the training module 120 may in providing indication (e.g., flagging) regarding missing and/or flawed scan data recognize that a particular user has received same and or similar indication in the past.","For instance, the training module 120 may ascertain that the user has received missing and/or flawed scan data at a given location multiple times, and/or has received missing and/or flawed scan data of similar tenor multiple times (e.g., although at differing locations, the user has repeatedly received indication reelecting double incisor edges suggestive of scanning at other than a 45-degrees-from-surface angle).","Where the training module 120 so finds an at-hand indication to be one for which same and/or similar indication has been received in the past, the training module 120 may act to highlight the indication (e.g., via a particular color).","As another illustration, with respect to a particular user and double incisor edge scan assistance indications, the training module 120 may, by consideration of such historical record and such training guidance data pool scanning technique change information, ascertain that the user's scanning technique is changing in such a fashion that the employed scanning is not yet the called-for 45 degrees-to-surface, but that the employed scanning angle is becoming over time closer to 45 degrees-to-surface.","In so doing the training module 120 may perform matching with training guidance data pool information in the vein of the noted differing degrees-to-surface scanning angles leading to double incisor edge scan assistance indication (e.g., matching older user data to pool data regarding 60-degree-to-surface scanning angle but more recent user data to pool data regarding 40-degree-to-surface scanning angle).","FIGS.","2A-3C illustrate flow diagrams of methods for performing intraoral scans of dental sites for patients.","These methods may be performed by processing logic that comprises hardware (e.g., circuitry, dedicated logic, programmable logic, microcode, etc.","), software (such as instructions run on a processing device), or a combination thereof.","In one embodiment, processing logic corresponds to computing device 105 of FIG.","1 (e.g., to a computing device 105 executing an intraoral scan application 108).","FIG.","2A illustrates a flow diagram for a method 200 of determining intraoral areas of interest during an intraoral scan session, in accordance with embodiments of the present invention.","At block 205 of method 200, an intraoral scan session of a dental site is started by a dental practitioner.","The scan session may be for an intraoral scan of a partial or full mandibular or maxillary arch, or a partial or full scan of both arches.","The dental practitioner may move an intraoral scanner to a first intraoral position and generate a first intraoral image.","At block 210, processing logic receives the first intraoral image.","The first intraoral image may be a discrete image (e.g., taken from a point-and-shoot mode) or a frame of an intraoral video (e.g., taken in a continuous scanning or video mode).","The intraoral image may be a three dimensional (3D) image having a particular height, width and depth.","In some embodiments, an intraoral scanner is used that generates 3D images having a depth of 12-14 mm, a height of 13-15 mm and a width of 17-19 mm (e.g., a depth of 13 mm, height of 14 mm and width of 18 mm in one particular embodiment).","At block 215, processing logic identifies one or more candidate intraoral areas of interest from the first intraoral image.","In one embodiment, a candidate intraoral area of interest is identified by processing the intraoral image to identify voxels in the intraoral image that satisfy one or more criteria.","Different criteria may be used to identify different classes of intraoral areas of interest.","In one embodiment, the a of missing image data is used to identify AOIs that might be voids.","For example, voxels at areas that were not captured by the intraoral image may be identified.","Processing logic may then determine one or more subsets of the identified voxels that are proximate to one another.","Two voxels may be considered to be proximate to one another if they are within a threshold distance from one another.","In one embodiment, two voxels are proximate if they are adjacent to one another.","All of the voxels in a determined subset (e.g., all of the voxels that are connected directly or via other identified voxels) are grouped into a volume that makes up the candidate area of interest.","One or multiple candidate areas of interest may be identified.","If the criterion used to identify voxels is a missing data, then the candidate intraoral area of interest may represent a void.","Other criteria may be used to identify other classes of AOI.","After the dental practitioner generates the first intraoral image, he or she moves the intraoral scanner to a second position and generates a next intraoral image.","At block 220, processing logic receives the next intraoral image.","At block 230, processing logic compares the second intraoral image to the first intraoral image.","To compare intraoral images, processing logic determines an alignment between the intraoral images based on geometric features shared by these intraoral images.","Determining the alignment may include performing transformations and/or rotations on one or both of the intraoral images and/or register the intraoral areas of interest to each other.","The aligned images may then be displayed by the processing logic.","Processing logic may also compare the first intraoral image to a corresponding intraoral image taken during a prior scan session.","This may identify areas of interest such as tooth wear, cavities, and so forth.","At block 232, processing logic determines whether any new candidate intraoral areas of interest are present based on the next intraoral image.","At block 235, processing logic determines whether the candidate intraoral areas of interest from the first intraoral image are verified as intraoral areas of interest.","Such verification may be performed by testing the proximity and/or geometric conditions of the AOI relative to a surface of the latest intraoral image.","In one embodiment, candidate intraoral areas of interest from an intraoral image are dismissed if they correspond to a surface (e.g., of a dental site) from another intraoral image.","Alternatively, if a candidate intraoral area of interest does not correspond to a region of a surface from another intraoral image, then the candidate intraoral image may be verified as an actual intraoral area of interest.","Accordingly, the second intraoral image may be used to confirm or dismiss candidate intraoral areas of interest from the first intraoral image.","If a portion of a candidate intraoral area of interest from the first intraoral image corresponds to (e.g., lines up with) a portion of a surface from the second intraoral image, then the shape and/or size of the candidate intraoral area of interest may be modified.","If none of the candidate intraoral areas of interest are verified as intraoral areas of interest (e.g., if a subsequent intraoral image provides image data for a candidate intraoral area of interest), the method proceeds to block 245.Otherwise, the method continues to block 240.At block 240, processing logic provides an indication of the one or more verified intraoral areas of interest.","In one embodiment, processing logic interpolates a shape for the intraoral area of interest based on geometric features surrounding the intraoral area of interest and/or based on geometric features of the intraoral area of interest (if such features exist).","For example, if the intraoral area of interest is a void, then the regions around the void may be used to interpolate a surface shape of the void.","The shape of the intraoral area of interest may be displayed in manner to contrast the intraoral area of interest from surrounding imagery.","For example, teeth may be shown in white, while the intraoral area of interest may be shown in red, black, blue, green, or another color.","Additionally or alternatively, an indicator such as a flag may be used as an indication of the intraoral area of interest.","The indicator may be remote from the intraoral area of interest but include a pointer to the intraoral area of interest.","The intraoral area of interest may be hidden or occluded in many views of the dental site.","However, the indicator may be visible in all or many such views.","For example, the indicator may be visible in all views of the scanned dental site unless the indicator is disabled.","The provided indications of the intraoral areas of interest may be displayed while the intraoral scan session is ongoing.","At block 245, processing logic determines whether the intraoral scan session is complete.","If so, the method continues to block 248.If additional intraoral images are to be taken and processed, the method returns to block 220.At block 248, a virtual 3D model of the dental site is generated.","The virtual model 3D may be generated as discussed above.","The virtual 3D model may be a virtual or digital model showing the surface features of the target area.","For a virtual 3D model of a full dental arch, the arch width of the virtual 3D model may be accurate to within 200 microns of the arch width of the patient's actual dental arch.","FIG.","2B illustrates a flow diagram for a method 250 of providing indications for intraoral areas of interest, in accordance with embodiments of the present invention.","The indications may be provided during an intraoral scan session (e.g., before generation of a virtual model of a dental site) or after an intraoral scan session is complete (e.g., based on a virtual model of the dental site).","At block 255, intraoral images of a dental site are received.","The intraoral images may be received from an intraoral scanner, from a data store, from another computing device, or from another source.","The intraoral images may be from a single intraoral scan session or from multiple intraoral scan sessions.","Additionally, or alternatively, one or more virtual models of a dental site may be received.","The virtual models may have been computed based on intraoral images from past intraoral scan sessions.","At block 260, processing logic identifies one or more voxels from the intraoral images and/or the virtual models that satisfy a criterion.","The criterion may be missing data, conflicting data, or data having particular characteristics.","In one embodiment, the intraoral images are first used to compute a virtual model, and the voxels are identified from the computed virtual model.","In another embodiment, the voxels are identified from individual intraoral images.","At block 265, one or more subsets of the identified voxels that are in close proximity to one another are identified.","At block 270, these subsets are grouped into candidate intraoral areas of interest.","At block 275, processing logic determines whether the candidate intraoral areas of interest are verified as intraoral areas of interest.","If any candidate intraoral areas of interest are verified as actual intraoral areas of interest, the method continues to block 280.Otherwise, the method proceeds to block 290.At block 280, classifications are determined for the intraoral areas of interest.","For example, AOIs may be classified as voids, conflicting surfaces, changes in a dental site, foreign objects, and so forth.","At block 285, processing logic provides indications of the intraoral areas of interest.","The indications may include information identifying the determined classifications of the intraoral areas of interest.","For example, an indicator may identify an intraoral area of interest as representing a void or insufficient image data.","Another indicator may identify an intraoral area of interest as representing a region for which there are conflicting surfaces from different images.","In one embodiment, the indications include flags that are remote from the intraoral areas of interest and that point to or otherwise direct a viewer's attention to the intraoral areas of interest.","The indications may be visible from views of the dental site at which the actual intraoral areas of interest are hidden.","At block 290, the dental site is displayed along with any of the indications for the intraoral areas of interest.","FIG.","3A illustrates a flow diagram for a method 300 of formulating scan assistance indications concerning missing and/or flawed scan data in accordance with examples of the present invention.","According to a first aspect, at block 305 of method 300 the processing logic may receive scan data from an intraoral scanner.","At block 310 the processing logic, may perform direct 3D point cloud analysis and/or direct virtual 3D model analysis.","At block 315 the processing logic may determine one or more pixels and/or other points to be missing from patient scan data and/or from one or more patient virtual 3D models.","At block 330, the processing logic may formulate one or more corresponding indications concerning missing and/or flawed scan data.","According to a second aspect of FIG.","3, at block 305 the processing logic may likewise receive scan data from the scanner.","At block 320, the processing logic may consider patient scan data and/or one or more patient virtual 3D models relative to entities indicated by pooled patient data and/or by pedagogical patient data to constitute complete and/or un-flawed data.","At block 325, the processing logic may ascertain the patient scan data and/or one or more patient virtual 3D models to be incomplete.","At block 330, the processing logic may likewise formulate one or more corresponding indications concerning missing and/or flawed scan data.","The indications regarding diagnostic assistance provided by the processing logic may include indications concerning tooth occlusion contacts, bite relation, tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries.","To facilitate understanding, examples of processing logic operations performed in connection with providing diagnostic assistance indications will now be discussed.","FIG.","3B illustrates a flow diagram for a method 340 of performing keying and display which conveys indication importance rank for intraoral areas of interest in accordance with that which is discussed hereinabove and in connection with examples of the present invention.","Processing logic may assign an importance rank to an indication via a process in which the processing logic considers the indication in view of one or more patient case details and/or one or more rank-altering weighting factors.","It is noted that one or more of the rank-altering weighting factors themselves may or may not regard patient case details.","Such patient case details may include a procedure being performed (e.g., preparation for application of a crown, preparation for application of an orthodontic alignment device, treatment of suspected caries and/or treatment of gingival swelling), patient age, patient gender, one or more previously-performed procedures (e.g., that a patient's last visit was to address a crown affected by marginal leakage), and/or patient dental records.","At block 345 of method 340 the processing logic may apply one or more weighting factors to each of the one or more under-consideration indications.","A weighting factor may set forth one or more particular properties and indicate one or more rank alterations to be performed where such properties are met.","The rank alterations may include increasing an indication's rank by a given value, decreasing an indication's rank by a given value, specifying that an indication be considered to possess a zenith rank, and/or that an indication be considered to possess a nadir rank.","With respect to a given indication, the processing logic may commence by assigning a particular start rank value (e.g., zero) to the indication.","The processing logic may then consider the one or more weighting factors.","Having applied those weighting factors, the processing logic may ascertain a finalized importance rank for the indication.","The processing logic may consider the finalized importance rank for the indication relative to one or more other indications for which it has performed like operations.","The origin of the rank-altering weighting factors considered by the processing logic may be set by processing logic which accesses pooled patient data and/or pedagogical patient data which includes correlations between foreseeable indications regarding diagnostic assistance (e.g., tooth wear and/or caries) and importance (e.g., the data might set forth importance information regarding each of tooth wear and caries that conveys that caries are of greater import than tooth wear).","Processing logic may set the rank-altering weighting factors such that missing and/or flawed scan data corresponding to a portion of teeth and/or gingivae that is larger than or equal to a certain size has an increased rank.","Rank-altering weighting factors such as missing and/or flawed scan data which corresponds to a portion of teeth and/or gingivae which has certain dimensional characteristics (e.g., having width magnitude being greater than or equal to height magnitude, a circumstance that might be viewed as being short and wide or square shaped) are assigned the zenith rank or more highly ranked.","Missing and/or flawed scan data which corresponds to a portion of teeth and/or gingivae which has other dimensional characteristics (e.g., having width magnitude being less than height magnitude, a circumstance that might be viewed as being long and narrow) may be assigned the nadir rank or more lowly ranked.","The origin of the rank-altering weighting factors considered by the processing logic may be set by processing logic which accesses pooled patient data and/or pedagogical patient data which includes correlations between foreseeable indications regarding foreign object recognition assistance (e.g., concerning fillings and/or implants) and importance (e.g., the data might set forth importance information regarding each of fillings and implants that conveys that fillings are of greater import than implants).","By consideration of such data-provided correlations—be they ones regarding scan assistance, diagnostic assistance, or foreign object recognition assistance—the processing logic may draw conclusions which it employs in setting rank-altering weighting factors.","The performed setting—be it done during a configuration operation or by processing logic—may provide for one or more weighting factors directed towards foreseeable indications.","One such weighting factor may specify that an indication relating to the vicinity of (e.g., to the interproximal areas of) one or more preparation teeth have its rank raised by a specified value.","Another such weighting factor may specify that an indication regarding insufficient preparation tooth margin line clarity have its rank raised by a specified value or that such indication should possess a zenith rank.","Yet another weighting factor may specify that an indication regarding unclear bite have its rank raised by a specified value.","A further weighting factor may specify that an indication regarding bite line shift have its rank raised by a specified value.","Another weighting factor may specify that an indication regarding double incisor edge have its rank raised by a specified value.","Yet another weighting factor may specify that an indication regarding a lack of gum line clarity have its rank raised by a first specified value in the case where the at-hand procedure does not concern gingival recess, but have its rank raised by a second specified value in the case where the at-hand procedure does concern gingival recess.","As one example, with respect to a first indication the processing logic may commence by assigning an importance rank of zero to the indication, determine that consideration of a first weighting factor finds indication that the indication's rank be raised by three, that consideration of a second weighting factor finds indication that the indication's rank be lowered by one, and that consideration of a third weighting factor finds indication that the indication's rank be raised by five.","The processing logic may then ascertain the finalized importance rank of the first indication to be seven.","Further, with respect to a second indication the processing logic may commence by assigning an importance rank of zero to the indication, determine that consideration of a first weighting factor finds indication that the indication's rank be lowered by two, that consideration of a second weighting factor finds indication that the indication's rank be lowered by three, and that consideration of a third weighting factor finds indication that the indication's rank be raised by six.","The processing logic may then ascertain the finalized importance rank of the second indication to be one.","With respect to a third indication the processing logic may again commence by assigning an importance rank of zero.","The processing logic may then find that consideration of a first weighting factor finds indication that the indication's rank be raised by four, that consideration of a second weighting factor finds indication that the indication be considered to possess a zenith rank, and that consideration of a third weighting factor finds indication that the indication's rank be lowered by eight.","The processing logic may then ascertain the finalized importance rank of the third indication to be the zenith rank.","As such, the second weighting factor, by indicating zenith rank, might be seen as having trumped that which was indicated by the other two weighting factors.","It is noted that had consideration of the second weighting factor instead found indication that the indication be considered to possess a nadir rank, the second weighting factor would have again trumped the other two weighting factors, but would have done so in a fashion that yielded a finalized importance rank of the nadir rank for the third indication.","At block 350, the processing logic may ascertain a finalized importance rank for each of the one or more under-consideration indications.","At block 355, the processing logic may consider relative to one another the finalized importance ranks of the one or more under-consideration indications.","Continuing the above example, the processing logic may consider the three finalized importance ranks—seven for the first indication, one for the second indication, and zenith rank for the third indication—relative to one another.","In so doing the processing logic may conclude the third indication to be highest-ranked, the first indication to be second-highest-ranked, and the second indication to be lowest-ranked.","At block 360, the processing logic may employ the finalized importance ranks in formulating a rescan order and/or a practitioner attention order.","The processing logic may employ the importance ranks of indications in suggesting a rescan order for one or more indications (e.g., indications regarding scan assistance such as indications concerning missing and/or flawed scan data) and/or in suggesting a practitioner attention order for one or more indications (e.g., indications regarding diagnostic assistance and/or indications regarding foreign object recognition assistance).","In formulating such rescan order and such practitioner attention orders the processing logic may or may not suppress one or more indications such that those indications are excluded from the rescan order or practitioner attention order.","As one illustration, the processing logic may suppress indications having rank lower than a certain value (e.g., a value specified by the user and/or during a configuration).","As another illustration, the processing logic may suppress indications having the nadir rank.","Such suppression may serve to eliminate indications determined by the processing logic to lack clinical significance (e.g., with respect to an at-hand procedure—say preparation for application of a crown or an orthotic alignment device).","As an illustration, suppressed indications may include missing and/or flawed scan data for which compensation can be performed (e.g., via the employ of extrapolation and/or generic data filling).","The processing logic may—for those indications which have not been suppressed—convey importance rank via keying of indications (e.g., via color, symbol, icon, size, text, and/or number key).","Then, at block 365 the processing logic may provide in connection with a depiction of teeth and/or gingivae (e.g., a 3D image or a virtual 3D model) one or more keyed indications (e.g., flags) conveying for each indication its location in the rescan order and/or in the practitioner attention order.","The processing logic may provide flags including numerals which each point to a particular portion of a depiction (e.g., a 3D image or a virtual 3D model) of teeth and/or gingivae of a patient and convey via the numeral the order-wise location of that oral portion.","As an illustration, suppose that there are four indications regarding scan assistance selectable by the processing logic for inclusion in a rescan order—an indication corresponding to teeth 15 and 16 (ISO 3950 notion), an indication corresponding to the gingiva of tooth 32 (ISO 3950 notation), an indication corresponding to teeth 18 and 17 (ISO 3950 notation), and an indication corresponding to tooth 44 (ISO 3950 notation).","Then suppose that the indication correspond to teeth 18 and 17 has the nadir rank, and that the processing logic suppresses this indication, thereby eliminating it from the rescan order.","Suppose further that the rescan order for the three remaining indications is such that the indication corresponding to the gingiva of tooth 32 has the highest importance rank of the remaining three and is first in the rescan order, that the indication corresponding to teeth 15 and 16 has the second highest importance rank of the remaining three and is second in the rescan order, and that the indication corresponding to tooth 44 has the lowest importance rank of the remaining three and is third in the rescan order.","The provision of flags by the processing logic may be such that the indication corresponding to the gingiva of tooth 32 is flagged with a “1,” the indication corresponding to teeth 15 and 16 is flagged with a “2,” and the indication corresponding to tooth 48 is flagged with a “3.” As another illustration, suppose that there are three indications regarding diagnostic assistance—an indication corresponding to breakage of teeth 11 and 21 (ISO 3950 notation), an indication corresponding to bite relation, and an indication corresponding to gingival recess at the base of tooth 27 (ISO 3950 notation).","Suppose further that the practitioner attention order is such that the indication corresponding to bite relation has the highest importance rank of the three and is first in the practitioner attention order, that the indication corresponding to the breakage has the second highest importance rank of the three and is second in the practitioner attention order, and that the indication corresponding to the gingival recess has the lowest importance rank of the three and is third in the practitioner attention order.","The provision of flags by the processing logic may be such that the indication corresponding to bite relation is flagged with a “1,” the indication corresponding to the breakage is flagged with a “2,” and the indication corresponding to the gingival recess is flagged with a “3.” As an additional illustration, suppose that there are two indications regarding foreign object recognition assistance—an indication corresponding to a filling in tooth 16 (ISO 3950 notation) and an indication corresponding to a bridge at the expected anatomical location of teeth 35-37 (ISO 3950 notation).","Suppose further that the practitioner attention order is such that the indication corresponding to the filling has the has the higher importance rank of the two and is first in the practitioner attention order, and that the indication corresponding to the bridge has the lower importance rank of the two and is second in the practitioner attention order.","The provision of flags by the processing logic may be such that the indication corresponding to the filling is flagged with a “1” and the indication corresponding to the bridge is flagged with a “2.” FIG.","3C illustrates a flow diagram for a method 370 of employing 3D intraoral images in providing indication of intraoral areas of interest, in accordance with examples of the present invention.","As discussed hereinabove, the processing logic may provide indication regarding scan assistance, diagnostic assistance, and/or foreign object recognition assistance.","As also discussed hereinabove, the processing logic may provide such indication during the user's (e.g., the practitioner's) scanner application, after the user's scanner application, and/or prior to and/or without construction of an intraoral virtual 3D model.","As additionally discussed hereinabove, in formulating such indication the processing logic may analyze intraoral scan data (e.g., 3D intraoral images, say 3D intraoral images provided by the scanner as 3D image point clouds) and/or intraoral virtual 3D models.","At block 372 of method 370 the processing logic may analyze one or more first 3D intraoral images to yield a candidate intraoral area of interest.","The processing logic may perform such analysis as discussed hereinabove with respect to AOI formulation, but consider the analysis result to constitute a candidate intraoral area of interest rather than an actual intraoral area of interest.","The processing logic may identify one or more points (e.g., one or more pixels and/or groups of pixels) corresponding to the candidate intraoral area of interest.","At block 374, the processing logic may identify one or more second 3D intraoral images which may be relevant to the candidate intraoral area of interest.","The one or more second 3D intraoral images may be ones which are intraorally proximal to the first one or more 3D intraoral images and/or ones which share geometrical relation to the first one or more 3D intraoral images.","The processing logic may determine such intraoral proximity by considering intraoral location information provided by the scanner in connection with 3D intraoral images.","The scanner might produce such information by way of incorporated accelerometers and/or other positioning hardware.","The processing logic may determine such shared geometrical relation by identifying common surface features (e.g., common peak and/or valley surface features).","At block 376, the processing logic may perform analysis with respect to one or more of the first 3D intraoral images and the second 3D intraoral images taken together.","In so doing the processing logic may or may not align the one or more first 3D intraoral images with the one or more second 3D intraoral images (e.g., the processing logic may align one or more point clouds corresponding to the first one or more 3D intraoral images with one or more point clouds corresponding to the second one or more 3D intraoral images).","At block 378, the processing logic may determine whether the first 3D intraoral images and the second 3D intraoral images, taken together, agree, disagree, or agree in part with the candidate intraoral area of interest.","As example, suppose that the candidate indication regards a scan assistance indication concerning missing and/or flawed scan data.","In the case where such taken-together analysis finds no missing and/or flawed scan data disagreement may occur.","As an illustration, such may occur where all of the one or more points (e.g., one or more pixels and/or groups of pixels) which correspond to missing scan data for the candidate indication are provided by the one or more second 3D intraoral images.","In the case where such taken-together analysis still finds missing and/or flawed scan data but the tenor of the missing and/or flawed scan data changes (e.g., the now-found missing and/or flawed scan data is of a larger size, of a smaller size, of a different location, and/or of a different morphology), partial agreement may occur.","As an illustration, such might occur where some points (e.g., one or more pixels and/or groups of pixels) which correspond to missing scan data for the candidate indication are provided by the one or more second 3D intraoral images while other of such missing scan data points are not provided by the one or more second 3D intraoral images such that a smaller amount of missing and/or flawed scan data is found.","In the case where such taken-together analysis finds the same tenor (e.g., the same amount of) missing and/or flawed scan data, agreement may occur.","As an illustration, such might occur where none of the points (e.g., one or more pixels and/or groups of pixels) which correspond to missing scan data for the candidate indication are provided by the one or more second 3D intraoral images.","As another example, suppose that the candidate indication regards a diagnostic assistance indication concerning caries.","In the case where such taken-together analysis no longer finds caries disagreement may occur.","As an illustration, such may occur where further taking into account the one or more second 3D intraoral images—say further taking into account one or more points (e.g., one or more pixels and/or groups of pixels) provided by the one or more second 3D intraoral images—yields a refined intraoral vantage point from which caries are no longer found.","In the case where such taken-together analysis still finds caries but the tenor of the found caries changes (e.g., the now-found caries are smaller, larger, of different location, and/or of different morphology), partial agreement may occur.","As an illustration, such might occur where further taking into account the one or more second 3D intraoral images—say further taking into account one or more points (e.g., one or more pixels and/or groups of pixels) provided by the one or more second 3D intraoral images—yields a refined intraoral vantage point from which the found caries differ in size and/or intraoral location.","In the case where such taken-together analysis finds caries of the same tenor as that found in connection with the candidate indication agreement may occur.","As an illustration, such might occur where further taking into account the one or more second 3D intraoral images—say further taking into account one or more points (e.g., one or more pixels and/or groups of pixels) provided by the one or more second 3D intraoral images—yields does not refine the intraoral vantage point in a way that causes the found caries to differ in size and/or in intraoral location.","Where the processing logic finds agreement, the processing logic may promote the candidate AOI to an indication of the sort discussed hereinabove (i.e., a full, non-candidate AOI) and employ it as discussed hereinabove (e.g., provide an indication of the AOI to a user in the form of flags).","Where the processing logic finds partial agreement, the processing logic may yield an AOI corresponding to the above-discussed different tenor (e.g., an AOI reflecting a smaller amount of missing data or an AOI reflecting a caries of different morphology) and employ it as discussed hereinabove.","Where the processing logic finds disagreement, the processing logic may reject the candidate AOI.","Where there is agreement the processing logic may proceed to block 380, in which the processing logic promotes the candidate indication to a full, non-candidate indication and employs the promoted indication as discussed above.","Where there is partial agreement the processing logic may proceed to block 382, in which the processing logic yields an indication corresponding to the tenor of the partial agreement, and employs that indication as discussed above.","Where there is disagreement the processing logic may proceed to block 384, in which the processing rejects the candidate indication.","Previously discussed pooled patient data and/or pedagogical patient data may include many different types of data and/or depictions.","Some examples of different pooled patient data and/or pedagogical patient data and its use is now discussed.","Pooled patient data and/or pedagogical patient data may include depictions of gum lines, bites, and/or bite lines, along with corresponding identifications thereof and/or clarity level indications thereof.","Indication regarding unclear gum line and/or unclear patient bite may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or virtual 3D models includes a gum line or bite that is unclearly imaged (e.g., deviates, in a fashion suggestive of unclarity, from gum line or bite indicated by the pooled and/or pedagogical data to possess clarity.","Pooled patient data and/or pedagogical patient data may additionally include depictions of margin lines, tooth stumps, and/or accumulations (e.g., blood and/or saliva accumulations) along with corresponding identifications thereof.","Indication regarding unclear margin line may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or a virtual 3D model constitute a margin line (e.g., an upper portion of a tooth stump which is to receive prosthetic crown).","Additionally, or alternatively, the processing logic may compare the margin line of under consideration patient scan data and/or one or more virtual 3D models of the patient to the margin line of an earlier-in-the-visit and/or dental record data to detect a margin line change suggestive of the buildup of blood, saliva, and/or like accumulation on the margin.","The processing logic may consider found margin lines together with found blood, saliva, and/or like accumulation to locate instances of such accumulation appearing in the vicinity of such margin lines, and to conclude such instances to constitute unclear margin lines.","Pooled patient data and/or pedagogical patient data may include depictions of incisor edges and/or of double incisor edges along with corresponding identifications thereof.","Indication regarding double incisor edge surface conflict may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or virtual 3D models include one or more incisor edges, and further to conclude such incisor edges to deviate, in a fashion suggestive of double incisor edge, from incisor edges indicated by the pooled and/or pedagogical data to be proper incisor edges.","Pooled patient data and/or pedagogical patient data may include depictions of tooth occlusion contacts and/or bite relations along with corresponding identifications thereof.","Indication regarding tooth occlusion contacts and/or bite relation may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or virtual 3D models constitute tooth occlusion contacts and/or bite relation.","The processing logic may further access one or more treatment goals (e.g., a desired degree of occlusion with respect to one or more indicated teeth and/or a desired bite relation).","Such goals may be provided by a practitioner (e.g., via a user interface) and/or be retrieved from an accessible data store.","The processing logic may then compare the tooth occlusion contacts and/or bite relation of the under consideration patient scan data and/or one or more virtual 3D models of the patient to the tooth occlusion contacts and/or bite relation of earlier-in-the-visit and/or dental record data to detect the degree of change (which might be null) of tooth occlusion contacts and/or bite relation.","The processing logic may then compare the determined change to a treatment goal and ascertain whether the change causes satisfaction of the treatment goal, or whether the change serves to approach or depart the goal.","The indication may include notification as to whether or not the change approaches, departs, meets the treatment goal, or results in no change relative to the treatment goal.","As one illustration, the aforementioned regarding tooth occlusion contacts may correspond to a circumstance in which a practitioner indicates a tooth occlusion contact treatment goal to the processing logic, has the processing logic receive scan data depicting a starting occlusion contact state of the patient, performs a dental procedure which serves to potentially alter that occlusion contact state, and that has the processing logic receive scan data depicting the post-procedure occlusion contact state.","Via processing in vein of that which is discussed above, the practitioner may receive indication as to whether his procedure has met the treatment goal, caused progress towards the treatment goal, caused departure from the treatment goal, or resulted in no change relative to the treatment goal.","As another illustration, the aforementioned regarding bite relation may correspond to a circumstance in which a practitioner indicates a bite relation treatment goal to the processing logic, has the processing logic receive scan data depicting a starting bite relation state of the patient, applies an orthotic alignment device to the patient, and has the patient return at a later data.","Then, at the later date, the practitioner has the processing logic receive scan data depicting the post-device-application bite relation state.","Via processing in vein of that which is discussed above, the practitioner may receive indication as to whether his device application has caused the treatment goal to be met, caused progress towards the treatment goal, caused departure from the treatment goal, or has resulted in no change relative to the treatment goal.","Pooled patient data and/or pedagogical patient data may include depictions of tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries along with corresponding identifications thereof.","Indication regarding tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or one or more virtual 3D models constitute tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries.","For example, the processing logic may employ pooled patient data and/or pedagogical patient data to recognize teeth and/or gingiva in intraoral images and/or virtual 3D models.","The processing logic may then compare the teeth and/or gingivae of the intraoral images and/or virtual 3D models to the teeth and/or gingivae of earlier intraoral images, virtual 3D models and/or dental record data to detect change indicative of tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries.","In performing such detection the processing logic may or may not perform image analysis (e.g., considering a discovered change to be indicative of tooth breakage in the case where the change possesses a jagged edge) and/or consult patient data and/or pedagogical patient data (e.g., considering a discovered change to be indicative of tooth breakage in the case where the change matches one or more items indicated by the patient data and/or pedagogical patient data to constitute breakage).","Indication concerning tooth breakage and/or caries may involve the processing logic performing direct analysis.","The processing logic may additionally or alternatively employ pooled patient data and/or pedagogical patient data to recognize that the patient scan data and/or one or more virtual 3D models includes areas that constitute teeth.","The processing logic may determine (e.g., via edge recognition) one or more of such teeth to possess one or more jagged edges.","The processing logic may consider such jagged edges to be indicative of tooth breakage.","The processing logic may determine (e.g., via shape recognition) one or more of such teeth to possess spots and/or lacunae.","The processing logic may consider such spots and/or lacunae to be indicative of caries.","The indications regarding foreign object recognition assistance provided by the processing logic may include indications concerning fillings, implants, and/or bridges.","Pooled patient data and/or pedagogical patient data may include depictions of fillings, implants, and/or bridges along with corresponding identifications thereof.","Indication regarding fillings, implants, and/or bridges may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize patient scan data and/or virtual 3D models which constitute fillings, implants, and/or bridges.","Indication regarding fillings, implants, and/or bridges may involve the processing logic comparing the under consideration patient scan data and/or one or more virtual 3D models of the patient to earlier in the patient visit data, dental record data of the patient, and/or data of the patient from prior to the at-hand patient visit.","The processing logic may consider objects which appear in the under consideration patient scan data and/or one or more virtual 3D models of the patient but not in the earlier in the patient visit data, dental record data of the patient, and/or data of the patient from prior to the at-hand patient visit to be possible foreign objects.","Such functionality might, for instance, be implemented from the viewpoint that new objects appearing in a patient's mouth have a certain likelihood of being foreign objects rather than naturally-occurring ones.","The processing logic may allow a practitioner to respond (e.g., via user interface) to such an indication with agreement and/or disagreement that processing logic-identified objects are foreign objects.","FIG.","4A illustrates an example scanned portion of a dental arch 400 during an intraoral scan session.","The dental arch 400 includes gums 404 and multiple teeth 410, 420.Multiple intraoral images 425, 430, 435, 440 have been taken of a dental site of a patient.","Each of the intraoral images 425-440 may have been generated by an intraoral scanner having a particular distance from the dental surface being imaged.","At the particular distance, the intraoral images 425-440 have a particular scan area and scan depth.","The shape and size of the scan area will generally depend on the scanner, and is herein represented by a rectangle.","Each image may have its own reference coordinate system and origin.","Each intraoral image may be generated by a scanner at a particular position (scanning station).","The location and orientation of scanning stations may be selected such that together the intraoral images adequately cover an entire target zone.","Preferably, scanning stations are selected such that there is overlap between the intraoral images 425-440 as shown.","Typically, the selected scanning stations will differ when different scanners are used for the same target area, depending on the capture characteristics of the scanner used.","Thus, a scanner capable of scanning a larger dental area with each scan (e.g., having a larger field of view) will use fewer scanning stations than a scanner that is only capable of capturing 3D data of a relatively smaller dental surface.","Similarly, the number and disposition of scanning stations for a scanner having a rectangular scanning grid (and thus providing projected scanning areas in the form of corresponding rectangles) will typically be different from those for a scanner having a circular or triangular scanning grid (which would provide projected scanning areas in the form of corresponding circles or triangles, respectively).","Intraoral areas of interest 448 and 447 have been computed as discussed herein above.","In the illustrated embodiment, the intraoral areas of interest 447, 448 represent portions of the patient's dental site that lack image data.","FIG.","4B illustrates a scanned portion of a dental arch 402 that is an update of dental arch 400.Additional intraoral images 458, 459 have been taken to provide image data corresponding to intraoral areas of interest 447, 448.Accordingly, intraoral areas of interest 447, 448 are no longer shown in dental arch 402.Additional intraoral images 460, 462, 464, 466 have also been generated.","These additional intraoral images 460-466 reveal teeth 450, 452, 454, 456.New intraoral areas of interest 470, 472 are also determined based on the additional intraoral images 460-466.A practitioner may generate still further intraoral images to resolve intraoral areas of interest 470, 472 and to provide data for a full dental arch.","FIG.","5A illustrates an example image of a dental arch 500 showing areas of interest.","The image of the dental arch 500 may be constructed from one or more intraoral scans prior to generation of a virtual 3D model.","Alternatively, the image of the dental arch 500 may be constructed from one or more scans of a physical model of a dental arch.","The image of the dental arch 500 includes gums 509 and multiple teeth 505-508.Multiple areas of interest 509, 515, 525 are also shown in the image of the dental arch 500.These areas of interest 509, 515, 525 represent missing scan data that satisfies a clinical importance criterion.","FIG.","5B illustrates an example image of a dental arch 550 showing areas of interest and indications pointing to the areas of interest.","The image of the dental arch 550 may be constructed from one or more intraoral scans.","Alternatively, the image of the dental arch 550 may be constructed from one or more scans of a physical model of a dental arch.","The image of the dental arch 550 includes gums and multiple teeth.","Multiple areas of interest 562, 564, 566, 568, 570, 572 are also shown in the image of the dental arch 550.These areas of interest 562, 564, 566, 568, 570, 572 represent missing scan data that satisfies a clinical importance criterion (e.g., intraoral areas of interest greater than a threshold size or having one or more dimensions that violate a geometric criterion).","However, some areas of interest 562, 570 are largely occluded in the example image of the dental arch 550.Additionally, there are other areas of interest that are completely hidden.","To ensure that a dental practitioner is made aware of such areas of interest, an indicator such as a flag is presented for each area of interest.","For example, the image of the dental arch 550 includes flags 552-559.These flags call the dental practitioners attention to areas of interest that should be addressed regardless of a present view.","FIG.","5C illustrates another example image of a dental arch 575 showing areas of interest and indications pointing to the areas of interest.","The image of the dental arch 575 may be constructed from one or more intraoral scans.","Alternatively, the image of the dental arch 575 may be constructed from one or more scans of a physical model of a dental arch.","The image of the dental arch 575 includes gums and multiple teeth.","Multiple areas of interest 576-584 are also shown in the image of the dental arch 575.These areas of interest 576-584 represent tooth wear that is identified based on a comparison between images and/or a virtual 3D model generated at a first date and images and/or a virtual 3D model generated at a second date.","However, some areas of interest 576, 578 are largely occluded in the example image of the dental arch 575.To ensure that a dental practitioner is made aware of such areas of interest, an indicator such as a flag is presented for each area of interest.","For example, the image of the dental arch 575 includes flags 586-594.These flags call the dental practitioners attention to areas of interest that should be addressed regardless of a present view.","FIG.","6 illustrates a screen shot 600 of an intraoral scan application (e.g., of intraoral scan application 108 of FIG.","1), in accordance with embodiments of the present invention.","The screen shot 600 shows multiple menus 602, 604, 606 for performing various operations.","Menu 602 provides icons that can be selected to perform global operations such as changing settings, saving data, obtaining assistance, generating a virtual 3D model from gathered intraoral images, switching to a view mode, and so forth.","Menu 604 provides icons for adjusting a view 607 of a scanned dental site 608.Menu 604 may include icons for panning, zooming, rotating, and so forth.","The view 607 of the scanned dental site 608 includes a dental arch made up of one or more previous intraoral images that have been registered and/aligned with one another.","The view 607 further includes an indication of a latest intraoral image 610 that has been added to the dental arch.","The dental ach includes multiple voids based on incomplete scan data.","Such voids are one type of intraoral area of interest that is called out by flags 612-624.Menu 606 includes scanning instructions that enable a user to proceed to a next scan, redo a last scan, rescan a segment, and so on.","A user may rescan one or more segments to provide scan data that can fill in the voids that are called out by flags 612-624.This can ensure that a final virtual 3D model that is generated based on the intraoral images is of high quality.","FIG.","7 illustrates a diagrammatic representation of a machine in the example form of a computing device 700 within which a set of instructions, for causing the machine to perform any one or more of the methodologies discussed herein, may be executed.","In alternative embodiments, the machine may be connected (e.g., networked) to other machines in a Local Area Network (LAN), an intranet, an extranet, or the Internet.","The machine may operate in the capacity of a server or a client machine in a client-server network environment, or as a peer machine in a peer-to-peer (or distributed) network environment.","The machine may be a personal computer (PC), a tablet computer, a set-top box (STB), a Personal Digital Assistant (PDA), a cellular telephone, a web appliance, a server, a network router, switch or bridge, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine.","Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines (e.g., computers) that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein.","The example computing device 700 includes a processing device 702, a main memory 704 (e.g., read-only memory (ROM), flash memory, dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), etc.","), a static memory 706 (e.g., flash memory, static random access memory (SRAM), etc.","), and a secondary memory (e.g., a data storage device 728), which communicate with each other via a bus 708.Processing device 702 represents one or more general-purpose processors such as a microprocessor, central processing unit, or the like.","More particularly, the processing device 702 may be a complex instruction set computing (CISC) microprocessor, reduced instruction set computing (RISC) microprocessor, very long instruction word (VLIW) microprocessor, processor implementing other instruction sets, or processors implementing a combination of instruction sets.","Processing device 702 may also be one or more special-purpose processing devices such as an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), network processor, or the like.","Processing device 702 is configured to execute the processing logic (instructions 726) for performing operations and steps discussed herein.","The computing device 700 may further include a network interface device 722 for communicating with a network 764.The computing device 700 also may include a video display unit 710 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)), an alphanumeric input device 712 (e.g., a keyboard), a cursor control device 714 (e.g., a mouse), and a signal generation device 720 (e.g., a speaker).","The data storage device 728 may include a machine-readable storage medium (or more specifically a non-transitory computer-readable storage medium) 724 on which is stored one or more sets of instructions 726 embodying any one or more of the methodologies or functions described herein.","A non-transitory storage medium refers to a storage medium other than a carrier wave.","The instructions 726 may also reside, completely or at least partially, within the main memory 704 and/or within the processing device 702 during execution thereof by the computer device 700, the main memory 704 and the processing device 702 also constituting computer-readable storage media.","The computer-readable storage medium 724 may also be used to store an intraoral scan application 750, which may correspond to the similarly named component of FIG.","1.The computer readable storage medium 724 may also store a software library containing methods for an intraoral scan application 750.While the computer-readable storage medium 724 is shown in an example embodiment to be a single medium, the term “computer-readable storage medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the one or more sets of instructions.","The term “computer-readable storage medium” shall also be taken to include any medium other than a carrier wave that is capable of storing or encoding a set of instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies of the present invention.","The term “computer-readable storage medium” shall accordingly be taken to include, but not be limited to, solid-state memories, and optical and magnetic media.","It is to be understood that the above description is intended to be illustrative, and not restrictive.","Many other embodiments will be apparent upon reading and understanding the above description.","Although embodiments of the present invention have been described with reference to specific example embodiments, it will be recognized that the invention is not limited to the embodiments described, but can be practiced with modification and alteration within the spirit and scope of the appended claims.","Accordingly, the specification and drawings are to be regarded in an illustrative sense rather than a restrictive sense.","The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled."]],"string":"[\n [\n \"IDENTIFICATION OF AREAS OF INTEREST DURING INTRAORAL SCANS\",\n \"A processing device receives a first virtual 3D model and a second virtual 3D model, each comprising one or more teeth of a patient.\",\n \"The processing device compares the first virtual 3D model to the second virtual 3D model and determines, as a result of the comparing, a difference between the first virtual 3D model and the second virtual 3D model at a dental site comprising a tooth of the one or more teeth.\",\n \"The processing device determines whether the difference comprises a first type of change to the tooth that is indicative of tooth wear or a second type of change to the tooth that is indicative of tooth movement associated with orthodontic treatment.\",\n \"Responsive to determining that the first difference comprises the first type of change to the first tooth, the processing device generates a first indicator of the tooth wear for the tooth.\"\n ],\n [\n \"1.A method of detecting tooth wear during orthodontic treatment, comprising: receiving a first virtual three-dimensional (3D) model comprising one or more teeth of a patient, wherein the first virtual 3D model is based on a first intraoral scan of the patient taken at a first time; receiving a second virtual 3D model comprising the one or more teeth of the patient, wherein the second virtual 3D model is based on a second intraoral scan of the patient taken at a second time; comparing, by a processing device, the first virtual 3D model to the second virtual 3D model; determining, as a result of the comparing, a first difference between the first virtual 3D model and the second virtual 3D model at a first dental site comprising a first tooth of the one or more teeth; determining whether the first difference comprises a first type of change to the first tooth that is indicative of tooth wear or a second type of change to the first tooth that is indicative of tooth movement; and responsive to determining that the first difference comprises the first type of change to the first tooth that is indicative of tooth wear, generating a first indicator of the tooth wear for the first tooth.\",\n \"2.The method of claim 1, further comprising: determining a path of a missing portion of the first tooth; and generating a contour comprising the path of the missing portion of the first tooth, wherein the indicator comprises the contour.\",\n \"3.The method of claim 1, wherein comparing the first virtual 3D model to the second virtual 3D model comprises determining an alignment between the first virtual 3D model and the second virtual 3D model based on geometric features shared by the first virtual 3D model and the second virtual 3D model.\",\n \"4.The method of claim 1, further comprising determining a first intraoral area of interest comprising the first dental site, wherein determining the first intraoral area of interest comprises: identifying a plurality of voxels in the second virtual 3D model that satisfy a first criterion; determining a subset of the plurality of voxels that are proximate to one another; and grouping the subset of the plurality of voxels into a volume.\",\n \"5.The method of claim 4, wherein the indicator comprises a flag that points to the first intraoral area of interest, wherein the first intraoral area of interest is hidden in one or more views of the one or more teeth, and wherein the flag is visible in the one or more views.\",\n \"6.The method of claim 1, further comprising: determining a first intraoral area of interest comprising the first dental site; and determining an importance rank for the first intraoral area of interest based on the tooth wear.\",\n \"7.The method of claim 1, further comprising: responsive to determining that the first difference comprises the second type of change to the first tooth that is indicative of tooth movement, generating a second indicator.\",\n \"8.The method of claim 1, further comprising: determining that the first difference satisfies a first criterion; determining that the first difference comprises a change to the first tooth that is indicative of tooth wear based on the first difference satisfying the first criterion; and generating the first indicator for the first tooth.\",\n \"9.The method of claim 8, further comprising: determining, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site comprising a second tooth of the one or more teeth; determining that the second difference satisfies a second criterion; determining that the second difference comprises the second type of change to the second tooth that is indicative of tooth movement; and generating a second indicator for the second tooth.\",\n \"10.The method of claim 1, further comprising: determining, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site; determining that the second difference satisfies a gum recession criterion; determining that the second difference is indicative of gum recession; and generating a second indicator associated with the gum recession.\",\n \"11.A system comprising: a memory; and a processing device operatively coupled to the memory, the processing device to: receive a first virtual three-dimensional (3D) model comprising one or more teeth of a patient, wherein the first virtual 3D model is based on a first intraoral scan of the patient taken at a first time; receive a second virtual 3D model comprising the one or more teeth of the patient, wherein the second virtual 3D model is based on a second intraoral scan of the patient taken at a second time; compare the first virtual 3D model to the second virtual 3D model; determine, as a result of the comparing, a first difference between the first virtual 3D model and the second virtual 3D model at a first dental site comprising a first tooth of the one or more teeth; determine whether the first difference comprises a first type of change to the first tooth that is indicative of tooth wear or a second type of change to the first tooth that is indicative of tooth movement; and responsive to determining that the first difference comprises the first type of change to first the tooth that is indicative of tooth wear, generate a first indicator of the tooth wear for the first tooth.\",\n \"12.The system of claim 11, wherein the processing device is further to: determine a path of a missing portion of the first tooth; and generate a contour comprising the path of the missing portion of the first tooth, wherein the indicator comprises the contour.\",\n \"13.The system of claim 11, wherein comparing the first virtual 3D model to the second virtual 3D model comprises determining an alignment between the first virtual 3D model and the second virtual 3D model based on geometric features shared by the first virtual 3D model and the second virtual 3D model.\",\n \"14.The system of claim 11, wherein the processing device is further to determine a first intraoral area of interest comprising the first dental site, wherein determining the first intraoral area of interest comprises: identifying a plurality of voxels in the second virtual 3D model that satisfy a criterion; determining a subset of the plurality of voxels that are proximate to one another; and grouping the subset of the plurality of voxels into a volume.\",\n \"15.The system of claim 14, wherein the indicator comprises a flag that points to the first intraoral area of interest, wherein the first intraoral area of interest is hidden in one or more views of the one or more teeth, and wherein the flag is visible in the one or more views.\",\n \"16.The system of claim 11, wherein the processing device is further to: determine a first intraoral area of interest comprising the first dental site; and determine an importance rank for the first intraoral area of interest based on the tooth wear.\",\n \"17.The system of claim 11, wherein the processing device is further to: generate a second indicator responsive to determining that the first difference comprises the second type of change to the first tooth that is indicative of tooth movement.\",\n \"18.The system of claim 11, wherein the processing device is further to: determine that the first difference satisfies a first criterion; determine that the first difference comprises a change to the first tooth that is indicative of tooth wear based on the first difference satisfying the first criterion; and generate the first indicator for the first tooth.\",\n \"19.The system of claim 18, wherein the processing device is further to: determine, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site comprising a second tooth of the one or more teeth; determine that the second difference satisfies a second criterion; determine that the second difference comprises the second type of change to the second tooth that is indicative of tooth movement; and generate a second indicator for the second tooth.\",\n \"20.The system of claim 11, wherein the processing device is further to: determine, as a result of the comparing, a second difference between the first virtual 3D model and the second virtual 3D model at a second dental site; determine that the second difference satisfies a gum recession criterion; determine that the second difference is indicative of gum recession; and generate a second indicator associated with the gum recession.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>In prosthodontic procedures designed to implant a dental prosthesis in the oral cavity, the dental site at which the prosthesis is to be implanted in many cases should be measured accurately and studied carefully, so that a prosthesis such as a crown, denture or bridge, for example, can be properly designed and dimensioned to fit in place.\",\n \"A good fit enables mechanical stresses to be properly transmitted between the prosthesis and the jaw, and to prevent infection of the gums via the interface between the prosthesis and the dental site, for example.\",\n \"Some procedures also call for removable prosthetics to be fabricated to replace one or more missing teeth, such as a partial or full denture, in which case the surface contours of the areas where the teeth are missing need to be reproduced accurately so that the resulting prosthetic fits over the edentulous region with even pressure on the soft tissues.\",\n \"In some practices, the dental site is prepared by a dental practitioner, and a positive physical model of the dental site is constructed using known methods.\",\n \"Alternatively, the dental site may be scanned to provide 3D data of the dental site.\",\n \"In either case, the virtual or real model of the dental site is sent to the dental lab, which manufactures the prosthesis based on the model.\",\n \"However, if the model is deficient or undefined in certain areas, or if the preparation was not optimally configured for receiving the prosthesis, the design of the prosthesis may be less than optimal.\",\n \"For example, if the insertion path implied by the preparation for a closely-fitting coping would result in the prosthesis colliding with adjacent teeth, the coping geometry has to be altered to avoid the collision, which may result in the coping design being less optimal.\",\n \"Further, it the area of the preparation containing a finish line lacks definition, it may not be possible to properly determine the finish line and thus the lower edge of the coping may not be properly designed.\",\n \"Indeed, in some circumstances, the model is rejected and the dental practitioner then re-scans the dental site, or reworks the preparation, so that a suitable prosthesis may be produced.\",\n \"In orthodontic procedures it can be important to provide a model of one or both jaws.\",\n \"Where such orthodontic procedures are designed virtually, a virtual model of the oral cavity is also beneficial.\",\n \"Such a virtual model may be obtained by scanning the oral cavity directly, or by producing a physical model of the dentition, and then scanning the model with a suitable scanner.\",\n \"Thus, in both prosthodontic and orthodontic procedures, obtaining a three-dimensional (3D) model of a dental site in the oral cavity is an initial procedure that is performed.\",\n \"When the 3D model is a virtual model, the more complete and accurate the scans of the dental site are, the higher the quality of the virtual model, and thus the greater the ability to design an optimal prosthesis or orthodontic treatment appliance(s).\"\n ],\n [\n \"<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings.\",\n \"FIG.\",\n \"1 illustrates one embodiment of a system for performing intraoral scanning and generating a virtual three dimensional model of a dental site.\",\n \"FIG.\",\n \"2A illustrates a flow diagram for a method of determining intraoral areas of interest during an intraoral scan session, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"2B illustrates a flow diagram for a method of providing indications for intraoral areas of interest, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"3A illustrates a flow diagram for a method of providing data indications of flawed scan data from an intraoral scan session, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"3B illustrates a flow diagram for a method of providing data indications of intraoral areas of interest, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"3C illustrates a flow diagram for a method of performing intraoral scanning, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"4A illustrates a portion of an example dental arch during an intraoral scan session.\",\n \"FIG.\",\n \"4B illustrates the example dental arch of FIG.\",\n \"4A during the intraoral scan session after the generation of further intraoral images.\",\n \"FIG.\",\n \"5A illustrates an example dental arch showing intraoral areas of interest.\",\n \"FIG.\",\n \"5B illustrates an example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.\",\n \"FIG.\",\n \"5C illustrates another example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.\",\n \"FIG.\",\n \"6 illustrates a screen shot of an intraoral scan application, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"7 illustrates a block diagram of an example computing device, in accordance with embodiments of the present invention.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"RELATED APPLICATIONS This patent application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/347,620, filed Nov. 9, 2016, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/705,788 filed May 6, 2015, now issued as U.S. Pat.\",\n \"No.\",\n \"9,510,757, which claims the benefit under 35 U.S.C.\",\n \"§ 119(e) of U.S.\",\n \"Provisional Application No.\",\n \"61/990,004 filed May 7, 2014, all of which are herein incorporated by reference.\",\n \"TECHNICAL FIELD Embodiments of the present invention relate to the field of intraoral scanning and, in particular, to a system and method for improving the results of intraoral scanning.\",\n \"BACKGROUND In prosthodontic procedures designed to implant a dental prosthesis in the oral cavity, the dental site at which the prosthesis is to be implanted in many cases should be measured accurately and studied carefully, so that a prosthesis such as a crown, denture or bridge, for example, can be properly designed and dimensioned to fit in place.\",\n \"A good fit enables mechanical stresses to be properly transmitted between the prosthesis and the jaw, and to prevent infection of the gums via the interface between the prosthesis and the dental site, for example.\",\n \"Some procedures also call for removable prosthetics to be fabricated to replace one or more missing teeth, such as a partial or full denture, in which case the surface contours of the areas where the teeth are missing need to be reproduced accurately so that the resulting prosthetic fits over the edentulous region with even pressure on the soft tissues.\",\n \"In some practices, the dental site is prepared by a dental practitioner, and a positive physical model of the dental site is constructed using known methods.\",\n \"Alternatively, the dental site may be scanned to provide 3D data of the dental site.\",\n \"In either case, the virtual or real model of the dental site is sent to the dental lab, which manufactures the prosthesis based on the model.\",\n \"However, if the model is deficient or undefined in certain areas, or if the preparation was not optimally configured for receiving the prosthesis, the design of the prosthesis may be less than optimal.\",\n \"For example, if the insertion path implied by the preparation for a closely-fitting coping would result in the prosthesis colliding with adjacent teeth, the coping geometry has to be altered to avoid the collision, which may result in the coping design being less optimal.\",\n \"Further, it the area of the preparation containing a finish line lacks definition, it may not be possible to properly determine the finish line and thus the lower edge of the coping may not be properly designed.\",\n \"Indeed, in some circumstances, the model is rejected and the dental practitioner then re-scans the dental site, or reworks the preparation, so that a suitable prosthesis may be produced.\",\n \"In orthodontic procedures it can be important to provide a model of one or both jaws.\",\n \"Where such orthodontic procedures are designed virtually, a virtual model of the oral cavity is also beneficial.\",\n \"Such a virtual model may be obtained by scanning the oral cavity directly, or by producing a physical model of the dentition, and then scanning the model with a suitable scanner.\",\n \"Thus, in both prosthodontic and orthodontic procedures, obtaining a three-dimensional (3D) model of a dental site in the oral cavity is an initial procedure that is performed.\",\n \"When the 3D model is a virtual model, the more complete and accurate the scans of the dental site are, the higher the quality of the virtual model, and thus the greater the ability to design an optimal prosthesis or orthodontic treatment appliance(s).\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings.\",\n \"FIG.\",\n \"1 illustrates one embodiment of a system for performing intraoral scanning and generating a virtual three dimensional model of a dental site.\",\n \"FIG.\",\n \"2A illustrates a flow diagram for a method of determining intraoral areas of interest during an intraoral scan session, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"2B illustrates a flow diagram for a method of providing indications for intraoral areas of interest, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"3A illustrates a flow diagram for a method of providing data indications of flawed scan data from an intraoral scan session, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"3B illustrates a flow diagram for a method of providing data indications of intraoral areas of interest, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"3C illustrates a flow diagram for a method of performing intraoral scanning, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"4A illustrates a portion of an example dental arch during an intraoral scan session.\",\n \"FIG.\",\n \"4B illustrates the example dental arch of FIG.\",\n \"4A during the intraoral scan session after the generation of further intraoral images.\",\n \"FIG.\",\n \"5A illustrates an example dental arch showing intraoral areas of interest.\",\n \"FIG.\",\n \"5B illustrates an example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.\",\n \"FIG.\",\n \"5C illustrates another example dental arch showing intraoral areas of interest and indicators pointing to the intraoral areas of interest.\",\n \"FIG.\",\n \"6 illustrates a screen shot of an intraoral scan application, in accordance with embodiments of the present invention.\",\n \"FIG.\",\n \"7 illustrates a block diagram of an example computing device, in accordance with embodiments of the present invention.\",\n \"DETAILED DESCRIPTION Described herein is a method and apparatus for improving the quality of scans, such as intraoral scans taken of dental sites for patients.\",\n \"During a scan session, a user (e.g., a dental practitioner) of a scanner may generate multiple different images (also referred to as scans) of a dental site, model of a dental site, or other object.\",\n \"The images may be discrete images (e.g., point-and-shoot images) or frames from a video (e.g., a continuous scan).\",\n \"These images may not capture all of the areas of the dental site and/or there may be areas for which there is conflicting data between images.\",\n \"In embodiments described herein, such missing areas and/or conflicting areas may be identified as areas of interest.\",\n \"This identification may be performed during a scan session.\",\n \"Accordingly, shortly after the user of the scanner has generated one or more images, the user may be notified of areas of interest that should be rescanned.\",\n \"The user may then rescan the areas of interest during the scan session.\",\n \"This can facilitate quick and accurate scan sessions.\",\n \"Additionally, indications or indicators of areas of interest can be generated during a scan session or after the scan session is complete.\",\n \"These indications may indicate classifications associated with areas of interest, a severity of the areas of interest, a size of the areas of interest, and additional information.\",\n \"The indications may be visible in views of the dental site or other scanned object in which the actual areas of interest are hidden.\",\n \"This can ensure that the user will be made aware of the areas of interest regardless of a current view.\",\n \"Embodiments described herein are discussed with reference to intraoral scanners, intraoral images, intraoral scan sessions, and so forth.\",\n \"However, it should be understood that embodiments also apply to other types of scanners than intraoral scanners.\",\n \"Embodiments may apply to any type of scanner that takes multiple images and stitches these images together to form a combined image or virtual model.\",\n \"For example, embodiments may apply to desktop model scanners, computed tomography (CT scanners, and so forth.\",\n \"Additionally, it should be understood that the intraoral scanners or other scanners may be used to scan objects other than dental sites in an oral cavity.\",\n \"For example, embodiments may apply to scans performed on physical models of a dental site or any other object.\",\n \"Accordingly, embodiments describing intraoral images should be understood as being generally applicable to any types of images generated by a scanner, embodiments describing intraoral scan sessions should be understood as being applicable to scan sessions for any type of object, and embodiments describing intraoral scanners should be understood as being generally applicable to many types of scanners.\",\n \"FIG.\",\n \"1 illustrates one embodiment of a system 100 for performing intraoral scanning and/or generating a virtual three dimensional model of a dental site.\",\n \"In one embodiment, system 100 carries out one or more operations of below described in methods 200, 250, 300, 340 and/or 370.System 100 includes a computing device 105 that may be coupled to a scanner 150 and/or a data store 110.Computing device 105 may include a processing device, memory, secondary storage, one or more input devices (e.g., such as a keyboard, mouse, tablet, and so on), one or more output devices (e.g., a display, a printer, etc.\",\n \"), and/or other hardware components.\",\n \"Computing device 105 may be connected to a data store 110 either directly or via a network.\",\n \"The network may be a local area network (LAN), a public wide area network (WAN) (e.g., the Internet), a private WAN (e.g., an intranet), or a combination thereof.\",\n \"The computing device 105 may be integrated into the scanner 150 in some embodiments to improve performance and mobility.\",\n \"Data store 110 may be an internal data store, or an external data store that is connected to computing device 105 directly or via a network.\",\n \"Examples of network data stores include a storage area network (SAN), a network attached storage (NAS), and a storage service provided by a cloud computing service provider.\",\n \"Data store 110 may include a file system, a database, or other data storage arrangement.\",\n \"In some embodiments, a scanner 150 for obtaining three-dimensional (3D) data of a dental site in a patient's oral cavity is operatively connected to the computing device 105.Scanner 150 may include a probe (e.g., a hand held probe) for optically capturing three dimensional structures (e.g., by confocal focusing of an array of light beams).\",\n \"One example of such a scanner 150 is the iTero® intraoral digital scanner manufactured by Align Technology, Inc. Other examples of intraoral scanners include the 1M™ True Definition Scanner and the Apollo DI intraoral scanner and CEREC AC intraoral scanner manufactured by Sirona®.\",\n \"The scanner 150 may be used to perform an intraoral scan of a patient's oral cavity.\",\n \"An intraoral scan application 108 running on computing device 105 may communicate with the scanner 150 to effectuate the intraoral scan.\",\n \"A result of the intraoral scan may be a sequence of intraoral images that have been discretely generated (e.g., by pressing on a “generate image” button of the scanner for each image).\",\n \"Alternatively, a result of the intraoral scan may be one or more videos of the patient's oral cavity.\",\n \"An operator may start recording the video with the scanner 150 at a first position in the oral cavity, move the scanner 150 within the oral cavity to a second position while the video is being taken, and then stop recording the video.\",\n \"In some embodiments, recording may start automatically as the scanner identities either teeth.\",\n \"The scanner 150 may transmit the discrete intraoral images or intraoral video (referred to collectively as intraoral image data 135) to the computing device 105.Computing device 105 may store the image data 135 in data store 110.Alternatively, scanner 150 may be connected to another system that stores the image data in data store 110.In such an embodiment, scanner 150 may not be connected to computing device 105.According to an example, a user (e.g., a practitioner) may subject a patient to intraoral scanning.\",\n \"In doing so, the user may apply scanner 150 to one or more patient intraoral locations.\",\n \"The scanning may be divided into one or more segments.\",\n \"As an example the segments may include a lower buccal region of the patient, a lower lingual region of the patient, a upper buccal region of the patient, an upper lingual region of the patient, one or more preparation teeth of the patient (e.g., teeth of the patient to which a dental device such as a crown or an orthodontic alignment device will be applied), one or more teeth which are contacts of preparation teeth (e.g., teeth not themselves subject to a dental device but which are located next to one or more such teeth or which interface with one or more such teeth upon mouth closure), and/or patient bite (e.g., scanning performed with closure of the patient's mouth with scan being directed towards an interface area of the patient's upper and lower teeth).\",\n \"Via such scanner application, the scanner 150 may provide image data (also referred to as scan data) 135 to computing device 105.The image data 135 may include 2D intraoral images and/or 3D intraoral images.\",\n \"Such images may be provided from the scanner to the computing device 105 in the form of one or more points (e.g., one or more pixels and/or groups of pixels).\",\n \"For instance, the scanner 150 may provide such a 3D image as one or more point clouds.\",\n \"The manner in which the oral cavity of a patient is to be scanned may depend on the procedure to be applied thereto.\",\n \"For example, if an upper or lower denture is to be created, then a full scan of the mandibular or maxillary edentulous arches may be performed.\",\n \"In contrast, if a bridge is to be created, then just a portion of a total arch may be scanned which includes an edentulous region, the neighboring abutment teeth and the opposing arch and dentition.\",\n \"Thus, the dental practitioner may input the identity of a procedure to be performed into intraoral scan application 108.For this purpose, the dental practitioner may choose the procedure from a number of preset options on a drop-down menu or the like, from icons or via any other suitable graphical input interface.\",\n \"Alternatively, the identity of the procedure may be input in any other suitable way, for example by means of preset code, notation or any other suitable manner, intraoral scan application 108 having been suitably programmed to recognize the choice made by the user.\",\n \"By way of non-limiting example, dental procedures may be broadly divided into prosthodontic (restorative) and orthodontic procedures, and then further subdivided into specific forms of these procedures.\",\n \"Additionally, dental procedures may include identification and treatment of gum disease, sleep apnea, and intraoral conditions.\",\n \"The term prosthodontic procedure refers, inter alia, to any procedure involving the oral cavity and directed to the design, manufacture or installation of a dental prosthesis at a dental site within the oral cavity, or a real or virtual model thereof, or directed to the design and preparation of the dental site to receive such a prosthesis.\",\n \"A prosthesis may include any restoration such as crowns, veneers, inlays, onlays, and bridges, for example, and any other artificial partial or complete denture.\",\n \"The term orthodontic procedure refers, inter alia, to any procedure involving the oral cavity and directed to the design, manufacture or installation of orthodontic elements at a dental site within the oral cavity, or a real or virtual model thereof, or directed to the design and preparation of the dental site to receive such orthodontic elements.\",\n \"These elements may be appliances including but not limited to brackets and wires, retainers, clear aligners, or functional appliances.\",\n \"A type of scanner to be used may also be input into intraoral scan application 108, typically by a dental practitioner choosing one among a plurality of options.\",\n \"If the scanner 150 that is being used is not recognizable by intraoral scan application 108, it may nevertheless be possible to input operating parameters of the scanner thereto instead.\",\n \"For example, the optimal spacing between a head of the scanner and scanned surface can be provided, as well as the capture area (and shape thereof) of the dental surface capable of being scanned at this distance.\",\n \"Alternatively, other suitable scanning parameters may be provided.\",\n \"Intraoral scan application 108 may identify spatial relationships that are suitable for scanning the dental site so that complete and accurate image data may be obtained for the procedure in question.\",\n \"Intraoral scan application 108 may establish an optimal manner for scanning a target area of the dental site.\",\n \"Intraoral scan application 108 may identify or determine a scanning protocol by relating the type of scanner, resolution thereof, capture area at an optimal spacing between the scanner head and the dental surface to the target area, etc.\",\n \"For a point-and-shoot scanning mode, the scanning protocol comprises a series of scanning stations spatially associated with the dental surfaces of the target area.\",\n \"Preferably, overlapping of the images or scans capable of being obtained at adjacent scanning stations is designed into the scanning protocol to enable accurate image registration, so that intraoral images can be stitched together to provide a composite 3D virtual model.\",\n \"For a continuous scanning mode (video scan), scanning stations may not be identified.\",\n \"Instead, a practitioner may activate the scanner and proceed to move the scanner within the oral cavity to capture a video of the target area from multiple different viewpoints.\",\n \"In one embodiment, intraoral scan application 108 includes an area of interest (AOI) identifying module 115, a flagging module 118 and a model generation module 125.Alternatively, the operations of one or more of the AOI identifying module 115, flagging module 118 and/or model generation module 125 may be combined into a single module and/or divided into multiple modules.\",\n \"AOI identifying module 115 is responsible for identifying areas of interest (AOIs) from intraoral scan data (e.g., intraoral images) and/or virtual 3D models generated from intraoral scan data.\",\n \"Such areas of interest may include voids (e.g., areas for which scan data is missing), areas of conflict or flawed scan data (e.g., areas for which overlapping surfaces of multiple intraoral images fail to match), areas indicative of foreign objects (e.g., studs, bridges, etc.\",\n \"), areas indicative of tooth wear, areas indicative of tooth decay, areas indicative of receding gums, unclear gum line, unclear patient bite, unclear margin line (e.g., margin line of one or more preparation teeth), and so forth.\",\n \"An identified void may be a void in a surface of an image.\",\n \"Examples of surface conflict include double incisor edge and/or other physiologically unlikely tooth edge, and/or bite line shift.\",\n \"The AOI identifying module 115 may, in identifying an AOI, analyze patient image data 135 (e.g., 3D image point clouds) and/or one or more virtual 3D models of the patient alone and/or relative to reference data 138.The analysis may involve direct analysis (e.g., pixel-based and/or other point-based analysis), the application of machine learning, and/or the application of image recognition.\",\n \"Such reference data 138 may include past data regarding the at-hand patient (e.g., intraoral images and/or virtual 3D models), pooled patient data, and/or pedagogical patient data, some or all of which may be stored in data store 110.The data regarding the at-hand patient may include X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models corresponding to the patient visit during which the scanning occurs.\",\n \"The data regarding the at-hand patient may additionally include past X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models of the patient (e.g., corresponding to past visits of the patient and/or to dental records of the patient).\",\n \"The pooled patient data may include X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models regarding a multitude of patients.\",\n \"Such a multitude of patients may or may not include the at-hand patient.\",\n \"The pooled patient data may be anonymized and/or employed in compliance with regional medical record privacy regulations (e.g., the Health Insurance Portability and Accountability Act (HIPAA)).\",\n \"The pooled patient data may include data corresponding to scanning of the sort discussed herein and/or other data.\",\n \"The pedagogical patient data may include X-rays, 2D intraoral images, 3D intraoral images, 2D models, virtual 3D models, and/or medical illustrations (e.g., medical illustration drawings and/or other images) employed in educational contexts.\",\n \"The pedagogical patient data may include volunteer data and/or cadaveric data.\",\n \"AOI identifying module 115 may analyze patient scan data from later in a patient visit during which the scanning occurs (e.g., one or more later-in-the-visit 3D image point clouds and/or one or more later-in-the-visit virtual 3D models of the patient) relative to additional patient scan data in the form of data from earlier in that patient visit (e.g., one or more earlier-in-the-visit 3D image point clouds and/or one or more earlier-in-the-visit virtual 3D models of the patient).\",\n \"AOI identifying module 115 may additionally or alternatively analyze patient scan data relative to reference data in the form of dental record data of the patient and/or data of the patient from prior to the patient visit (e.g., one or more prior-to-the-visit 3D image point clouds and/or one or more prior-to-the-visit virtual 3D models of the patient).\",\n \"AOI identifying module 115 may additionally or alternatively analyze patient scan data relative to pooled patient data and/or pedagogical patient data.\",\n \"In an example, AOI identifying module 115 may generate a first virtual model of a dental site based on a first scan session of the dental site taken at a first time and later generate a second virtual model of the dental site based on a second scan session of the dental site taken at a second time.\",\n \"The AOI identifying module 115 may then compare the first virtual model to the second virtual model to determine a change in the dental site and identify an AOI to represent the change.\",\n \"Identifying of areas of interest concerning missing and/or flawed scan data may involve the AOI identifying module 115 performing direct analysis, for instance determining one or more pixels or other points to be missing from patient scan data and/or one or more virtual 3D models of the patient.\",\n \"Identification of areas of interest concerning missing and/or flawed scan data may additionally or alternatively involve employing pooled patient data and/or pedagogical patient data to ascertain patient scan data and/or virtual 3D models as being incomplete (e.g., possessing discontinuities) relative to that which is indicated by the pooled patient data and/or pedagogical patient data.\",\n \"Flagging module 118 is responsible for determining how to present and/or call out the identified areas of interest.\",\n \"Flagging module 118 may provide indications or indicators regarding scan assistance, diagnostic assistance, and/or foreign object recognition assistance.\",\n \"Areas of interest may be determined, and indicators of the areas of interest may be provided, during and/or after an intraoral scan session.\",\n \"Such indications may be provided prior to and/or without construction of an intraoral virtual 3D model.\",\n \"Alternatively, indications may be provided after constructions of an intraoral virtual 3D model of a dental site.\",\n \"Examples of the flagging module 118 providing indications regarding scan assistance, diagnostic assistance, and/or foreign object recognition assistance will now be discussed.\",\n \"The flagging module 118 may provide the indications during and/or after an intraoral scan session.\",\n \"The indications may be presented (e.g., via a user interface) to a user (e.g., a practitioner) in connection with and/or apart from one or more depictions of teeth and/or gingivae of a patient (e.g., in connection with one or more X-rays, 2D intraoral images, 3D intraoral images, 2D models, and/or virtual 3D models of the patient).\",\n \"Indication presentation in connection with depictions of patient teeth and/or gingivae may involve the indications being placed so as to correlate an indication with the corresponding portion of the teeth and/or gingivae.\",\n \"As an illustration, a diagnostic assistance indication regarding a broken tooth might be placed so as to identify the broken tooth.\",\n \"The indications may be provided in the form of flags, markings, contours, text, images, and/or sounds (e.g., in the form of speech).\",\n \"Such a contour may be placed (e.g., via contour fitting) so as to follow an extant tooth contour and/or gingival contour.\",\n \"As an illustration, a contour corresponding to a tooth wear diagnostic assistance indication may be placed so as to follow a contour of the worn tooth.\",\n \"Such a contour may be placed (e.g., via contour extrapolation) with respect to a missing tooth contour and/or gingival contour so as to follow a projected path of the missing contour.\",\n \"As an illustration, a contour corresponding to missing tooth scan data may be placed so as to follow the projected path of the tooth portion which is missing, or a contour corresponding to missing gingival scan data may be placed so as to follow the projected path of the gingival portion which is missing.\",\n \"In presenting indications (e.g., flags), the flagging module 118 may perform one or more operations to pursue proper indication display.\",\n \"For instance, where indications are displayed in connection with one or more depictions of teeth and/or gingivae (e.g., a corresponding virtual 3D model), such operations may act to display a single indication rather than, say, multiple indications for a single AOI.\",\n \"Additionally, processing logic may select a location in 3D space for indication placement.\",\n \"Where indications are displayed in connection with a 3D teeth and/or gingiva depiction (e.g., in connection with a virtual 3D model), the flagging module 118 may divide the 3D space into cubes (e.g., voxels corresponding to one or more pixels of the 3D space).\",\n \"The flagging module 118 may then consider the voxels relative to the voxels of determined AOIs and tag voxels so as to indicate the indications (e.g., flags) to which they correspond.\",\n \"As an illustration, suppose that two indications are to be brought to the attention of the user via flagging: a first indication which regards missing scan data and a second indication which regards a caries.\",\n \"With regard to the missing scan data indication, the flagging module 118 may consider the pixels which correspond to the missing scan data relative to the cubes and tag each cube which encompasses one or more of those pixels.\",\n \"The flagging module 118 may perform likewise with regard to the caries indication.\",\n \"Where more than one cube is tagged with respect to a given one of the indications, the flagging module 118 may act such that only one of the tagged voxel receives flag placement.\",\n \"Moreover, the flagging module 118 may choose a particular voxel which it determines will provide for ease of viewing by the user.\",\n \"For instance, such choice of a voxel may take into account the totality of indications to be flagged and may endeavor to avoid crowding a single cube with multiple flags where such can be avoided.\",\n \"In placing indications (e.g., flags) the flagging module 118 may or may not take into account factors other than seeking to avoid crowding.\",\n \"For instance, the flagging module 118 may take into account available lighting, available angle, available zoom, available axes of rotation, and/or other factors corresponding to user viewing of the teeth and/or gingiva depiction (e.g., the virtual 3D model), and may seek indication (e.g., flag) placement which seeks to optimize user viewing in view of these factors).\",\n \"The flagging module 118 may key the indications (e.g., via color, symbol, icon, size, text, and/or number).\",\n \"The keying of an indication may serve to convey information about that indication.\",\n \"The conveyed information may include classification of an AOI, a size of an AOI and/or an importance rank of an AOI.\",\n \"Accordingly, different flags or indicators may be used to identify different types of AOIs.\",\n \"For example, pink indicators may be used to indicate gingival recession and white indicators may be used to indicate tooth wear.\",\n \"Flagging module 118 may determine a classification, size and/or importance rank of an AOI, and may then determine a color, symbol, icon, text, etc.\",\n \"for an indicator of that AOI based on the classification, size and/or importance rank.\",\n \"Turning to keying which conveys indication size, the processing logic may, in implementing such size-oriented keying, employ one or more size thresholds.\",\n \"The origin of the thresholds may be set (e.g., by a dental expert) during a configuration operation and/or may be preset.\",\n \"The origin of the thresholds may be set by processing logic which accesses pooled patient data and/or pedagogical patient data correlating size information for foreseeable indications regarding scan assistance (e.g., information regarding sizes of oral-anatomical portions not imaged or poorly imaged due to missing and/or flawed scan data) and degree of success of procedure outcome (e.g., degree of success in orthotic alignment device construction and/or orthotic alignment device patient fit).\",\n \"Larger size may be indicative of greater clinical importance.\",\n \"For example, a large void may impair manufacture of an accurate orthodontic aligner, while a large void may not.\",\n \"As an illustration, three thresholds might be set with respect to areas of missing data and/or caries.\",\n \"Implementation may be such that indications falling into the largest of the three size thresholds are keyed red and/or with the numeral “1,” that indications falling into the smallest of the three size thresholds are keyed purple and/or with the numeral “3,” and/or that indications falling into the middle-sized of the three thresholds are keyed yellow and/or with the numeral “2.” Turning to keying which conveys AOI classification, indicators may identify classifications assigned to intraoral areas of interest.\",\n \"For examples, AOIs may be classified as voids, changes, conflicts, foreign objects, or other types of AOI.\",\n \"AOIs representing changes in patient dentition may represent tooth decay, receding gums, tooth wear, a broken tooth, gum disease, gum color, moles, lesions, tooth shade, tooth color, an improvement in orthodontic alignment, degradation in orthodontic alignment, and so on.\",\n \"Different criteria may be used for identifying each such class of AOI.\",\n \"For example, a void may be identified by lack of image data, a conflict may be identified by conflicting surfaces in image data, changes may be identified based on differences in image data, and so on.\",\n \"In an example of a surface conflict AOI, a first bite line component may correspond to one portion of a patient's teeth (e.g., the upper jaw or to the right side of the jaw).\",\n \"A second bite line component may correspond to another portion of the patient's teeth (e.g., the lower jaw or to the left side of the jaw).\",\n \"The AOI identifying module 115 may compare the first bite line component to the second bite line component to check for a deviation.\",\n \"Such a deviation might be suggestive of the patient having moved his jaw during scanning (e.g., the patient having moved his jaw in an interim between a practitioner's scanning of the lower jaw and the practitioner's scanning of the upper jaw, or in an interim between the practitioner's scanning of the left side of the jaw and the and the practitioner's scanning of right side of the jaw).\",\n \"In performing a bite line shift surface conflict operation, the AOI identifying module 115 may or may not take into account a deviation threshold (e.g., set during a configuration operation).\",\n \"The flagging module 118 may or may not then provide indication thereof in the case where the found deviation meets the threshold, and not provide indication otherwise.\",\n \"The intraoral scan application 108 may or may not apply corrective measures (e.g., averaging) to such found deviations which do not meet the threshold.\",\n \"Where such a threshold is not taken into account, the flagging module 118 may provide indication of all found deviations.\",\n \"Although the foregoing is, to facilitate discussion, cast in terms of bite line shift surface conflict, analogous operations may be performed, for instance, with regard to other surface conflict indications.\",\n \"Keying may also include importance rank, which is discussed in greater detail with reference to FIG.\",\n \"3B.\",\n \"When a scan session is complete (e.g., all images for a dental site have been captured), model generation module 125 may generate a virtual 3D model of the scanned dental site.\",\n \"AOI identifying module 115 and/or flagging module 118 may perform operations to identify AOIs and/or to indicate such AOIs before or after a virtual 3D model has been generated.\",\n \"To generate the virtual model, model generation module 125 may register (i.e., “stitch” together) the intraoral images generated from the intraoral scan session.\",\n \"In one embodiment, performing image registration includes capturing 3D data of various points of a surface in multiple images (views from a camera), and registering the images by computing transformations between the images.\",\n \"The images may then be integrated into a common reference frame by applying appropriate transformations to points of each registered image.\",\n \"In one embodiment, processing logic performs image registration in a manner discussed in U.S. Pat.\",\n \"No.\",\n \"6,542,249, filed Jul.\",\n \"20, 1999, which is incorporated herein by reference.\",\n \"In one embodiment, image registration is performed for each pair of adjacent or overlapping intraoral images (e.g., each successive frame of an intraoral video).\",\n \"Image registration algorithms are carried out to register two adjacent intraoral images, which essentially involves determination of the transformations which align one image with the other.\",\n \"Each registration between a pair of images may be accurate to within 10-15 microns.\",\n \"Image registration may involve identifying multiple points in each image (e.g., point clouds) of an image pair, surface fitting to the points of each image, and using local searches around points to match points of the two adjacent images.\",\n \"For example, model generation module 125 may match points of one image with the closest points interpolated on the surface of the other image, and iteratively minimize the distance between matched points.\",\n \"Model generation module 125 may also find the best match of curvature features at points of one image with curvature features at points interpolated on the surface of the other image, without iteration.\",\n \"Model generation module 125 may also find the best match of spin-image point features at points of one image with spin-image point features at points interpolated on the surface of the other image, without iteration.\",\n \"Other techniques that may be used for image registration include those based on determining point-to-point correspondences using other features and minimization of point-to-surface distances, for example.\",\n \"Other image registration techniques may also be used.\",\n \"Many image registration algorithms perform the fitting of a surface to the points in adjacent images, which can be done in numerous ways.\",\n \"Parametric surfaces such as Bezier and B-Spline surfaces are most common, although others may be used.\",\n \"A single surface patch may be fit to all points of an image, or alternatively, separate surface patches may be fit to any number of a subset of points of the image.\",\n \"Separate surface patches may be fit to have common boundaries or they may be fit to overlap.\",\n \"Surfaces or surface patches may be fit to interpolate multiple points by using a control-point net having the same number of points as a grid of points being fit, or the surface may approximate the points by using a control-point net which has fewer number of control points than the grid of points being fit.\",\n \"Various matching techniques may also be employed by the image registration algorithms.\",\n \"In one embodiment, model generation module 125 may determine a point match between images, which may take the form of a two dimensional (2D) curvature array.\",\n \"A local search for a matching point feature in a corresponding surface patch of an adjacent image is carried out by computing features at points sampled in a region surrounding the parametrically similar point.\",\n \"Once corresponding point sets are determined between surface patches of the two images, determination of the transformation between the two sets of corresponding points in two coordinate frames can be solved.\",\n \"Essentially, an image registration algorithm may compute a transformation between two adjacent images that will minimize the distances between points on one surface, and the closest points to them found in the interpolated region on the other image surface used as a reference.\",\n \"Model generation module 125 repeats image registration for all adjacent image pairs of a sequence of intraoral images to obtain a transformation between each pair of images, to register each image with the previous one.\",\n \"Model generation module 125 then integrates all images into a single virtual 3D model by applying the appropriate determined transformations to each of the images.\",\n \"Each transformation may include rotations about one to three axes and translations within one to three planes.\",\n \"In one embodiment, intraoral scan application 108 includes a training module 120.The training module 120 may provide a user (e.g., a practitioner) with training guidance as to scanning technique, and/or may highlight scan assistance indications of the sort discussed hereinabove (e.g., ones corresponding to missing and/or flawed scan data) which have occurred in the past and/or have been reoccurring for that user.\",\n \"The training module 120 may consider, relative to a training guidance data pool, scan data (e.g., 3D image point clouds) and/or one or more virtual 3D models arising from scanning performed by that user which led to scan assistance indications.\",\n \"The training guidance data pool may include, with respect to the scanning performances of multiple users (e.g., multiple practitioners), scan data and/or one or more virtual 3D models (e.g., one which led to scan assistance indications) along with information describing scanning technique changes which might have prevented and/or mitigated the circumstances which led to the scan assistance indications.\",\n \"The scan data and/or one or more virtual 3D models of the training guidance data pool may be anonymized and/or employed in compliance with regional medical record privacy regulations.\",\n \"The training module 120 may match the scan data and/or one or more virtual 3D models arising from scanning performed by the user to scan data and/or virtual 3D models of the training guidance data pool, access corresponding information describing scanning technique changes, and present such scanning change technique information to the user (e.g., via a user interface).\",\n \"As an illustration, the training guidance data pool might, for scan data and/or one or more virtual 3D models which led to double incisor edge scan assistance indications such as ones corresponding to particular angles of scanning, include information indicating that having performed scanning with a specified angular change might have been preventative and/or mitigating.\",\n \"For instance, such data might, for scan data and/or one or more virtual 3D models which led to double incisor edge scan assistance indications in a fashion indicative of scanning at a 35 degree-to-surface angle—instead of a desired 45 degree-to-surface angle—include information indicating that an angular increase of ten degrees-to-surface might be preventative and/or curative.\",\n \"Moreover, such data might for scan data and/or one or more virtual 3D models which led to double incisor edge scan assistance indications in a fashion indicative of scanning with a 40 degree-to-surface angle—instead of the desired 45 degree-to-surface angle—include information indicating that an angular increase of five degrees-to-surface might be preventative and/or curative.\",\n \"As another illustration, the training guidance data pool might, for scan data and/or one or more virtual 3D models which led to missing and/or flawed scan data scan assistance indications (e.g., ones corresponding to particular geometrical areas, width-height dimensions, width-to-height or other dimensional relationships, and/or oral locations), include information indicating that having performed scanning at one or more specified speeds, cadences, angles, and/or distances-from-surface might have been preventative and/or mitigating.\",\n \"The training module 120 may with respect to particular users (e.g., practitioners) keep historical record (e.g., according to user identifier) of scan assistance indications over time.\",\n \"The training module 120 may employ this historical record to highlight scan assistance indications which have occurred in the past and/or have been reoccurring for a particular user, to identify improvements and/or declines in user scanning technique over time, and/or to provide scanning technique training guidance which takes into account multiple scanning performances of the user.\",\n \"The training module 120 may or may not consider the noted training guidance data pool information describing scanning technique changes which may be preventative and/or mitigating.\",\n \"As one illustration, the training module 120 may in providing indication (e.g., flagging) regarding missing and/or flawed scan data recognize that a particular user has received same and or similar indication in the past.\",\n \"For instance, the training module 120 may ascertain that the user has received missing and/or flawed scan data at a given location multiple times, and/or has received missing and/or flawed scan data of similar tenor multiple times (e.g., although at differing locations, the user has repeatedly received indication reelecting double incisor edges suggestive of scanning at other than a 45-degrees-from-surface angle).\",\n \"Where the training module 120 so finds an at-hand indication to be one for which same and/or similar indication has been received in the past, the training module 120 may act to highlight the indication (e.g., via a particular color).\",\n \"As another illustration, with respect to a particular user and double incisor edge scan assistance indications, the training module 120 may, by consideration of such historical record and such training guidance data pool scanning technique change information, ascertain that the user's scanning technique is changing in such a fashion that the employed scanning is not yet the called-for 45 degrees-to-surface, but that the employed scanning angle is becoming over time closer to 45 degrees-to-surface.\",\n \"In so doing the training module 120 may perform matching with training guidance data pool information in the vein of the noted differing degrees-to-surface scanning angles leading to double incisor edge scan assistance indication (e.g., matching older user data to pool data regarding 60-degree-to-surface scanning angle but more recent user data to pool data regarding 40-degree-to-surface scanning angle).\",\n \"FIGS.\",\n \"2A-3C illustrate flow diagrams of methods for performing intraoral scans of dental sites for patients.\",\n \"These methods may be performed by processing logic that comprises hardware (e.g., circuitry, dedicated logic, programmable logic, microcode, etc.\",\n \"), software (such as instructions run on a processing device), or a combination thereof.\",\n \"In one embodiment, processing logic corresponds to computing device 105 of FIG.\",\n \"1 (e.g., to a computing device 105 executing an intraoral scan application 108).\",\n \"FIG.\",\n \"2A illustrates a flow diagram for a method 200 of determining intraoral areas of interest during an intraoral scan session, in accordance with embodiments of the present invention.\",\n \"At block 205 of method 200, an intraoral scan session of a dental site is started by a dental practitioner.\",\n \"The scan session may be for an intraoral scan of a partial or full mandibular or maxillary arch, or a partial or full scan of both arches.\",\n \"The dental practitioner may move an intraoral scanner to a first intraoral position and generate a first intraoral image.\",\n \"At block 210, processing logic receives the first intraoral image.\",\n \"The first intraoral image may be a discrete image (e.g., taken from a point-and-shoot mode) or a frame of an intraoral video (e.g., taken in a continuous scanning or video mode).\",\n \"The intraoral image may be a three dimensional (3D) image having a particular height, width and depth.\",\n \"In some embodiments, an intraoral scanner is used that generates 3D images having a depth of 12-14 mm, a height of 13-15 mm and a width of 17-19 mm (e.g., a depth of 13 mm, height of 14 mm and width of 18 mm in one particular embodiment).\",\n \"At block 215, processing logic identifies one or more candidate intraoral areas of interest from the first intraoral image.\",\n \"In one embodiment, a candidate intraoral area of interest is identified by processing the intraoral image to identify voxels in the intraoral image that satisfy one or more criteria.\",\n \"Different criteria may be used to identify different classes of intraoral areas of interest.\",\n \"In one embodiment, the a of missing image data is used to identify AOIs that might be voids.\",\n \"For example, voxels at areas that were not captured by the intraoral image may be identified.\",\n \"Processing logic may then determine one or more subsets of the identified voxels that are proximate to one another.\",\n \"Two voxels may be considered to be proximate to one another if they are within a threshold distance from one another.\",\n \"In one embodiment, two voxels are proximate if they are adjacent to one another.\",\n \"All of the voxels in a determined subset (e.g., all of the voxels that are connected directly or via other identified voxels) are grouped into a volume that makes up the candidate area of interest.\",\n \"One or multiple candidate areas of interest may be identified.\",\n \"If the criterion used to identify voxels is a missing data, then the candidate intraoral area of interest may represent a void.\",\n \"Other criteria may be used to identify other classes of AOI.\",\n \"After the dental practitioner generates the first intraoral image, he or she moves the intraoral scanner to a second position and generates a next intraoral image.\",\n \"At block 220, processing logic receives the next intraoral image.\",\n \"At block 230, processing logic compares the second intraoral image to the first intraoral image.\",\n \"To compare intraoral images, processing logic determines an alignment between the intraoral images based on geometric features shared by these intraoral images.\",\n \"Determining the alignment may include performing transformations and/or rotations on one or both of the intraoral images and/or register the intraoral areas of interest to each other.\",\n \"The aligned images may then be displayed by the processing logic.\",\n \"Processing logic may also compare the first intraoral image to a corresponding intraoral image taken during a prior scan session.\",\n \"This may identify areas of interest such as tooth wear, cavities, and so forth.\",\n \"At block 232, processing logic determines whether any new candidate intraoral areas of interest are present based on the next intraoral image.\",\n \"At block 235, processing logic determines whether the candidate intraoral areas of interest from the first intraoral image are verified as intraoral areas of interest.\",\n \"Such verification may be performed by testing the proximity and/or geometric conditions of the AOI relative to a surface of the latest intraoral image.\",\n \"In one embodiment, candidate intraoral areas of interest from an intraoral image are dismissed if they correspond to a surface (e.g., of a dental site) from another intraoral image.\",\n \"Alternatively, if a candidate intraoral area of interest does not correspond to a region of a surface from another intraoral image, then the candidate intraoral image may be verified as an actual intraoral area of interest.\",\n \"Accordingly, the second intraoral image may be used to confirm or dismiss candidate intraoral areas of interest from the first intraoral image.\",\n \"If a portion of a candidate intraoral area of interest from the first intraoral image corresponds to (e.g., lines up with) a portion of a surface from the second intraoral image, then the shape and/or size of the candidate intraoral area of interest may be modified.\",\n \"If none of the candidate intraoral areas of interest are verified as intraoral areas of interest (e.g., if a subsequent intraoral image provides image data for a candidate intraoral area of interest), the method proceeds to block 245.Otherwise, the method continues to block 240.At block 240, processing logic provides an indication of the one or more verified intraoral areas of interest.\",\n \"In one embodiment, processing logic interpolates a shape for the intraoral area of interest based on geometric features surrounding the intraoral area of interest and/or based on geometric features of the intraoral area of interest (if such features exist).\",\n \"For example, if the intraoral area of interest is a void, then the regions around the void may be used to interpolate a surface shape of the void.\",\n \"The shape of the intraoral area of interest may be displayed in manner to contrast the intraoral area of interest from surrounding imagery.\",\n \"For example, teeth may be shown in white, while the intraoral area of interest may be shown in red, black, blue, green, or another color.\",\n \"Additionally or alternatively, an indicator such as a flag may be used as an indication of the intraoral area of interest.\",\n \"The indicator may be remote from the intraoral area of interest but include a pointer to the intraoral area of interest.\",\n \"The intraoral area of interest may be hidden or occluded in many views of the dental site.\",\n \"However, the indicator may be visible in all or many such views.\",\n \"For example, the indicator may be visible in all views of the scanned dental site unless the indicator is disabled.\",\n \"The provided indications of the intraoral areas of interest may be displayed while the intraoral scan session is ongoing.\",\n \"At block 245, processing logic determines whether the intraoral scan session is complete.\",\n \"If so, the method continues to block 248.If additional intraoral images are to be taken and processed, the method returns to block 220.At block 248, a virtual 3D model of the dental site is generated.\",\n \"The virtual model 3D may be generated as discussed above.\",\n \"The virtual 3D model may be a virtual or digital model showing the surface features of the target area.\",\n \"For a virtual 3D model of a full dental arch, the arch width of the virtual 3D model may be accurate to within 200 microns of the arch width of the patient's actual dental arch.\",\n \"FIG.\",\n \"2B illustrates a flow diagram for a method 250 of providing indications for intraoral areas of interest, in accordance with embodiments of the present invention.\",\n \"The indications may be provided during an intraoral scan session (e.g., before generation of a virtual model of a dental site) or after an intraoral scan session is complete (e.g., based on a virtual model of the dental site).\",\n \"At block 255, intraoral images of a dental site are received.\",\n \"The intraoral images may be received from an intraoral scanner, from a data store, from another computing device, or from another source.\",\n \"The intraoral images may be from a single intraoral scan session or from multiple intraoral scan sessions.\",\n \"Additionally, or alternatively, one or more virtual models of a dental site may be received.\",\n \"The virtual models may have been computed based on intraoral images from past intraoral scan sessions.\",\n \"At block 260, processing logic identifies one or more voxels from the intraoral images and/or the virtual models that satisfy a criterion.\",\n \"The criterion may be missing data, conflicting data, or data having particular characteristics.\",\n \"In one embodiment, the intraoral images are first used to compute a virtual model, and the voxels are identified from the computed virtual model.\",\n \"In another embodiment, the voxels are identified from individual intraoral images.\",\n \"At block 265, one or more subsets of the identified voxels that are in close proximity to one another are identified.\",\n \"At block 270, these subsets are grouped into candidate intraoral areas of interest.\",\n \"At block 275, processing logic determines whether the candidate intraoral areas of interest are verified as intraoral areas of interest.\",\n \"If any candidate intraoral areas of interest are verified as actual intraoral areas of interest, the method continues to block 280.Otherwise, the method proceeds to block 290.At block 280, classifications are determined for the intraoral areas of interest.\",\n \"For example, AOIs may be classified as voids, conflicting surfaces, changes in a dental site, foreign objects, and so forth.\",\n \"At block 285, processing logic provides indications of the intraoral areas of interest.\",\n \"The indications may include information identifying the determined classifications of the intraoral areas of interest.\",\n \"For example, an indicator may identify an intraoral area of interest as representing a void or insufficient image data.\",\n \"Another indicator may identify an intraoral area of interest as representing a region for which there are conflicting surfaces from different images.\",\n \"In one embodiment, the indications include flags that are remote from the intraoral areas of interest and that point to or otherwise direct a viewer's attention to the intraoral areas of interest.\",\n \"The indications may be visible from views of the dental site at which the actual intraoral areas of interest are hidden.\",\n \"At block 290, the dental site is displayed along with any of the indications for the intraoral areas of interest.\",\n \"FIG.\",\n \"3A illustrates a flow diagram for a method 300 of formulating scan assistance indications concerning missing and/or flawed scan data in accordance with examples of the present invention.\",\n \"According to a first aspect, at block 305 of method 300 the processing logic may receive scan data from an intraoral scanner.\",\n \"At block 310 the processing logic, may perform direct 3D point cloud analysis and/or direct virtual 3D model analysis.\",\n \"At block 315 the processing logic may determine one or more pixels and/or other points to be missing from patient scan data and/or from one or more patient virtual 3D models.\",\n \"At block 330, the processing logic may formulate one or more corresponding indications concerning missing and/or flawed scan data.\",\n \"According to a second aspect of FIG.\",\n \"3, at block 305 the processing logic may likewise receive scan data from the scanner.\",\n \"At block 320, the processing logic may consider patient scan data and/or one or more patient virtual 3D models relative to entities indicated by pooled patient data and/or by pedagogical patient data to constitute complete and/or un-flawed data.\",\n \"At block 325, the processing logic may ascertain the patient scan data and/or one or more patient virtual 3D models to be incomplete.\",\n \"At block 330, the processing logic may likewise formulate one or more corresponding indications concerning missing and/or flawed scan data.\",\n \"The indications regarding diagnostic assistance provided by the processing logic may include indications concerning tooth occlusion contacts, bite relation, tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries.\",\n \"To facilitate understanding, examples of processing logic operations performed in connection with providing diagnostic assistance indications will now be discussed.\",\n \"FIG.\",\n \"3B illustrates a flow diagram for a method 340 of performing keying and display which conveys indication importance rank for intraoral areas of interest in accordance with that which is discussed hereinabove and in connection with examples of the present invention.\",\n \"Processing logic may assign an importance rank to an indication via a process in which the processing logic considers the indication in view of one or more patient case details and/or one or more rank-altering weighting factors.\",\n \"It is noted that one or more of the rank-altering weighting factors themselves may or may not regard patient case details.\",\n \"Such patient case details may include a procedure being performed (e.g., preparation for application of a crown, preparation for application of an orthodontic alignment device, treatment of suspected caries and/or treatment of gingival swelling), patient age, patient gender, one or more previously-performed procedures (e.g., that a patient's last visit was to address a crown affected by marginal leakage), and/or patient dental records.\",\n \"At block 345 of method 340 the processing logic may apply one or more weighting factors to each of the one or more under-consideration indications.\",\n \"A weighting factor may set forth one or more particular properties and indicate one or more rank alterations to be performed where such properties are met.\",\n \"The rank alterations may include increasing an indication's rank by a given value, decreasing an indication's rank by a given value, specifying that an indication be considered to possess a zenith rank, and/or that an indication be considered to possess a nadir rank.\",\n \"With respect to a given indication, the processing logic may commence by assigning a particular start rank value (e.g., zero) to the indication.\",\n \"The processing logic may then consider the one or more weighting factors.\",\n \"Having applied those weighting factors, the processing logic may ascertain a finalized importance rank for the indication.\",\n \"The processing logic may consider the finalized importance rank for the indication relative to one or more other indications for which it has performed like operations.\",\n \"The origin of the rank-altering weighting factors considered by the processing logic may be set by processing logic which accesses pooled patient data and/or pedagogical patient data which includes correlations between foreseeable indications regarding diagnostic assistance (e.g., tooth wear and/or caries) and importance (e.g., the data might set forth importance information regarding each of tooth wear and caries that conveys that caries are of greater import than tooth wear).\",\n \"Processing logic may set the rank-altering weighting factors such that missing and/or flawed scan data corresponding to a portion of teeth and/or gingivae that is larger than or equal to a certain size has an increased rank.\",\n \"Rank-altering weighting factors such as missing and/or flawed scan data which corresponds to a portion of teeth and/or gingivae which has certain dimensional characteristics (e.g., having width magnitude being greater than or equal to height magnitude, a circumstance that might be viewed as being short and wide or square shaped) are assigned the zenith rank or more highly ranked.\",\n \"Missing and/or flawed scan data which corresponds to a portion of teeth and/or gingivae which has other dimensional characteristics (e.g., having width magnitude being less than height magnitude, a circumstance that might be viewed as being long and narrow) may be assigned the nadir rank or more lowly ranked.\",\n \"The origin of the rank-altering weighting factors considered by the processing logic may be set by processing logic which accesses pooled patient data and/or pedagogical patient data which includes correlations between foreseeable indications regarding foreign object recognition assistance (e.g., concerning fillings and/or implants) and importance (e.g., the data might set forth importance information regarding each of fillings and implants that conveys that fillings are of greater import than implants).\",\n \"By consideration of such data-provided correlations—be they ones regarding scan assistance, diagnostic assistance, or foreign object recognition assistance—the processing logic may draw conclusions which it employs in setting rank-altering weighting factors.\",\n \"The performed setting—be it done during a configuration operation or by processing logic—may provide for one or more weighting factors directed towards foreseeable indications.\",\n \"One such weighting factor may specify that an indication relating to the vicinity of (e.g., to the interproximal areas of) one or more preparation teeth have its rank raised by a specified value.\",\n \"Another such weighting factor may specify that an indication regarding insufficient preparation tooth margin line clarity have its rank raised by a specified value or that such indication should possess a zenith rank.\",\n \"Yet another weighting factor may specify that an indication regarding unclear bite have its rank raised by a specified value.\",\n \"A further weighting factor may specify that an indication regarding bite line shift have its rank raised by a specified value.\",\n \"Another weighting factor may specify that an indication regarding double incisor edge have its rank raised by a specified value.\",\n \"Yet another weighting factor may specify that an indication regarding a lack of gum line clarity have its rank raised by a first specified value in the case where the at-hand procedure does not concern gingival recess, but have its rank raised by a second specified value in the case where the at-hand procedure does concern gingival recess.\",\n \"As one example, with respect to a first indication the processing logic may commence by assigning an importance rank of zero to the indication, determine that consideration of a first weighting factor finds indication that the indication's rank be raised by three, that consideration of a second weighting factor finds indication that the indication's rank be lowered by one, and that consideration of a third weighting factor finds indication that the indication's rank be raised by five.\",\n \"The processing logic may then ascertain the finalized importance rank of the first indication to be seven.\",\n \"Further, with respect to a second indication the processing logic may commence by assigning an importance rank of zero to the indication, determine that consideration of a first weighting factor finds indication that the indication's rank be lowered by two, that consideration of a second weighting factor finds indication that the indication's rank be lowered by three, and that consideration of a third weighting factor finds indication that the indication's rank be raised by six.\",\n \"The processing logic may then ascertain the finalized importance rank of the second indication to be one.\",\n \"With respect to a third indication the processing logic may again commence by assigning an importance rank of zero.\",\n \"The processing logic may then find that consideration of a first weighting factor finds indication that the indication's rank be raised by four, that consideration of a second weighting factor finds indication that the indication be considered to possess a zenith rank, and that consideration of a third weighting factor finds indication that the indication's rank be lowered by eight.\",\n \"The processing logic may then ascertain the finalized importance rank of the third indication to be the zenith rank.\",\n \"As such, the second weighting factor, by indicating zenith rank, might be seen as having trumped that which was indicated by the other two weighting factors.\",\n \"It is noted that had consideration of the second weighting factor instead found indication that the indication be considered to possess a nadir rank, the second weighting factor would have again trumped the other two weighting factors, but would have done so in a fashion that yielded a finalized importance rank of the nadir rank for the third indication.\",\n \"At block 350, the processing logic may ascertain a finalized importance rank for each of the one or more under-consideration indications.\",\n \"At block 355, the processing logic may consider relative to one another the finalized importance ranks of the one or more under-consideration indications.\",\n \"Continuing the above example, the processing logic may consider the three finalized importance ranks—seven for the first indication, one for the second indication, and zenith rank for the third indication—relative to one another.\",\n \"In so doing the processing logic may conclude the third indication to be highest-ranked, the first indication to be second-highest-ranked, and the second indication to be lowest-ranked.\",\n \"At block 360, the processing logic may employ the finalized importance ranks in formulating a rescan order and/or a practitioner attention order.\",\n \"The processing logic may employ the importance ranks of indications in suggesting a rescan order for one or more indications (e.g., indications regarding scan assistance such as indications concerning missing and/or flawed scan data) and/or in suggesting a practitioner attention order for one or more indications (e.g., indications regarding diagnostic assistance and/or indications regarding foreign object recognition assistance).\",\n \"In formulating such rescan order and such practitioner attention orders the processing logic may or may not suppress one or more indications such that those indications are excluded from the rescan order or practitioner attention order.\",\n \"As one illustration, the processing logic may suppress indications having rank lower than a certain value (e.g., a value specified by the user and/or during a configuration).\",\n \"As another illustration, the processing logic may suppress indications having the nadir rank.\",\n \"Such suppression may serve to eliminate indications determined by the processing logic to lack clinical significance (e.g., with respect to an at-hand procedure—say preparation for application of a crown or an orthotic alignment device).\",\n \"As an illustration, suppressed indications may include missing and/or flawed scan data for which compensation can be performed (e.g., via the employ of extrapolation and/or generic data filling).\",\n \"The processing logic may—for those indications which have not been suppressed—convey importance rank via keying of indications (e.g., via color, symbol, icon, size, text, and/or number key).\",\n \"Then, at block 365 the processing logic may provide in connection with a depiction of teeth and/or gingivae (e.g., a 3D image or a virtual 3D model) one or more keyed indications (e.g., flags) conveying for each indication its location in the rescan order and/or in the practitioner attention order.\",\n \"The processing logic may provide flags including numerals which each point to a particular portion of a depiction (e.g., a 3D image or a virtual 3D model) of teeth and/or gingivae of a patient and convey via the numeral the order-wise location of that oral portion.\",\n \"As an illustration, suppose that there are four indications regarding scan assistance selectable by the processing logic for inclusion in a rescan order—an indication corresponding to teeth 15 and 16 (ISO 3950 notion), an indication corresponding to the gingiva of tooth 32 (ISO 3950 notation), an indication corresponding to teeth 18 and 17 (ISO 3950 notation), and an indication corresponding to tooth 44 (ISO 3950 notation).\",\n \"Then suppose that the indication correspond to teeth 18 and 17 has the nadir rank, and that the processing logic suppresses this indication, thereby eliminating it from the rescan order.\",\n \"Suppose further that the rescan order for the three remaining indications is such that the indication corresponding to the gingiva of tooth 32 has the highest importance rank of the remaining three and is first in the rescan order, that the indication corresponding to teeth 15 and 16 has the second highest importance rank of the remaining three and is second in the rescan order, and that the indication corresponding to tooth 44 has the lowest importance rank of the remaining three and is third in the rescan order.\",\n \"The provision of flags by the processing logic may be such that the indication corresponding to the gingiva of tooth 32 is flagged with a “1,” the indication corresponding to teeth 15 and 16 is flagged with a “2,” and the indication corresponding to tooth 48 is flagged with a “3.” As another illustration, suppose that there are three indications regarding diagnostic assistance—an indication corresponding to breakage of teeth 11 and 21 (ISO 3950 notation), an indication corresponding to bite relation, and an indication corresponding to gingival recess at the base of tooth 27 (ISO 3950 notation).\",\n \"Suppose further that the practitioner attention order is such that the indication corresponding to bite relation has the highest importance rank of the three and is first in the practitioner attention order, that the indication corresponding to the breakage has the second highest importance rank of the three and is second in the practitioner attention order, and that the indication corresponding to the gingival recess has the lowest importance rank of the three and is third in the practitioner attention order.\",\n \"The provision of flags by the processing logic may be such that the indication corresponding to bite relation is flagged with a “1,” the indication corresponding to the breakage is flagged with a “2,” and the indication corresponding to the gingival recess is flagged with a “3.” As an additional illustration, suppose that there are two indications regarding foreign object recognition assistance—an indication corresponding to a filling in tooth 16 (ISO 3950 notation) and an indication corresponding to a bridge at the expected anatomical location of teeth 35-37 (ISO 3950 notation).\",\n \"Suppose further that the practitioner attention order is such that the indication corresponding to the filling has the has the higher importance rank of the two and is first in the practitioner attention order, and that the indication corresponding to the bridge has the lower importance rank of the two and is second in the practitioner attention order.\",\n \"The provision of flags by the processing logic may be such that the indication corresponding to the filling is flagged with a “1” and the indication corresponding to the bridge is flagged with a “2.” FIG.\",\n \"3C illustrates a flow diagram for a method 370 of employing 3D intraoral images in providing indication of intraoral areas of interest, in accordance with examples of the present invention.\",\n \"As discussed hereinabove, the processing logic may provide indication regarding scan assistance, diagnostic assistance, and/or foreign object recognition assistance.\",\n \"As also discussed hereinabove, the processing logic may provide such indication during the user's (e.g., the practitioner's) scanner application, after the user's scanner application, and/or prior to and/or without construction of an intraoral virtual 3D model.\",\n \"As additionally discussed hereinabove, in formulating such indication the processing logic may analyze intraoral scan data (e.g., 3D intraoral images, say 3D intraoral images provided by the scanner as 3D image point clouds) and/or intraoral virtual 3D models.\",\n \"At block 372 of method 370 the processing logic may analyze one or more first 3D intraoral images to yield a candidate intraoral area of interest.\",\n \"The processing logic may perform such analysis as discussed hereinabove with respect to AOI formulation, but consider the analysis result to constitute a candidate intraoral area of interest rather than an actual intraoral area of interest.\",\n \"The processing logic may identify one or more points (e.g., one or more pixels and/or groups of pixels) corresponding to the candidate intraoral area of interest.\",\n \"At block 374, the processing logic may identify one or more second 3D intraoral images which may be relevant to the candidate intraoral area of interest.\",\n \"The one or more second 3D intraoral images may be ones which are intraorally proximal to the first one or more 3D intraoral images and/or ones which share geometrical relation to the first one or more 3D intraoral images.\",\n \"The processing logic may determine such intraoral proximity by considering intraoral location information provided by the scanner in connection with 3D intraoral images.\",\n \"The scanner might produce such information by way of incorporated accelerometers and/or other positioning hardware.\",\n \"The processing logic may determine such shared geometrical relation by identifying common surface features (e.g., common peak and/or valley surface features).\",\n \"At block 376, the processing logic may perform analysis with respect to one or more of the first 3D intraoral images and the second 3D intraoral images taken together.\",\n \"In so doing the processing logic may or may not align the one or more first 3D intraoral images with the one or more second 3D intraoral images (e.g., the processing logic may align one or more point clouds corresponding to the first one or more 3D intraoral images with one or more point clouds corresponding to the second one or more 3D intraoral images).\",\n \"At block 378, the processing logic may determine whether the first 3D intraoral images and the second 3D intraoral images, taken together, agree, disagree, or agree in part with the candidate intraoral area of interest.\",\n \"As example, suppose that the candidate indication regards a scan assistance indication concerning missing and/or flawed scan data.\",\n \"In the case where such taken-together analysis finds no missing and/or flawed scan data disagreement may occur.\",\n \"As an illustration, such may occur where all of the one or more points (e.g., one or more pixels and/or groups of pixels) which correspond to missing scan data for the candidate indication are provided by the one or more second 3D intraoral images.\",\n \"In the case where such taken-together analysis still finds missing and/or flawed scan data but the tenor of the missing and/or flawed scan data changes (e.g., the now-found missing and/or flawed scan data is of a larger size, of a smaller size, of a different location, and/or of a different morphology), partial agreement may occur.\",\n \"As an illustration, such might occur where some points (e.g., one or more pixels and/or groups of pixels) which correspond to missing scan data for the candidate indication are provided by the one or more second 3D intraoral images while other of such missing scan data points are not provided by the one or more second 3D intraoral images such that a smaller amount of missing and/or flawed scan data is found.\",\n \"In the case where such taken-together analysis finds the same tenor (e.g., the same amount of) missing and/or flawed scan data, agreement may occur.\",\n \"As an illustration, such might occur where none of the points (e.g., one or more pixels and/or groups of pixels) which correspond to missing scan data for the candidate indication are provided by the one or more second 3D intraoral images.\",\n \"As another example, suppose that the candidate indication regards a diagnostic assistance indication concerning caries.\",\n \"In the case where such taken-together analysis no longer finds caries disagreement may occur.\",\n \"As an illustration, such may occur where further taking into account the one or more second 3D intraoral images—say further taking into account one or more points (e.g., one or more pixels and/or groups of pixels) provided by the one or more second 3D intraoral images—yields a refined intraoral vantage point from which caries are no longer found.\",\n \"In the case where such taken-together analysis still finds caries but the tenor of the found caries changes (e.g., the now-found caries are smaller, larger, of different location, and/or of different morphology), partial agreement may occur.\",\n \"As an illustration, such might occur where further taking into account the one or more second 3D intraoral images—say further taking into account one or more points (e.g., one or more pixels and/or groups of pixels) provided by the one or more second 3D intraoral images—yields a refined intraoral vantage point from which the found caries differ in size and/or intraoral location.\",\n \"In the case where such taken-together analysis finds caries of the same tenor as that found in connection with the candidate indication agreement may occur.\",\n \"As an illustration, such might occur where further taking into account the one or more second 3D intraoral images—say further taking into account one or more points (e.g., one or more pixels and/or groups of pixels) provided by the one or more second 3D intraoral images—yields does not refine the intraoral vantage point in a way that causes the found caries to differ in size and/or in intraoral location.\",\n \"Where the processing logic finds agreement, the processing logic may promote the candidate AOI to an indication of the sort discussed hereinabove (i.e., a full, non-candidate AOI) and employ it as discussed hereinabove (e.g., provide an indication of the AOI to a user in the form of flags).\",\n \"Where the processing logic finds partial agreement, the processing logic may yield an AOI corresponding to the above-discussed different tenor (e.g., an AOI reflecting a smaller amount of missing data or an AOI reflecting a caries of different morphology) and employ it as discussed hereinabove.\",\n \"Where the processing logic finds disagreement, the processing logic may reject the candidate AOI.\",\n \"Where there is agreement the processing logic may proceed to block 380, in which the processing logic promotes the candidate indication to a full, non-candidate indication and employs the promoted indication as discussed above.\",\n \"Where there is partial agreement the processing logic may proceed to block 382, in which the processing logic yields an indication corresponding to the tenor of the partial agreement, and employs that indication as discussed above.\",\n \"Where there is disagreement the processing logic may proceed to block 384, in which the processing rejects the candidate indication.\",\n \"Previously discussed pooled patient data and/or pedagogical patient data may include many different types of data and/or depictions.\",\n \"Some examples of different pooled patient data and/or pedagogical patient data and its use is now discussed.\",\n \"Pooled patient data and/or pedagogical patient data may include depictions of gum lines, bites, and/or bite lines, along with corresponding identifications thereof and/or clarity level indications thereof.\",\n \"Indication regarding unclear gum line and/or unclear patient bite may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or virtual 3D models includes a gum line or bite that is unclearly imaged (e.g., deviates, in a fashion suggestive of unclarity, from gum line or bite indicated by the pooled and/or pedagogical data to possess clarity.\",\n \"Pooled patient data and/or pedagogical patient data may additionally include depictions of margin lines, tooth stumps, and/or accumulations (e.g., blood and/or saliva accumulations) along with corresponding identifications thereof.\",\n \"Indication regarding unclear margin line may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or a virtual 3D model constitute a margin line (e.g., an upper portion of a tooth stump which is to receive prosthetic crown).\",\n \"Additionally, or alternatively, the processing logic may compare the margin line of under consideration patient scan data and/or one or more virtual 3D models of the patient to the margin line of an earlier-in-the-visit and/or dental record data to detect a margin line change suggestive of the buildup of blood, saliva, and/or like accumulation on the margin.\",\n \"The processing logic may consider found margin lines together with found blood, saliva, and/or like accumulation to locate instances of such accumulation appearing in the vicinity of such margin lines, and to conclude such instances to constitute unclear margin lines.\",\n \"Pooled patient data and/or pedagogical patient data may include depictions of incisor edges and/or of double incisor edges along with corresponding identifications thereof.\",\n \"Indication regarding double incisor edge surface conflict may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or virtual 3D models include one or more incisor edges, and further to conclude such incisor edges to deviate, in a fashion suggestive of double incisor edge, from incisor edges indicated by the pooled and/or pedagogical data to be proper incisor edges.\",\n \"Pooled patient data and/or pedagogical patient data may include depictions of tooth occlusion contacts and/or bite relations along with corresponding identifications thereof.\",\n \"Indication regarding tooth occlusion contacts and/or bite relation may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or virtual 3D models constitute tooth occlusion contacts and/or bite relation.\",\n \"The processing logic may further access one or more treatment goals (e.g., a desired degree of occlusion with respect to one or more indicated teeth and/or a desired bite relation).\",\n \"Such goals may be provided by a practitioner (e.g., via a user interface) and/or be retrieved from an accessible data store.\",\n \"The processing logic may then compare the tooth occlusion contacts and/or bite relation of the under consideration patient scan data and/or one or more virtual 3D models of the patient to the tooth occlusion contacts and/or bite relation of earlier-in-the-visit and/or dental record data to detect the degree of change (which might be null) of tooth occlusion contacts and/or bite relation.\",\n \"The processing logic may then compare the determined change to a treatment goal and ascertain whether the change causes satisfaction of the treatment goal, or whether the change serves to approach or depart the goal.\",\n \"The indication may include notification as to whether or not the change approaches, departs, meets the treatment goal, or results in no change relative to the treatment goal.\",\n \"As one illustration, the aforementioned regarding tooth occlusion contacts may correspond to a circumstance in which a practitioner indicates a tooth occlusion contact treatment goal to the processing logic, has the processing logic receive scan data depicting a starting occlusion contact state of the patient, performs a dental procedure which serves to potentially alter that occlusion contact state, and that has the processing logic receive scan data depicting the post-procedure occlusion contact state.\",\n \"Via processing in vein of that which is discussed above, the practitioner may receive indication as to whether his procedure has met the treatment goal, caused progress towards the treatment goal, caused departure from the treatment goal, or resulted in no change relative to the treatment goal.\",\n \"As another illustration, the aforementioned regarding bite relation may correspond to a circumstance in which a practitioner indicates a bite relation treatment goal to the processing logic, has the processing logic receive scan data depicting a starting bite relation state of the patient, applies an orthotic alignment device to the patient, and has the patient return at a later data.\",\n \"Then, at the later date, the practitioner has the processing logic receive scan data depicting the post-device-application bite relation state.\",\n \"Via processing in vein of that which is discussed above, the practitioner may receive indication as to whether his device application has caused the treatment goal to be met, caused progress towards the treatment goal, caused departure from the treatment goal, or has resulted in no change relative to the treatment goal.\",\n \"Pooled patient data and/or pedagogical patient data may include depictions of tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries along with corresponding identifications thereof.\",\n \"Indication regarding tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize that patient scan data and/or one or more virtual 3D models constitute tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries.\",\n \"For example, the processing logic may employ pooled patient data and/or pedagogical patient data to recognize teeth and/or gingiva in intraoral images and/or virtual 3D models.\",\n \"The processing logic may then compare the teeth and/or gingivae of the intraoral images and/or virtual 3D models to the teeth and/or gingivae of earlier intraoral images, virtual 3D models and/or dental record data to detect change indicative of tooth breakage, tooth wear, gingival swelling, gingival recess, and/or caries.\",\n \"In performing such detection the processing logic may or may not perform image analysis (e.g., considering a discovered change to be indicative of tooth breakage in the case where the change possesses a jagged edge) and/or consult patient data and/or pedagogical patient data (e.g., considering a discovered change to be indicative of tooth breakage in the case where the change matches one or more items indicated by the patient data and/or pedagogical patient data to constitute breakage).\",\n \"Indication concerning tooth breakage and/or caries may involve the processing logic performing direct analysis.\",\n \"The processing logic may additionally or alternatively employ pooled patient data and/or pedagogical patient data to recognize that the patient scan data and/or one or more virtual 3D models includes areas that constitute teeth.\",\n \"The processing logic may determine (e.g., via edge recognition) one or more of such teeth to possess one or more jagged edges.\",\n \"The processing logic may consider such jagged edges to be indicative of tooth breakage.\",\n \"The processing logic may determine (e.g., via shape recognition) one or more of such teeth to possess spots and/or lacunae.\",\n \"The processing logic may consider such spots and/or lacunae to be indicative of caries.\",\n \"The indications regarding foreign object recognition assistance provided by the processing logic may include indications concerning fillings, implants, and/or bridges.\",\n \"Pooled patient data and/or pedagogical patient data may include depictions of fillings, implants, and/or bridges along with corresponding identifications thereof.\",\n \"Indication regarding fillings, implants, and/or bridges may involve the processing logic employing pooled patient data and/or pedagogical patient data to recognize patient scan data and/or virtual 3D models which constitute fillings, implants, and/or bridges.\",\n \"Indication regarding fillings, implants, and/or bridges may involve the processing logic comparing the under consideration patient scan data and/or one or more virtual 3D models of the patient to earlier in the patient visit data, dental record data of the patient, and/or data of the patient from prior to the at-hand patient visit.\",\n \"The processing logic may consider objects which appear in the under consideration patient scan data and/or one or more virtual 3D models of the patient but not in the earlier in the patient visit data, dental record data of the patient, and/or data of the patient from prior to the at-hand patient visit to be possible foreign objects.\",\n \"Such functionality might, for instance, be implemented from the viewpoint that new objects appearing in a patient's mouth have a certain likelihood of being foreign objects rather than naturally-occurring ones.\",\n \"The processing logic may allow a practitioner to respond (e.g., via user interface) to such an indication with agreement and/or disagreement that processing logic-identified objects are foreign objects.\",\n \"FIG.\",\n \"4A illustrates an example scanned portion of a dental arch 400 during an intraoral scan session.\",\n \"The dental arch 400 includes gums 404 and multiple teeth 410, 420.Multiple intraoral images 425, 430, 435, 440 have been taken of a dental site of a patient.\",\n \"Each of the intraoral images 425-440 may have been generated by an intraoral scanner having a particular distance from the dental surface being imaged.\",\n \"At the particular distance, the intraoral images 425-440 have a particular scan area and scan depth.\",\n \"The shape and size of the scan area will generally depend on the scanner, and is herein represented by a rectangle.\",\n \"Each image may have its own reference coordinate system and origin.\",\n \"Each intraoral image may be generated by a scanner at a particular position (scanning station).\",\n \"The location and orientation of scanning stations may be selected such that together the intraoral images adequately cover an entire target zone.\",\n \"Preferably, scanning stations are selected such that there is overlap between the intraoral images 425-440 as shown.\",\n \"Typically, the selected scanning stations will differ when different scanners are used for the same target area, depending on the capture characteristics of the scanner used.\",\n \"Thus, a scanner capable of scanning a larger dental area with each scan (e.g., having a larger field of view) will use fewer scanning stations than a scanner that is only capable of capturing 3D data of a relatively smaller dental surface.\",\n \"Similarly, the number and disposition of scanning stations for a scanner having a rectangular scanning grid (and thus providing projected scanning areas in the form of corresponding rectangles) will typically be different from those for a scanner having a circular or triangular scanning grid (which would provide projected scanning areas in the form of corresponding circles or triangles, respectively).\",\n \"Intraoral areas of interest 448 and 447 have been computed as discussed herein above.\",\n \"In the illustrated embodiment, the intraoral areas of interest 447, 448 represent portions of the patient's dental site that lack image data.\",\n \"FIG.\",\n \"4B illustrates a scanned portion of a dental arch 402 that is an update of dental arch 400.Additional intraoral images 458, 459 have been taken to provide image data corresponding to intraoral areas of interest 447, 448.Accordingly, intraoral areas of interest 447, 448 are no longer shown in dental arch 402.Additional intraoral images 460, 462, 464, 466 have also been generated.\",\n \"These additional intraoral images 460-466 reveal teeth 450, 452, 454, 456.New intraoral areas of interest 470, 472 are also determined based on the additional intraoral images 460-466.A practitioner may generate still further intraoral images to resolve intraoral areas of interest 470, 472 and to provide data for a full dental arch.\",\n \"FIG.\",\n \"5A illustrates an example image of a dental arch 500 showing areas of interest.\",\n \"The image of the dental arch 500 may be constructed from one or more intraoral scans prior to generation of a virtual 3D model.\",\n \"Alternatively, the image of the dental arch 500 may be constructed from one or more scans of a physical model of a dental arch.\",\n \"The image of the dental arch 500 includes gums 509 and multiple teeth 505-508.Multiple areas of interest 509, 515, 525 are also shown in the image of the dental arch 500.These areas of interest 509, 515, 525 represent missing scan data that satisfies a clinical importance criterion.\",\n \"FIG.\",\n \"5B illustrates an example image of a dental arch 550 showing areas of interest and indications pointing to the areas of interest.\",\n \"The image of the dental arch 550 may be constructed from one or more intraoral scans.\",\n \"Alternatively, the image of the dental arch 550 may be constructed from one or more scans of a physical model of a dental arch.\",\n \"The image of the dental arch 550 includes gums and multiple teeth.\",\n \"Multiple areas of interest 562, 564, 566, 568, 570, 572 are also shown in the image of the dental arch 550.These areas of interest 562, 564, 566, 568, 570, 572 represent missing scan data that satisfies a clinical importance criterion (e.g., intraoral areas of interest greater than a threshold size or having one or more dimensions that violate a geometric criterion).\",\n \"However, some areas of interest 562, 570 are largely occluded in the example image of the dental arch 550.Additionally, there are other areas of interest that are completely hidden.\",\n \"To ensure that a dental practitioner is made aware of such areas of interest, an indicator such as a flag is presented for each area of interest.\",\n \"For example, the image of the dental arch 550 includes flags 552-559.These flags call the dental practitioners attention to areas of interest that should be addressed regardless of a present view.\",\n \"FIG.\",\n \"5C illustrates another example image of a dental arch 575 showing areas of interest and indications pointing to the areas of interest.\",\n \"The image of the dental arch 575 may be constructed from one or more intraoral scans.\",\n \"Alternatively, the image of the dental arch 575 may be constructed from one or more scans of a physical model of a dental arch.\",\n \"The image of the dental arch 575 includes gums and multiple teeth.\",\n \"Multiple areas of interest 576-584 are also shown in the image of the dental arch 575.These areas of interest 576-584 represent tooth wear that is identified based on a comparison between images and/or a virtual 3D model generated at a first date and images and/or a virtual 3D model generated at a second date.\",\n \"However, some areas of interest 576, 578 are largely occluded in the example image of the dental arch 575.To ensure that a dental practitioner is made aware of such areas of interest, an indicator such as a flag is presented for each area of interest.\",\n \"For example, the image of the dental arch 575 includes flags 586-594.These flags call the dental practitioners attention to areas of interest that should be addressed regardless of a present view.\",\n \"FIG.\",\n \"6 illustrates a screen shot 600 of an intraoral scan application (e.g., of intraoral scan application 108 of FIG.\",\n \"1), in accordance with embodiments of the present invention.\",\n \"The screen shot 600 shows multiple menus 602, 604, 606 for performing various operations.\",\n \"Menu 602 provides icons that can be selected to perform global operations such as changing settings, saving data, obtaining assistance, generating a virtual 3D model from gathered intraoral images, switching to a view mode, and so forth.\",\n \"Menu 604 provides icons for adjusting a view 607 of a scanned dental site 608.Menu 604 may include icons for panning, zooming, rotating, and so forth.\",\n \"The view 607 of the scanned dental site 608 includes a dental arch made up of one or more previous intraoral images that have been registered and/aligned with one another.\",\n \"The view 607 further includes an indication of a latest intraoral image 610 that has been added to the dental arch.\",\n \"The dental ach includes multiple voids based on incomplete scan data.\",\n \"Such voids are one type of intraoral area of interest that is called out by flags 612-624.Menu 606 includes scanning instructions that enable a user to proceed to a next scan, redo a last scan, rescan a segment, and so on.\",\n \"A user may rescan one or more segments to provide scan data that can fill in the voids that are called out by flags 612-624.This can ensure that a final virtual 3D model that is generated based on the intraoral images is of high quality.\",\n \"FIG.\",\n \"7 illustrates a diagrammatic representation of a machine in the example form of a computing device 700 within which a set of instructions, for causing the machine to perform any one or more of the methodologies discussed herein, may be executed.\",\n \"In alternative embodiments, the machine may be connected (e.g., networked) to other machines in a Local Area Network (LAN), an intranet, an extranet, or the Internet.\",\n \"The machine may operate in the capacity of a server or a client machine in a client-server network environment, or as a peer machine in a peer-to-peer (or distributed) network environment.\",\n \"The machine may be a personal computer (PC), a tablet computer, a set-top box (STB), a Personal Digital Assistant (PDA), a cellular telephone, a web appliance, a server, a network router, switch or bridge, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine.\",\n \"Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines (e.g., computers) that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein.\",\n \"The example computing device 700 includes a processing device 702, a main memory 704 (e.g., read-only memory (ROM), flash memory, dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), etc.\",\n \"), a static memory 706 (e.g., flash memory, static random access memory (SRAM), etc.\",\n \"), and a secondary memory (e.g., a data storage device 728), which communicate with each other via a bus 708.Processing device 702 represents one or more general-purpose processors such as a microprocessor, central processing unit, or the like.\",\n \"More particularly, the processing device 702 may be a complex instruction set computing (CISC) microprocessor, reduced instruction set computing (RISC) microprocessor, very long instruction word (VLIW) microprocessor, processor implementing other instruction sets, or processors implementing a combination of instruction sets.\",\n \"Processing device 702 may also be one or more special-purpose processing devices such as an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), network processor, or the like.\",\n \"Processing device 702 is configured to execute the processing logic (instructions 726) for performing operations and steps discussed herein.\",\n \"The computing device 700 may further include a network interface device 722 for communicating with a network 764.The computing device 700 also may include a video display unit 710 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)), an alphanumeric input device 712 (e.g., a keyboard), a cursor control device 714 (e.g., a mouse), and a signal generation device 720 (e.g., a speaker).\",\n \"The data storage device 728 may include a machine-readable storage medium (or more specifically a non-transitory computer-readable storage medium) 724 on which is stored one or more sets of instructions 726 embodying any one or more of the methodologies or functions described herein.\",\n \"A non-transitory storage medium refers to a storage medium other than a carrier wave.\",\n \"The instructions 726 may also reside, completely or at least partially, within the main memory 704 and/or within the processing device 702 during execution thereof by the computer device 700, the main memory 704 and the processing device 702 also constituting computer-readable storage media.\",\n \"The computer-readable storage medium 724 may also be used to store an intraoral scan application 750, which may correspond to the similarly named component of FIG.\",\n \"1.The computer readable storage medium 724 may also store a software library containing methods for an intraoral scan application 750.While the computer-readable storage medium 724 is shown in an example embodiment to be a single medium, the term “computer-readable storage medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the one or more sets of instructions.\",\n \"The term “computer-readable storage medium” shall also be taken to include any medium other than a carrier wave that is capable of storing or encoding a set of instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies of the present invention.\",\n \"The term “computer-readable storage medium” shall accordingly be taken to include, but not be limited to, solid-state memories, and optical and magnetic media.\",\n \"It is to be understood that the above description is intended to be illustrative, and not restrictive.\",\n \"Many other embodiments will be apparent upon reading and understanding the above description.\",\n \"Although embodiments of the present invention have been described with reference to specific example embodiments, it will be recognized that the invention is not limited to the embodiments described, but can be practiced with modification and alteration within the spirit and scope of the appended claims.\",\n \"Accordingly, the specification and drawings are to be regarded in an illustrative sense rather than a restrictive sense.\",\n \"The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874686"}}},{"rowIdx":4494671,"cells":{"text":{"kind":"list like","value":[["SENSING FOR COMPENSATION OF PIXEL VOLTAGES","A display device may include rows of pixels that may display image data on a display and a circuit.","The circuit may perform a progressive scan across the rows of pixels to display the image data using a plurality of pixels, supply test data to a pixel of plurality of pixels that corresponds to a first row of the rows of pixels during one frame of the progressive scan, and initiate a sensing period for determining one or more sensitivity properties associated with the pixel based on the performance of the pixel with respect to the test data in response to receiving a pulse of a first global signal.","The circuit may then end the sensing period in response to receiving a second global signal and resume the progressive scan across the rows of pixels to display the image data after the sensing period ends."],["1.A display device, comprising: a plurality of rows of pixels configured to display image data on a display; and a circuit configured to: perform a progressive scan across a plurality of rows of pixels to display the image data using a plurality of pixels; supply test data to a pixel of plurality of pixels that corresponds to a first row of the plurality of rows of pixels during one frame of the progressive scan; initiate a sensing period for determining one or more sensitivity properties associated with the pixel based on the performance of the pixel with respect to the test data in response to receiving a pulse of a first global signal; end the sensing period in response to receiving a second global signal; and resume the progressive scan across the plurality of rows of pixels to display the image data after the sensing period ends.","2.The display device of claim 1, wherein the pulse of the first global signal is configured to cause an emission turn-on signal to be provided to the pixel via the circuit.","3.The display device of claim 2, wherein the first global signal is configured to delay the emission turn-on signal from being provided to the pixel.","4.The display device of claim 2, wherein the circuit is configured to disconnect the emission turn-on signal from the pixel based on the second global signal.","5.The display device of claim 4, wherein the second global signal is between 1 and 2 μs.","6.The display device of claim 1, wherein the circuit is configured to supply a data voltage to the pixel based on the image data after supplying the test data to the pixel.","7.The display device of claim 1, wherein the one or more sensitivity properties comprise luminance values, color values, power values, or any combination thereof associated with the pixel.","8.A circuit, comprising: a plurality of semiconductor devices configured to generate a plurality of emission turn-on signals configured to enable a pixel of a row of pixels in a display to receive a plurality of test voltages during a single frame of image data, wherein the plurality of semiconductor devices is configured to: receive a first pulse of a first global signal, wherein the first pulse of the first global signal is configured to cause the pixel to receive a first emission turn-on signal of the plurality of emission turn-on signals, wherein the first emission turn-on signal is configured to initiate a sensing period for determining a first set of sensitivity properties associated with the pixel based on the performance of the pixel with respect to a first test voltage of the plurality of test voltages; and receive a first pulse of a second global signal, wherein the first pulse of the second global signal is configured to end the sensing period; and a processor configured to determine a compensation factor for a data voltage provided to the pixel based on the first set of sensitivity properties.","9.The circuit of claim 8, wherein the plurality of semiconductor devices is configured to: receive a second pulse of the first global signal, wherein the second pulse of the first global signal is configured to cause the pixel to receive a second emission turn-on signal of the plurality of emission turn-on signals, wherein the second emission turn-on signal is configured to initiate a second sensing period for determining a second set of sensitivity properties associated with the pixel based on the performance of the pixel with respect to a second test voltage of the plurality of test voltages; and receive a second pulse of the second global signal, wherein the second pulse of the second global signal is configured to end the second sensing period.","10.The circuit of claim 9, wherein the processor is configured to determine the compensation factor for the data voltage provided to the pixel based on the first and second sets of sensitivity properties.","11.The circuit of claim 8, wherein the first pulse of the second global signal comprises less time than an off pulse of an emission clock signal provided to the plurality of semiconductor devices.","12.The circuit of claim 8, wherein the first pulse of the second global signal is between 1 and 2 μs.","13.The circuit of claim 8, wherein the first emission turn-on signal is configured to start a transmission of a second emission turn-on signal in second row of pixels following the row of pixels.","14.The circuit of claim 8, comprising a set of circuit components configured to adjust the data voltage provided to the pixel based on the compensation factor.","15.A method, comprising: performing, via circuitry, a progressive scan across a plurality of rows of pixels to display the image data using a plurality of pixels in a display; supplying, via the circuitry, test data to at least one pixel of plurality of pixels that corresponds to a first row of a plurality of rows of pixels during the progressive scan; obtaining, via the circuitry, a set of sensitivity properties associated with the at least one pixel based on the performance of the at least one pixel when the test data is provided to the at least one pixel in response to a first pulse of a first global signal provided to the circuitry; and resuming, via the circuitry, the progressive scan at the at least one pixel to display the image data for the at least one pixel and a remaining portion of the plurality of pixels in the first row and remaining rows of the plurality of rows in response to a second global signal provided to the circuitry.","16.The method of claim 15, comprising providing, via the circuitry, the test data to the at least one pixel prior to the first pulse and providing a data voltage to the at least one pixel after the first pulse.","17.The method of claim 15, comprising delaying, via the circuitry, an emission signal provided to the first row during the progressive scan based on the first global signal.","18.The method of claim 15, wherein the second global signal comprises a pulse between 1 and 2 μs.","19.The method of claim 15, comprising determining, via the circuitry, a compensation factor for data voltage provided to the at least one pixel based on the set of sensitivity properties.","20.The method of claim 19, comprising supplying, via the circuitry, the at least one pixel with an adjusted data voltage based on the data voltage and the compensation factor."],["<SOH> BACKGROUND <EOH>The present disclosure relates to systems and methods for sensing characteristics of pixels in electronic display devices to compensate for non-uniformity in luminance or color of a pixel with respect to other pixels in the electronic display device.","This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present techniques, which are described and/or claimed below.","This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.","Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.","As electronic displays are employed in a variety of electronic devices, such as mobile phones, televisions, tablet computing devices, and the like, manufacturers of the electronic displays continuously seek ways to improve the consistency of colors depicted on the electronic display devices.","For example, given variations in manufacturing, various noise sources present within a display device, or various ambient conditions in which each display device operates, different pixels within a display device might emit a different color value or gray level even when provided with the same electrical input.","It is desirable, however, for the pixels to uniformly depict the same color or gray level when the pixels programmed to do so to avoid visual display artifacts due to inconsistent color."],["<SOH> SUMMARY <EOH>A summary of certain embodiments disclosed herein is set forth below.","It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.","Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.","In certain electronic display devices, light-emitting diodes such as organic light-emitting diodes (OLEDs), micro-LEDs (μLEDs), or active matrix organic light-emitting diodes (AMOLEDs) may be employed as pixels to depict a range of gray levels for display.","However, due to various properties associated with the operation of these pixels within the display device, a particular gray level output by one pixel in a display device may be different from a gray level output by another pixel in the same display device upon receiving the same electrical input.","As such, the electrical inputs may be calibrated to account for these differences by sensing the electrical values that get stored into the pixels and adjusting the input electrical values accordingly.","Since a more accurate and/or precise determination of the sensed electrical value in the pixel may be used to obtain a more consistent and/or exact calibration, the present disclosure details various systems and methods that may be employed to implement a sensing scheme to sense variations in pixel properties (e.g., current, voltage) and modify a data voltage applied to a respective pixel based on the sensed variation.","The corrected data voltage, when applied to the respective pixel, may compensate for the variations in the pixel properties to achieve a more uniform image that will be depicted on the display device.","In one embodiment, a sensing system of a display device may sense a pixel voltage applied to a respective pixel during a panel scan for data program.","That is, the sensing system may transmit pixel data to each row of pixels during a panel scan.","During the panel scan for one row of pixels, the sensing system may interrupt the panel scan for a portion of the panel scan to send a first data voltage (e.g., known test voltage) to drive a thin film transistor (TFT) of a respective pixel.","After the first data voltage is transmitted to the TFT, the sensing system may determine the sensitivity properties of the respective pixel based on the detected power output by the respective pixel.","The sensitivity properties may include current or voltage properties related to the respective pixel that vary as a function of certain pixel properties.","The variation in the current or voltage properties may be sensed, amplified, digitized, and applied as a correction factors of the pixel data voltage to compensate for the pixel property variations.","After determining the sensitivity properties for the respective pixel, the sensing system may then resume the panel scan for the remaining portion of the one row of pixels.","As such, the sensing system may transmit data voltages to the remaining pixels of the display device.","In certain embodiments, the sensing system may perform the sensing scheme described above a number of times and may provide the results of the sensing scheme to another component that may determine a compensation voltage for each respective pixel.","That is, based on the results of the sensing scheme, a processor (or other like device) may determine an amount of disparity exists between the first data voltage used to drive the respective pixel during a sensing period and the resulting power emitted by the respective pixel.","Based on the detected discrepancies over each sensing period, the processor may determine a compensation voltage to apply to the respective pixel to cause the respective pixel to emit a desired (e.g., uniform) color and/or luminance with respect to the other pixels of the display device.","To interrupt the panel scan to perform the sensing scheme described above, the sensing system may employ a pixel driving circuit for each respective pixel that uses a data input, two scan line inputs (Scan 1 , Scan 2 ), and two emission turn-on inputs (EM 1 , EM 2 ) to implement a pixel driving scheme that uses a portion of a panel scan of a row of pixels to send a data signal (e.g., voltage) used to determine the sensitivity properties of a respective pixel and then transmit the appropriate data signal, as per the desired image data to be depicted, to the respective pixel.","In one embodiment, the sensing system may coordinate the two scan line inputs (Scan 1 , Scan 2 ) and the two emission turn-on inputs (EM 1 , EM 2 ) to cause the pixel driving circuit to suspend the data transmission to a respective pixel for a period of time when the sensing operation is performed.","After the sensing operation is performed, the pixel driving circuit may trigger the data transmission to resume for the remaining pixels of the respective row of pixels.","By suspending the data programming of a respective pixel and performing a real-time sensing operations for the respective pixel during the panel scan, the sensing system determines the sensitivity properties of each pixel in the display device while the display device is displaying image data.","In this way, the sensing system may provide data to other components that may be used to determine compensation values (e.g., voltage) to provide each respective pixel based on the properties of the respective pixel during operation (e.g., display of image data).","As such, the compensated values account for a variety of sources for pixel color and luminance variations among the pixels of the display.","Moreover, the display driver may adjust the original pixel data provides to the pixels based on the compensated values while the display device is in operation to compensate for the determined sensitivity properties.","Various refinements of the features noted above may exist in relation to various aspects of the present disclosure.","Further features may also be incorporated in these various aspects as well.","These refinements and additional features may exist individually or in any combination.","For instance, various features discussed below in relation to one or more of the illustrated embodiments may be incorporated into any of the above-described aspects of the present disclosure alone or in any combination.","The brief summary presented above is intended only to familiarize the reader with certain aspects and contexts of embodiments of the present disclosure without limitation to the claimed subject matter."],["CROSS REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of U.S. patent application Ser.","No.","15/271,115, filed Sep. 20, 2016, and entitled “SENSING FOR COMPENSATION OF PIXEL VOLTAGES,” the disclosure of which is incorporated herein by reference in its entirety and for all purposes.","BACKGROUND The present disclosure relates to systems and methods for sensing characteristics of pixels in electronic display devices to compensate for non-uniformity in luminance or color of a pixel with respect to other pixels in the electronic display device.","This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present techniques, which are described and/or claimed below.","This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.","Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.","As electronic displays are employed in a variety of electronic devices, such as mobile phones, televisions, tablet computing devices, and the like, manufacturers of the electronic displays continuously seek ways to improve the consistency of colors depicted on the electronic display devices.","For example, given variations in manufacturing, various noise sources present within a display device, or various ambient conditions in which each display device operates, different pixels within a display device might emit a different color value or gray level even when provided with the same electrical input.","It is desirable, however, for the pixels to uniformly depict the same color or gray level when the pixels programmed to do so to avoid visual display artifacts due to inconsistent color.","SUMMARY A summary of certain embodiments disclosed herein is set forth below.","It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.","Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.","In certain electronic display devices, light-emitting diodes such as organic light-emitting diodes (OLEDs), micro-LEDs (μLEDs), or active matrix organic light-emitting diodes (AMOLEDs) may be employed as pixels to depict a range of gray levels for display.","However, due to various properties associated with the operation of these pixels within the display device, a particular gray level output by one pixel in a display device may be different from a gray level output by another pixel in the same display device upon receiving the same electrical input.","As such, the electrical inputs may be calibrated to account for these differences by sensing the electrical values that get stored into the pixels and adjusting the input electrical values accordingly.","Since a more accurate and/or precise determination of the sensed electrical value in the pixel may be used to obtain a more consistent and/or exact calibration, the present disclosure details various systems and methods that may be employed to implement a sensing scheme to sense variations in pixel properties (e.g., current, voltage) and modify a data voltage applied to a respective pixel based on the sensed variation.","The corrected data voltage, when applied to the respective pixel, may compensate for the variations in the pixel properties to achieve a more uniform image that will be depicted on the display device.","In one embodiment, a sensing system of a display device may sense a pixel voltage applied to a respective pixel during a panel scan for data program.","That is, the sensing system may transmit pixel data to each row of pixels during a panel scan.","During the panel scan for one row of pixels, the sensing system may interrupt the panel scan for a portion of the panel scan to send a first data voltage (e.g., known test voltage) to drive a thin film transistor (TFT) of a respective pixel.","After the first data voltage is transmitted to the TFT, the sensing system may determine the sensitivity properties of the respective pixel based on the detected power output by the respective pixel.","The sensitivity properties may include current or voltage properties related to the respective pixel that vary as a function of certain pixel properties.","The variation in the current or voltage properties may be sensed, amplified, digitized, and applied as a correction factors of the pixel data voltage to compensate for the pixel property variations.","After determining the sensitivity properties for the respective pixel, the sensing system may then resume the panel scan for the remaining portion of the one row of pixels.","As such, the sensing system may transmit data voltages to the remaining pixels of the display device.","In certain embodiments, the sensing system may perform the sensing scheme described above a number of times and may provide the results of the sensing scheme to another component that may determine a compensation voltage for each respective pixel.","That is, based on the results of the sensing scheme, a processor (or other like device) may determine an amount of disparity exists between the first data voltage used to drive the respective pixel during a sensing period and the resulting power emitted by the respective pixel.","Based on the detected discrepancies over each sensing period, the processor may determine a compensation voltage to apply to the respective pixel to cause the respective pixel to emit a desired (e.g., uniform) color and/or luminance with respect to the other pixels of the display device.","To interrupt the panel scan to perform the sensing scheme described above, the sensing system may employ a pixel driving circuit for each respective pixel that uses a data input, two scan line inputs (Scan1, Scan2), and two emission turn-on inputs (EM1, EM2) to implement a pixel driving scheme that uses a portion of a panel scan of a row of pixels to send a data signal (e.g., voltage) used to determine the sensitivity properties of a respective pixel and then transmit the appropriate data signal, as per the desired image data to be depicted, to the respective pixel.","In one embodiment, the sensing system may coordinate the two scan line inputs (Scan1, Scan2) and the two emission turn-on inputs (EM1, EM2) to cause the pixel driving circuit to suspend the data transmission to a respective pixel for a period of time when the sensing operation is performed.","After the sensing operation is performed, the pixel driving circuit may trigger the data transmission to resume for the remaining pixels of the respective row of pixels.","By suspending the data programming of a respective pixel and performing a real-time sensing operations for the respective pixel during the panel scan, the sensing system determines the sensitivity properties of each pixel in the display device while the display device is displaying image data.","In this way, the sensing system may provide data to other components that may be used to determine compensation values (e.g., voltage) to provide each respective pixel based on the properties of the respective pixel during operation (e.g., display of image data).","As such, the compensated values account for a variety of sources for pixel color and luminance variations among the pixels of the display.","Moreover, the display driver may adjust the original pixel data provides to the pixels based on the compensated values while the display device is in operation to compensate for the determined sensitivity properties.","Various refinements of the features noted above may exist in relation to various aspects of the present disclosure.","Further features may also be incorporated in these various aspects as well.","These refinements and additional features may exist individually or in any combination.","For instance, various features discussed below in relation to one or more of the illustrated embodiments may be incorporated into any of the above-described aspects of the present disclosure alone or in any combination.","The brief summary presented above is intended only to familiarize the reader with certain aspects and contexts of embodiments of the present disclosure without limitation to the claimed subject matter.","BRIEF DESCRIPTION OF THE DRAWINGS Various aspects of this disclosure may be better understood upon reading the following detailed description and upon reference to the drawings in which: FIG.","1 is a simplified block diagram of components of an electronic device that may depict image data on a display, in accordance with embodiments described herein; FIG.","2 is a perspective view of the electronic device of FIG.","1 in the form of a notebook computing device, in accordance with embodiments described herein; FIG.","3 is a front view of the electronic device of FIG.","1 in the form of a desktop computing device, in accordance with embodiments described herein; FIG.","4 is a front view of the electronic device of FIG.","1 in the form of a handheld portable electronic device, in accordance with embodiments described herein; FIG.","5 is a front view of the electronic device of FIG.","1 in the form of a tablet computing device, in accordance with embodiments described herein; FIG.","6 is a circuit diagram of an array of self-emissive pixels of the electronic display of the electronic device of FIG.","1, in accordance with aspects of the present disclosure; FIG.","7 is an example of a progressive scan that includes a sensing period implemented on a display of the electronic device of FIG.","1, in accordance with embodiments described herein; FIG.","8 is a circuit diagram of a pixel driving circuit that implements a sensing period while a progressive panel scan is being performed in the display of the electronic device of FIG.","1, in accordance with aspects of the present disclosure; FIG.","9 is a collection of waveforms related to different driving schemes that may be implemented by the pixel driving circuit of FIG.","8 to provide a sensing period for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.","10 is a collection of waveforms related to emission signals provided to a number of rows of a display by the pixel driving circuit to provide a sensing period for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.","11 is a collection of waveforms related to scan signals provided to a number of rows of a display by the pixel driving circuit to provide a sensing period for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.","12 is a circuit diagram of an emission signal waveform generator that provides an emission signal to the respective pixel to a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.","13 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display at a first frequency while an emission signal for real-time sensing is provided to the display at a second frequency, in accordance with an embodiment; FIG.","14 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display at a first frequency while an adjusted emission signal for real-time sensing is provided to the display at a second frequency to accommodate the data program of a pixel in the top half of the display, in accordance with an embodiment; FIG.","15 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display at a first frequency while an adjusted emission signal for real-time sensing is provided to the display at a second frequency to accommodate the data program of a pixel in the bottom half of the display, in accordance with an embodiment; FIG.","16 illustrates an example block diagram of a number of emission signal waveform generators that may be employed to transmit emission signals to the display, in accordance with an embodiment; FIG.","17 illustrates an example circuit diagram for a input signal generator that may be coupled to the emission signal generator of FIG.","12, in accordance with aspects of the present disclosure; FIG.","18 illustrates a timing diagram that represents the operation of the input signal generator of FIG.","17, in accordance with an embodiment; FIG.","19 illustrates a circuit block diagram that represents how input signals may be provided to the input signal generator of FIG.","17, in accordance with an embodiment; FIG.","20 is a circuit diagram of an emission signal waveform generator that provides an emission signal to the respective pixel to a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.","21 illustrates a timing diagram related to emission signals provided to a number of rows of the display by the pixel driving circuit to provide multiple sensing periods for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; and FIG.","22 illustrates a timing diagram related to emission signals provided to a number of rows of the display by the pixel driving circuit to provide multiple sensing periods for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure.","DETAILED DESCRIPTION One or more specific embodiments of the present disclosure will be described below.","These described embodiments are only examples of the presently disclosed techniques.","Additionally, in an effort to provide a concise description of these embodiments, all features of an actual implementation may not be described in the specification.","It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another.","Moreover, it should be appreciated that such a development effort might be complex and time consuming, but may nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.","When introducing elements of various embodiments of the present disclosure, the articles “a,” “an,” and “the” are intended to mean that there are one or more of the elements.","The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.","Additionally, it should be understood that references to “one embodiment” or “an embodiment” of the present disclosure are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features.","Organic light-emitting diode (e.g., OLED, AMOLED) display panels provide opportunities to make thin, flexible, high-contrast, and color-rich electronic displays.","Generally, OLED display devices are current driven devices and use thin film transistors (TFTs) as current sources to provide certain amount of current to generate a certain level of luminance to a respective pixel electrode.","OLED Luminance to current ratio is generally represented as OLED efficiency with units: cd/A (Luminance/Current Density or (cd/m2)/(A/m2)).","Each respective TFT, which provides current to a respective pixel, may be controlled by gate to source voltage (Vgs), which is stored on a capacitor (Cst) electrically coupled to the LED of the pixel.","Generally, the application of the gate-to-source voltage Vgson the capacitor Cst is performed by programming voltage on a corresponding data line to be provided to a respective pixel.","However, when providing the voltage on a data line, several sources of noise or variation in the OLED-TFT system can result in either localized (e.g., in-panel) or global (e.g., panel to panel) non-uniformity in luminance or color.","Variations in the TFT system may be addressed in a number of ways.","For instance, an in-pixel compensation scheme may involve in-pixel sensing of a threshold voltage for a respective TFT before applying an intended data voltage to the respective pixel.","However, in-pixel sensing could involve multiple stages (e.g., initialization, sensing, and data application) for pixels in every row that correspond to relatively long row times (e.g., tens of microseconds).","With this in mind, displays with large number of rows that are driven at 120 Hz, as opposed to 60 Hz, provide relatively small row times (e.g., 3-4 μs) for programming.","As such, in-pixel compensation may not provide a feasible way to compensate voltages provided on a data line to the respective pixel.","In one embodiment, the data values provided to the pixels may be compensated using a compensation system.","For example, a display driver may employ a sensing system to implement voltage or current sensing schemes to sense operational variations among pixels, then digitize and transmit this information to processor(s) external to the display that adjust the image data before it is provided to the display.","In particular, the processor(s) may modify the image data based on the sensed variation and transmit the modified data voltage to the respective pixel.","The modified data voltage, when applied to the pixels, helps realize a uniform image.","To effectively perform the external compensation scheme generally described above, variations in pixel properties may be sensed at various times by the display driver when the display is off, during a blanking time, or during a progressive scan of the display device.","The main point for external compensation is that only data is programmed into the pixel during regular row time.","As such, the display driver may sense variations in various properties (e.g., color, luminance) of a pixel using relatively short row times, as compared to using in-pixel sensing schemes.","For fast sensing schemes (e.g., real time or near-real time), the display driver (e.g., sensing system) may embed a certain amount of time to sense variations in certain properties of a pixel in one row during the regular panel scan for data program of the respective pixel.","In order to embed this sensing time into the progressive panel scan, the display driver may employ different circuits to generate emission signals and scan signals in a particular manner to trigger a sensing period during the progressive scan and trigger the resumption of the progressive scan after the sensing period.","In one embodiment, the display driver may employ a pixel driving circuit for each respective pixel that uses four inputs (two scan inputs and two emission signal inputs) to pause the transmission of data to the respective pixel, sense the properties of the pixel, and resume the transmission of data to the respective during a progressive scan of the display.","As a result, the display driver may acquire information related to the properties of the respective pixel.","The display driver may then send the acquired information to a processor that may determine a compensation value for data signals provided to the respective pixel based on the information and provide corrected data signals to the display driver, which may provide the corrected data signals to the respective pixels.","Additional details with regard to the systems and techniques involved with enabling the display driver to perform fast (e.g., real-time or near real-time) sensing of pixel sensitivity properties during a progressive scan is detailed below with reference to FIGS.","1-22.By way of introduction, FIG.","1 is a block diagram illustrating an example of an electronic device 10 that may include the sensing system mentioned above.","The electronic device 10 may be any suitable electronic device, such as a laptop or desktop computer, a mobile phone, a digital media player, television, or the like.","By way of example, the electronic device 10 may be a portable electronic device, such as a model of an iPod® or iPhone®, available from Apple Inc. of Cupertino, Calif.","The electronic device 10 may be a desktop or notebook computer, such as a model of a MacBook®, MacBook® Pro, MacBook Air®, iMac®, Mac® Mini, or Mac Pro®, available from Apple Inc.","In other embodiments, electronic device 10 may be a model of an electronic device from another manufacturer.","As shown in FIG.","1, the electronic device 10 may include various components.","The functional blocks shown in FIG.","1 may represent hardware elements (including circuitry), software elements (including code stored on a computer-readable medium) or a combination of both hardware and software elements.","In the example of FIG.","1, the electronic device 10 includes input/output (I/O) ports 12, input structures 14, one or more processors 16, a memory 18, nonvolatile storage 20, networking device 22, power source 24, display 26, and one or more imaging devices 28.It should be appreciated, however, that the components illustrated in FIG.","1 are provided only as an example.","Other embodiments of the electronic device 10 may include more or fewer components.","To provide one example, some embodiments of the electronic device 10 may not include the imaging device(s) 28.Before continuing further, it should be noted that the system block diagram of the device 10 shown in FIG.","1 is intended to be a high-level control diagram depicting various components that may be included in such a device 10.That is, the connection lines between each individual component shown in FIG.","1 may not necessarily represent paths or directions through which data flows or is transmitted between various components of the device 10.Indeed, as discussed below, the depicted processor(s) 16 may, in some embodiments, include multiple processors, such as a main processor (e.g., CPU), and dedicated image and/or video processors.","In such embodiments, the processing of image data may be primarily handled by these dedicated processors, thus effectively offloading such tasks from a main processor (CPU).","Considering each of the components of FIG.","1, the I/O ports 12 may represent ports to connect to a variety of devices, such as a power source, an audio output device, or other electronic devices.","The input structures 14 may enable user input to the electronic device, and may include hardware keys, a touch-sensitive element of the display 26, and/or a microphone.","The processor(s) 16 may control the general operation of the device 10.For instance, the processor(s) 16 may execute an operating system, programs, user and application interfaces, and other functions of the electronic device 10.The processor(s) 16 may include one or more microprocessors and/or application-specific microprocessors (ASICs), or a combination of such processing components.","For example, the processor(s) 16 may include one or more instruction set (e.g., RISC) processors, as well as graphics processors (GPU), video processors, audio processors and/or related chip sets.","As may be appreciated, the processor(s) 16 may be coupled to one or more data buses for transferring data and instructions between various components of the device 10.In certain embodiments, the processor(s) 16 may provide the processing capability to execute an imaging applications on the electronic device 10, such as Photo Booth®, Aperture®, iPhoto®, Preview®, iMovie®, or Final Cut Pro® available from Apple Inc., or the “Camera” and/or “Photo” applications provided by Apple Inc. and available on some models of the iPhone®, iPod®, and iPad®.","A computer-readable medium, such as the memory 18 or the nonvolatile storage 20, may store the instructions or data to be processed by the processor(s) 16.The memory 18 may include any suitable memory device, such as random access memory (RAM) or read only memory (ROM).","The nonvolatile storage 20 may include flash memory, a hard drive, or any other optical, magnetic, and/or solid-state storage media.","The memory 18 and/or the nonvolatile storage 20 may store firmware, data files, image data, software programs and applications, and so forth.","The network device 22 may be a network controller or a network interface card (NIC), and may enable network communication over a local area network (LAN) (e.g., Wi-Fi), a personal area network (e.g., Bluetooth), and/or a wide area network (WAN) (e.g., a 3G or 4G data network).","The power source 24 of the device 10 may include a Li-ion battery and/or a power supply unit (PSU) to draw power from an electrical outlet or an alternating-current (AC) power supply.","The display 26 may display various images generated by device 10, such as a GUI for an operating system or image data (including still images and video data).","The display 26 may be any suitable type of display, such as a liquid crystal display (LCD), plasma display, or an organic light emitting diode (OLED) display, for example.","In one embodiment, the display 26 may include self-emissive pixels such as organic light emitting diodes (OLEDs) or micro-light-emitting-diodes (μ-LEDs).","Additionally, as mentioned above, the display 26 may include a touch-sensitive element that may represent an input structure 14 of the electronic device 10.The imaging device(s) 28 of the electronic device 10 may represent a digital camera that may acquire both still images and video.","Each imaging device 28 may include a lens and an image sensor capture and convert light into electrical signals.","In certain embodiments, the electronic device 10 may include a sensing system 30, which may include a chip, such as processor or ASIC, that may control various aspects of the display 26.For instance, the sensing system 30 may use a voltage signal that is to be provided to a pixel of the display 26 to sense the gray level depicted by the pixel.","Generally, when the same voltage signal is provided to each pixel of the display 26, each pixel should depict the same gray level.","However, due to various sources of noise, the same voltage being applied to a number of pixels may result in a variety of different gray levels depicted across the number of pixels.","As such, the sensing system 30 may sense a threshold voltage of each pixel, a power output by each pixel, an amount of current provided to each pixel and the sensing system 30 may send the threshold voltage to the processor(s) 16 or other circuit component to determine a compensation value for each pixel.","The processor(s) 16 may then adjust the data signals provided to each pixel based on the compensation value.","Although the sensing system 30 is described as providing the threshold voltage or sensitivity characteristics to another circuit component that may determine a compensation value, it should be noted that, in some embodiments, the sensing system 30 may also perform the determination of the compensation value and the modification of the data provided to a pixel based on the compensation value.","As mentioned above, the electronic device 10 may take any number of suitable forms.","Some examples of these possible forms appear in FIGS.","2-5.Turning to FIG.","2, a notebook computer 40 may include a housing 42, the display 26, the I/O ports 12, and the input structures 14.The input structures 14 may include a keyboard and a touchpad mouse that are integrated with the housing 42.Additionally, the input structure 14 may include various other buttons and/or switches which may be used to interact with the computer 40, such as to power on or start the computer, to operate a GUI or an application running on the computer 40, as well as adjust various other aspects relating to operation of the computer 40 (e.g., sound volume, display brightness, etc.).","The computer 40 may also include various I/O ports 12 that provide for connectivity to additional devices, as discussed above, such as a FireWire® or USB port, a high definition multimedia interface (HDMI) port, or any other type of port that is suitable for connecting to an external device.","Additionally, the computer 40 may include network connectivity (e.g., network device 22), memory (e.g., memory 18), and storage capabilities (e.g., storage device 20), as described above with respect to FIG.","1.The notebook computer 40 may include an integrated imaging device 28 (e.g., a camera).","In other embodiments, the notebook computer 40 may use an external camera (e.g., an external USB camera or a “webcam”) connected to one or more of the I/O ports 12 instead of or in addition to the integrated imaging device 28.In certain embodiments, the depicted notebook computer 40 may be a model of a MacBook®, MacBook® Pro, MacBook Air®, or PowerBook® available from Apple Inc.","In other embodiments, the computer 40 may be portable tablet computing device, such as a model of an iPad® from Apple Inc.","FIG.","3 shows the electronic device 10 in the form of a desktop computer 50.The desktop computer 50 may include a number of features that may be generally similar to those provided by the notebook computer 40 shown in FIG.","4, but may have a generally larger overall form factor.","As shown, the desktop computer 50 may be housed in an enclosure 42 that includes the display 26, as well as various other components discussed above with regard to the block diagram shown in FIG.","1.Further, the desktop computer 50 may include an external keyboard and mouse (input structures 14) that may be coupled to the computer 50 via one or more I/O ports 12 (e.g., USB) or may communicate with the computer 50 wirelessly (e.g., RF, Bluetooth, etc.).","The desktop computer 50 also includes an imaging device 28, which may be an integrated or external camera, as discussed above.","In certain embodiments, the depicted desktop computer 50 may be a model of an iMac®, Mac® mini, or Mac Pro®, available from Apple Inc.","The electronic device 10 may also take the form of portable handheld device 60 or 70, as shown in FIGS.","4 and 5.By way of example, the handheld device 60 or 70 may be a model of an iPod® or iPhone® available from Apple Inc.","The handheld device 60 or 70 includes an enclosure 42, which may function to protect the interior components from physical damage and to shield them from electromagnetic interference.","The enclosure 42 also includes various user input structures 14 through which a user may interface with the handheld device 60 or 70.Each input structure 14 may control various device functions when pressed or actuated.","As shown in FIGS.","4 and 5, the handheld device 60 or 70 may also include various I/O ports 12.For instance, the depicted I/O ports 12 may include a proprietary connection port for transmitting and receiving data files or for charging a power source 24.Further, the I/O ports 12 may also be used to output voltage, current, and power to other connected devices.","The display 26 may display images generated by the handheld device 60 or 70.For example, the display 26 may display system indicators that may indicate device power status, signal strength, external device connections, and so forth.","The display 26 may also display a GUI 52 that allows a user to interact with the device 60 or 70, as discussed above with reference to FIG.","3.The GUI 52 may include graphical elements, such as the icons, which may correspond to various applications that may be opened or executed upon detecting a user selection of a respective icon.","Having provided some context with regard to possible forms that the electronic device 10 may take, the present discussion will now focus on the sensing system 30 of FIG.","1.Generally, the brightness depicted by each respective pixel in the display 26 is generally controlled by varying an electric field associated with each respective pixel in the display 26.Keeping this in mind, FIG.","6 illustrates one embodiment of a circuit diagram of display 26 that may generate the electrical field that energizes each respective pixel and causes each respective pixel to emit light at an intensity corresponding to an applied voltage.","As shown, display 26 may include a self-emissive pixel array 80 having an array of self-emissive pixels 82.The self-emissive pixel array 80 is shown having a controller 84, a power driver 86A, an image driver 86B, and the array of self-emissive pixels 82.The self-emissive pixels 82 are driven by the power driver 86A and image driver 86B.","Each power driver 86A and image driver 86B may drive one or more self-emissive pixels 82.In some embodiments, the power driver 86A and the image driver 86B may include multiple channels for independently driving multiple self-emissive pixels 82.The self-emissive pixels may include any suitable light-emitting elements, such as organic light emitting diodes (OLEDs), micro-light-emitting-diodes (μ-LEDs), and the like.","The power driver 86A may be connected to the self-emissive pixels 82 by way of scan lines S0, S1, .",".",".","Sm-1, and Sm and driving lines D0, D1, .",".",".","Dm-1, and Dm.","The self-emissive pixels 82 receive on/off instructions through the scan lines S0, S1, Sm-1, and Sm and generate driving currents corresponding to data voltages transmitted from the driving lines D0, D1, .",".",".","Dm-1, and Dm.","The driving currents are applied to each self-emissive pixel 82 to emit light according to instructions from the image driver 86B through driving lines M0, M1, .",".",".","Mn-1, and Mn.","Both the power driver 86A and the image driver 86B transmit voltage signals through respective driving lines to operate each self-emissive pixel 82 at a state determined by the controller 84 to emit light.","Each driver may supply voltage signals at a duty cycle and/or amplitude sufficient to operate each self-emissive pixel 82.The controller 84 may control the color of the self-emissive pixels 82 using image data generated by the processor(s) 16 and stored into the memory 18 or provided directly from the processor(s) 16 to the controller 84.The sensing system 30 may provide a signal to the controller 84 to adjust the data signals transmitted to the self-emissive pixels 82 such that the self-emissive pixels 82 may depict substantially uniform color and luminance provided the same current input in accordance with the techniques that will be described in detail below.","With the foregoing in mind, FIG.","7 illustrates an embodiment in which the sensing system 30 may incorporate a sensing period during a progressive data scan of the display 26.In one embodiment, the controller 84 may send data (e.g., gray level voltages or currents) to each self-emissive pixel 82 via the power driver 86A on a row-by-row basis.","That is, the controller 84 may initially cause the power driver 86A to send data signals to the pixels 82 of the first row of pixels on the display 26, then the second row of pixels on the display 26, and so forth.","When incorporating a sensing period, the sensing system 30 may cause the controller 84 to pause the transmission of data via the power driver 86A for a period of time (e.g., 100 microseconds) during the progressive data scan at a particular row of the display (e.g., for row X).","The period of time in which the power driver 86A stops transmitting data corresponds to a sensing period 102.As shown in FIG.","7, the progressive scan 104 is performed between a back porch 106 and a front porch 108 of a frame 110 of data.","The progressive scan 104 is interrupted by the sensing period 102 while the power driver 86A is transmitting data to row X of the display 26.The sensing period 102 corresponds to a period of time in which a data signal may be transmitted to a respective pixel 82, and the sensing system 30 may determine certain sensitivity properties associated to the respective pixel 82 based on the pixel's reaction to the data signal.","The sensitivity properties may include, for example, the power, luminance, and color values of the respective pixel when driven by the provided data signal.","After the sensing period 102 expires, the sensing system 30 may cause the power driver 86A to resume the progressive scan 104.As such, the progressive scan 104 may be delayed by a data program delay 112 due to the sensing period 102.In order to incorporate the sensing period 102 into the progressive scans of a display, pixel driving circuitry, in one embodiment, the sensing system 30 may transmit data signals to pixels of each row of the display 26 and may pause its transmission of data signals during any portion of the progressive scan to determine the sensitivity properties of any pixel on any row of the display 26.Moreover, as sizes of displays 26 decrease and smaller bezel or border regions are available around the display 26, integrated gate driver circuits may be developed using a similar thin film transistor process as used to produce the transistors of the pixels 82.However, to effectively use the integrated gate driver circuits to incorporate the sensing period 102 into the progressive scan 104, the sensing system 30 may include a pixel driving circuit 120, as provided in FIG.","8, for each row of pixels of the display 26.Referring to FIG.","8, the pixel driving circuit 120 may include a number of semiconductor devices that may coordinate the transmission of data signals to a light-emitting diode (LED) 122 of a respective pixel 82.In one embodiment, the pixel driving circuit 120 may receive four input signals (e.g., emission signals 1 and 2, scan signals 1 and 2), which may be coordinated in a manner to cause the pixel driving circuit 120 to perform the progressive scan for a respective row of pixels of the display 26, pause the progressive scan for the respective row of pixels, transmit a test data signal used to determine the sensitivity properties of the LED 122, and resume the progressive scan being performed on the display 26.With this in mind, the pixel driving circuit 120 may include, in one embodiment, an N-type semiconductor device 124 and three P-type semiconductor devices 126, 128, and 130.Although the following description of the pixel driving circuit 120 will be discussed with the N-type semiconductor device 124 and the three P-type semiconductor devices 126, 128, and 130 described above, it should be noted that the pixel driving circuit 120 may be designed using any suitable combination of N-type or P-type semiconductor devices.","That is, depending of the type of semiconductor devices used within the pixel driving circuit 120, the waveforms or signals provided to each semiconductor device should be coordinated in a manner to cause the pixel driving circuit 120 to pause the progressive scan for a row of pixels, transmit a data test signal to a respective pixel, and resume the progressive scan.","As shown in FIG.","8, the N-type semiconductor device 124 and the three P-type semiconductor devices 126, 128, and 130 may be driven by a first scan signal (Scan1), a first emission signal (EM1), a second emission signal (EM2), and a second scan signal (Scan2), respectively.","Based on these four input signals, the pixel driving circuit 120 may implement a number of pixel driving schemes for a respective pixel.","Four example pixel-driving schemes are illustrated in FIG.","9.Each pixel driving scheme depicted in FIG.","9 illustrate sample waveforms that may be used for the four control signals: first scan signal (Scan1), first emission signal (EM1), a second emission signal (EM2), and second scan signal (Scan2).","The scan2 signal and the EM1 signal may be generated using standard shift register circuits where either the drain or the source of a buffer TFT is connected to a clock signal (CLK), and the other source or drain terminal is connected to the Scan2 line.","As such, the clock (CLK) waveforms may be modified to realize a desired waveform for the EM1 signal, which may then be derived as inversion of the Scan2 signal.","In each pixel-driving scheme, the sensing period 102 for detecting current flow through a drive TFT of a respective pixel 82 may be enabled based on the Scan2 input signal or the EM2 signal.","For instance, the sensing period 102 may be triggered by either the falling edge of the Scan2 input signal, as depicted in Drive Scheme 2, or on the falling edge of the EM2 signal, as depicted in Drive Schemes 3 and 4.Regardless of the pixel-driving scheme employed to enable a respective pixel 82 to have a sensing period 102, the EM2 signal and the Scan1 input signal may transmit a first pixel data voltage to the respective pixel and then transmit a second data voltage that corresponds to the image data being depicted via the progressive scan.","With this in mind, FIG.","10 illustrates example EM2 signal waveforms that may be transmitted to seven rows of pixels in the display 26, and FIG.","11 illustrates corresponding example Scan1 input signals that may be transmitted to the same seven rows of pixels.","Referring first to FIG.","10, a collection 140 of example EM2 signals for seven rows of the display 26 is illustrated.","It should be noted that the EM2 signals are provided to the P-type semiconductor device 128, and, as such, the P-type semiconductor device 128 is active or on when the EM2 signal is low.","As shown in FIG.","10, the EM2 signals provided to row 1-4 are slightly offset with each other.","That is, the EM2 signal provided to each row 2, 3, and 4 includes the same waveform but offset in time.","As such, emission is enabled progressively one after the other for rows 1 to 4.The emission time (Emit_Time) for each row may be fixed or variable depending upon ambient light level, grey scale, or other considerations.","To enable the sensing period 102 in row 5, the EM2 signal may be delayed by the amount of time that corresponds to the sensing period 102.That is, the emission turn-on signal (e.g., falling edge of EM2 signal) may be delayed by a certain amount of time (e.g., Sense_Time) for row 5.The progressive emission turn-on pattern then resumes at row 6 onwards, such that the turn-on period is offset by the same amount for each row of the display 26 during the following frame.","As such, the rows following row 5 may have a turn-off period (e.g., high EM2 value) for a shorter duration as compared to the rows preceding row 5 in the frame immediately following the frame that included the sensing period 102.It should again be noted that although the collection 140 of EM2 signal waveforms is detailed in FIG.","10 for the P-type semiconductor device (e.g., TFT) 128, it should be noted that the polarity of the EM2 signals can be reversed for N-type semiconductor devices.","During the sensing period 102, the pixel driving circuit 120 may transmit a Scan1 input signal that includes a first voltage that may be used to determine the sensitivity properties of the respective pixel 82 and a second voltage that corresponds to the data intended to be depicted during the progressive scan based on input image data.","With this in mind, FIG.","9 illustrates a collection 150 of Scan1 input signals that may be transmitted to seven rows of the display 26.The following description of FIG.","11 should be read in light of the description of FIG.","10 above.","It should be noted that the collection 140 of waveforms and the collection 150 of waveform are not to scale with respect to one another.","Referring to FIG.","11, the collection 150 of Scan1 input signal waveforms may represent pixel switch control signals for rows 1-7 of the display 26.The Scan1 input signal is provided to the N-type semiconductor device 124 of the pixel driving circuit 120.As such, a high Scan1 input signal may activate the N-type semiconductor device 124, while a low Scan1 input signal may turn off the N-type semiconductor device 124.In any case, the Scan1 input signal may be used to apply a data voltage to capacitor Cst of the pixel driving circuit 120 or apply some reference voltage (Vref) on the other side of the capacitor Cst.","In any case, during operation for rows 1 to 4, the progressive scan is enabled for each row progressively one after the other.","When the pixel driving circuit 120 prepares to transmit the Scan1 input signal to the respective pixel 82 of row 5, the sensing system 30 may provide, in one example, a pre-defined pixel voltage (V1) (e.g., test data) during a first Scan1 input signal pulse (S1).","The pre-defined pixel voltage (V1) may correspond to a pixel data voltage that enables the sensing system 30 to perform the real-time sensing techniques described herein for row 5.That is, instead of the progressive scan continuing at its expected time slot during the first Scan1 input signal pulse (S1), the sensing system 30 may coordinate with the pixel driving circuit 120 to provide the pre-defined pixel voltage (V1) when the pixel driving circuit 120 would otherwise provide the pixel data voltage (V2) that corresponds to the image data to be depicted in the respective pixel 82.After transmitting the pre-defined pixel voltage (V1), the sensing system 30 may retrieve data regarding certain properties (e.g., luminance, color) associated with the respective pixel 82 based on the pre-defined pixel voltage (V1).","After transmitting the pre-defined pixel voltage (V1) during the first Scan1 input signal pulse (S1), the sensing system 30 may cause the pixel driving circuit 120 to transmit pixel data voltage (V2) during the second Scan1 input pulse (S2).","As mentioned above, the pixel data voltage (V2) may correspond to the intended image data to be depicted on the respective pixel 82 in accordance with the progressive scan previously being performed.","In other words, the progressive scan may resume at the second Scan1 input pulse (S2) and for the remaining rows of the display 26.In some embodiments, the sensing system 30 may determine sensitivity properties regarding each pixel in the display 26 during the progressive scan at different frames of image data.","The sensing system 30 may the store data related to the properties associated with each pixel.","Using the stored data, the sensing system 30 may determine whether each pixel reacts to the pre-defined voltage in the same manner (e.g., output of power, luminance).","The sensing system 30 may determine a compensation factor or voltage for each pixel to enable each of the pixels in the display 26 to display a uniform color and luminance when receiving the same input voltage.","In one embodiment, the sensing system 30 may then apply the determined compensation factor or voltage to data voltage related to image data to be depicted by each pixel.","As a result, the pixels of the display 26 may exhibit substantially similar luminance, color, and power properties when provided the same original data voltage inputs.","It should be understood that although preceding description of the Scan1 input signal is described with respect to the N-type semiconductor device 124, it should be noted that the polarity of the Scan1 input signals can be reversed when used with a corresponding P-type semiconductor device.","With the foregoing descriptions of FIGS.","10 and 11 in mind, FIG.","12 illustrates an embodiment of an EM2 signal waveform generator circuit 160 that may be used to provide the EM2 signal described above with reference to FIG.","10.The circuit 160 may include a 2-phase EM integrated gate driver circuit (e.g., high emission voltage (VEH) and low emission voltage (VEL)), which enables pulse-width modulation (PWM) based emission control, and three additional thin film transistors (TFTs): Tx, Ty, and Tz.","The additional TFTs may enable the total emission time for each row following the row having the pixel being sensed to be the same as each other while incorporating the sense time delay of the sensing period 102.In one embodiment, a first global signal (GLB1) may be positioned in a manner to delay VEH to VEL transition on all EM lines downstream of the row (n) that corresponds to the row having the pixel having its sensitivity properties being evaluated.","Generally, the TFT Ty may provide positive feedback between nodes Q2 and QB to ensure that VEL to VEH transitions on the EM2 signal occur when the first global signal (GLB1) is provided to the TFT Tx.","A second global signal (GLB2) may provide an extended start pulse for the EM2 signal (n) provide to the sensing row (n).","In this way, the EM2 signal output of each row may act as a start pulse for the next row.","In other words, the EM2 signal for row (n-1) may act as a start pulse for the EM2 signal for row (n).","However, due to the sensing time or sensing delay associated with the sensing period 102, the EM2 signal should enable emission (e.g., on emission) for the row (n) even when the EM2 signal for the row (n-1) is already off when an emission clock signal (ECLK) is high.","To circumvent this issue, the second global signal (GLB2) is provided to the TFT Tz for the sensing time.","The operation of the EM2 signal waveform generator circuit 160 based on the two global signals may be as follows.","If the two global inputs are low, the EM2 signal waveform generator circuit 160 may transition into a low emission voltage (VEL) state.","If the two global signals are high, the EM2 signal waveform generator circuit 160 may transition into a high emission voltage (VEH) state.","If the first global signal (GLB1) is low and the second global signal (GLB2) is high, the EM2 signal waveform generator circuit 160 may maintain an expected emission operation.","Moreover, if the first global signal (GLB1) is high and the second global signal (GLB2) is low, the EM2 signal waveform generator circuit 160 may retain the current state of the emission signal.","During the sensing operation, the VEL and the VEH edge may be shifted by the sensing time.","To ensure proper operation of the EM2 signal waveform generator circuit 160, a minimum EM high (VEH) pulse to disable the emission may be 2H +sensing time.","That is, 1H is the line time to apply desired data voltage that corresponds to the desired image to one row of the pixel.","If there are N rows in the panel, there will be N line times or N* 1H time.","Like the pixel driving circuit 120, although the EM2 signal waveform generator circuit 160 is illustrated using P-type semiconductor devices, it should be noted that these devices may be replaced with N-type semiconductor devices when the VEL and VEH are interchanged and when the polarities of the emission clock signal (ECLK), the global signal (GLB1), and the global signal (GLB2) is reversed.","As a result of using the EM2 signal waveform generator circuit 160 as described above, the pixel driving circuit 120 may be capable of pausing the progressive scan of the display 26, as depicted in FIG.","7.However, in some instances when the emission rate (e.g., 240 Hz) is faster than the data refresh rate (e.g., 120 Hz), using a single global signal (GLB1) to create an emission time that enables real-time sensing may be extended for an unintended row.","For example, FIG.","13 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display 26 at 120 Hz while the EM2 signal for real-time sensing is provided to the display 26 at 240 Hz.","As seen in FIG.","13, because the EM2 signal is provided at 240 Hz, the emission time delay at time t1 for real-time sensing in row Y creates a similar emission time delay for row X for the progressive scan of the data program.","To avoid affecting the progressive scan of the data program in the display 26 when performing the real-time sensing techniques described herein with respect to the EM2 signal provided to the display 26, the sensing system 30 may adjust the operation of the pixel driving circuit 120 as will be detailed below.","In one embodiment, to prevent the emission delay time provided by the EM2 signal from delaying the progressive scan of the data program, the sensing system 30 may disable the EM2 signal in a preceding frame when real-time sensing is to be performed for a row in a top half of the display 26 for a particular frame.","For instance, FIG.","14 illustrates the data program of a progressive scan being performed in the first frame and a sensing period 102 being added to the data program of the progressive scan during a second frame.","In comparison to the data program illustrated in FIG.","13, the EM2 signal preceding the data program of frame 2 is disabled to prevent two rows from experiencing the sensing period 102 at the same time.","In another embodiment, if the sensing period is to be performed on a row of the display 26 in the bottom half of the display 26, the sensing system 30 may cause the pixel driving circuit 120 to disable the EM2 signal in the frame that includes the respective row being sensed.","For instance, FIG.","15 illustrates the data program of a progressive scan being performed in the first frame, followed by the EM2 signal being transmitted in between the first and second frames, and a sensing period 102 being added to the data program of the progressive scan during a third frame and a bottom half of the display 26.As shown in FIG.","15, the EM2 signal that would have been transmitted following the data program of frame 2 is disabled to prevent two rows from experiencing the sensing period 102 at the same time.","In yet another embodiment, the sensing system 30 may provide separate global signals for the top and bottom halves of the display 26.Referring briefly back to FIG.","12, two global signals (e.g., GLB1 and GLB2) may be employed for the EM2 signal generator 160.With this in mind, FIG.","16 illustrates an example block diagram of a number of EM2 signal generators 160 that may be employed to transmit EM2 signals to the display 26.As shown in FIG.","16, the top half of the display 26 may use two global signals (e.g., GLB1_TOP and GLB2_TOP) as inputs into respective EM2 signal generators 160, and the bottom half of the display 26 may use two global signals (e.g., GLB1_BOT and GLB2_BOT) as inputs into respective EM2 signal generators 160.In this way, since the global signals are separated for the top and bottom halves of the display 26, the sensing performed in one half of the display 26 does not impact the emission time on onset in the other half of the display 26.With the foregoing in mind, FIG.","17 illustrates an example circuit diagram for a Scan1 input signal generator 170 that may be coupled to the EM2 signal generator 160.The Scan1 input signal generator 170 may include circuit block 172 and circuit block 174, both of which may be coupled to different portions of the EM2 signal generator 160.The circuit block 172 may receive two signals, each of which may emit a start pulse (EVST1) to the EM2 signal generator 160.One of the two signals provided to the circuit block 172 may include a global start pulse (EVST2) for starting a sensing period 102 in a pixel of a row in the display 26.The other signal provided to the circuit block 172 may include a Scan input signal provided via a previous stage (e.g., frame, row).","To determine which source to use to initiate the start pulse (EVST), a 2:1 de-multiplexer 176 may be implemented with two control signals (e.g., CNT_A and CNT_B).","In one embodiment, these two control signals may be locally generated in the circuit block 174.According to the circuit block 174, the second control signal (CNT_B) is enabled (e.g., low) or disabled (e.g., high) based on whether a global signal (INIT) is equal to a low emission level (VEL).","To enable sensing for row N of the display 26, the sensing system 30 may transition the first global signal (GLB1) signal from high to low at t1, as illustrated in FIG.","18.According to the Scan1 input signal generator 170, when the first global signal (GLB1) signal, QB(n), and Scan (N+1) are low, the polarity of the first control signal (CNT_A) and the second control signal (CNT_B) may flip.","As a result, for row N, the start pulse (EVST1) may be derived from the global start pulse (EVST2).","This helps to delay the start of data programming from row N after the sensing (T_sense) has been performed.","The first global signal (GLB1) may remain high to prevent row (N+1) and subsequent rows from activating (e.g., high) during the sensing period 102.FIG.","18 illustrates a timing diagram 190 that represents the operation of the Scan1 input signal generator 170.At time t1, the first global signal (GLB1) may be enabled (low) and the initialization signal (INIT) may be disabled (high) just before the Scan1 signal (SCAN (N)) is provided to row N. At time t2, the first global signal (GLB1) may be disabled after the second clock signal (ECLK2) transitions from low to high.","At time t3, the falling edge of the global start pulse (EVST2) may determine the falling edge of the Scan1 signal for row N because the control signal (CNT_A) may be enabled.","Afterwards, at time t4, the global start pulse (EVST2) may enable the second Scan1 signal for row N. The first Scan1 signal provided just after time t1 may program the pre-defined pixel voltage (V1), as discussed above.","The second Scan1 signal just after time t4 may then provide the pixel data voltage (V2) that corresponds to the image data to be depicted in the respective pixel 82.At time t5, the initialization signal (INIT) may be enabled (low) after the second pulse of the Scan1 signal for row N. As a result, the remaining rows after row N may continue receiving their respective pixel data voltages as per the image data.","It should be noted again that the Scan1 input signal generator 170 may also be implemented using N-type semiconductor devices if the P-type semiconductor devices are replaced by N- type semiconductor devices, and the high emission voltage (VEH) and low emission voltage (VEL) are interchanged.","In addition, the polarities of the clock signal (ECLK), the global signals (GLB1 and GLB2), the initialization signal (INIT), and the start signal (EVST) are reversed.","In some embodiments, the global signals (GLB1 and GLB) may be split into multiple signals.","That is, the first global signal (GLB1) may be split into a first odd global signal (GLB1_odd) and a first even global signal (GLB1_even) for even and odd stages (e.g., rows).","Similarly, the sensing system 30 may also generate two separate global signals for the top half and the bottom half of the display such as signals (GLB1_1 and GLB_2) for global signal (GLB1) and signal (GLB2_1 and GLB2_2) for global signal (GLB2).","With the foregoing in mind, FIG.","19 illustrates a circuit block diagram 200 that represents how input signals (ECLK1, ECLK2, GLB1, GLB2, INIT) may be provided to the Scan1 input signal generator 170 for each row N of the display 26.In addition, the circuit block diagram 200 illustrates the outputs of the Scan1 input signal generator 170 and the manner in which each output is routed to other Scan1 input signal generators 170 for driving each row of the display 26.The circuitry described above is related to systems and method for incorporating a sensing period during a progressive scan.","In some embodiments, it may be useful to incorporate multiple sensing periods for a particular row of pixels on the display 26.With this in mind, the previously described pixel driving circuit 120, as provided in FIG.","8, may not be capable of implementing multiple sensing periods for any particular row of pixels.","That is, as discussed above, the pixel driving circuit 120 may initiate the sensing period 102 based on either the falling edge of the Scan2 input signal or on the falling edge of the EM2 signal.","The rising edge of the Scan2 input signal may then be used to resume the progressive scan for the remaining rows of the display 26, as illustrated in the different driving scheme depicted in FIG.","9.Keeping this in mind, in some instances, the TFTs of the various circuits described above may experience the hysteresis effect due to capacitance voltages and other residual electrical and magnetic properties present on the circuit.","As such, in certain embodiments, the EM2 signal waveform generator circuit 160 of FIG.","12 may be modified to include additional circuit components that enable the display 26 to implement multiple sensing periods 102 during the progressive scan.","That is, the sensing system 30 may employ an EM2 signal waveform generator circuit 210, as illustrated in FIG.","20, to perform multiple toggles of the sensing period 102, thereby providing the opportunity to apply some reference voltage (Vref) on the capacitor Cst of the pixel driving circuit 120 multiple times.","By providing the ability to perform the real-time sensing techniques described herein during multiple sensing periods 102, the waveform generator circuit 210 may improve the ability of the sensing system 30 to determine the sensitivity properties associated with a pixel.","In some embodiments, the EM2 signal waveform generator circuit 210 may be arranged like the EM2 signal waveform generator circuit 160 of FIG.","12 with additional circuitry that uses a third global signal (GLB3) to implement multiple sensing periods 102 during a progressive scan.","For the purposes of discussion, FIG.","21 illustrates a timing diagram 220 related to emission signals provided to a number of rows of the display 26 by the pixel driving circuit to provide multiple sensing periods 102 for a respective pixel 82 of the display 26 during a progressive panel scan, in accordance with aspects of the present disclosure.","Referring to FIGS.","20 and 21, in operation, the EM2 signal waveform generator circuit 210 may operate similarly to the EM2 signal waveform generator circuit 160 of FIG.","12.That is, in some embodiments, a first global signal (GLB1) may be positioned in a manner to delay VEH to VEL transition on each EM line downstream of the row (n) that corresponds to the row having the pixel having its sensitivity properties being evaluated.","Generally, the TFT Ty may provide positive feedback between nodes Q2 and QB to ensure that VEL to VEH transitions on the EM2 signal occur when the first global signal (GLB1) is provided to the TFT Tx.","In addition, the second global signal (GLB2) may provide an extended start pulse for the EM2 signal (n) provide to the sensing row (n).","In this way, the EM2 signal output of each row may act as a start pulse for the next row.","That is, the EM2 signal for row (n−1) may act as a start pulse for the EM2 signal for row (n).","However, due to the sensing time or sensing delay associated with the sensing period 102, the EM2 signal should enable emission (e.g., on emission) for the row (n) even when the EM2 signal for the row (n−1) is already off when an emission clock signal (ECLK) is high.","To avoid this issue, the second global signal (GLB2) is provided to the TFT Tz during the sensing period 102.That is, the second global signal GLB2 remains high and prevents TFT Tz from turning on and transitioning the EM2 signal waveform generator circuit 210 to a high emission voltage (VEH) state until the third global signal GLB3 is pulsed to a low voltage level.","For example, referring to the timing diagram 220 of FIG.","21, at time t0, a start pulse (EVST_EM) may be provided to the EM2 signal waveform generator circuit 210 while the first global signal GLB1 is low.","As such, when the first emission clock signal (ECLK1_EM) is pulsed to a low voltage state, the scan lines 1 and 2, which are coupled to the output of the EM2 signal waveform generator circuit 210 become active (e.g., capable of emission).","At time t1, the start pulse EVST_EM may return to a low state and thus cause the scan lines 1 and 2 to return to an inactive state upon the falling edge of the first emission clock signal ECLK1_EM.","Since the previous emission signals provided to preceding scan lines may be provided to the EM2 signal waveform generator circuit 210 at the source side of the TFT T3, when the emission signals to scan lines 1 and 2 are removed (e.g., transition from high to low at time t1), the emission signals to scan lines 3 and 4 may return to a low voltage state at time t2 after the second emission clock signal ECLK2_EM transitions from high to low, thereby turning off TFT T1.To enable a respective pixel 82 coupled to the EM2 signal waveform generator circuit 210 to implement a sensing period 102, the first global signal GLB1 transitions to a high voltage state just before time t3 when the first emission clock signal ECLK1_EM goes low, while the start pulse EVST_EM is in a low voltage state.","At time t3, although the first emission clock signal ECLK1_EM is low, the emission signals for scan lines 5 and 6 remain high (e.g., VEH) because the first global signal GLB1 transitions is in a high voltage state, thereby preventing TFT T1 from turning off and the emission signals for scan lines 5 and 6 from going low (e.g., VEL).","However, just before time t4, the first global signal GLB1 may return to a low voltage state, thereby turning TFT TX on.","As such, at time t4 when the first emission clock signal ECLK1_EM returns to a low voltage state to allow the respective pixel associated with scan line 5 or 6 with the sensing period 102.That is, the respective pixel may not display color data, but instead perform sensing operations, as discussed above.","By way of operation, the EM2 signal waveform generator circuit 210 may use a low voltage pulse provided by the third global signal GLB3 at time t5 to terminate the sensing period 102 for the scan lines 5 and 6.That is, just before time t5, the emission signals to scan lines 3 and 4 are at a low voltage state thereby connecting the high voltage (VEH) to the gate of the TFT T5 via the TFT T4.Moreover, at time t5, the emission signals for scan lines 5 and 6 may return to an off state to enable the respective pixel to receive a data voltage that corresponds to the desired pixel voltage for the respective image data to be depicted via the display 26.With this in mind, just before time t5, TFT T4 remains open and node QB is in a low voltage state and the third global signal GLB3 is provided to the gates of TFTs 2a and 2b via the TFT T11.Since the third global signal GLB3 transitions to a low voltage state at time t5, the TFTs 2a and 2b close at time t5 and return the emission signals for scan lines 5 and 6 to a high voltage state (VEH).","The respective pixel 82 may then begin emitting according to the provided data signal after the first global signal GLB1 is returned to a low voltage stage and the first emission clock signal ECLK1_EM subsequently returns to a low voltage state at time t6.The EM2 signal waveform generator circuit 210 may then resume its cyclical operation at time t6, such that the emission signals for scan lines 7 and 8 returns to a low voltage state at time t7 because the emission signals for the preceding scan lines 5 and 6, the first global signal GLB1, and the second emission clock signal ECLK2_EM are in a low voltage state.","To ensure that the third global signal GLB3 causes the appropriate sensing period 102 to end, the time period of the third global signal GLB3 may be less than the off period of either emission clock signal (ECLK1 or ECLK2) or approximately between 1 and 2 μs.","To reinitiate the progressive scan from at the first scan lines 1 and 2, the start pulse EVST_EM may return to a high voltage state, while the first global signal GLB1 remains low.","In some embodiments, the EM2 signal waveform generator circuit 210 may pause the progressive scan of the display 26 by transitioning maintain the second global signal GLB2 at a low voltage state while keeping start pulse EVST_EM is in a high voltage state.","The EM2 signal waveform generator circuit 210 may resume the progressive scan by returning the second global signal GLB2 to a high voltage state, as shown just before time t8.At time t8, when the first emission clock goes to a low voltage state, the corresponding emission signals (e.g.","for scan lines 5 and 6) will transition to the high voltage state.","By integrating the use of the third global signal GLB3 into the EM2 signal waveform generator circuit 210, the EM2 signal waveform generator circuit 210 may enable the progressive scan of the display 26 to implement multiple sensing periods 102.By way of example, FIG.","22 illustrates how the first global signal GLB1 may be used to initiate a sensing period 102 and the third global signal GLB3 is used to end a sensing period 102 multiple times on N-type semiconductor devices.","That is, like the pixel driving circuit 120 and the EM2 signal waveform generator circuit 160 described above, although the EM2 signal waveform generator circuit 210 is illustrated using P-type semiconductor devices, it should be noted that these devices may be replaced with N-type semiconductor devices when the VEL and VEH are interchanged and when the polarities of the emission clock signals (ECLK1_EM and ECLK2_EM), the global signals (GLB1, GLB2, and GLB3), and the start pulse (EVST_EM) are reversed.","With this in mind, FIG.","22 depicts a timing diagram 230 that corresponds to implementing multiple sensing periods 102 using the EM2 signal waveform generator circuit 210 equipped with N-type semiconductor devices.","As such, the polarities of each signal illustrated in the collection of waveforms 230 is reversed as compared to the polarities of the signals illustrated in FIG.","21.Nevertheless, it is apparent from the collection of waveforms 230 that third global signal GLB3 may end a respective sensing period 102 multiple times by way of operation of the EM2 signal waveform generator circuit 210.As a result, sensing system 30 may sense various characteristics of the display 26 multiple times to ensure that the pixels 82 of the display perform in the same manner and provide a consistent picture.","That is, by incorporating multiple sensing periods 102, the sensing system 30 may sense a threshold voltage of each pixel, a power output by each pixel, an amount of current provided to each pixel multiple times to ensure that an accurate compensation value is determined for each pixel.","The processor(s) 16 may then adjust the data signals provided to each pixel based on the compensation value, as discussed above.","The specific embodiments described above have been shown by way of example, and it should be understood that these embodiments may be susceptible to various modifications and alternative forms.","It should be further understood that the claims are not intended to be limited to the particular forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure."]],"string":"[\n [\n \"SENSING FOR COMPENSATION OF PIXEL VOLTAGES\",\n \"A display device may include rows of pixels that may display image data on a display and a circuit.\",\n \"The circuit may perform a progressive scan across the rows of pixels to display the image data using a plurality of pixels, supply test data to a pixel of plurality of pixels that corresponds to a first row of the rows of pixels during one frame of the progressive scan, and initiate a sensing period for determining one or more sensitivity properties associated with the pixel based on the performance of the pixel with respect to the test data in response to receiving a pulse of a first global signal.\",\n \"The circuit may then end the sensing period in response to receiving a second global signal and resume the progressive scan across the rows of pixels to display the image data after the sensing period ends.\"\n ],\n [\n \"1.A display device, comprising: a plurality of rows of pixels configured to display image data on a display; and a circuit configured to: perform a progressive scan across a plurality of rows of pixels to display the image data using a plurality of pixels; supply test data to a pixel of plurality of pixels that corresponds to a first row of the plurality of rows of pixels during one frame of the progressive scan; initiate a sensing period for determining one or more sensitivity properties associated with the pixel based on the performance of the pixel with respect to the test data in response to receiving a pulse of a first global signal; end the sensing period in response to receiving a second global signal; and resume the progressive scan across the plurality of rows of pixels to display the image data after the sensing period ends.\",\n \"2.The display device of claim 1, wherein the pulse of the first global signal is configured to cause an emission turn-on signal to be provided to the pixel via the circuit.\",\n \"3.The display device of claim 2, wherein the first global signal is configured to delay the emission turn-on signal from being provided to the pixel.\",\n \"4.The display device of claim 2, wherein the circuit is configured to disconnect the emission turn-on signal from the pixel based on the second global signal.\",\n \"5.The display device of claim 4, wherein the second global signal is between 1 and 2 μs.\",\n \"6.The display device of claim 1, wherein the circuit is configured to supply a data voltage to the pixel based on the image data after supplying the test data to the pixel.\",\n \"7.The display device of claim 1, wherein the one or more sensitivity properties comprise luminance values, color values, power values, or any combination thereof associated with the pixel.\",\n \"8.A circuit, comprising: a plurality of semiconductor devices configured to generate a plurality of emission turn-on signals configured to enable a pixel of a row of pixels in a display to receive a plurality of test voltages during a single frame of image data, wherein the plurality of semiconductor devices is configured to: receive a first pulse of a first global signal, wherein the first pulse of the first global signal is configured to cause the pixel to receive a first emission turn-on signal of the plurality of emission turn-on signals, wherein the first emission turn-on signal is configured to initiate a sensing period for determining a first set of sensitivity properties associated with the pixel based on the performance of the pixel with respect to a first test voltage of the plurality of test voltages; and receive a first pulse of a second global signal, wherein the first pulse of the second global signal is configured to end the sensing period; and a processor configured to determine a compensation factor for a data voltage provided to the pixel based on the first set of sensitivity properties.\",\n \"9.The circuit of claim 8, wherein the plurality of semiconductor devices is configured to: receive a second pulse of the first global signal, wherein the second pulse of the first global signal is configured to cause the pixel to receive a second emission turn-on signal of the plurality of emission turn-on signals, wherein the second emission turn-on signal is configured to initiate a second sensing period for determining a second set of sensitivity properties associated with the pixel based on the performance of the pixel with respect to a second test voltage of the plurality of test voltages; and receive a second pulse of the second global signal, wherein the second pulse of the second global signal is configured to end the second sensing period.\",\n \"10.The circuit of claim 9, wherein the processor is configured to determine the compensation factor for the data voltage provided to the pixel based on the first and second sets of sensitivity properties.\",\n \"11.The circuit of claim 8, wherein the first pulse of the second global signal comprises less time than an off pulse of an emission clock signal provided to the plurality of semiconductor devices.\",\n \"12.The circuit of claim 8, wherein the first pulse of the second global signal is between 1 and 2 μs.\",\n \"13.The circuit of claim 8, wherein the first emission turn-on signal is configured to start a transmission of a second emission turn-on signal in second row of pixels following the row of pixels.\",\n \"14.The circuit of claim 8, comprising a set of circuit components configured to adjust the data voltage provided to the pixel based on the compensation factor.\",\n \"15.A method, comprising: performing, via circuitry, a progressive scan across a plurality of rows of pixels to display the image data using a plurality of pixels in a display; supplying, via the circuitry, test data to at least one pixel of plurality of pixels that corresponds to a first row of a plurality of rows of pixels during the progressive scan; obtaining, via the circuitry, a set of sensitivity properties associated with the at least one pixel based on the performance of the at least one pixel when the test data is provided to the at least one pixel in response to a first pulse of a first global signal provided to the circuitry; and resuming, via the circuitry, the progressive scan at the at least one pixel to display the image data for the at least one pixel and a remaining portion of the plurality of pixels in the first row and remaining rows of the plurality of rows in response to a second global signal provided to the circuitry.\",\n \"16.The method of claim 15, comprising providing, via the circuitry, the test data to the at least one pixel prior to the first pulse and providing a data voltage to the at least one pixel after the first pulse.\",\n \"17.The method of claim 15, comprising delaying, via the circuitry, an emission signal provided to the first row during the progressive scan based on the first global signal.\",\n \"18.The method of claim 15, wherein the second global signal comprises a pulse between 1 and 2 μs.\",\n \"19.The method of claim 15, comprising determining, via the circuitry, a compensation factor for data voltage provided to the at least one pixel based on the set of sensitivity properties.\",\n \"20.The method of claim 19, comprising supplying, via the circuitry, the at least one pixel with an adjusted data voltage based on the data voltage and the compensation factor.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>The present disclosure relates to systems and methods for sensing characteristics of pixels in electronic display devices to compensate for non-uniformity in luminance or color of a pixel with respect to other pixels in the electronic display device.\",\n \"This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present techniques, which are described and/or claimed below.\",\n \"This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.\",\n \"Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.\",\n \"As electronic displays are employed in a variety of electronic devices, such as mobile phones, televisions, tablet computing devices, and the like, manufacturers of the electronic displays continuously seek ways to improve the consistency of colors depicted on the electronic display devices.\",\n \"For example, given variations in manufacturing, various noise sources present within a display device, or various ambient conditions in which each display device operates, different pixels within a display device might emit a different color value or gray level even when provided with the same electrical input.\",\n \"It is desirable, however, for the pixels to uniformly depict the same color or gray level when the pixels programmed to do so to avoid visual display artifacts due to inconsistent color.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>A summary of certain embodiments disclosed herein is set forth below.\",\n \"It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.\",\n \"Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.\",\n \"In certain electronic display devices, light-emitting diodes such as organic light-emitting diodes (OLEDs), micro-LEDs (μLEDs), or active matrix organic light-emitting diodes (AMOLEDs) may be employed as pixels to depict a range of gray levels for display.\",\n \"However, due to various properties associated with the operation of these pixels within the display device, a particular gray level output by one pixel in a display device may be different from a gray level output by another pixel in the same display device upon receiving the same electrical input.\",\n \"As such, the electrical inputs may be calibrated to account for these differences by sensing the electrical values that get stored into the pixels and adjusting the input electrical values accordingly.\",\n \"Since a more accurate and/or precise determination of the sensed electrical value in the pixel may be used to obtain a more consistent and/or exact calibration, the present disclosure details various systems and methods that may be employed to implement a sensing scheme to sense variations in pixel properties (e.g., current, voltage) and modify a data voltage applied to a respective pixel based on the sensed variation.\",\n \"The corrected data voltage, when applied to the respective pixel, may compensate for the variations in the pixel properties to achieve a more uniform image that will be depicted on the display device.\",\n \"In one embodiment, a sensing system of a display device may sense a pixel voltage applied to a respective pixel during a panel scan for data program.\",\n \"That is, the sensing system may transmit pixel data to each row of pixels during a panel scan.\",\n \"During the panel scan for one row of pixels, the sensing system may interrupt the panel scan for a portion of the panel scan to send a first data voltage (e.g., known test voltage) to drive a thin film transistor (TFT) of a respective pixel.\",\n \"After the first data voltage is transmitted to the TFT, the sensing system may determine the sensitivity properties of the respective pixel based on the detected power output by the respective pixel.\",\n \"The sensitivity properties may include current or voltage properties related to the respective pixel that vary as a function of certain pixel properties.\",\n \"The variation in the current or voltage properties may be sensed, amplified, digitized, and applied as a correction factors of the pixel data voltage to compensate for the pixel property variations.\",\n \"After determining the sensitivity properties for the respective pixel, the sensing system may then resume the panel scan for the remaining portion of the one row of pixels.\",\n \"As such, the sensing system may transmit data voltages to the remaining pixels of the display device.\",\n \"In certain embodiments, the sensing system may perform the sensing scheme described above a number of times and may provide the results of the sensing scheme to another component that may determine a compensation voltage for each respective pixel.\",\n \"That is, based on the results of the sensing scheme, a processor (or other like device) may determine an amount of disparity exists between the first data voltage used to drive the respective pixel during a sensing period and the resulting power emitted by the respective pixel.\",\n \"Based on the detected discrepancies over each sensing period, the processor may determine a compensation voltage to apply to the respective pixel to cause the respective pixel to emit a desired (e.g., uniform) color and/or luminance with respect to the other pixels of the display device.\",\n \"To interrupt the panel scan to perform the sensing scheme described above, the sensing system may employ a pixel driving circuit for each respective pixel that uses a data input, two scan line inputs (Scan 1 , Scan 2 ), and two emission turn-on inputs (EM 1 , EM 2 ) to implement a pixel driving scheme that uses a portion of a panel scan of a row of pixels to send a data signal (e.g., voltage) used to determine the sensitivity properties of a respective pixel and then transmit the appropriate data signal, as per the desired image data to be depicted, to the respective pixel.\",\n \"In one embodiment, the sensing system may coordinate the two scan line inputs (Scan 1 , Scan 2 ) and the two emission turn-on inputs (EM 1 , EM 2 ) to cause the pixel driving circuit to suspend the data transmission to a respective pixel for a period of time when the sensing operation is performed.\",\n \"After the sensing operation is performed, the pixel driving circuit may trigger the data transmission to resume for the remaining pixels of the respective row of pixels.\",\n \"By suspending the data programming of a respective pixel and performing a real-time sensing operations for the respective pixel during the panel scan, the sensing system determines the sensitivity properties of each pixel in the display device while the display device is displaying image data.\",\n \"In this way, the sensing system may provide data to other components that may be used to determine compensation values (e.g., voltage) to provide each respective pixel based on the properties of the respective pixel during operation (e.g., display of image data).\",\n \"As such, the compensated values account for a variety of sources for pixel color and luminance variations among the pixels of the display.\",\n \"Moreover, the display driver may adjust the original pixel data provides to the pixels based on the compensated values while the display device is in operation to compensate for the determined sensitivity properties.\",\n \"Various refinements of the features noted above may exist in relation to various aspects of the present disclosure.\",\n \"Further features may also be incorporated in these various aspects as well.\",\n \"These refinements and additional features may exist individually or in any combination.\",\n \"For instance, various features discussed below in relation to one or more of the illustrated embodiments may be incorporated into any of the above-described aspects of the present disclosure alone or in any combination.\",\n \"The brief summary presented above is intended only to familiarize the reader with certain aspects and contexts of embodiments of the present disclosure without limitation to the claimed subject matter.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of U.S. patent application Ser.\",\n \"No.\",\n \"15/271,115, filed Sep. 20, 2016, and entitled “SENSING FOR COMPENSATION OF PIXEL VOLTAGES,” the disclosure of which is incorporated herein by reference in its entirety and for all purposes.\",\n \"BACKGROUND The present disclosure relates to systems and methods for sensing characteristics of pixels in electronic display devices to compensate for non-uniformity in luminance or color of a pixel with respect to other pixels in the electronic display device.\",\n \"This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present techniques, which are described and/or claimed below.\",\n \"This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure.\",\n \"Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.\",\n \"As electronic displays are employed in a variety of electronic devices, such as mobile phones, televisions, tablet computing devices, and the like, manufacturers of the electronic displays continuously seek ways to improve the consistency of colors depicted on the electronic display devices.\",\n \"For example, given variations in manufacturing, various noise sources present within a display device, or various ambient conditions in which each display device operates, different pixels within a display device might emit a different color value or gray level even when provided with the same electrical input.\",\n \"It is desirable, however, for the pixels to uniformly depict the same color or gray level when the pixels programmed to do so to avoid visual display artifacts due to inconsistent color.\",\n \"SUMMARY A summary of certain embodiments disclosed herein is set forth below.\",\n \"It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure.\",\n \"Indeed, this disclosure may encompass a variety of aspects that may not be set forth below.\",\n \"In certain electronic display devices, light-emitting diodes such as organic light-emitting diodes (OLEDs), micro-LEDs (μLEDs), or active matrix organic light-emitting diodes (AMOLEDs) may be employed as pixels to depict a range of gray levels for display.\",\n \"However, due to various properties associated with the operation of these pixels within the display device, a particular gray level output by one pixel in a display device may be different from a gray level output by another pixel in the same display device upon receiving the same electrical input.\",\n \"As such, the electrical inputs may be calibrated to account for these differences by sensing the electrical values that get stored into the pixels and adjusting the input electrical values accordingly.\",\n \"Since a more accurate and/or precise determination of the sensed electrical value in the pixel may be used to obtain a more consistent and/or exact calibration, the present disclosure details various systems and methods that may be employed to implement a sensing scheme to sense variations in pixel properties (e.g., current, voltage) and modify a data voltage applied to a respective pixel based on the sensed variation.\",\n \"The corrected data voltage, when applied to the respective pixel, may compensate for the variations in the pixel properties to achieve a more uniform image that will be depicted on the display device.\",\n \"In one embodiment, a sensing system of a display device may sense a pixel voltage applied to a respective pixel during a panel scan for data program.\",\n \"That is, the sensing system may transmit pixel data to each row of pixels during a panel scan.\",\n \"During the panel scan for one row of pixels, the sensing system may interrupt the panel scan for a portion of the panel scan to send a first data voltage (e.g., known test voltage) to drive a thin film transistor (TFT) of a respective pixel.\",\n \"After the first data voltage is transmitted to the TFT, the sensing system may determine the sensitivity properties of the respective pixel based on the detected power output by the respective pixel.\",\n \"The sensitivity properties may include current or voltage properties related to the respective pixel that vary as a function of certain pixel properties.\",\n \"The variation in the current or voltage properties may be sensed, amplified, digitized, and applied as a correction factors of the pixel data voltage to compensate for the pixel property variations.\",\n \"After determining the sensitivity properties for the respective pixel, the sensing system may then resume the panel scan for the remaining portion of the one row of pixels.\",\n \"As such, the sensing system may transmit data voltages to the remaining pixels of the display device.\",\n \"In certain embodiments, the sensing system may perform the sensing scheme described above a number of times and may provide the results of the sensing scheme to another component that may determine a compensation voltage for each respective pixel.\",\n \"That is, based on the results of the sensing scheme, a processor (or other like device) may determine an amount of disparity exists between the first data voltage used to drive the respective pixel during a sensing period and the resulting power emitted by the respective pixel.\",\n \"Based on the detected discrepancies over each sensing period, the processor may determine a compensation voltage to apply to the respective pixel to cause the respective pixel to emit a desired (e.g., uniform) color and/or luminance with respect to the other pixels of the display device.\",\n \"To interrupt the panel scan to perform the sensing scheme described above, the sensing system may employ a pixel driving circuit for each respective pixel that uses a data input, two scan line inputs (Scan1, Scan2), and two emission turn-on inputs (EM1, EM2) to implement a pixel driving scheme that uses a portion of a panel scan of a row of pixels to send a data signal (e.g., voltage) used to determine the sensitivity properties of a respective pixel and then transmit the appropriate data signal, as per the desired image data to be depicted, to the respective pixel.\",\n \"In one embodiment, the sensing system may coordinate the two scan line inputs (Scan1, Scan2) and the two emission turn-on inputs (EM1, EM2) to cause the pixel driving circuit to suspend the data transmission to a respective pixel for a period of time when the sensing operation is performed.\",\n \"After the sensing operation is performed, the pixel driving circuit may trigger the data transmission to resume for the remaining pixels of the respective row of pixels.\",\n \"By suspending the data programming of a respective pixel and performing a real-time sensing operations for the respective pixel during the panel scan, the sensing system determines the sensitivity properties of each pixel in the display device while the display device is displaying image data.\",\n \"In this way, the sensing system may provide data to other components that may be used to determine compensation values (e.g., voltage) to provide each respective pixel based on the properties of the respective pixel during operation (e.g., display of image data).\",\n \"As such, the compensated values account for a variety of sources for pixel color and luminance variations among the pixels of the display.\",\n \"Moreover, the display driver may adjust the original pixel data provides to the pixels based on the compensated values while the display device is in operation to compensate for the determined sensitivity properties.\",\n \"Various refinements of the features noted above may exist in relation to various aspects of the present disclosure.\",\n \"Further features may also be incorporated in these various aspects as well.\",\n \"These refinements and additional features may exist individually or in any combination.\",\n \"For instance, various features discussed below in relation to one or more of the illustrated embodiments may be incorporated into any of the above-described aspects of the present disclosure alone or in any combination.\",\n \"The brief summary presented above is intended only to familiarize the reader with certain aspects and contexts of embodiments of the present disclosure without limitation to the claimed subject matter.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Various aspects of this disclosure may be better understood upon reading the following detailed description and upon reference to the drawings in which: FIG.\",\n \"1 is a simplified block diagram of components of an electronic device that may depict image data on a display, in accordance with embodiments described herein; FIG.\",\n \"2 is a perspective view of the electronic device of FIG.\",\n \"1 in the form of a notebook computing device, in accordance with embodiments described herein; FIG.\",\n \"3 is a front view of the electronic device of FIG.\",\n \"1 in the form of a desktop computing device, in accordance with embodiments described herein; FIG.\",\n \"4 is a front view of the electronic device of FIG.\",\n \"1 in the form of a handheld portable electronic device, in accordance with embodiments described herein; FIG.\",\n \"5 is a front view of the electronic device of FIG.\",\n \"1 in the form of a tablet computing device, in accordance with embodiments described herein; FIG.\",\n \"6 is a circuit diagram of an array of self-emissive pixels of the electronic display of the electronic device of FIG.\",\n \"1, in accordance with aspects of the present disclosure; FIG.\",\n \"7 is an example of a progressive scan that includes a sensing period implemented on a display of the electronic device of FIG.\",\n \"1, in accordance with embodiments described herein; FIG.\",\n \"8 is a circuit diagram of a pixel driving circuit that implements a sensing period while a progressive panel scan is being performed in the display of the electronic device of FIG.\",\n \"1, in accordance with aspects of the present disclosure; FIG.\",\n \"9 is a collection of waveforms related to different driving schemes that may be implemented by the pixel driving circuit of FIG.\",\n \"8 to provide a sensing period for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.\",\n \"10 is a collection of waveforms related to emission signals provided to a number of rows of a display by the pixel driving circuit to provide a sensing period for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.\",\n \"11 is a collection of waveforms related to scan signals provided to a number of rows of a display by the pixel driving circuit to provide a sensing period for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.\",\n \"12 is a circuit diagram of an emission signal waveform generator that provides an emission signal to the respective pixel to a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.\",\n \"13 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display at a first frequency while an emission signal for real-time sensing is provided to the display at a second frequency, in accordance with an embodiment; FIG.\",\n \"14 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display at a first frequency while an adjusted emission signal for real-time sensing is provided to the display at a second frequency to accommodate the data program of a pixel in the top half of the display, in accordance with an embodiment; FIG.\",\n \"15 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display at a first frequency while an adjusted emission signal for real-time sensing is provided to the display at a second frequency to accommodate the data program of a pixel in the bottom half of the display, in accordance with an embodiment; FIG.\",\n \"16 illustrates an example block diagram of a number of emission signal waveform generators that may be employed to transmit emission signals to the display, in accordance with an embodiment; FIG.\",\n \"17 illustrates an example circuit diagram for a input signal generator that may be coupled to the emission signal generator of FIG.\",\n \"12, in accordance with aspects of the present disclosure; FIG.\",\n \"18 illustrates a timing diagram that represents the operation of the input signal generator of FIG.\",\n \"17, in accordance with an embodiment; FIG.\",\n \"19 illustrates a circuit block diagram that represents how input signals may be provided to the input signal generator of FIG.\",\n \"17, in accordance with an embodiment; FIG.\",\n \"20 is a circuit diagram of an emission signal waveform generator that provides an emission signal to the respective pixel to a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; FIG.\",\n \"21 illustrates a timing diagram related to emission signals provided to a number of rows of the display by the pixel driving circuit to provide multiple sensing periods for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure; and FIG.\",\n \"22 illustrates a timing diagram related to emission signals provided to a number of rows of the display by the pixel driving circuit to provide multiple sensing periods for a respective pixel of the display during a progressive panel scan, in accordance with aspects of the present disclosure.\",\n \"DETAILED DESCRIPTION One or more specific embodiments of the present disclosure will be described below.\",\n \"These described embodiments are only examples of the presently disclosed techniques.\",\n \"Additionally, in an effort to provide a concise description of these embodiments, all features of an actual implementation may not be described in the specification.\",\n \"It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another.\",\n \"Moreover, it should be appreciated that such a development effort might be complex and time consuming, but may nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.\",\n \"When introducing elements of various embodiments of the present disclosure, the articles “a,” “an,” and “the” are intended to mean that there are one or more of the elements.\",\n \"The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.\",\n \"Additionally, it should be understood that references to “one embodiment” or “an embodiment” of the present disclosure are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features.\",\n \"Organic light-emitting diode (e.g., OLED, AMOLED) display panels provide opportunities to make thin, flexible, high-contrast, and color-rich electronic displays.\",\n \"Generally, OLED display devices are current driven devices and use thin film transistors (TFTs) as current sources to provide certain amount of current to generate a certain level of luminance to a respective pixel electrode.\",\n \"OLED Luminance to current ratio is generally represented as OLED efficiency with units: cd/A (Luminance/Current Density or (cd/m2)/(A/m2)).\",\n \"Each respective TFT, which provides current to a respective pixel, may be controlled by gate to source voltage (Vgs), which is stored on a capacitor (Cst) electrically coupled to the LED of the pixel.\",\n \"Generally, the application of the gate-to-source voltage Vgson the capacitor Cst is performed by programming voltage on a corresponding data line to be provided to a respective pixel.\",\n \"However, when providing the voltage on a data line, several sources of noise or variation in the OLED-TFT system can result in either localized (e.g., in-panel) or global (e.g., panel to panel) non-uniformity in luminance or color.\",\n \"Variations in the TFT system may be addressed in a number of ways.\",\n \"For instance, an in-pixel compensation scheme may involve in-pixel sensing of a threshold voltage for a respective TFT before applying an intended data voltage to the respective pixel.\",\n \"However, in-pixel sensing could involve multiple stages (e.g., initialization, sensing, and data application) for pixels in every row that correspond to relatively long row times (e.g., tens of microseconds).\",\n \"With this in mind, displays with large number of rows that are driven at 120 Hz, as opposed to 60 Hz, provide relatively small row times (e.g., 3-4 μs) for programming.\",\n \"As such, in-pixel compensation may not provide a feasible way to compensate voltages provided on a data line to the respective pixel.\",\n \"In one embodiment, the data values provided to the pixels may be compensated using a compensation system.\",\n \"For example, a display driver may employ a sensing system to implement voltage or current sensing schemes to sense operational variations among pixels, then digitize and transmit this information to processor(s) external to the display that adjust the image data before it is provided to the display.\",\n \"In particular, the processor(s) may modify the image data based on the sensed variation and transmit the modified data voltage to the respective pixel.\",\n \"The modified data voltage, when applied to the pixels, helps realize a uniform image.\",\n \"To effectively perform the external compensation scheme generally described above, variations in pixel properties may be sensed at various times by the display driver when the display is off, during a blanking time, or during a progressive scan of the display device.\",\n \"The main point for external compensation is that only data is programmed into the pixel during regular row time.\",\n \"As such, the display driver may sense variations in various properties (e.g., color, luminance) of a pixel using relatively short row times, as compared to using in-pixel sensing schemes.\",\n \"For fast sensing schemes (e.g., real time or near-real time), the display driver (e.g., sensing system) may embed a certain amount of time to sense variations in certain properties of a pixel in one row during the regular panel scan for data program of the respective pixel.\",\n \"In order to embed this sensing time into the progressive panel scan, the display driver may employ different circuits to generate emission signals and scan signals in a particular manner to trigger a sensing period during the progressive scan and trigger the resumption of the progressive scan after the sensing period.\",\n \"In one embodiment, the display driver may employ a pixel driving circuit for each respective pixel that uses four inputs (two scan inputs and two emission signal inputs) to pause the transmission of data to the respective pixel, sense the properties of the pixel, and resume the transmission of data to the respective during a progressive scan of the display.\",\n \"As a result, the display driver may acquire information related to the properties of the respective pixel.\",\n \"The display driver may then send the acquired information to a processor that may determine a compensation value for data signals provided to the respective pixel based on the information and provide corrected data signals to the display driver, which may provide the corrected data signals to the respective pixels.\",\n \"Additional details with regard to the systems and techniques involved with enabling the display driver to perform fast (e.g., real-time or near real-time) sensing of pixel sensitivity properties during a progressive scan is detailed below with reference to FIGS.\",\n \"1-22.By way of introduction, FIG.\",\n \"1 is a block diagram illustrating an example of an electronic device 10 that may include the sensing system mentioned above.\",\n \"The electronic device 10 may be any suitable electronic device, such as a laptop or desktop computer, a mobile phone, a digital media player, television, or the like.\",\n \"By way of example, the electronic device 10 may be a portable electronic device, such as a model of an iPod® or iPhone®, available from Apple Inc. of Cupertino, Calif.\",\n \"The electronic device 10 may be a desktop or notebook computer, such as a model of a MacBook®, MacBook® Pro, MacBook Air®, iMac®, Mac® Mini, or Mac Pro®, available from Apple Inc.\",\n \"In other embodiments, electronic device 10 may be a model of an electronic device from another manufacturer.\",\n \"As shown in FIG.\",\n \"1, the electronic device 10 may include various components.\",\n \"The functional blocks shown in FIG.\",\n \"1 may represent hardware elements (including circuitry), software elements (including code stored on a computer-readable medium) or a combination of both hardware and software elements.\",\n \"In the example of FIG.\",\n \"1, the electronic device 10 includes input/output (I/O) ports 12, input structures 14, one or more processors 16, a memory 18, nonvolatile storage 20, networking device 22, power source 24, display 26, and one or more imaging devices 28.It should be appreciated, however, that the components illustrated in FIG.\",\n \"1 are provided only as an example.\",\n \"Other embodiments of the electronic device 10 may include more or fewer components.\",\n \"To provide one example, some embodiments of the electronic device 10 may not include the imaging device(s) 28.Before continuing further, it should be noted that the system block diagram of the device 10 shown in FIG.\",\n \"1 is intended to be a high-level control diagram depicting various components that may be included in such a device 10.That is, the connection lines between each individual component shown in FIG.\",\n \"1 may not necessarily represent paths or directions through which data flows or is transmitted between various components of the device 10.Indeed, as discussed below, the depicted processor(s) 16 may, in some embodiments, include multiple processors, such as a main processor (e.g., CPU), and dedicated image and/or video processors.\",\n \"In such embodiments, the processing of image data may be primarily handled by these dedicated processors, thus effectively offloading such tasks from a main processor (CPU).\",\n \"Considering each of the components of FIG.\",\n \"1, the I/O ports 12 may represent ports to connect to a variety of devices, such as a power source, an audio output device, or other electronic devices.\",\n \"The input structures 14 may enable user input to the electronic device, and may include hardware keys, a touch-sensitive element of the display 26, and/or a microphone.\",\n \"The processor(s) 16 may control the general operation of the device 10.For instance, the processor(s) 16 may execute an operating system, programs, user and application interfaces, and other functions of the electronic device 10.The processor(s) 16 may include one or more microprocessors and/or application-specific microprocessors (ASICs), or a combination of such processing components.\",\n \"For example, the processor(s) 16 may include one or more instruction set (e.g., RISC) processors, as well as graphics processors (GPU), video processors, audio processors and/or related chip sets.\",\n \"As may be appreciated, the processor(s) 16 may be coupled to one or more data buses for transferring data and instructions between various components of the device 10.In certain embodiments, the processor(s) 16 may provide the processing capability to execute an imaging applications on the electronic device 10, such as Photo Booth®, Aperture®, iPhoto®, Preview®, iMovie®, or Final Cut Pro® available from Apple Inc., or the “Camera” and/or “Photo” applications provided by Apple Inc. and available on some models of the iPhone®, iPod®, and iPad®.\",\n \"A computer-readable medium, such as the memory 18 or the nonvolatile storage 20, may store the instructions or data to be processed by the processor(s) 16.The memory 18 may include any suitable memory device, such as random access memory (RAM) or read only memory (ROM).\",\n \"The nonvolatile storage 20 may include flash memory, a hard drive, or any other optical, magnetic, and/or solid-state storage media.\",\n \"The memory 18 and/or the nonvolatile storage 20 may store firmware, data files, image data, software programs and applications, and so forth.\",\n \"The network device 22 may be a network controller or a network interface card (NIC), and may enable network communication over a local area network (LAN) (e.g., Wi-Fi), a personal area network (e.g., Bluetooth), and/or a wide area network (WAN) (e.g., a 3G or 4G data network).\",\n \"The power source 24 of the device 10 may include a Li-ion battery and/or a power supply unit (PSU) to draw power from an electrical outlet or an alternating-current (AC) power supply.\",\n \"The display 26 may display various images generated by device 10, such as a GUI for an operating system or image data (including still images and video data).\",\n \"The display 26 may be any suitable type of display, such as a liquid crystal display (LCD), plasma display, or an organic light emitting diode (OLED) display, for example.\",\n \"In one embodiment, the display 26 may include self-emissive pixels such as organic light emitting diodes (OLEDs) or micro-light-emitting-diodes (μ-LEDs).\",\n \"Additionally, as mentioned above, the display 26 may include a touch-sensitive element that may represent an input structure 14 of the electronic device 10.The imaging device(s) 28 of the electronic device 10 may represent a digital camera that may acquire both still images and video.\",\n \"Each imaging device 28 may include a lens and an image sensor capture and convert light into electrical signals.\",\n \"In certain embodiments, the electronic device 10 may include a sensing system 30, which may include a chip, such as processor or ASIC, that may control various aspects of the display 26.For instance, the sensing system 30 may use a voltage signal that is to be provided to a pixel of the display 26 to sense the gray level depicted by the pixel.\",\n \"Generally, when the same voltage signal is provided to each pixel of the display 26, each pixel should depict the same gray level.\",\n \"However, due to various sources of noise, the same voltage being applied to a number of pixels may result in a variety of different gray levels depicted across the number of pixels.\",\n \"As such, the sensing system 30 may sense a threshold voltage of each pixel, a power output by each pixel, an amount of current provided to each pixel and the sensing system 30 may send the threshold voltage to the processor(s) 16 or other circuit component to determine a compensation value for each pixel.\",\n \"The processor(s) 16 may then adjust the data signals provided to each pixel based on the compensation value.\",\n \"Although the sensing system 30 is described as providing the threshold voltage or sensitivity characteristics to another circuit component that may determine a compensation value, it should be noted that, in some embodiments, the sensing system 30 may also perform the determination of the compensation value and the modification of the data provided to a pixel based on the compensation value.\",\n \"As mentioned above, the electronic device 10 may take any number of suitable forms.\",\n \"Some examples of these possible forms appear in FIGS.\",\n \"2-5.Turning to FIG.\",\n \"2, a notebook computer 40 may include a housing 42, the display 26, the I/O ports 12, and the input structures 14.The input structures 14 may include a keyboard and a touchpad mouse that are integrated with the housing 42.Additionally, the input structure 14 may include various other buttons and/or switches which may be used to interact with the computer 40, such as to power on or start the computer, to operate a GUI or an application running on the computer 40, as well as adjust various other aspects relating to operation of the computer 40 (e.g., sound volume, display brightness, etc.).\",\n \"The computer 40 may also include various I/O ports 12 that provide for connectivity to additional devices, as discussed above, such as a FireWire® or USB port, a high definition multimedia interface (HDMI) port, or any other type of port that is suitable for connecting to an external device.\",\n \"Additionally, the computer 40 may include network connectivity (e.g., network device 22), memory (e.g., memory 18), and storage capabilities (e.g., storage device 20), as described above with respect to FIG.\",\n \"1.The notebook computer 40 may include an integrated imaging device 28 (e.g., a camera).\",\n \"In other embodiments, the notebook computer 40 may use an external camera (e.g., an external USB camera or a “webcam”) connected to one or more of the I/O ports 12 instead of or in addition to the integrated imaging device 28.In certain embodiments, the depicted notebook computer 40 may be a model of a MacBook®, MacBook® Pro, MacBook Air®, or PowerBook® available from Apple Inc.\",\n \"In other embodiments, the computer 40 may be portable tablet computing device, such as a model of an iPad® from Apple Inc.\",\n \"FIG.\",\n \"3 shows the electronic device 10 in the form of a desktop computer 50.The desktop computer 50 may include a number of features that may be generally similar to those provided by the notebook computer 40 shown in FIG.\",\n \"4, but may have a generally larger overall form factor.\",\n \"As shown, the desktop computer 50 may be housed in an enclosure 42 that includes the display 26, as well as various other components discussed above with regard to the block diagram shown in FIG.\",\n \"1.Further, the desktop computer 50 may include an external keyboard and mouse (input structures 14) that may be coupled to the computer 50 via one or more I/O ports 12 (e.g., USB) or may communicate with the computer 50 wirelessly (e.g., RF, Bluetooth, etc.).\",\n \"The desktop computer 50 also includes an imaging device 28, which may be an integrated or external camera, as discussed above.\",\n \"In certain embodiments, the depicted desktop computer 50 may be a model of an iMac®, Mac® mini, or Mac Pro®, available from Apple Inc.\",\n \"The electronic device 10 may also take the form of portable handheld device 60 or 70, as shown in FIGS.\",\n \"4 and 5.By way of example, the handheld device 60 or 70 may be a model of an iPod® or iPhone® available from Apple Inc.\",\n \"The handheld device 60 or 70 includes an enclosure 42, which may function to protect the interior components from physical damage and to shield them from electromagnetic interference.\",\n \"The enclosure 42 also includes various user input structures 14 through which a user may interface with the handheld device 60 or 70.Each input structure 14 may control various device functions when pressed or actuated.\",\n \"As shown in FIGS.\",\n \"4 and 5, the handheld device 60 or 70 may also include various I/O ports 12.For instance, the depicted I/O ports 12 may include a proprietary connection port for transmitting and receiving data files or for charging a power source 24.Further, the I/O ports 12 may also be used to output voltage, current, and power to other connected devices.\",\n \"The display 26 may display images generated by the handheld device 60 or 70.For example, the display 26 may display system indicators that may indicate device power status, signal strength, external device connections, and so forth.\",\n \"The display 26 may also display a GUI 52 that allows a user to interact with the device 60 or 70, as discussed above with reference to FIG.\",\n \"3.The GUI 52 may include graphical elements, such as the icons, which may correspond to various applications that may be opened or executed upon detecting a user selection of a respective icon.\",\n \"Having provided some context with regard to possible forms that the electronic device 10 may take, the present discussion will now focus on the sensing system 30 of FIG.\",\n \"1.Generally, the brightness depicted by each respective pixel in the display 26 is generally controlled by varying an electric field associated with each respective pixel in the display 26.Keeping this in mind, FIG.\",\n \"6 illustrates one embodiment of a circuit diagram of display 26 that may generate the electrical field that energizes each respective pixel and causes each respective pixel to emit light at an intensity corresponding to an applied voltage.\",\n \"As shown, display 26 may include a self-emissive pixel array 80 having an array of self-emissive pixels 82.The self-emissive pixel array 80 is shown having a controller 84, a power driver 86A, an image driver 86B, and the array of self-emissive pixels 82.The self-emissive pixels 82 are driven by the power driver 86A and image driver 86B.\",\n \"Each power driver 86A and image driver 86B may drive one or more self-emissive pixels 82.In some embodiments, the power driver 86A and the image driver 86B may include multiple channels for independently driving multiple self-emissive pixels 82.The self-emissive pixels may include any suitable light-emitting elements, such as organic light emitting diodes (OLEDs), micro-light-emitting-diodes (μ-LEDs), and the like.\",\n \"The power driver 86A may be connected to the self-emissive pixels 82 by way of scan lines S0, S1, .\",\n \".\",\n \".\",\n \"Sm-1, and Sm and driving lines D0, D1, .\",\n \".\",\n \".\",\n \"Dm-1, and Dm.\",\n \"The self-emissive pixels 82 receive on/off instructions through the scan lines S0, S1, Sm-1, and Sm and generate driving currents corresponding to data voltages transmitted from the driving lines D0, D1, .\",\n \".\",\n \".\",\n \"Dm-1, and Dm.\",\n \"The driving currents are applied to each self-emissive pixel 82 to emit light according to instructions from the image driver 86B through driving lines M0, M1, .\",\n \".\",\n \".\",\n \"Mn-1, and Mn.\",\n \"Both the power driver 86A and the image driver 86B transmit voltage signals through respective driving lines to operate each self-emissive pixel 82 at a state determined by the controller 84 to emit light.\",\n \"Each driver may supply voltage signals at a duty cycle and/or amplitude sufficient to operate each self-emissive pixel 82.The controller 84 may control the color of the self-emissive pixels 82 using image data generated by the processor(s) 16 and stored into the memory 18 or provided directly from the processor(s) 16 to the controller 84.The sensing system 30 may provide a signal to the controller 84 to adjust the data signals transmitted to the self-emissive pixels 82 such that the self-emissive pixels 82 may depict substantially uniform color and luminance provided the same current input in accordance with the techniques that will be described in detail below.\",\n \"With the foregoing in mind, FIG.\",\n \"7 illustrates an embodiment in which the sensing system 30 may incorporate a sensing period during a progressive data scan of the display 26.In one embodiment, the controller 84 may send data (e.g., gray level voltages or currents) to each self-emissive pixel 82 via the power driver 86A on a row-by-row basis.\",\n \"That is, the controller 84 may initially cause the power driver 86A to send data signals to the pixels 82 of the first row of pixels on the display 26, then the second row of pixels on the display 26, and so forth.\",\n \"When incorporating a sensing period, the sensing system 30 may cause the controller 84 to pause the transmission of data via the power driver 86A for a period of time (e.g., 100 microseconds) during the progressive data scan at a particular row of the display (e.g., for row X).\",\n \"The period of time in which the power driver 86A stops transmitting data corresponds to a sensing period 102.As shown in FIG.\",\n \"7, the progressive scan 104 is performed between a back porch 106 and a front porch 108 of a frame 110 of data.\",\n \"The progressive scan 104 is interrupted by the sensing period 102 while the power driver 86A is transmitting data to row X of the display 26.The sensing period 102 corresponds to a period of time in which a data signal may be transmitted to a respective pixel 82, and the sensing system 30 may determine certain sensitivity properties associated to the respective pixel 82 based on the pixel's reaction to the data signal.\",\n \"The sensitivity properties may include, for example, the power, luminance, and color values of the respective pixel when driven by the provided data signal.\",\n \"After the sensing period 102 expires, the sensing system 30 may cause the power driver 86A to resume the progressive scan 104.As such, the progressive scan 104 may be delayed by a data program delay 112 due to the sensing period 102.In order to incorporate the sensing period 102 into the progressive scans of a display, pixel driving circuitry, in one embodiment, the sensing system 30 may transmit data signals to pixels of each row of the display 26 and may pause its transmission of data signals during any portion of the progressive scan to determine the sensitivity properties of any pixel on any row of the display 26.Moreover, as sizes of displays 26 decrease and smaller bezel or border regions are available around the display 26, integrated gate driver circuits may be developed using a similar thin film transistor process as used to produce the transistors of the pixels 82.However, to effectively use the integrated gate driver circuits to incorporate the sensing period 102 into the progressive scan 104, the sensing system 30 may include a pixel driving circuit 120, as provided in FIG.\",\n \"8, for each row of pixels of the display 26.Referring to FIG.\",\n \"8, the pixel driving circuit 120 may include a number of semiconductor devices that may coordinate the transmission of data signals to a light-emitting diode (LED) 122 of a respective pixel 82.In one embodiment, the pixel driving circuit 120 may receive four input signals (e.g., emission signals 1 and 2, scan signals 1 and 2), which may be coordinated in a manner to cause the pixel driving circuit 120 to perform the progressive scan for a respective row of pixels of the display 26, pause the progressive scan for the respective row of pixels, transmit a test data signal used to determine the sensitivity properties of the LED 122, and resume the progressive scan being performed on the display 26.With this in mind, the pixel driving circuit 120 may include, in one embodiment, an N-type semiconductor device 124 and three P-type semiconductor devices 126, 128, and 130.Although the following description of the pixel driving circuit 120 will be discussed with the N-type semiconductor device 124 and the three P-type semiconductor devices 126, 128, and 130 described above, it should be noted that the pixel driving circuit 120 may be designed using any suitable combination of N-type or P-type semiconductor devices.\",\n \"That is, depending of the type of semiconductor devices used within the pixel driving circuit 120, the waveforms or signals provided to each semiconductor device should be coordinated in a manner to cause the pixel driving circuit 120 to pause the progressive scan for a row of pixels, transmit a data test signal to a respective pixel, and resume the progressive scan.\",\n \"As shown in FIG.\",\n \"8, the N-type semiconductor device 124 and the three P-type semiconductor devices 126, 128, and 130 may be driven by a first scan signal (Scan1), a first emission signal (EM1), a second emission signal (EM2), and a second scan signal (Scan2), respectively.\",\n \"Based on these four input signals, the pixel driving circuit 120 may implement a number of pixel driving schemes for a respective pixel.\",\n \"Four example pixel-driving schemes are illustrated in FIG.\",\n \"9.Each pixel driving scheme depicted in FIG.\",\n \"9 illustrate sample waveforms that may be used for the four control signals: first scan signal (Scan1), first emission signal (EM1), a second emission signal (EM2), and second scan signal (Scan2).\",\n \"The scan2 signal and the EM1 signal may be generated using standard shift register circuits where either the drain or the source of a buffer TFT is connected to a clock signal (CLK), and the other source or drain terminal is connected to the Scan2 line.\",\n \"As such, the clock (CLK) waveforms may be modified to realize a desired waveform for the EM1 signal, which may then be derived as inversion of the Scan2 signal.\",\n \"In each pixel-driving scheme, the sensing period 102 for detecting current flow through a drive TFT of a respective pixel 82 may be enabled based on the Scan2 input signal or the EM2 signal.\",\n \"For instance, the sensing period 102 may be triggered by either the falling edge of the Scan2 input signal, as depicted in Drive Scheme 2, or on the falling edge of the EM2 signal, as depicted in Drive Schemes 3 and 4.Regardless of the pixel-driving scheme employed to enable a respective pixel 82 to have a sensing period 102, the EM2 signal and the Scan1 input signal may transmit a first pixel data voltage to the respective pixel and then transmit a second data voltage that corresponds to the image data being depicted via the progressive scan.\",\n \"With this in mind, FIG.\",\n \"10 illustrates example EM2 signal waveforms that may be transmitted to seven rows of pixels in the display 26, and FIG.\",\n \"11 illustrates corresponding example Scan1 input signals that may be transmitted to the same seven rows of pixels.\",\n \"Referring first to FIG.\",\n \"10, a collection 140 of example EM2 signals for seven rows of the display 26 is illustrated.\",\n \"It should be noted that the EM2 signals are provided to the P-type semiconductor device 128, and, as such, the P-type semiconductor device 128 is active or on when the EM2 signal is low.\",\n \"As shown in FIG.\",\n \"10, the EM2 signals provided to row 1-4 are slightly offset with each other.\",\n \"That is, the EM2 signal provided to each row 2, 3, and 4 includes the same waveform but offset in time.\",\n \"As such, emission is enabled progressively one after the other for rows 1 to 4.The emission time (Emit_Time) for each row may be fixed or variable depending upon ambient light level, grey scale, or other considerations.\",\n \"To enable the sensing period 102 in row 5, the EM2 signal may be delayed by the amount of time that corresponds to the sensing period 102.That is, the emission turn-on signal (e.g., falling edge of EM2 signal) may be delayed by a certain amount of time (e.g., Sense_Time) for row 5.The progressive emission turn-on pattern then resumes at row 6 onwards, such that the turn-on period is offset by the same amount for each row of the display 26 during the following frame.\",\n \"As such, the rows following row 5 may have a turn-off period (e.g., high EM2 value) for a shorter duration as compared to the rows preceding row 5 in the frame immediately following the frame that included the sensing period 102.It should again be noted that although the collection 140 of EM2 signal waveforms is detailed in FIG.\",\n \"10 for the P-type semiconductor device (e.g., TFT) 128, it should be noted that the polarity of the EM2 signals can be reversed for N-type semiconductor devices.\",\n \"During the sensing period 102, the pixel driving circuit 120 may transmit a Scan1 input signal that includes a first voltage that may be used to determine the sensitivity properties of the respective pixel 82 and a second voltage that corresponds to the data intended to be depicted during the progressive scan based on input image data.\",\n \"With this in mind, FIG.\",\n \"9 illustrates a collection 150 of Scan1 input signals that may be transmitted to seven rows of the display 26.The following description of FIG.\",\n \"11 should be read in light of the description of FIG.\",\n \"10 above.\",\n \"It should be noted that the collection 140 of waveforms and the collection 150 of waveform are not to scale with respect to one another.\",\n \"Referring to FIG.\",\n \"11, the collection 150 of Scan1 input signal waveforms may represent pixel switch control signals for rows 1-7 of the display 26.The Scan1 input signal is provided to the N-type semiconductor device 124 of the pixel driving circuit 120.As such, a high Scan1 input signal may activate the N-type semiconductor device 124, while a low Scan1 input signal may turn off the N-type semiconductor device 124.In any case, the Scan1 input signal may be used to apply a data voltage to capacitor Cst of the pixel driving circuit 120 or apply some reference voltage (Vref) on the other side of the capacitor Cst.\",\n \"In any case, during operation for rows 1 to 4, the progressive scan is enabled for each row progressively one after the other.\",\n \"When the pixel driving circuit 120 prepares to transmit the Scan1 input signal to the respective pixel 82 of row 5, the sensing system 30 may provide, in one example, a pre-defined pixel voltage (V1) (e.g., test data) during a first Scan1 input signal pulse (S1).\",\n \"The pre-defined pixel voltage (V1) may correspond to a pixel data voltage that enables the sensing system 30 to perform the real-time sensing techniques described herein for row 5.That is, instead of the progressive scan continuing at its expected time slot during the first Scan1 input signal pulse (S1), the sensing system 30 may coordinate with the pixel driving circuit 120 to provide the pre-defined pixel voltage (V1) when the pixel driving circuit 120 would otherwise provide the pixel data voltage (V2) that corresponds to the image data to be depicted in the respective pixel 82.After transmitting the pre-defined pixel voltage (V1), the sensing system 30 may retrieve data regarding certain properties (e.g., luminance, color) associated with the respective pixel 82 based on the pre-defined pixel voltage (V1).\",\n \"After transmitting the pre-defined pixel voltage (V1) during the first Scan1 input signal pulse (S1), the sensing system 30 may cause the pixel driving circuit 120 to transmit pixel data voltage (V2) during the second Scan1 input pulse (S2).\",\n \"As mentioned above, the pixel data voltage (V2) may correspond to the intended image data to be depicted on the respective pixel 82 in accordance with the progressive scan previously being performed.\",\n \"In other words, the progressive scan may resume at the second Scan1 input pulse (S2) and for the remaining rows of the display 26.In some embodiments, the sensing system 30 may determine sensitivity properties regarding each pixel in the display 26 during the progressive scan at different frames of image data.\",\n \"The sensing system 30 may the store data related to the properties associated with each pixel.\",\n \"Using the stored data, the sensing system 30 may determine whether each pixel reacts to the pre-defined voltage in the same manner (e.g., output of power, luminance).\",\n \"The sensing system 30 may determine a compensation factor or voltage for each pixel to enable each of the pixels in the display 26 to display a uniform color and luminance when receiving the same input voltage.\",\n \"In one embodiment, the sensing system 30 may then apply the determined compensation factor or voltage to data voltage related to image data to be depicted by each pixel.\",\n \"As a result, the pixels of the display 26 may exhibit substantially similar luminance, color, and power properties when provided the same original data voltage inputs.\",\n \"It should be understood that although preceding description of the Scan1 input signal is described with respect to the N-type semiconductor device 124, it should be noted that the polarity of the Scan1 input signals can be reversed when used with a corresponding P-type semiconductor device.\",\n \"With the foregoing descriptions of FIGS.\",\n \"10 and 11 in mind, FIG.\",\n \"12 illustrates an embodiment of an EM2 signal waveform generator circuit 160 that may be used to provide the EM2 signal described above with reference to FIG.\",\n \"10.The circuit 160 may include a 2-phase EM integrated gate driver circuit (e.g., high emission voltage (VEH) and low emission voltage (VEL)), which enables pulse-width modulation (PWM) based emission control, and three additional thin film transistors (TFTs): Tx, Ty, and Tz.\",\n \"The additional TFTs may enable the total emission time for each row following the row having the pixel being sensed to be the same as each other while incorporating the sense time delay of the sensing period 102.In one embodiment, a first global signal (GLB1) may be positioned in a manner to delay VEH to VEL transition on all EM lines downstream of the row (n) that corresponds to the row having the pixel having its sensitivity properties being evaluated.\",\n \"Generally, the TFT Ty may provide positive feedback between nodes Q2 and QB to ensure that VEL to VEH transitions on the EM2 signal occur when the first global signal (GLB1) is provided to the TFT Tx.\",\n \"A second global signal (GLB2) may provide an extended start pulse for the EM2 signal (n) provide to the sensing row (n).\",\n \"In this way, the EM2 signal output of each row may act as a start pulse for the next row.\",\n \"In other words, the EM2 signal for row (n-1) may act as a start pulse for the EM2 signal for row (n).\",\n \"However, due to the sensing time or sensing delay associated with the sensing period 102, the EM2 signal should enable emission (e.g., on emission) for the row (n) even when the EM2 signal for the row (n-1) is already off when an emission clock signal (ECLK) is high.\",\n \"To circumvent this issue, the second global signal (GLB2) is provided to the TFT Tz for the sensing time.\",\n \"The operation of the EM2 signal waveform generator circuit 160 based on the two global signals may be as follows.\",\n \"If the two global inputs are low, the EM2 signal waveform generator circuit 160 may transition into a low emission voltage (VEL) state.\",\n \"If the two global signals are high, the EM2 signal waveform generator circuit 160 may transition into a high emission voltage (VEH) state.\",\n \"If the first global signal (GLB1) is low and the second global signal (GLB2) is high, the EM2 signal waveform generator circuit 160 may maintain an expected emission operation.\",\n \"Moreover, if the first global signal (GLB1) is high and the second global signal (GLB2) is low, the EM2 signal waveform generator circuit 160 may retain the current state of the emission signal.\",\n \"During the sensing operation, the VEL and the VEH edge may be shifted by the sensing time.\",\n \"To ensure proper operation of the EM2 signal waveform generator circuit 160, a minimum EM high (VEH) pulse to disable the emission may be 2H +sensing time.\",\n \"That is, 1H is the line time to apply desired data voltage that corresponds to the desired image to one row of the pixel.\",\n \"If there are N rows in the panel, there will be N line times or N* 1H time.\",\n \"Like the pixel driving circuit 120, although the EM2 signal waveform generator circuit 160 is illustrated using P-type semiconductor devices, it should be noted that these devices may be replaced with N-type semiconductor devices when the VEL and VEH are interchanged and when the polarities of the emission clock signal (ECLK), the global signal (GLB1), and the global signal (GLB2) is reversed.\",\n \"As a result of using the EM2 signal waveform generator circuit 160 as described above, the pixel driving circuit 120 may be capable of pausing the progressive scan of the display 26, as depicted in FIG.\",\n \"7.However, in some instances when the emission rate (e.g., 240 Hz) is faster than the data refresh rate (e.g., 120 Hz), using a single global signal (GLB1) to create an emission time that enables real-time sensing may be extended for an unintended row.\",\n \"For example, FIG.\",\n \"13 illustrates a timing diagram that represents a progressive scan of a data program being performed on the display 26 at 120 Hz while the EM2 signal for real-time sensing is provided to the display 26 at 240 Hz.\",\n \"As seen in FIG.\",\n \"13, because the EM2 signal is provided at 240 Hz, the emission time delay at time t1 for real-time sensing in row Y creates a similar emission time delay for row X for the progressive scan of the data program.\",\n \"To avoid affecting the progressive scan of the data program in the display 26 when performing the real-time sensing techniques described herein with respect to the EM2 signal provided to the display 26, the sensing system 30 may adjust the operation of the pixel driving circuit 120 as will be detailed below.\",\n \"In one embodiment, to prevent the emission delay time provided by the EM2 signal from delaying the progressive scan of the data program, the sensing system 30 may disable the EM2 signal in a preceding frame when real-time sensing is to be performed for a row in a top half of the display 26 for a particular frame.\",\n \"For instance, FIG.\",\n \"14 illustrates the data program of a progressive scan being performed in the first frame and a sensing period 102 being added to the data program of the progressive scan during a second frame.\",\n \"In comparison to the data program illustrated in FIG.\",\n \"13, the EM2 signal preceding the data program of frame 2 is disabled to prevent two rows from experiencing the sensing period 102 at the same time.\",\n \"In another embodiment, if the sensing period is to be performed on a row of the display 26 in the bottom half of the display 26, the sensing system 30 may cause the pixel driving circuit 120 to disable the EM2 signal in the frame that includes the respective row being sensed.\",\n \"For instance, FIG.\",\n \"15 illustrates the data program of a progressive scan being performed in the first frame, followed by the EM2 signal being transmitted in between the first and second frames, and a sensing period 102 being added to the data program of the progressive scan during a third frame and a bottom half of the display 26.As shown in FIG.\",\n \"15, the EM2 signal that would have been transmitted following the data program of frame 2 is disabled to prevent two rows from experiencing the sensing period 102 at the same time.\",\n \"In yet another embodiment, the sensing system 30 may provide separate global signals for the top and bottom halves of the display 26.Referring briefly back to FIG.\",\n \"12, two global signals (e.g., GLB1 and GLB2) may be employed for the EM2 signal generator 160.With this in mind, FIG.\",\n \"16 illustrates an example block diagram of a number of EM2 signal generators 160 that may be employed to transmit EM2 signals to the display 26.As shown in FIG.\",\n \"16, the top half of the display 26 may use two global signals (e.g., GLB1_TOP and GLB2_TOP) as inputs into respective EM2 signal generators 160, and the bottom half of the display 26 may use two global signals (e.g., GLB1_BOT and GLB2_BOT) as inputs into respective EM2 signal generators 160.In this way, since the global signals are separated for the top and bottom halves of the display 26, the sensing performed in one half of the display 26 does not impact the emission time on onset in the other half of the display 26.With the foregoing in mind, FIG.\",\n \"17 illustrates an example circuit diagram for a Scan1 input signal generator 170 that may be coupled to the EM2 signal generator 160.The Scan1 input signal generator 170 may include circuit block 172 and circuit block 174, both of which may be coupled to different portions of the EM2 signal generator 160.The circuit block 172 may receive two signals, each of which may emit a start pulse (EVST1) to the EM2 signal generator 160.One of the two signals provided to the circuit block 172 may include a global start pulse (EVST2) for starting a sensing period 102 in a pixel of a row in the display 26.The other signal provided to the circuit block 172 may include a Scan input signal provided via a previous stage (e.g., frame, row).\",\n \"To determine which source to use to initiate the start pulse (EVST), a 2:1 de-multiplexer 176 may be implemented with two control signals (e.g., CNT_A and CNT_B).\",\n \"In one embodiment, these two control signals may be locally generated in the circuit block 174.According to the circuit block 174, the second control signal (CNT_B) is enabled (e.g., low) or disabled (e.g., high) based on whether a global signal (INIT) is equal to a low emission level (VEL).\",\n \"To enable sensing for row N of the display 26, the sensing system 30 may transition the first global signal (GLB1) signal from high to low at t1, as illustrated in FIG.\",\n \"18.According to the Scan1 input signal generator 170, when the first global signal (GLB1) signal, QB(n), and Scan (N+1) are low, the polarity of the first control signal (CNT_A) and the second control signal (CNT_B) may flip.\",\n \"As a result, for row N, the start pulse (EVST1) may be derived from the global start pulse (EVST2).\",\n \"This helps to delay the start of data programming from row N after the sensing (T_sense) has been performed.\",\n \"The first global signal (GLB1) may remain high to prevent row (N+1) and subsequent rows from activating (e.g., high) during the sensing period 102.FIG.\",\n \"18 illustrates a timing diagram 190 that represents the operation of the Scan1 input signal generator 170.At time t1, the first global signal (GLB1) may be enabled (low) and the initialization signal (INIT) may be disabled (high) just before the Scan1 signal (SCAN (N)) is provided to row N. At time t2, the first global signal (GLB1) may be disabled after the second clock signal (ECLK2) transitions from low to high.\",\n \"At time t3, the falling edge of the global start pulse (EVST2) may determine the falling edge of the Scan1 signal for row N because the control signal (CNT_A) may be enabled.\",\n \"Afterwards, at time t4, the global start pulse (EVST2) may enable the second Scan1 signal for row N. The first Scan1 signal provided just after time t1 may program the pre-defined pixel voltage (V1), as discussed above.\",\n \"The second Scan1 signal just after time t4 may then provide the pixel data voltage (V2) that corresponds to the image data to be depicted in the respective pixel 82.At time t5, the initialization signal (INIT) may be enabled (low) after the second pulse of the Scan1 signal for row N. As a result, the remaining rows after row N may continue receiving their respective pixel data voltages as per the image data.\",\n \"It should be noted again that the Scan1 input signal generator 170 may also be implemented using N-type semiconductor devices if the P-type semiconductor devices are replaced by N- type semiconductor devices, and the high emission voltage (VEH) and low emission voltage (VEL) are interchanged.\",\n \"In addition, the polarities of the clock signal (ECLK), the global signals (GLB1 and GLB2), the initialization signal (INIT), and the start signal (EVST) are reversed.\",\n \"In some embodiments, the global signals (GLB1 and GLB) may be split into multiple signals.\",\n \"That is, the first global signal (GLB1) may be split into a first odd global signal (GLB1_odd) and a first even global signal (GLB1_even) for even and odd stages (e.g., rows).\",\n \"Similarly, the sensing system 30 may also generate two separate global signals for the top half and the bottom half of the display such as signals (GLB1_1 and GLB_2) for global signal (GLB1) and signal (GLB2_1 and GLB2_2) for global signal (GLB2).\",\n \"With the foregoing in mind, FIG.\",\n \"19 illustrates a circuit block diagram 200 that represents how input signals (ECLK1, ECLK2, GLB1, GLB2, INIT) may be provided to the Scan1 input signal generator 170 for each row N of the display 26.In addition, the circuit block diagram 200 illustrates the outputs of the Scan1 input signal generator 170 and the manner in which each output is routed to other Scan1 input signal generators 170 for driving each row of the display 26.The circuitry described above is related to systems and method for incorporating a sensing period during a progressive scan.\",\n \"In some embodiments, it may be useful to incorporate multiple sensing periods for a particular row of pixels on the display 26.With this in mind, the previously described pixel driving circuit 120, as provided in FIG.\",\n \"8, may not be capable of implementing multiple sensing periods for any particular row of pixels.\",\n \"That is, as discussed above, the pixel driving circuit 120 may initiate the sensing period 102 based on either the falling edge of the Scan2 input signal or on the falling edge of the EM2 signal.\",\n \"The rising edge of the Scan2 input signal may then be used to resume the progressive scan for the remaining rows of the display 26, as illustrated in the different driving scheme depicted in FIG.\",\n \"9.Keeping this in mind, in some instances, the TFTs of the various circuits described above may experience the hysteresis effect due to capacitance voltages and other residual electrical and magnetic properties present on the circuit.\",\n \"As such, in certain embodiments, the EM2 signal waveform generator circuit 160 of FIG.\",\n \"12 may be modified to include additional circuit components that enable the display 26 to implement multiple sensing periods 102 during the progressive scan.\",\n \"That is, the sensing system 30 may employ an EM2 signal waveform generator circuit 210, as illustrated in FIG.\",\n \"20, to perform multiple toggles of the sensing period 102, thereby providing the opportunity to apply some reference voltage (Vref) on the capacitor Cst of the pixel driving circuit 120 multiple times.\",\n \"By providing the ability to perform the real-time sensing techniques described herein during multiple sensing periods 102, the waveform generator circuit 210 may improve the ability of the sensing system 30 to determine the sensitivity properties associated with a pixel.\",\n \"In some embodiments, the EM2 signal waveform generator circuit 210 may be arranged like the EM2 signal waveform generator circuit 160 of FIG.\",\n \"12 with additional circuitry that uses a third global signal (GLB3) to implement multiple sensing periods 102 during a progressive scan.\",\n \"For the purposes of discussion, FIG.\",\n \"21 illustrates a timing diagram 220 related to emission signals provided to a number of rows of the display 26 by the pixel driving circuit to provide multiple sensing periods 102 for a respective pixel 82 of the display 26 during a progressive panel scan, in accordance with aspects of the present disclosure.\",\n \"Referring to FIGS.\",\n \"20 and 21, in operation, the EM2 signal waveform generator circuit 210 may operate similarly to the EM2 signal waveform generator circuit 160 of FIG.\",\n \"12.That is, in some embodiments, a first global signal (GLB1) may be positioned in a manner to delay VEH to VEL transition on each EM line downstream of the row (n) that corresponds to the row having the pixel having its sensitivity properties being evaluated.\",\n \"Generally, the TFT Ty may provide positive feedback between nodes Q2 and QB to ensure that VEL to VEH transitions on the EM2 signal occur when the first global signal (GLB1) is provided to the TFT Tx.\",\n \"In addition, the second global signal (GLB2) may provide an extended start pulse for the EM2 signal (n) provide to the sensing row (n).\",\n \"In this way, the EM2 signal output of each row may act as a start pulse for the next row.\",\n \"That is, the EM2 signal for row (n−1) may act as a start pulse for the EM2 signal for row (n).\",\n \"However, due to the sensing time or sensing delay associated with the sensing period 102, the EM2 signal should enable emission (e.g., on emission) for the row (n) even when the EM2 signal for the row (n−1) is already off when an emission clock signal (ECLK) is high.\",\n \"To avoid this issue, the second global signal (GLB2) is provided to the TFT Tz during the sensing period 102.That is, the second global signal GLB2 remains high and prevents TFT Tz from turning on and transitioning the EM2 signal waveform generator circuit 210 to a high emission voltage (VEH) state until the third global signal GLB3 is pulsed to a low voltage level.\",\n \"For example, referring to the timing diagram 220 of FIG.\",\n \"21, at time t0, a start pulse (EVST_EM) may be provided to the EM2 signal waveform generator circuit 210 while the first global signal GLB1 is low.\",\n \"As such, when the first emission clock signal (ECLK1_EM) is pulsed to a low voltage state, the scan lines 1 and 2, which are coupled to the output of the EM2 signal waveform generator circuit 210 become active (e.g., capable of emission).\",\n \"At time t1, the start pulse EVST_EM may return to a low state and thus cause the scan lines 1 and 2 to return to an inactive state upon the falling edge of the first emission clock signal ECLK1_EM.\",\n \"Since the previous emission signals provided to preceding scan lines may be provided to the EM2 signal waveform generator circuit 210 at the source side of the TFT T3, when the emission signals to scan lines 1 and 2 are removed (e.g., transition from high to low at time t1), the emission signals to scan lines 3 and 4 may return to a low voltage state at time t2 after the second emission clock signal ECLK2_EM transitions from high to low, thereby turning off TFT T1.To enable a respective pixel 82 coupled to the EM2 signal waveform generator circuit 210 to implement a sensing period 102, the first global signal GLB1 transitions to a high voltage state just before time t3 when the first emission clock signal ECLK1_EM goes low, while the start pulse EVST_EM is in a low voltage state.\",\n \"At time t3, although the first emission clock signal ECLK1_EM is low, the emission signals for scan lines 5 and 6 remain high (e.g., VEH) because the first global signal GLB1 transitions is in a high voltage state, thereby preventing TFT T1 from turning off and the emission signals for scan lines 5 and 6 from going low (e.g., VEL).\",\n \"However, just before time t4, the first global signal GLB1 may return to a low voltage state, thereby turning TFT TX on.\",\n \"As such, at time t4 when the first emission clock signal ECLK1_EM returns to a low voltage state to allow the respective pixel associated with scan line 5 or 6 with the sensing period 102.That is, the respective pixel may not display color data, but instead perform sensing operations, as discussed above.\",\n \"By way of operation, the EM2 signal waveform generator circuit 210 may use a low voltage pulse provided by the third global signal GLB3 at time t5 to terminate the sensing period 102 for the scan lines 5 and 6.That is, just before time t5, the emission signals to scan lines 3 and 4 are at a low voltage state thereby connecting the high voltage (VEH) to the gate of the TFT T5 via the TFT T4.Moreover, at time t5, the emission signals for scan lines 5 and 6 may return to an off state to enable the respective pixel to receive a data voltage that corresponds to the desired pixel voltage for the respective image data to be depicted via the display 26.With this in mind, just before time t5, TFT T4 remains open and node QB is in a low voltage state and the third global signal GLB3 is provided to the gates of TFTs 2a and 2b via the TFT T11.Since the third global signal GLB3 transitions to a low voltage state at time t5, the TFTs 2a and 2b close at time t5 and return the emission signals for scan lines 5 and 6 to a high voltage state (VEH).\",\n \"The respective pixel 82 may then begin emitting according to the provided data signal after the first global signal GLB1 is returned to a low voltage stage and the first emission clock signal ECLK1_EM subsequently returns to a low voltage state at time t6.The EM2 signal waveform generator circuit 210 may then resume its cyclical operation at time t6, such that the emission signals for scan lines 7 and 8 returns to a low voltage state at time t7 because the emission signals for the preceding scan lines 5 and 6, the first global signal GLB1, and the second emission clock signal ECLK2_EM are in a low voltage state.\",\n \"To ensure that the third global signal GLB3 causes the appropriate sensing period 102 to end, the time period of the third global signal GLB3 may be less than the off period of either emission clock signal (ECLK1 or ECLK2) or approximately between 1 and 2 μs.\",\n \"To reinitiate the progressive scan from at the first scan lines 1 and 2, the start pulse EVST_EM may return to a high voltage state, while the first global signal GLB1 remains low.\",\n \"In some embodiments, the EM2 signal waveform generator circuit 210 may pause the progressive scan of the display 26 by transitioning maintain the second global signal GLB2 at a low voltage state while keeping start pulse EVST_EM is in a high voltage state.\",\n \"The EM2 signal waveform generator circuit 210 may resume the progressive scan by returning the second global signal GLB2 to a high voltage state, as shown just before time t8.At time t8, when the first emission clock goes to a low voltage state, the corresponding emission signals (e.g.\",\n \"for scan lines 5 and 6) will transition to the high voltage state.\",\n \"By integrating the use of the third global signal GLB3 into the EM2 signal waveform generator circuit 210, the EM2 signal waveform generator circuit 210 may enable the progressive scan of the display 26 to implement multiple sensing periods 102.By way of example, FIG.\",\n \"22 illustrates how the first global signal GLB1 may be used to initiate a sensing period 102 and the third global signal GLB3 is used to end a sensing period 102 multiple times on N-type semiconductor devices.\",\n \"That is, like the pixel driving circuit 120 and the EM2 signal waveform generator circuit 160 described above, although the EM2 signal waveform generator circuit 210 is illustrated using P-type semiconductor devices, it should be noted that these devices may be replaced with N-type semiconductor devices when the VEL and VEH are interchanged and when the polarities of the emission clock signals (ECLK1_EM and ECLK2_EM), the global signals (GLB1, GLB2, and GLB3), and the start pulse (EVST_EM) are reversed.\",\n \"With this in mind, FIG.\",\n \"22 depicts a timing diagram 230 that corresponds to implementing multiple sensing periods 102 using the EM2 signal waveform generator circuit 210 equipped with N-type semiconductor devices.\",\n \"As such, the polarities of each signal illustrated in the collection of waveforms 230 is reversed as compared to the polarities of the signals illustrated in FIG.\",\n \"21.Nevertheless, it is apparent from the collection of waveforms 230 that third global signal GLB3 may end a respective sensing period 102 multiple times by way of operation of the EM2 signal waveform generator circuit 210.As a result, sensing system 30 may sense various characteristics of the display 26 multiple times to ensure that the pixels 82 of the display perform in the same manner and provide a consistent picture.\",\n \"That is, by incorporating multiple sensing periods 102, the sensing system 30 may sense a threshold voltage of each pixel, a power output by each pixel, an amount of current provided to each pixel multiple times to ensure that an accurate compensation value is determined for each pixel.\",\n \"The processor(s) 16 may then adjust the data signals provided to each pixel based on the compensation value, as discussed above.\",\n \"The specific embodiments described above have been shown by way of example, and it should be understood that these embodiments may be susceptible to various modifications and alternative forms.\",\n \"It should be further understood that the claims are not intended to be limited to the particular forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874687"}}},{"rowIdx":4494672,"cells":{"text":{"kind":"list like","value":[["DETECT AND DIFFERENTIATE TOUCHES FROM DIFFERENT SIZE CONDUCTIVE OBJECTS ON A CAPACITIVE BUTTON","Apparatuses and methods of distinguishing between a finger and stylus proximate to a touch surface are described.","One apparatus includes a first circuit to obtain capacitance measurements of sense elements when a conductive object is proximate to a touch surface.","The apparatus also includes a second circuit coupled to the first circuit.","The second circuit is operable to detect whether the conductive object activates the first sense element, second sense element, or both, in view of the capacitance measurements.","To distinguish between a stylus and a finger as the conductive object, the second circuit determines the conductive object as being the stylus when the second sense element is activated and the first sense element is not activated and determines the conductive object as being the finger when the first sense element and the second sense element are activated."],["1-20.","(canceled) 21.An apparatus comprising: a processing device coupled to a first electrode and a second electrode, wherein an inner perimeter of the first electrode surrounds an outer perimeter of the second electrode, wherein the processing device is configured to: measure a first capacitance of the first electrode and measure a second capacitance of the second electrode; measure an additional capacitance of the second electrode responsive to the second electrode being in proximity to a conductive object and the first electrode not being in proximity to the conductive object; and distinguish between a first type of conductive object and a second type of conductive object based on the first capacitance and the second capacitance, wherein the conductive object is the first type when the second capacitance indicates that second electrode is in proximity to the conductive object and the first capacitance indicates that the first electrode is not in proximity to the conductive object, and wherein the conductive object is the second type when the first capacitance of the first electrode and the second capacitance of the second electrode indicate that the conductive object is in proximity to both the first and second conductive objects.","22.The apparatus of claim 21, wherein the processing device is further configured to distinguish between a stylus and a finger as the conductive object based on one or more of the first electrode and the second electrode being in proximity to the conductive object.","23.The apparatus of claim 22, wherein one or more of the first electrode and the second electrode is determined to be in proximity to the conductive object based on the first capacitance and the second capacitance, wherein the conductive object is identified as the stylus when the second electrode in proximity to the conductive object and the first electrode is not in proximity to the conductive object, and wherein the conductive object is identified as the finger when the first electrode and the second electrode are both in proximity to the conductive object.","24.The apparatus of claim 21 further comprising: a first circuit coupled with the first electrode and the second electrode; and a second circuit coupled with the first circuit.","25.The apparatus of claim 24, wherein the first circuit is a capacitance-sensing circuit configured to measure signals and to convert the measured signals to digital values representative of capacitance, and wherein the second circuit is processing logic.","26.The apparatus of claim 25, wherein the capacitance-sensing circuit is configured to measure self-capacitances of the first electrode and the second electrode, and wherein the capacitance-sensing circuit is configured to measure a mutual capacitance formed between the first electrode and the second electrode.","27.The apparatus of claim 25 further comprising a third electrode, wherein the capacitance-sensing circuit is configured to drive a first drive signal on the third electrode, wherein the first capacitance is a first mutual capacitance formed between the third electrode and the first electrode, and wherein the second capacitance is a second mutual capacitance formed between the third electrode and the second electrode.","28.The apparatus of claim 27, wherein an inner perimeter of the first electrode is disposed to surround an outer perimeter of the third electrode and an inner perimeter of the third electrode is disposed to surround the outer perimeter of the second electrode.","29.The apparatus of claim 21, wherein the first and the second electrode are formed to define a capacitive touch button.","30.The apparatus of claim 21, wherein an inner perimeter of the first electrode is disposed to surround an outer perimeter of the second electrode.","31.A system comprising: a capacitive button comprising: a first electrode; a second electrode, wherein an inner perimeter of the first electrode surrounds an outer perimeter of the second electrode; a processing device coupled to capacitive button, wherein the processing device is configured to: measure a first capacitance of the first electrode and measure a second capacitance of the second electrode; measure an additional capacitance of the second electrode responsive to the second electrode being in proximity to a conductive object and the first electrode not being in proximity to by the conductive object; and distinguish between a first type of conductive object and a second type of conductive object responsive to one or more of the first electrode and the second electrode detected in proximity to the conductive object, wherein the proximity of the first and second electrode to the conductive object is based on the first capacitance and the second capacitance, wherein the conductive object is the first type when the second electrode is in proximity to the conductive object and the first electrode is not in proximity to the conductive object, and wherein the conductive object is the second type when the first electrode and the second electrode are both in proximity to the conductive object.","32.The system of claim 31, wherein the processing device is further configured to distinguish between a stylus and a finger as the conductive object based on the proximity of one or more of the first electrode and the second electrodes to the conductive object.","33.The system of claim 32, wherein the proximity of one or more of the first electrode and the second electrode is determined based on the first capacitance and the second capacitance, wherein the conductive object is identified as the stylus when the second capacitance is greater than a second threshold and the first capacitance is less than a first threshold, and wherein the conductive object is identified as the finger when the first and second capacitance are greater than the first and second thresholds, respectively.","34.The system of claim 31, wherein the processing device comprises: a first circuit coupled to the capacitive button, wherein the first circuit is a capacitance-sensing circuit configured to measure self-capacitances of the first electrode and the second electrode, and wherein the capacitance-sensing circuit is configured to measure mutual capacitances of intersections associated with the first electrode and the second electrode; and a second circuit coupled to the first circuit, the second circuit comprising processing logic.","35.The system of claim 34 further comprising a third electrode, wherein the capacitance-sensing circuit is configured to drive a first drive signal on the third electrode, wherein the first capacitance is a first mutual capacitance formed between the third electrode and the first electrode, and wherein the second capacitance is a second mutual capacitance formed between the third electrode and the second electrode.","36.The system of claim 35, wherein an inner perimeter of the first electrode is disposed to surround an outer perimeter of the third electrode and an inner perimeter of the third electrode is disposed to surround the outer perimeter of the second electrode.","37.A method comprising: measuring a first capacitance of a first electrode and a second capacitance of a second electrode; measuring an additional capacitance of the second electrode responsive to the second electrode in proximity to a conductive object and the first electrode is not in proximity to the conductive object; and distinguishing between a first type of conductive object and a second type of conductive object responsive to the one or more of the first electrode and the second electrode in proximity to the conductive object, wherein the first and second electrodes in proximity to the conductive object is determined based on the first capacitance and the second capacitance, wherein the conductive object is the first type when the second electrode is in proximity to the conductive object and the first electrode is not in proximity to the conductive object, and wherein the conductive object is the second type when the first electrode and the second electrode are both in proximity to the conductive object.","38.The method of claim 37 further comprising distinguishing between a stylus and a finger as the conductive object based on the one or more of the first electrode and the second electrodes in proximity to the conductive object.","39.The method of claim 38, wherein the proximity of one or more of the first electrode and the second electrode is determined based on the first capacitance and the second capacitance, wherein the conductive object is identified as the stylus when the second capacitance is greater than a second threshold and the first capacitance is less than a first threshold, and wherein the conductive object is identified as the finger when the first and second capacitance are greater than the first and second thresholds, respectively.","40.The method of claim 37, wherein the measuring of the additional capacitance further comprises: adjusting a sensing parameter from a first value to a second value when the second electrode is in proximity to the conductive object and the first electrode is not in proximity to the conductive object; and measuring, with the sensing parameter adjusted to the second value, the additional capacitance of the second electrode."],["<SOH> BACKGROUND <EOH>Capacitance sensing systems can sense electrical signals generated on electrodes that reflect changes in capacitance.","Such changes in capacitance can indicate a human touch event (i.e., the proximity of an object to particular electrodes).","Capacitive sense elements may be used to replace mechanical buttons, knobs and other similar mechanical user interface controls.","The use of a capacitive sense element allows for the elimination of complicated mechanical switches and buttons, providing reliable operation under harsh conditions.","In addition, capacitive sense elements are widely used in modern customer applications, providing new user interface options in existing products.","Capacitive sense elements can range from a single button to a large number arranged in the form of a capacitive sense array for a touch-sensing surface.","Devices that utilize capacitive sense buttons or arrays are ubiquitous in today's industrial and consumer markets.","They can be found on cellular phones, GPS devices, set-top boxes, cameras, computer screens, MP3 players, digital tablets, and the like.","The capacitive sense arrays work by measuring the capacitance of a capacitive sense element, and looking for a delta in capacitance indicating a touch or presence of a conductive object.","When a conductive object (e.g., a finger, hand, or other object) comes into contact or close proximity with a capacitive sense element, the capacitance changes and the conductive object is detected.","The capacitance changes of the capacitive touch sense elements can be measured by an electrical circuit.","The electrical circuit converts the measured capacitances of the capacitive sense elements into digital values.","There are two typical types of capacitance: 1) mutual capacitance where the capacitance-sensing circuit has access to both electrodes of the capacitor; 2) self-capacitance where the capacitance-sensing circuit has only access to one electrode of the capacitor where the second electrode is tied to a DC voltage level or is parasitically coupled to Earth Ground.","A touch panel has a distributed load of capacitance of both types (1) and (2) and Cypress' touch solutions sense both capacitances either uniquely or in hybrid form with its various sense modes."],["<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The present invention is illustrated by way of example, and not of limitation, in the figures of the accompanying drawings.","FIG.","1 illustrates a capacitive button according to one implementation.","FIG.","2 illustrates a capacitive button according to one embodiment.","FIG.","3 illustrates a capacitive button according to another embodiment.","FIG.","4 illustrates a block diagram of one embodiment of an electronic system 400 including a processing device that may be configured to measure capacitances of a capacitive button 421 .","FIG.","5 is a block diagram illustrating another embodiment of an electronic system that processed touch data of a capacitive button.","FIG.","6 illustrates capacitance output of digital converter with a finger touch according to one embodiment.","FIG.","7 is a flow diagram of a method of sensing a capacitive button according to one embodiment.","FIG.","8 illustrates two capacitive buttons according to another embodiment.","FIG.","9 is a block diagram of a mobile device with a touchscreen and two capacitive buttons according to one embodiment.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["RELATED APPLICATIONS This application is a Continuation of U.S. patent application Ser.","No.","15/660,754, filed Jul.","26, 2017, which is a Continuation of U.S. patent application Ser.","No.","14/468,630, filed Aug. 26, 2014, now U.S. Pat.","No.","9,746,507, issued Aug. 29, 2017, which is a Continuation of U.S. patent application Ser.","No.","14/224,854, filed Mar.","25, 2014, now U.S. Pat.","No.","8,823,399, issued Sep. 2, 2014, which claims the benefit of U.S.","Provisional Application No.","61/887,868, filed Oct. 7, 2013, all of which are incorporated by reference herein.","TECHNICAL FIELD The present disclosure relates generally to sensing systems, and more particularly to capacitance-sensing systems configurable to detect and differentiate touches from different size conductive objects on a capacitive button.","BACKGROUND Capacitance sensing systems can sense electrical signals generated on electrodes that reflect changes in capacitance.","Such changes in capacitance can indicate a human touch event (i.e., the proximity of an object to particular electrodes).","Capacitive sense elements may be used to replace mechanical buttons, knobs and other similar mechanical user interface controls.","The use of a capacitive sense element allows for the elimination of complicated mechanical switches and buttons, providing reliable operation under harsh conditions.","In addition, capacitive sense elements are widely used in modern customer applications, providing new user interface options in existing products.","Capacitive sense elements can range from a single button to a large number arranged in the form of a capacitive sense array for a touch-sensing surface.","Devices that utilize capacitive sense buttons or arrays are ubiquitous in today's industrial and consumer markets.","They can be found on cellular phones, GPS devices, set-top boxes, cameras, computer screens, MP3 players, digital tablets, and the like.","The capacitive sense arrays work by measuring the capacitance of a capacitive sense element, and looking for a delta in capacitance indicating a touch or presence of a conductive object.","When a conductive object (e.g., a finger, hand, or other object) comes into contact or close proximity with a capacitive sense element, the capacitance changes and the conductive object is detected.","The capacitance changes of the capacitive touch sense elements can be measured by an electrical circuit.","The electrical circuit converts the measured capacitances of the capacitive sense elements into digital values.","There are two typical types of capacitance: 1) mutual capacitance where the capacitance-sensing circuit has access to both electrodes of the capacitor; 2) self-capacitance where the capacitance-sensing circuit has only access to one electrode of the capacitor where the second electrode is tied to a DC voltage level or is parasitically coupled to Earth Ground.","A touch panel has a distributed load of capacitance of both types (1) and (2) and Cypress' touch solutions sense both capacitances either uniquely or in hybrid form with its various sense modes.","BRIEF DESCRIPTION OF THE DRAWINGS The present invention is illustrated by way of example, and not of limitation, in the figures of the accompanying drawings.","FIG.","1 illustrates a capacitive button according to one implementation.","FIG.","2 illustrates a capacitive button according to one embodiment.","FIG.","3 illustrates a capacitive button according to another embodiment.","FIG.","4 illustrates a block diagram of one embodiment of an electronic system 400 including a processing device that may be configured to measure capacitances of a capacitive button 421.FIG.","5 is a block diagram illustrating another embodiment of an electronic system that processed touch data of a capacitive button.","FIG.","6 illustrates capacitance output of digital converter with a finger touch according to one embodiment.","FIG.","7 is a flow diagram of a method of sensing a capacitive button according to one embodiment.","FIG.","8 illustrates two capacitive buttons according to another embodiment.","FIG.","9 is a block diagram of a mobile device with a touchscreen and two capacitive buttons according to one embodiment.","DETAILED DESCRIPTION In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention.","It will be evident, however, to one skilled in the art that the present invention may be practiced without these specific details.","In other instances, well-known circuits, structures, and techniques are not shown in detail, but rather in a block diagram in order to avoid unnecessarily obscuring an understanding of this description.","Reference in the description to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention.","The phrase “in one embodiment” located in various places in this description does not necessarily refer to the same embodiment.","Apparatuses and methods of capacitive buttons and detecting and differentiating touches from different size conductive objects on the capacitive buttons.","One apparatus includes a capacitance-sensing circuit coupled to a capacitive button.","The capacitive button includes a first sense element and a second sense element.","The capacitance-sensing circuit is operative to measure signals from the first sense element and the second sense element with a sensing parameter set to a first value (also referred to as tuning properties).","The signals correspond to capacitances of the first sense element and second sense element.","An inner perimeter of the first sense element is disposed to surround an outer perimeter of the second sense element.","It should be noted that “surround” as used herein means the sense element is disposed to completely surround the other sense element in a circular fashion or to surround most of the other sense element.","That is, it is not required that the outer sense element completely encircle the inner sense element for proper operation.","For example, the sense elements may have shapes that prevent the outer sense element from completely encircling the inner sense element, but surrounds most of the inner sense element or a majority of the inner sense element.","The apparatus further includes processing logic coupled to the capacitance-sensing circuit.","The processing logic is operative to detect whether the first sense element is activated by a conductive object proximate to the capacitive button based on the measured signals.","The processing logic detects whether the second sense element is activated by the conductive object proximate to the capacitive button based on the measured signals.","The processing logic adjusts the sensing parameter to a second value when the second sense element is activated and the first sense element is not activated.","The capacitance-sensing circuit is operative to measure an additional signal from the second sense element with the sensing parameter set to the second value when the second sense element is activated and the first sense element is not activated.","The capacitance-sensing circuit measures additional signals from the first sense element and the second sense element with the sensing parameter set to the first value when the first and second sense elements are activated.","In some embodiments, a surface area of the second sense element is at least partially encompassed by the first sense element.","In other embodiments, the first sense element encompasses an area of the second sense element.","In other embodiments, at least a portion of the first sense element is at least partially outside an outer perimeter of the second sense element.","In other embodiments, touches from objects with 1 mm, 3 mm 5 mm and 10 mm diameter can be detected using this technique.","For each diameter, there needs would be separate values used for the sensing parameter.","In other embodiments more sense elements than just two sense elements (inner and outer) can be added.","Additional sense elements may increase the accuracy of detection from objects of multiple sizes, for example.","It should be noted that in the embodiments described herein discuss the capacitive button has having sense elements.","The sense elements are electrodes disposed in various configurations and the self-capacitance of an electrode or a mutual capacitance between two electrodes can be measured to detect a conductive object proximate to the capacitive sense button.","Sense elements are sometimes referred to as sensors, but it should be understood that the sensors do not include circuitry to measure the capacitance.","Rather, capacitance-sensing circuit, which can also be referred to as a capacitance sensor, measures the capacitances of the sensors (herein referred to as electrodes or sense elements).","Various embodiments described herein may be used in other touch sensing technologies than just capacitive buttons.","FIG.","1 illustrates a capacitive button 100 according to one implementation.","Conventionally, implementation of the capacitive button 100 can be used to detect a touch from a conductive object.","The capacitive button 100 can include a capacitive sense element 102 that can be tuned by a touch controller (not illustrated in FIG.","1) to detect a touch by a conductive object of a specific size or dimension.","That is a sensing parameter, such as sensitivity of measurements of the capacitive sense element 102 can be programmed for an expected size of conductive objects to be interacting with the capacitive button 100.Although this sensing parameter may be tunable to detect different sizes of conductive objects for different applications, such as to detect fingers or to detect styli.","That is the touch controller is programmed with one sensitivity value before operation to detect fingers and the touch controller can also be programmed with another sensitivity value before operation to detect styli.","It was not possible with the conventional touch controller to effectively detect and differentiate touches from conductive objects with two different sizes and dimensions.","For example, it is not possible to efficiently detect and differentiate touches from a human finger, typically has 10 mm diameter, and touches from small conductive objectives like 3 mm stylus, these solutions have various limitations to accommodate both types of touches.","Styli can be other diameters like 4 mm, 3 mm, or 1 mm.","The capacitive button 100 includes an optional hole 103 used for backlight.","The capacitive button 100 is disposed within a touch area 205.Today, users frequently operate devices with capacitive technologies both with their fingers and a stylus.","Currently, the only method to detect touches from both smaller conductive objects from bigger conductive objects is to make the capacitance-sensing circuit to be more sensitive to detect the touches from both big and small conductive objects.","This may create false touches or a “hover effect” for touches from larger conductive objects.","For example, making a sense element have very high sensitivity to detect touches from smaller objects makes the sense element extremely sensitive to touches from bigger fingers, creating a “hover” effect for bigger fingers.","This may reduce the immunity of the sense element to external noises and can create false touches in presence of external noises.","As such, making the sense element to have higher sensitivity can only be used to detect touches from small conductive objects, but it cannot differentiate touches from small and big fingers.","FIG.","2 illustrates a capacitive button 200 according to one embodiment.","The capacitive button 200 includes a first sense element 202 and a second sense element 204 that can be used to detect a conductive object proximate to the capacitive button 200.The capacitive button 200 includes an optional hole 203 used for an optional backlight.","In other embodiments, different size objects can be detected with or without the optional hole 203.The capacitive button 200 is disposed within a touch area 205.In this embodiment, the touch area 205 (or a physical sense element such as sense element 102 previously used in the touch area 105) is split into two different sense elements 202, 204.The capacitive button 200 can be used in connection with a touch controller, such as a processing device including a capacitance-sensing circuit and processing logic, to detect and differentiate between touch objects with different sizes and dimensions.","The first sense element 202 is considered an outer sense element (or outer electrode) and the second sense element 204 is considered an inner sense element 204 (or inner electrode).","An inner perimeter of the first sense element 202 is disposed to surround, at least in part or in whole, an outer perimeter of the second sense element 204.These sense elements 202, 204 are connected to two sense pins (or terminals or inputs) of a capacitive touch controller (not illustrated in FIG.","2).","As described in more detail below, a signal produced by the outer sense element 202 is used detect size of a touch object, as well as to dynamically modify one or more tuning parameters used by the capacitive touch controller to measure signals on the inner sense element 204.The inner sense element 204 is used to detect touches from a larger conductive object like a finger.","Then, based on the signal produced by the outer sense element 202, the one or more tuning parameters of the capacitive touch controller to measure signals on the inner sense element 202 are dynamically modified to detect and differentiate touches by larger and smaller conductive objects, such as fingers and styli.","In other embodiments, both sense elements 202, 204 can be used together to track the touches by the larger conductive objects once a large conductive object is differentiated from a smaller conductive object.","Similarly, once a smaller object is differentiated, both sense elements 202, 204 can be used together to track touches by the smaller conductive object.","In other embodiments, additional sense elements than two sense elements can be used to detect different types of conductive objects (e.g., between finger and stylus or between big finger and smaller finger).","For example, self-capacitance measurements of more than two sense elements can be used to detect and differentiate multiple finger sizes with more accuracy.","The outer sense element 202 and inner sense element 204 can be conductive materials like copper, indium tin oxide (ITO), carbon, silver or the like.","The outer sense element 202 and inner sense element 204 can be constructed on a printed circuit board (PCB), a touch screen, plexi-glass, or the like.","Using the capacitive button 200, the touch controller can measure self-capacitance of the outer sense element 202 and inner sense element 204.In other embodiments, the touch controller can measure mutual capacitance of a capacitive button, such as illustrated and described with respect to FIG.","3.FIG.","3 illustrates a capacitive button 300 according to another embodiment.","The capacitive button 300 includes a first sense element 302, a second sense element 304, and a third sense element 306 that can be used to detect a conductive object proximate to the capacitive button 300.The capacitive button 300 includes a hole 303 used for an optional backlight.","The capacitive button 300 is disposed within a touch area 305.In this embodiment, the touch area 305 (or a physical sense element such as sense element 102 previously used in the touch area 105) is split into three different sense elements 302, 304, 306.The capacitive button 300 can be used in connection with a touch controller, such as a processing device including a capacitance-sensing circuit and processing logic, to detect and differentiate between touch objects with different sizes and dimensions.","The first sense element 302 is considered an outer sense element (or outer electrode), the second sense element 304 is considered an inner sense element 304 (or inner electrode), and the third sense element 306 is considered a middle sense element 306 (or middle electrode).","An inner perimeter of the first sense element 302 is disposed to surround, at least in part or in whole, an outer perimeter of the second sense element 304.The inner perimeter of the first sense element 302 is also disposed to surround an outer perimeter of the third sense element 306 and an inner perimeter of the third sense element 306 is disposed to surround the outer perimeter of the second sense element 304.These sense elements 302, 304, 306 are connected to three sense pins (or terminals or inputs) of a capacitive touch controller (not illustrated in FIG.","3).","The middle sense element 306 can be used by the touch controller as a transmit (TX) electrode for a TX drive signal and the outer sense element 302 and the inner sense element 304 can be used by the touch controller as receive (RX) electrodes to measure RX signals on the RX electrodes caused by the TX signal applied to the TX electrode.","As described in more detail below, a signal produced by the outer sense element 302 is used detect size of a touch object, as well as to dynamically modify one or more tuning parameters used by the capacitive touch controller to measure signals on the inner sense element 304.The inner sense element 304 is used to detect touches from a larger conductive object like a finger.","Then, based on the signal produced by the outer sense element 302, the one or more tuning parameters of the capacitive touch controller to measure signals on the inner sense element 302 are dynamically modified to detect and differentiate touches by larger and smaller conductive objects, such as fingers and styli.","In other embodiments, both sense elements 302, 304 can be used together to track touches by the larger conductive objects once a large conductive object is differentiated from a smaller conductive object.","Similarly, once a smaller object is differentiated, both sense elements 302, 304 can be used together to track touches by the smaller conductive object.","The outer sense element 302, inner sense element 304, and middle sense element 306 can be conductive materials like copper, ITO, carbon, silver or the like.","The outer sense element 302, inner sense element 304, and middle sense element 306 can be constructed on a PCB, a touch screen, plexi-glass, or the like.","Using the capacitive button 300, the touch controller can measure a mutual capacitance between the middle sense element 306 and outer sense element 302 and a mutual capacitance between the middle sense element 306 and inner sense element 304.In other embodiments where two sense elements (instead of three sense elements) are used, the touch controller can also measure a mutual capacitance between the two sense elements in connection with measuring the self-capacitance of the two sense elements.","There are two types of capacitive sensing methods, mutual capacitive sensing and self-capacitance sensing, that can be used for measuring capacitance(s) of the capacitive buttons 200, 300.When implementing the capacitive button solution using self-capacitance sensing, only two electrodes are used (inner and outer).","The outer sense element may be big in size, as compared to the inner sense element.","When a finger (big finger) approaches the button touch area, the outer sense element produces a large signal as finger covers the complete area of outer sense element electrode.","When button is touched using smaller conductive object, like a smaller finger or a stylus, no area of the outer sense element is covered by the small finger (or stylus); therefore, no signal or a smaller signal is produced on the outer sense element when the capacitive button is touched by small finger.","The tuning properties of inner sense element are modified based on the signal produced by outer sense element to detect a touch.","When there is no signal or a small signal produced by outer sense element electrode, the inner sense element is tuned to detect touches from the smaller finger (or stylus).","When the outer sense element produces a large signal, the large signal indicates a presence of larger finger; therefore, tuning properties of inner sense element is modified to detect touches of big finger.","When implementing the capacitive button solution using mutual capacitance sensing, three electrodes are used for sensing, including one transmit electrode and two receive electrodes.","In some embodiments, such as illustrated in FIG.","3, the transmit electrode is a middle electrode disposed between an outer electrode and an inner electrode.","The outer electrode is placed around the transmit electrode and the transmit electrode is placed around the inner electrode.","The embodiments described herein implement detection of different size conductive objects, such as different sizes of fingers.","The embodiments described herein implement detection of different types of conductive objects based on size.","That is the embodiments implement detection and differentiation of a finger touch from a stylus touch as described herein.","Touches from a small finger may be detected by tuning at least one of the sense elements to a higher sensitivity.","Tuning the sense element makes the sense element more sensitive to touches by conductive objects proximate to the capacitive button.","A sense element with very high sensitivity can detect the touches from smaller objects, such as a smaller finger or a stylus.","The embodiments described herein can provide various advantages or benefits as the conventional solutions.","For example, the touches from stylus and touches from smaller human fingers can be detected without making the sense element overly sensitive for touches from larger human fingers.","The embodiments may also avoid a “hover” effect on a capacitive button while implementing stylus and finger touches.","The embodiments may avoid or greatly reduces the probability for false touches from a capacitive button when it is tuned for higher sensitivity to detect smaller fingers.","The embodiments may enable detection of touches from multiple sizes of fingers, like 10 mm or larger human finger, 3 mm stylus and 1 mm stylus.","The embodiments can be used to not only detect touches by big and small fingers, but also differentiate between touches by big and small fingers and report that detected touch on the capacitive button was by a big or small finger.","There is no additional material cost for the embodiments described herein to detect touches and differentiate those touches as being by a stylus and a finger.","Also, the embodiments described herein can be implemented using existing touch controllers.","It should be noted that touch controllers in the embodiments above measure capacitance(s) of the capacitive button.","In other embodiments, other circuitry can be used to measure the capacitance(s) of the capacitive button.","In one embodiment, a processing device, including a capacitance-sensing circuit and processing logic, can be used to measure capacitances as described herein and differentiate between touches by larger conductive objects and smaller conductive objects.","The embodiment described herein, as compared to conventional solutions, can offer finger and passive stylus touch detection on capacitive buttons without additional cost or system-level implementation complications.","Providing the passive stylus detection and on capacitive button may provide seamless user interface experience for users.","The embodiments described herein can be used in touch screen applications, as well as in other touch sensitive interfaces.","For example, the capacitive buttons and corresponding method of operating the same can be implemented in products that are operated using finger and stylus.","Examples for such products may include touchscreen smart phones, tablets, mobile phones, media devices, game consoles, or other consumer electronics.","The embodiments described herein may also be used in control panels of various devices, including appliances.","For example, a control panel can differentiate between a smaller finger, such as that of a child, from a larger finger for safety purposes.","Also, the ability to differentiate between different size touches can be used in other applications, where a device performs different operations based on the different size of touches detected.","These embodiments can be used in any device to enable the stylus and finger detection on one or more capacitive buttons.","This may permit the devices to have a better, intuitive user interface experience, as well as create more design possibilities for these types of devices, especially mobile devices.","In other embodiments, the self-capacitance measurement and mutual-capacitance measurements, such as described with respect to FIGS.","2 and 3, can be used to implement a water tolerance solution.","For example, each sense element (inner and outer) can be configured as self-capacitance sense elements to be used to detect finger or stylus.","Then one of the two sense elements can be configured as a TX electrode (inner or outer) and the other one of the two sense elements can be configured to be an RX electrode and a mutual capacitance between the TX electrode and the RX electrode can be measured.","The self-capacitance measurement can be used to detect different size fingers and stylus.","A water droplet (which is an ungrounded conductor) has different signal profiles for self-capacitance measurement and for mutual capacitance measurement.","This difference in signal profile can be used to detect and differentiate between whether water or finger is present on the sense elements, and the self-capacitance measurements can be used to identify whether the object is a finger or a stylus as described herein.","The embodiments described herein may also be used to detect and differentiate touches from different types of touch objects, such as a touch from a bare finger and a touch from a finger covered in a glove.","For example, a stylus has small tip and touches the sensor on very limited area, as compared to a gloved finger that has as large area.","However, the glove finger produces a smaller signal than the finger without a glove.","So the signal amplitude and pattern for a stylus, gloved finger and finger (without glove) will be different for each.","The stylus may also result in a small amount of signal on the inner sense element and very small or no signal on the outer sense element.","A gloved finger, however, results in a small amount of signal on both inner and outer sense elements because the gloved finger covers both the inner and outer sense elements, as compared to a stylus that does not cover both.","A finger without a glove results in a larger amount of signal on inner sense element, as well as on the outer sense element, as compared to the signal produced by the gloved finger.","Also, in other embodiments, two or more sense elements can be ganged together to form one larger sense element for different purposes.","FIG.","4 illustrates a block diagram of one embodiment of an electronic system 400 including a processing device 410 that may be configured to measure capacitances of a capacitive button 421.The electronic system 400 includes a capacitive button 421 coupled to the processing device 410.The capacitive button 421 may be the capacitive button 200 or the capacitive button 300.The processing device is coupled to a host 450.In one embodiment, a multiplexer circuit may be used to connect a capacitance-sensing circuit 401 of the processing device 410 with a capacitive button 421.In one embodiment, the capacitive button 421 is disposed in connection a touch-sensing surface 416 of the electronic system 400.The electrodes of the capacitive button 421 can be disposed beneath an overlay, cover of the device, or the like.","As described herein, the capacitive button 421 can include two electrodes, such as for self-capacitance sensing embodiments, or can include three electrodes, such as for mutual capacitance sensing embodiments.","The capacitive button 421 may also be one of many capacitive buttons.","The electrodes of the capacitive button 421 are coupled to pins 413(1)-413(N) of the processing device 410 via one or more analog buses 415 transporting multiple signals.","In an alternative embodiment without an analog bus, each pin may instead be connected either to a circuit that generates a transmit (TX) signal or to an individual receive (RX) channel of the capacitance-sensing circuit.","The capacitive button 421 may be disposed to have a flat surface profile.","Alternatively, the capacitive button 421 may have non-flat surface profiles.","Alternatively, other configurations, layout, combinations of one or more capacitive buttons may be used.","In one embodiment, the capacitive button 421 may be included in an ITO panel or a touch screen panel.","In other embodiments, the capacitive button 421 can be implemented separate from the ITO panel or touch screen.","In one embodiment, the capacitance-sensing circuit 401 may include a relaxation oscillator or other means to convert a capacitance into a measured value.","The capacitance-sensing circuit 401 may also include a counter or timer to measure the oscillator output.","The processing device 410 may further include software components to convert the count value (e.g., capacitance value) into a touch detection decision (also referred to as switch detection decision) or relative magnitude.","It should be noted that there are various known methods for measuring capacitance, such as current versus voltage phase shift measurement, resistor-capacitor charge timing, capacitive bridge divider, charge transfer, successive approximation, sigma-delta modulators, charge-accumulation circuits, field effect, mutual capacitance, frequency shift, or other capacitance measurement algorithms.","It should be noted however, instead of evaluating the raw counts relative to a threshold, the capacitance-sensing circuit 401 may be evaluating other measurements to determine the user interaction.","For example, in the capacitance-sensing circuit 401 having a sigma-delta modulator, the capacitance-sensing circuit 401 is evaluating the ratio of pulse widths of the output (i.e., density domain), instead of the raw counts being over or under a certain threshold.","In another embodiment, the capacitance-sensing circuit 401 includes a TX signal generator to generate a TX signal to be applied to the TX electrode and a receiver (also referred to as a sensing channel), such as an integrator, coupled to measure an RX signal on the RX electrode.","In a further embodiment, the capacitance-sensing circuit includes an analog-to-digital converter (ADC) coupled to an output of the receiver to convert the measured RX signal to a digital value (capacitance value).","The processing device 410, the host 450 or both, can further process the digital value.","The processing device 410 is configured to detect one or more touches on one or more of the capacitive button(s) 421.The processing device 410 can detect conductive objects, such as touch objects (fingers or passive styluses, an active stylus, or any combination thereof).","The capacitance-sensing circuit 401 can measure touch data on the capacitive button 421.In some cases, the capacitive button 421 can be considered a unit cell of one or more electrodes.","In some cases, a unit cell is the electrode itself.","In other cases, a unit cell is an intersection between two or more electrodes.","For example, when multiple electrodes are measured, the touch data may be represented as multiple cells, each cell representing an intersection of sense elements (e.g., electrodes) of the capacitive button 421.An intersection between two sense elements may be understood as a location at which one sense electrode crosses over or overlaps another, while maintaining galvanic isolation from each other.","The capacitive sense elements are electrodes of conductive material, such as copper.","The sense elements may also be part of an ITO panel.","The capacitive sense elements can be configurable to allow the capacitance-sensing circuit 401 to measure self-capacitance, mutual capacitance, or any combination thereof.","In another embodiment, the processing device 410 is a microcontroller that obtains a capacitance touch signal data set, and finger detection firmware executing on the microcontroller identifies data set areas that indicate touches, detects and processes peaks, calculates the coordinates, differentiates between smaller and larger touches, or any combination therefore.","The microcontroller can report the precise coordinates to a host processor 450, as well as other information.","In one embodiment, the processing device 410 further includes processing logic 402.Operations of the processing logic 402 may be implemented in firmware; alternatively, they may be implemented in hardware or software.","The processing logic 402 may receive signals from the capacitance-sensing circuit 401, and determine the state of the capacitive button 421, such as whether an object (e.g., a finger) is detected on or in proximity to the capacitive button 421 (e.g., determining the presence of the object), or other information related to an object detected at the capacitive button 421.For example, the processing logic 402 can differentiate between touches by smaller and larger conductive objects as described herein.","In one embodiment, the processing logic 402 is processing logic that can be programmed to perform various functions.","In another embodiment, instead of performing the operations of the processing logic 402 in the processing device 410, the processing device 410 may send the raw data or partially processed data to the host 450.The host 450, as illustrated in FIG.","4, may include decision logic 451 that performs some or all of the operations of the processing logic 402.Operations of the decision logic 451 may be implemented in firmware, hardware, software, or a combination thereof.","The host 450 may include a high-level Application Programming Interface (API) in applications 452 that perform routines on the received data, such as compensating for sensitivity differences, other compensation algorithms, baseline update routines, start-up and/or initialization routines, interpolation operations, or scaling operations.","The operations described with respect to the processing logic 402 may be implemented in the decision logic 451, the applications 452, or in other hardware, software, and/or firmware external to the processing device 410.In some other embodiments, the processing device 410 is the host 450.In another embodiment, the processing device 410 may also include a non-sensing actions block 403.This block 403 may be used to process and/or receive/transmit data to and from the host 450.For example, additional components may be implemented to operate with the processing device 410 along with the capacitive button 421 (e.g., keyboard, keypad, mouse, trackball, LEDs, displays, or other peripheral devices).","As illustrated, capacitance-sensing circuit 401 may be integrated into processing device 410.Capacitance-sensing circuit 401 may include analog I/O for coupling to an external component, such the capacitive button 421, and/or touch-sensor pad (not shown), touch-sensor slider (not shown), touch-sensor buttons (not shown), touch screen and/or other devices.","The capacitance-sensing circuit 401 may be configurable to measure capacitance using mutual-capacitance sensing techniques, self-capacitance sensing technique, charge coupling techniques, or the like.","In one embodiment, capacitance-sensing circuit 401 operates using a charge accumulation circuit, a capacitance modulation circuit, or other capacitance sensing methods known by those skilled in the art.","In an embodiment, the capacitance-sensing circuit 401 is of the Cypress TMA-3xx, TMA-4xx, or TMA-xx families of touch screen controllers.","Alternatively, other capacitance-sensing circuits may be used.","The capacitive button 42 may include may include a portion (or all) that is transparent and disposed on, in, or under either a visual display itself (e.g.","LCD monitor), or a transparent substrate in front of the display.","When a touch object, such as a finger or stylus, approaches the capacitive button 421, the object causes a decrease in mutual capacitance between some of the TX/RX electrodes.","In another embodiment, the presence of a finger increases the coupling capacitance of the electrodes.","For example, in self-capacitance sensing, the self-capacitance may increase when a touch object approaches the capacitive button 42a.","It should also be noted that the embodiments described herein are not limited to having a configuration of a processing device coupled to a host, but may include a system that measures the capacitance on the sensing device and sends the raw data to a host computer where it is analyzed by an application.","In effect, the processing that is done by processing device 410 may also be done in the host.","The processing device 410 may reside on a common carrier substrate such as, for example, an integrated circuit (IC) die substrate, or a multi-chip module substrate.","Alternatively, the components of the processing device 410 may be one or more separate integrated circuits and/or discrete components.","In one embodiment, the processing device 410 may be the Programmable System on a Chip (PSoC®) processing device, developed by Cypress Semiconductor Corporation, San Jose, Calif. Alternatively, the processing device 410 may be one or more other processing devices known by those of ordinary skill in the art, such as a microprocessor or central processing unit, a controller, special-purpose processor, digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other programmable device.","In an alternative embodiment, for example, the processing device 410 may be a network processor having multiple processors including a core unit and multiple micro-engines.","Additionally, the processing device 410 may include any combination of general-purpose processing device(s) and special-purpose processing device(s).","Capacitance-sensing circuit 401 may be integrated into the IC of the processing device 410, or alternatively, in a separate IC.","Alternatively, descriptions of capacitance-sensing circuit 401 may be generated and compiled for incorporation into other integrated circuits.","For example, behavioral level code describing the capacitance-sensing circuit 401, or portions thereof, may be generated using a hardware descriptive language, such as VHDL or Verilog, and stored to a machine-accessible medium (e.g., CD-ROM, hard disk, floppy disk, etc.).","Furthermore, the behavioral level code can be compiled into register transfer level (“RTL”) code, a netlist, or even a circuit layout and stored to a machine-accessible medium.","The behavioral level code, the RTL code, the netlist, and the circuit layout may represent various levels of abstraction to describe capacitance-sensing circuit 404.It should be noted that the components of electronic system 400 may include all the components described above.","Alternatively, electronic system 400 may include some of the components described above.","In one embodiment, the electronic system 400 is used in a tablet computer.","Alternatively, the electronic device may be used in other applications, such as a notebook computer, a mobile handset, a personal data assistant (“PDA”), a keyboard, a television, a remote control, a monitor, a handheld multi-media device, a handheld media (audio and/or video) player, a handheld gaming device, a signature input device for point of sale transactions, an eBook reader, global position system (“GPS”) or a control panel.","The embodiments described herein are not limited to capacitive buttons in touch-sensitive interfaces, but can be used in other capacitive sensing implementations.","For example, the capacitive button can be used in connection with any sensing device, such as a touch screen, touch pad, touch-sensor slider (not shown) or a panel of touch-sensor buttons.","In one embodiment, these sensing devices include one or more capacitive sensors or other types of capacitance-sensing circuitry.","The operations described herein are not limited to device button operations, but can include other operations, such as lighting control (dimmer), volume control, graphic equalizer control, speed control, or other control operations requiring gradual or discrete adjustments.","It should also be noted that these embodiments of capacitive sensing implementations may be used in conjunction with non-capacitive sensing elements, including but not limited to pick buttons, sliders (ex.","display brightness and contrast), scroll-wheels, multi-media control (ex.","volume, track advance, etc.)","handwriting recognition, and numeric keypad operation.","In another embodiment, the processing device 410 is coupled to a capacitive button 421 includes at least two electrodes disposed such that an inner perimeter of a first electrode of the at least two electrodes at least partially surrounds an outer perimeter of a second electrode of the at least two electrodes.","The processing device 410 is operative to detect a combination of activations of the first electrode and the second electrode caused by a conductive object proximate to the capacitive button 421.The processing device 410 distinguishes between a first type of conductive object and a second type of conductive object based on the combination of activations.","The combination of activations may include a combination of measured signals from the first electrode and the second electrode.","The combination of measured signals may be the result of self-capacitance measurements of the first electrode and the second electrode.","In another embodiment, the processing device is further operative to apply a first drive signal to a third electrode of the at least two electrodes of the capacitive button.","In this case, the combination of activations includes a combination of measured signals from the first electrode and the second electrode.","The combination of measured receive signals may be the result of mutual-capacitance measurements between the third electrode and the first electrode and between the third electrode and the second electrode.","In one embodiment, an inner perimeter of the third electrode at least partially surrounds the outer perimeter of the second electrode and the inner perimeter of the first electrode at least partially surrounds an outer perimeter of the third electrode.","In one embodiment, the processing device includes a capacitance-sensing circuit coupled to the first electrode and the second electrode, such as capacitance-sensing circuit 401.The capacitance-sensing circuit is operative to measure a first self-capacitance of the first electrode and a second self-capacitance of the second electrode.","The processing device 410 is operative to compare the first and second self-capacitances against one or more thresholds to detect the combination of activations.","In another embodiment, the processing device 410 is coupled to the three electrodes and the capacitance-sensing circuit is operative to measure a first mutual capacitance between the third electrode and the first electrode and a second mutual capacitance between the third electrode and the second electrode.","The processing device 410 is operative to compare the first and second mutual capacitances against one or more thresholds to detect the combination of activations.","FIG.","5 is a block diagram illustrating another embodiment of an electronic system 500 that processed touch data of a capacitive button in a capacitive sense array 521.The capacitive sense array 521 include NXM electrode matrix including multiple capacitive buttons.","A capacitance-sensing circuit 501 may measure mutual capacitances for intersections between the transmit and receive electrodes in the respective capacitive buttons of the sense array 521.The activations of the capacitive buttons are calculated based on changes in the measured capacitances relative to the capacitances of the same touch capacitive button in an un-touched state.","In one embodiment, capacitive sense array 521 and capacitance-sensing circuit 501 are implemented in a system or device such as electronic system 400.Capacitive sense array 521 includes a matrix 525 of NxM capacitive buttons, with each capacitive button including and one TX electrode 522 and two RX electrodes 523.The electrodes in the matrix are connected with capacitance sensing circuit 501 through demultiplexer 512 and multiplexer 513.That is the TX electrodes can be connected to the demultiplexer 512 and the RX electrodes can be coupled to the multiplexer 513 to permit multiple electrodes to be driven or sensed by the capacitance-sensing circuit 501.Capacitance-sensing circuit 501 includes multiplexer control 511, demultiplexer 512, multiplexer 513, clock generator 514, signal generator 515, demodulation circuit 516, and analog to digital converter (ADC) 517.ADC 517 is further coupled with touch coordinate converter 518.Touch coordinate converter 518 may be implemented in the processing logic 402.The transmit and receive electrodes in the electrode matrix 525 may be arranged so that each of the transmit electrodes overlap and cross each of the receive electrodes such as to form an array of intersections, while maintaining galvanic isolation from each other.","Thus, each transmit electrode may be capacitively coupled with each of the receive electrodes.","For example, transmit electrode 522 is capacitively coupled with two receive electrode 523 at the point where transmit electrode 522 and receive electrodes 523 overlap.","Clock generator 514 supplies a clock signal to signal generator 515, which produces a TX signal 524 to be supplied to the transmit electrode 522 of touch capacitive button.","In one embodiment, the signal generator 515 includes a set of switches that operate according to the clock signal from clock generator 514.The switches may generate a TX signal 524 by periodically connecting the output of signal generator 515 to a first voltage and then to a second voltage, where said first and second voltages are different.","The output of signal generator 515 is connected with demultiplexer 512, which allows the TX signal 524 to be applied to any of the M transmit electrodes of capacitive buttons.","In one embodiment, multiplexer control 511 controls demultiplexer 512 so that the TX signal 524 is applied to each transmit electrode 522 in a controlled sequence.","Demultiplexer 512 may also be used to ground, float, or connect an alternate signal to the other transmit electrodes to which the TX signal 524 is not currently being applied.","In an alternate embodiment the TX signal 524 may be presented in a true form to a subset of the transmit electrodes 522 and in complement form to a second subset of the transmit electrodes 522.There may be no overlap in members of the first and second subset of transmit electrodes 522.Because of the capacitive coupling between the transmit and receive electrodes, the TX signal 524 applied to each transmit electrode induces a current within each of the receive electrodes.","For instance, when the TX signal 524 is applied to transmit electrode 252 through demultiplexer 512, the TX signal 524 induces an RX signal 527 on the receive electrodes in matrix 525.The RX signal 527 on each of the receive electrodes can then be measured in sequence by using multiplexer 513 to connect each of the N receive electrodes to demodulation circuit 516 in sequence.","The mutual capacitance associated with the intersections of all TX electrodes and RX electrodes can be measured by selecting every available combination of TX electrode and an RX electrode using demultiplexer 512 and multiplexer 513.To improve performance, multiplexer 513 may also be segmented to allow more than one of the receive electrodes in matrix 525 to be routed to additional demodulation circuits 516.In an optimized configuration, wherein there is a 1-to-1 correspondence of instances of demodulation circuit 516 with receive electrodes, multiplexer 513 may not be present in the system.","When a conductive object, such as a finger, approaches the electrode matrix 525, the object causes a decrease in the measured mutual capacitance between only some of the electrodes.","For example, if a finger is placed near the intersection of transmit electrode 522 and receive electrode 523, the presence of the finger will decrease the charge coupled between electrodes 522 and 523.Thus, the location of the finger on the touchpad can be determined by identifying the one or more receive electrodes having a decrease in measured mutual capacitance in addition to identifying the transmit electrode to which the TX signal 524 was applied at the time the decrease in capacitance was measured on the one or more receive electrodes.","By determining changes in the mutual capacitances associated with each intersection of electrodes in the matrix 525, the presence and locations of one or more conductive objects may be determined.","The determination may be sequential, in parallel, or may occur more frequently at commonly used electrodes.","In alternative embodiments, other methods for detecting the presence of a finger or other conductive object may be used where the finger or conductive object causes an increase in measured capacitance at one or more electrodes, which may be arranged in a grid or other pattern.","For example, a finger placed near an electrode of a capacitance-sensing circuit may introduce an additional capacitance to ground that increases the total capacitance between the electrode and ground.","The location of the finger can be determined based on the locations of one or more electrodes at which a change in measured capacitance is detected, and the associated magnitude of capacitance change at each respective electrode.","Demodulation circuit 516 integrates the induced current signal 527.The rectified current output by demodulation circuit 516 can then be filtered and converted to a digital code by ADC 517.A series of such digital codes measured from adjacent electrode intersections, when compared to or offset by the associated codes of these same electrodes in an un-touched state, may be converted to touch coordinates indicating a position of an input on touch capacitive button by touch coordinate converter 518.The touch coordinates may then be used to detect gestures or perform other functions by the processing logic 402.For self-capacitance sensing, a sense element has capacitance associated with the sense element, which is referred as parasitic capacitance CP.","When finger touches sensing area, an additional capacitance is added to circuit due to the presence of human finger.","This capacitance is referred as finger capacitance CF.","The total capacitance of sense element without finger presence is equal to CP of sense element and with presence, it is sum of CP and CF.","A capacitance-sensing circuit, such as a touch controller, implements a Capacitance-to-Digital Converter to convert the measured capacitances to digital values (also called digital counts).","When there is a finger touch, there is an increase in the output of capacitance to count converter as illustrated in FIG.","6.FIG.","6 illustrates capacitance output 600 of digital converter with a finger touch according to one embodiment.","The raw counts are the digital values corresponding to the measured capacitances on the sense element.","The baseline is initialized to raw counts at system start.","Later, it slowly tracks raw counts if variation in raw counts is less than noise threshold.","This feature helps to adapt to different environment conditions and avoid false touch detection.","A signal is calculated by subtracting the baseline from raw counts.","This represents capacitance added by finger touch.","The finger threshold defines the increase in capacitance on sense element, which can be qualified as a valid touch.","The finger threshold value can be changed dynamically as one of the tuning parameters as described herein.","The output of capacitance to ‘digital count converter’ is passed through a simple signal processing algorithms to detect increase in sense element capacitance due to finger touch.","Firmware algorithms use this information to differentiate between an actual finger touch and spurious noise, such as any minimal capacitances induced by variance in temperature, pressure or other environmental factors.","If the increase in sense element capacitance is more than a predetermined value (also called finger threshold), the touch controller declares presence of finger on the sense element.","Capacitive sensing devices may use charge transfer and delta-sigma modulator based capacitance to digital conversion (referred as CSD) and charge transfer and successive approximation based sensing methods (referred as CSA).","Alternatively, other methods of measuring capacitance can be used to convert capacitance to digital counts.","Regardless of the conversion method, the embodiments described herein detect and differentiate touches from big and small fingers or stylus.","For mutual capacitance sensing, the capacitance that exists between two electrodes are measured using a capacitance to digital count converter sensing method.","With finger presence, there is decrease in capacitance between two electrodes and the algorithm to detect finger presence measures the difference in capacitance.","Described bellow is a method that enables detection of small and big finger touches without the capacitive button being overly sensitive to big finger touches.","This method requires different types of sense element construction and decision logic.","A touch by small finger (e.g.","touches from a stylus) and big finger (human finger) touch surface area of sense element shall produce a combination of signals from sense elements.","The combination of signals can be used to differentiate or otherwise identify small and big finger touches.","In the following method, it is assumed that 8 mm represents a big finger and 3 mm represents a stylus or a small finger.","FIG.","7 is a flow diagram of a method of sensing a capacitive button according to one embodiment.","The method 700 may be performed by processing logic that may include hardware (circuitry, dedicated logic, etc.","), software (such as is run on a general purpose computing system or a dedicated machine), firmware (embedded software), or any combination thereof.","In one embodiment, the processing device 410 of FIG.","4 performs some or all of method 700.In another embodiment, the processing logic 402 of FIG.","4 or FIG.","5 performs some or all of the operations of method 700.In other embodiments, the capacitance-sensing circuit 401 of FIG.","4, or the capacitance-sensing circuit 501 of FIG.","5, performs some of the operations of method 700.Alternatively, other components of the electronic system 400 of FIG.","4 perform some or all of the operations of method 700.In FIG.","7, method 700 begins with the processing logic initializing sense elements and setting default finger thresholds (e.g., 3 mm stylus threshold for inner sense element) (block 702).","The processing logic scans an inner sense element and an outer sense element and updates a baseline for both sense elements (block 704).","The processing logic determines if the outer sense element is active (block 706).","When the outer sense element is not active at block 706, the processing logic sets the 3 mm stylus threshold for the inner sensor element (block 708).","However, when the outer sense element is active at block 706, the processing logic sets 8 mm finger threshold for inner sense element (block 710).","At block 712, the processing logic determines if both inner and outer sense elements are active.","When the processing logic determines that both inner and outer sense elements are active at block 712, the processing logic detects the 8 mm finger on the capacitive button (block 714) and returns to block 704.When the processing logic determines that both inner and outer sense elements are not active at block 712, the processing logic determines if only the inner sense element is active (block 716).","If the inner sense element is active at block 716, the processing logic increments a 3 mm stylus delay counter (block 718).","However, if the inner sense element is not active at block 716, the processing logic determines if a 3 mm stylus mode timeout happened (block 724).","If the 3 mm stylus mode timeout did happen at block 724, the processing logic resets the 3 mm stylus delay counter and continues back to block 704.When the 3 mm stylus mode timeout happened, the processing logic continues to block 704.When the 3 mm stylus delay counter is incremented, the processing logic determines if the 3 mm stylus delay counter is in an overflow condition (block 720).","When in overflow at block 720, the processing logic detects the 3 mm finger on the capacitive button (block 722); otherwise, the method 700 continues back to block 704.In this embodiment, two sense elements can be used.","In another embodiment, the method 700 scans three sense elements as described herein.","In another embodiment of a method, the processing logic measures signals from a first sense element and a second sense element of a capacitive button using a capacitance-sensing circuit programmed with a sensing parameter set to a first value.","The signals correspond to capacitances of the first sense element and the second sense element.","An inner perimeter of the first sense element is disposed to surround an outer perimeter of the second sense element.","The processing logic detects, by processing logic whether a conductive object proximate to the capacitive button activates the first sense element based on the measured signals.","The processing logic detects, by the processing logic, whether the conductive object proximate to the capacitive button activates the second sense element based on the measured signals.","The processing logic adjusts, by the processing logic, the sensing parameter set to the first value to a second value when the second sense element is activated and the first sense element is not activated.","The processing logic measures an additional signal from the second sense element using the capacitance-sensing circuit with the sensing parameter set to the second value when the second sense element is activated and the first sense element is not activated.","In a further embodiment, the processing logic measuring, by the capacitance-sensing circuit with the sensing parameter set to the first value, additional signals from the first sense element and the second sense element when the second sense element and the first sense element are activated.","In another embodiment, the measuring with the sensing parameter set to the first value or the second value includes measuring self-capacitances of the first sense element and the second sense element.","Alternatively, the processing logic, by the capacitance-sensing circuit, applies or drives a first drive signal on a third sense element of the capacitive button.","The measuring may be done with the sensing parameter set to the first value or the second value to measure a first mutual capacitance between the third sense element and the first sense element and a second mutual capacitance between the third sense element and the second sense element.","The processing logic distinguishes between a first type of conductive object and a second type of conductive object using the processing logic based on the signals measured with the sensing parameter set to the first value.","The conductive object is the first type when the second sense element is activated and the first sense element is not activated and the conductive object is the second type when the first sense element and the second sense element are activated.","In another embodiment, the processing logic distinguishes between a stylus and a finger as the conductive object.","The conductive object is the stylus when the second sense element is activated and the first sense element is not activated and the conductive object is the finger when the first sense element and the second sense element are activated.","In another embodiment, the processing logic measures the signals from the first sense element and the second sense element using a first sensitivity and measures the additional signal using a second sensitivity.","The first sensitivity is less than the second sensitivity.","Alternatively, multiple activation thresholds can be used as the tuning parameters.","Instead of changing the sensitivity of the capacitance-sensing circuit, the finger or stylus thresholds can be adjusted.","In another embodiment, the processing logic measures the signals from the first sense element and the second sense element and compares the signals against a first activation threshold and measures the additional signal and compares the additional signal against a second activation threshold.","The first activation threshold is higher than the second activation threshold.","FIG.","8 illustrates two capacitive buttons 800 according to another embodiment.","The two capacitive buttons 800 may be used as buttons on a mobile phone, as illustrated in FIG.","10.FIG.","9 is a block diagram of a mobile device 900 with a touchscreen 902 and two capacitive buttons 904, 906 according to one embodiment.","The mobile device 900 also includes a host processor 950 and a processing device 910.The processing device 910 can be a touch controller that controls the touchscreen 902 in connection with the host processor 950.In addition, the processing device 910 can detect touches on capacitive buttons 904 and 906 as described herein.","Described herein is a new sense element layout for detecting and differentiating touches from big and small fingers or styli.","The old sense element layout is illustrated in FIG.","1 and embodiments of the news sense element layout is illustrated in FIGS.","2, 3 and 8.Also, described herein is a new data processing algorithm for detecting and differentiating touches from big and small fingers or styli.","One embodiment of this new data processing algorithm is illustrated in FIG.","7.The embodiments described herein have the ability to detect and differentiate touches from finger with smaller diameter and touches from finger with bigger diameter on a capacitive button, without making capacitive button overly sensitive to false touches from bigger fingers.","The embodiments also have the ability to detect and differentiate human finger touch and passive stylus touch on a capacitive button.","These embodiments can also avoid false touches caused by the hover effect on sense element when operating with big finger.","The embodiments described herein may also have the ability to reject touches when human finger is not exactly on button.","For example, an algorithm can accurately accept/reject when human finger is overlapping with button below certain percentage set in firmware, such as illustrated in Table 1 below.","Table 1 includes signal measurements from inner and outer sense elements: Signal from Signal from outer sense inner sense Output of decision # Input element element logic/algorithm 1 Big Finger, 75 20 Reject - low signal 25% touch on inner sense element (8 mm finger) 2 Big Finger, 105 40 Accept - good signal 50% touch on inner and outer (8 mm finger) sense elements 3 Big Finger, 120 90 Accept - good signal 100% touch on inner and outer (8 mm finger) sense elements 4 Small Finger 45 20 Reject - low signal on outer sense from inner sense element (3 mm element stylus) 5 Small Finger 30 30 Accept - good signal on inner sense on inner and outer element (3 mm sense elements stylus) 6 Small Finger 35 30 Accept - good signal at center (3 mm on inner and outer stylus) sense elements In some embodiments, the tuning parameter can be dynamically changed to detect small and big fingers based on a host command.","In this case, the end product of application needs “somehow need to know” whether user is operating the product with small of big finger.","In other embodiments, the processing logic can automatically detect and differentiate the big and small finger touches without a command from host.","The processing logic can be implemented in a capacitive touch screen controller.","In one embodiment, the capacitive touch screen controller is the TrueTouch® capacitive touchscreen controllers, such as the CY8CTMA3xx family of TrueTouch® Multi-Touch All-Points touchscreen controllers, developed by Cypress Semiconductor Corporation of San Jose, Calif.","The TrueTouch® capacitive touchscreen controllers sensing technology to resolve touch locations of multiple fingers and a stylus on the touch-screens, supports leading operating systems, and is optimized for low-power multi-touch gesture and all-point touchscreen functionality.","Alternatively, the touch position calculation features may be implemented in other touchscreen controllers, or other touch controllers of touch-sensing devices.","In one embodiment, the touch position calculation features may be implemented with other touch filtering algorithms as would be appreciated by one of ordinary skill in the art having the benefit of this disclosure.","The embodiments described herein may be used in various designs of mutual-capacitance sensing arrays of the capacitance sensing system, or in self-capacitance sensing arrays.","In one embodiment, the capacitance sensing system detects multiple sense elements that are activated in the array, and can analyze a signal pattern on the neighboring sense elements to separate noise from actual signal.","The embodiments described herein are not tied to a particular capacitive sensing solution and can be used as well with other sensing solutions, including optical sensing solutions, as would be appreciated by one of ordinary skill in the art having the benefit of this disclosure.","In the above description, numerous details are set forth.","It will be apparent, however, to one of ordinary skill in the art having the benefit of this disclosure, that embodiments of the present invention may be practiced without these specific details.","In some instances, well-known structures and devices are shown in block diagram form, rather than in detail, in order to avoid obscuring the description.","Some portions of the detailed description are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory.","These algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art.","An algorithm is here and generally, conceived to be a self-consistent sequence of steps leading to a desired result.","The steps are those requiring physical manipulations of physical quantities.","Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared and otherwise manipulated.","It has proven convenient at times, principally for reasons of common usage, to refer to these signals as bits, values, elements, symbols, characters, terms, numbers or the like.","It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities.","Unless specifically stated otherwise as apparent from the above discussion, it is appreciated that throughout the description, discussions utilizing terms such as “encrypting,” “decrypting,” “storing,” “providing.” “deriving,” “obtaining,” “receiving,” “authenticating.” “deleting,” “executing,” “requesting.” “communicating,” or the like, refer to the actions and processes of a computing system, or similar electronic computing device, that manipulates and transforms data represented as physical (e.g., electronic) quantities within the computing system's registers and memories into other data similarly represented as physical quantities within the computing system memories or registers or other such information storage, transmission or display devices.","The words “example” or “exemplary” are used herein to mean serving as an example, instance or illustration.","Any aspect or design described herein as “example’ or “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs.","Rather, use of the words “example” or “exemplary” is intended to present concepts in a concrete fashion.","As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or.” That is, unless specified otherwise, or clear from context, “X includes A or B” is intended to mean any of the natural inclusive permutations.","That is, if X includes A; X includes B; or X includes both A and B, then “X includes A or B” is satisfied under any of the foregoing instances.","In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form.","Moreover, use of the term “an embodiment” or “one embodiment” or “an implementation” or “one implementation” throughout is not intended to mean the same embodiment or implementation unless described as such.","Embodiments descried herein may also relate to an apparatus for performing the operations herein.","This apparatus may be specially constructed for the required purposes, or it may comprise a general-purpose computer selectively activated or reconfigured by a computer program stored in the computer.","Such a computer program may be stored in a non-transitory computer-readable storage medium, such as, but not limited to, any type of disk including floppy disks, optical disks, CD-ROMs and magnetic-optical disks, read-only memories (ROMs), random access memories (RAMs), EPROMs, EEPROMs, magnetic or optical cards, flash memory, or any type of media suitable for storing electronic instructions.","The term “computer-readable storage medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database and/or associated caches and servers) that store one or more sets of instructions.","The term “computer-readable medium” shall also be taken to include any medium that is capable of storing, encoding or carrying a set of instructions for execution by the machine and that causes the machine to perform any one or more of the methodologies of the present embodiments.","The term “computer-readable storage medium” shall accordingly be taken to include, but not be limited to, solid-state memories, optical media, magnetic media, any medium that is capable of storing a set of instructions for execution by the machine and that causes the machine to perform any one or more of the methodologies of the present embodiments.","The algorithms and displays presented herein are not inherently related to any particular computer or other apparatus.","Various general-purpose systems may be used with programs in accordance with the teachings herein, or it may prove convenient to construct a more specialized apparatus to perform the required method steps.","The required structure for a variety of these systems will appear from the description below.","In addition, the present embodiments are not described with reference to any particular programming language.","It will be appreciated that a variety of programming languages may be used to implement the teachings of the embodiments as described herein.","The above description sets forth numerous specific details such as examples of specific systems, components, methods and so forth, in order to provide a good understanding of several embodiments of the present invention.","It will be apparent to one skilled in the art, however, that at least some embodiments of the present invention may be practiced without these specific details.","In other instances, well-known components or methods are not described in detail or are presented in simple block diagram format in order to avoid unnecessarily obscuring the present invention.","Thus, the specific details set forth above are merely exemplary.","Particular implementations may vary from these exemplary details and still be contemplated to be within the scope of the present invention.","It is to be understood that the above description is intended to be illustrative and not restrictive.","Many other embodiments will be apparent to those of skill in the art upon reading and understanding the above description.","The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled."]],"string":"[\n [\n \"DETECT AND DIFFERENTIATE TOUCHES FROM DIFFERENT SIZE CONDUCTIVE OBJECTS ON A CAPACITIVE BUTTON\",\n \"Apparatuses and methods of distinguishing between a finger and stylus proximate to a touch surface are described.\",\n \"One apparatus includes a first circuit to obtain capacitance measurements of sense elements when a conductive object is proximate to a touch surface.\",\n \"The apparatus also includes a second circuit coupled to the first circuit.\",\n \"The second circuit is operable to detect whether the conductive object activates the first sense element, second sense element, or both, in view of the capacitance measurements.\",\n \"To distinguish between a stylus and a finger as the conductive object, the second circuit determines the conductive object as being the stylus when the second sense element is activated and the first sense element is not activated and determines the conductive object as being the finger when the first sense element and the second sense element are activated.\"\n ],\n [\n \"1-20.\",\n \"(canceled) 21.An apparatus comprising: a processing device coupled to a first electrode and a second electrode, wherein an inner perimeter of the first electrode surrounds an outer perimeter of the second electrode, wherein the processing device is configured to: measure a first capacitance of the first electrode and measure a second capacitance of the second electrode; measure an additional capacitance of the second electrode responsive to the second electrode being in proximity to a conductive object and the first electrode not being in proximity to the conductive object; and distinguish between a first type of conductive object and a second type of conductive object based on the first capacitance and the second capacitance, wherein the conductive object is the first type when the second capacitance indicates that second electrode is in proximity to the conductive object and the first capacitance indicates that the first electrode is not in proximity to the conductive object, and wherein the conductive object is the second type when the first capacitance of the first electrode and the second capacitance of the second electrode indicate that the conductive object is in proximity to both the first and second conductive objects.\",\n \"22.The apparatus of claim 21, wherein the processing device is further configured to distinguish between a stylus and a finger as the conductive object based on one or more of the first electrode and the second electrode being in proximity to the conductive object.\",\n \"23.The apparatus of claim 22, wherein one or more of the first electrode and the second electrode is determined to be in proximity to the conductive object based on the first capacitance and the second capacitance, wherein the conductive object is identified as the stylus when the second electrode in proximity to the conductive object and the first electrode is not in proximity to the conductive object, and wherein the conductive object is identified as the finger when the first electrode and the second electrode are both in proximity to the conductive object.\",\n \"24.The apparatus of claim 21 further comprising: a first circuit coupled with the first electrode and the second electrode; and a second circuit coupled with the first circuit.\",\n \"25.The apparatus of claim 24, wherein the first circuit is a capacitance-sensing circuit configured to measure signals and to convert the measured signals to digital values representative of capacitance, and wherein the second circuit is processing logic.\",\n \"26.The apparatus of claim 25, wherein the capacitance-sensing circuit is configured to measure self-capacitances of the first electrode and the second electrode, and wherein the capacitance-sensing circuit is configured to measure a mutual capacitance formed between the first electrode and the second electrode.\",\n \"27.The apparatus of claim 25 further comprising a third electrode, wherein the capacitance-sensing circuit is configured to drive a first drive signal on the third electrode, wherein the first capacitance is a first mutual capacitance formed between the third electrode and the first electrode, and wherein the second capacitance is a second mutual capacitance formed between the third electrode and the second electrode.\",\n \"28.The apparatus of claim 27, wherein an inner perimeter of the first electrode is disposed to surround an outer perimeter of the third electrode and an inner perimeter of the third electrode is disposed to surround the outer perimeter of the second electrode.\",\n \"29.The apparatus of claim 21, wherein the first and the second electrode are formed to define a capacitive touch button.\",\n \"30.The apparatus of claim 21, wherein an inner perimeter of the first electrode is disposed to surround an outer perimeter of the second electrode.\",\n \"31.A system comprising: a capacitive button comprising: a first electrode; a second electrode, wherein an inner perimeter of the first electrode surrounds an outer perimeter of the second electrode; a processing device coupled to capacitive button, wherein the processing device is configured to: measure a first capacitance of the first electrode and measure a second capacitance of the second electrode; measure an additional capacitance of the second electrode responsive to the second electrode being in proximity to a conductive object and the first electrode not being in proximity to by the conductive object; and distinguish between a first type of conductive object and a second type of conductive object responsive to one or more of the first electrode and the second electrode detected in proximity to the conductive object, wherein the proximity of the first and second electrode to the conductive object is based on the first capacitance and the second capacitance, wherein the conductive object is the first type when the second electrode is in proximity to the conductive object and the first electrode is not in proximity to the conductive object, and wherein the conductive object is the second type when the first electrode and the second electrode are both in proximity to the conductive object.\",\n \"32.The system of claim 31, wherein the processing device is further configured to distinguish between a stylus and a finger as the conductive object based on the proximity of one or more of the first electrode and the second electrodes to the conductive object.\",\n \"33.The system of claim 32, wherein the proximity of one or more of the first electrode and the second electrode is determined based on the first capacitance and the second capacitance, wherein the conductive object is identified as the stylus when the second capacitance is greater than a second threshold and the first capacitance is less than a first threshold, and wherein the conductive object is identified as the finger when the first and second capacitance are greater than the first and second thresholds, respectively.\",\n \"34.The system of claim 31, wherein the processing device comprises: a first circuit coupled to the capacitive button, wherein the first circuit is a capacitance-sensing circuit configured to measure self-capacitances of the first electrode and the second electrode, and wherein the capacitance-sensing circuit is configured to measure mutual capacitances of intersections associated with the first electrode and the second electrode; and a second circuit coupled to the first circuit, the second circuit comprising processing logic.\",\n \"35.The system of claim 34 further comprising a third electrode, wherein the capacitance-sensing circuit is configured to drive a first drive signal on the third electrode, wherein the first capacitance is a first mutual capacitance formed between the third electrode and the first electrode, and wherein the second capacitance is a second mutual capacitance formed between the third electrode and the second electrode.\",\n \"36.The system of claim 35, wherein an inner perimeter of the first electrode is disposed to surround an outer perimeter of the third electrode and an inner perimeter of the third electrode is disposed to surround the outer perimeter of the second electrode.\",\n \"37.A method comprising: measuring a first capacitance of a first electrode and a second capacitance of a second electrode; measuring an additional capacitance of the second electrode responsive to the second electrode in proximity to a conductive object and the first electrode is not in proximity to the conductive object; and distinguishing between a first type of conductive object and a second type of conductive object responsive to the one or more of the first electrode and the second electrode in proximity to the conductive object, wherein the first and second electrodes in proximity to the conductive object is determined based on the first capacitance and the second capacitance, wherein the conductive object is the first type when the second electrode is in proximity to the conductive object and the first electrode is not in proximity to the conductive object, and wherein the conductive object is the second type when the first electrode and the second electrode are both in proximity to the conductive object.\",\n \"38.The method of claim 37 further comprising distinguishing between a stylus and a finger as the conductive object based on the one or more of the first electrode and the second electrodes in proximity to the conductive object.\",\n \"39.The method of claim 38, wherein the proximity of one or more of the first electrode and the second electrode is determined based on the first capacitance and the second capacitance, wherein the conductive object is identified as the stylus when the second capacitance is greater than a second threshold and the first capacitance is less than a first threshold, and wherein the conductive object is identified as the finger when the first and second capacitance are greater than the first and second thresholds, respectively.\",\n \"40.The method of claim 37, wherein the measuring of the additional capacitance further comprises: adjusting a sensing parameter from a first value to a second value when the second electrode is in proximity to the conductive object and the first electrode is not in proximity to the conductive object; and measuring, with the sensing parameter adjusted to the second value, the additional capacitance of the second electrode.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Capacitance sensing systems can sense electrical signals generated on electrodes that reflect changes in capacitance.\",\n \"Such changes in capacitance can indicate a human touch event (i.e., the proximity of an object to particular electrodes).\",\n \"Capacitive sense elements may be used to replace mechanical buttons, knobs and other similar mechanical user interface controls.\",\n \"The use of a capacitive sense element allows for the elimination of complicated mechanical switches and buttons, providing reliable operation under harsh conditions.\",\n \"In addition, capacitive sense elements are widely used in modern customer applications, providing new user interface options in existing products.\",\n \"Capacitive sense elements can range from a single button to a large number arranged in the form of a capacitive sense array for a touch-sensing surface.\",\n \"Devices that utilize capacitive sense buttons or arrays are ubiquitous in today's industrial and consumer markets.\",\n \"They can be found on cellular phones, GPS devices, set-top boxes, cameras, computer screens, MP3 players, digital tablets, and the like.\",\n \"The capacitive sense arrays work by measuring the capacitance of a capacitive sense element, and looking for a delta in capacitance indicating a touch or presence of a conductive object.\",\n \"When a conductive object (e.g., a finger, hand, or other object) comes into contact or close proximity with a capacitive sense element, the capacitance changes and the conductive object is detected.\",\n \"The capacitance changes of the capacitive touch sense elements can be measured by an electrical circuit.\",\n \"The electrical circuit converts the measured capacitances of the capacitive sense elements into digital values.\",\n \"There are two typical types of capacitance: 1) mutual capacitance where the capacitance-sensing circuit has access to both electrodes of the capacitor; 2) self-capacitance where the capacitance-sensing circuit has only access to one electrode of the capacitor where the second electrode is tied to a DC voltage level or is parasitically coupled to Earth Ground.\",\n \"A touch panel has a distributed load of capacitance of both types (1) and (2) and Cypress' touch solutions sense both capacitances either uniquely or in hybrid form with its various sense modes.\"\n ],\n [\n \"<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The present invention is illustrated by way of example, and not of limitation, in the figures of the accompanying drawings.\",\n \"FIG.\",\n \"1 illustrates a capacitive button according to one implementation.\",\n \"FIG.\",\n \"2 illustrates a capacitive button according to one embodiment.\",\n \"FIG.\",\n \"3 illustrates a capacitive button according to another embodiment.\",\n \"FIG.\",\n \"4 illustrates a block diagram of one embodiment of an electronic system 400 including a processing device that may be configured to measure capacitances of a capacitive button 421 .\",\n \"FIG.\",\n \"5 is a block diagram illustrating another embodiment of an electronic system that processed touch data of a capacitive button.\",\n \"FIG.\",\n \"6 illustrates capacitance output of digital converter with a finger touch according to one embodiment.\",\n \"FIG.\",\n \"7 is a flow diagram of a method of sensing a capacitive button according to one embodiment.\",\n \"FIG.\",\n \"8 illustrates two capacitive buttons according to another embodiment.\",\n \"FIG.\",\n \"9 is a block diagram of a mobile device with a touchscreen and two capacitive buttons according to one embodiment.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"RELATED APPLICATIONS This application is a Continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/660,754, filed Jul.\",\n \"26, 2017, which is a Continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/468,630, filed Aug. 26, 2014, now U.S. Pat.\",\n \"No.\",\n \"9,746,507, issued Aug. 29, 2017, which is a Continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/224,854, filed Mar.\",\n \"25, 2014, now U.S. Pat.\",\n \"No.\",\n \"8,823,399, issued Sep. 2, 2014, which claims the benefit of U.S.\",\n \"Provisional Application No.\",\n \"61/887,868, filed Oct. 7, 2013, all of which are incorporated by reference herein.\",\n \"TECHNICAL FIELD The present disclosure relates generally to sensing systems, and more particularly to capacitance-sensing systems configurable to detect and differentiate touches from different size conductive objects on a capacitive button.\",\n \"BACKGROUND Capacitance sensing systems can sense electrical signals generated on electrodes that reflect changes in capacitance.\",\n \"Such changes in capacitance can indicate a human touch event (i.e., the proximity of an object to particular electrodes).\",\n \"Capacitive sense elements may be used to replace mechanical buttons, knobs and other similar mechanical user interface controls.\",\n \"The use of a capacitive sense element allows for the elimination of complicated mechanical switches and buttons, providing reliable operation under harsh conditions.\",\n \"In addition, capacitive sense elements are widely used in modern customer applications, providing new user interface options in existing products.\",\n \"Capacitive sense elements can range from a single button to a large number arranged in the form of a capacitive sense array for a touch-sensing surface.\",\n \"Devices that utilize capacitive sense buttons or arrays are ubiquitous in today's industrial and consumer markets.\",\n \"They can be found on cellular phones, GPS devices, set-top boxes, cameras, computer screens, MP3 players, digital tablets, and the like.\",\n \"The capacitive sense arrays work by measuring the capacitance of a capacitive sense element, and looking for a delta in capacitance indicating a touch or presence of a conductive object.\",\n \"When a conductive object (e.g., a finger, hand, or other object) comes into contact or close proximity with a capacitive sense element, the capacitance changes and the conductive object is detected.\",\n \"The capacitance changes of the capacitive touch sense elements can be measured by an electrical circuit.\",\n \"The electrical circuit converts the measured capacitances of the capacitive sense elements into digital values.\",\n \"There are two typical types of capacitance: 1) mutual capacitance where the capacitance-sensing circuit has access to both electrodes of the capacitor; 2) self-capacitance where the capacitance-sensing circuit has only access to one electrode of the capacitor where the second electrode is tied to a DC voltage level or is parasitically coupled to Earth Ground.\",\n \"A touch panel has a distributed load of capacitance of both types (1) and (2) and Cypress' touch solutions sense both capacitances either uniquely or in hybrid form with its various sense modes.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The present invention is illustrated by way of example, and not of limitation, in the figures of the accompanying drawings.\",\n \"FIG.\",\n \"1 illustrates a capacitive button according to one implementation.\",\n \"FIG.\",\n \"2 illustrates a capacitive button according to one embodiment.\",\n \"FIG.\",\n \"3 illustrates a capacitive button according to another embodiment.\",\n \"FIG.\",\n \"4 illustrates a block diagram of one embodiment of an electronic system 400 including a processing device that may be configured to measure capacitances of a capacitive button 421.FIG.\",\n \"5 is a block diagram illustrating another embodiment of an electronic system that processed touch data of a capacitive button.\",\n \"FIG.\",\n \"6 illustrates capacitance output of digital converter with a finger touch according to one embodiment.\",\n \"FIG.\",\n \"7 is a flow diagram of a method of sensing a capacitive button according to one embodiment.\",\n \"FIG.\",\n \"8 illustrates two capacitive buttons according to another embodiment.\",\n \"FIG.\",\n \"9 is a block diagram of a mobile device with a touchscreen and two capacitive buttons according to one embodiment.\",\n \"DETAILED DESCRIPTION In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention.\",\n \"It will be evident, however, to one skilled in the art that the present invention may be practiced without these specific details.\",\n \"In other instances, well-known circuits, structures, and techniques are not shown in detail, but rather in a block diagram in order to avoid unnecessarily obscuring an understanding of this description.\",\n \"Reference in the description to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention.\",\n \"The phrase “in one embodiment” located in various places in this description does not necessarily refer to the same embodiment.\",\n \"Apparatuses and methods of capacitive buttons and detecting and differentiating touches from different size conductive objects on the capacitive buttons.\",\n \"One apparatus includes a capacitance-sensing circuit coupled to a capacitive button.\",\n \"The capacitive button includes a first sense element and a second sense element.\",\n \"The capacitance-sensing circuit is operative to measure signals from the first sense element and the second sense element with a sensing parameter set to a first value (also referred to as tuning properties).\",\n \"The signals correspond to capacitances of the first sense element and second sense element.\",\n \"An inner perimeter of the first sense element is disposed to surround an outer perimeter of the second sense element.\",\n \"It should be noted that “surround” as used herein means the sense element is disposed to completely surround the other sense element in a circular fashion or to surround most of the other sense element.\",\n \"That is, it is not required that the outer sense element completely encircle the inner sense element for proper operation.\",\n \"For example, the sense elements may have shapes that prevent the outer sense element from completely encircling the inner sense element, but surrounds most of the inner sense element or a majority of the inner sense element.\",\n \"The apparatus further includes processing logic coupled to the capacitance-sensing circuit.\",\n \"The processing logic is operative to detect whether the first sense element is activated by a conductive object proximate to the capacitive button based on the measured signals.\",\n \"The processing logic detects whether the second sense element is activated by the conductive object proximate to the capacitive button based on the measured signals.\",\n \"The processing logic adjusts the sensing parameter to a second value when the second sense element is activated and the first sense element is not activated.\",\n \"The capacitance-sensing circuit is operative to measure an additional signal from the second sense element with the sensing parameter set to the second value when the second sense element is activated and the first sense element is not activated.\",\n \"The capacitance-sensing circuit measures additional signals from the first sense element and the second sense element with the sensing parameter set to the first value when the first and second sense elements are activated.\",\n \"In some embodiments, a surface area of the second sense element is at least partially encompassed by the first sense element.\",\n \"In other embodiments, the first sense element encompasses an area of the second sense element.\",\n \"In other embodiments, at least a portion of the first sense element is at least partially outside an outer perimeter of the second sense element.\",\n \"In other embodiments, touches from objects with 1 mm, 3 mm 5 mm and 10 mm diameter can be detected using this technique.\",\n \"For each diameter, there needs would be separate values used for the sensing parameter.\",\n \"In other embodiments more sense elements than just two sense elements (inner and outer) can be added.\",\n \"Additional sense elements may increase the accuracy of detection from objects of multiple sizes, for example.\",\n \"It should be noted that in the embodiments described herein discuss the capacitive button has having sense elements.\",\n \"The sense elements are electrodes disposed in various configurations and the self-capacitance of an electrode or a mutual capacitance between two electrodes can be measured to detect a conductive object proximate to the capacitive sense button.\",\n \"Sense elements are sometimes referred to as sensors, but it should be understood that the sensors do not include circuitry to measure the capacitance.\",\n \"Rather, capacitance-sensing circuit, which can also be referred to as a capacitance sensor, measures the capacitances of the sensors (herein referred to as electrodes or sense elements).\",\n \"Various embodiments described herein may be used in other touch sensing technologies than just capacitive buttons.\",\n \"FIG.\",\n \"1 illustrates a capacitive button 100 according to one implementation.\",\n \"Conventionally, implementation of the capacitive button 100 can be used to detect a touch from a conductive object.\",\n \"The capacitive button 100 can include a capacitive sense element 102 that can be tuned by a touch controller (not illustrated in FIG.\",\n \"1) to detect a touch by a conductive object of a specific size or dimension.\",\n \"That is a sensing parameter, such as sensitivity of measurements of the capacitive sense element 102 can be programmed for an expected size of conductive objects to be interacting with the capacitive button 100.Although this sensing parameter may be tunable to detect different sizes of conductive objects for different applications, such as to detect fingers or to detect styli.\",\n \"That is the touch controller is programmed with one sensitivity value before operation to detect fingers and the touch controller can also be programmed with another sensitivity value before operation to detect styli.\",\n \"It was not possible with the conventional touch controller to effectively detect and differentiate touches from conductive objects with two different sizes and dimensions.\",\n \"For example, it is not possible to efficiently detect and differentiate touches from a human finger, typically has 10 mm diameter, and touches from small conductive objectives like 3 mm stylus, these solutions have various limitations to accommodate both types of touches.\",\n \"Styli can be other diameters like 4 mm, 3 mm, or 1 mm.\",\n \"The capacitive button 100 includes an optional hole 103 used for backlight.\",\n \"The capacitive button 100 is disposed within a touch area 205.Today, users frequently operate devices with capacitive technologies both with their fingers and a stylus.\",\n \"Currently, the only method to detect touches from both smaller conductive objects from bigger conductive objects is to make the capacitance-sensing circuit to be more sensitive to detect the touches from both big and small conductive objects.\",\n \"This may create false touches or a “hover effect” for touches from larger conductive objects.\",\n \"For example, making a sense element have very high sensitivity to detect touches from smaller objects makes the sense element extremely sensitive to touches from bigger fingers, creating a “hover” effect for bigger fingers.\",\n \"This may reduce the immunity of the sense element to external noises and can create false touches in presence of external noises.\",\n \"As such, making the sense element to have higher sensitivity can only be used to detect touches from small conductive objects, but it cannot differentiate touches from small and big fingers.\",\n \"FIG.\",\n \"2 illustrates a capacitive button 200 according to one embodiment.\",\n \"The capacitive button 200 includes a first sense element 202 and a second sense element 204 that can be used to detect a conductive object proximate to the capacitive button 200.The capacitive button 200 includes an optional hole 203 used for an optional backlight.\",\n \"In other embodiments, different size objects can be detected with or without the optional hole 203.The capacitive button 200 is disposed within a touch area 205.In this embodiment, the touch area 205 (or a physical sense element such as sense element 102 previously used in the touch area 105) is split into two different sense elements 202, 204.The capacitive button 200 can be used in connection with a touch controller, such as a processing device including a capacitance-sensing circuit and processing logic, to detect and differentiate between touch objects with different sizes and dimensions.\",\n \"The first sense element 202 is considered an outer sense element (or outer electrode) and the second sense element 204 is considered an inner sense element 204 (or inner electrode).\",\n \"An inner perimeter of the first sense element 202 is disposed to surround, at least in part or in whole, an outer perimeter of the second sense element 204.These sense elements 202, 204 are connected to two sense pins (or terminals or inputs) of a capacitive touch controller (not illustrated in FIG.\",\n \"2).\",\n \"As described in more detail below, a signal produced by the outer sense element 202 is used detect size of a touch object, as well as to dynamically modify one or more tuning parameters used by the capacitive touch controller to measure signals on the inner sense element 204.The inner sense element 204 is used to detect touches from a larger conductive object like a finger.\",\n \"Then, based on the signal produced by the outer sense element 202, the one or more tuning parameters of the capacitive touch controller to measure signals on the inner sense element 202 are dynamically modified to detect and differentiate touches by larger and smaller conductive objects, such as fingers and styli.\",\n \"In other embodiments, both sense elements 202, 204 can be used together to track the touches by the larger conductive objects once a large conductive object is differentiated from a smaller conductive object.\",\n \"Similarly, once a smaller object is differentiated, both sense elements 202, 204 can be used together to track touches by the smaller conductive object.\",\n \"In other embodiments, additional sense elements than two sense elements can be used to detect different types of conductive objects (e.g., between finger and stylus or between big finger and smaller finger).\",\n \"For example, self-capacitance measurements of more than two sense elements can be used to detect and differentiate multiple finger sizes with more accuracy.\",\n \"The outer sense element 202 and inner sense element 204 can be conductive materials like copper, indium tin oxide (ITO), carbon, silver or the like.\",\n \"The outer sense element 202 and inner sense element 204 can be constructed on a printed circuit board (PCB), a touch screen, plexi-glass, or the like.\",\n \"Using the capacitive button 200, the touch controller can measure self-capacitance of the outer sense element 202 and inner sense element 204.In other embodiments, the touch controller can measure mutual capacitance of a capacitive button, such as illustrated and described with respect to FIG.\",\n \"3.FIG.\",\n \"3 illustrates a capacitive button 300 according to another embodiment.\",\n \"The capacitive button 300 includes a first sense element 302, a second sense element 304, and a third sense element 306 that can be used to detect a conductive object proximate to the capacitive button 300.The capacitive button 300 includes a hole 303 used for an optional backlight.\",\n \"The capacitive button 300 is disposed within a touch area 305.In this embodiment, the touch area 305 (or a physical sense element such as sense element 102 previously used in the touch area 105) is split into three different sense elements 302, 304, 306.The capacitive button 300 can be used in connection with a touch controller, such as a processing device including a capacitance-sensing circuit and processing logic, to detect and differentiate between touch objects with different sizes and dimensions.\",\n \"The first sense element 302 is considered an outer sense element (or outer electrode), the second sense element 304 is considered an inner sense element 304 (or inner electrode), and the third sense element 306 is considered a middle sense element 306 (or middle electrode).\",\n \"An inner perimeter of the first sense element 302 is disposed to surround, at least in part or in whole, an outer perimeter of the second sense element 304.The inner perimeter of the first sense element 302 is also disposed to surround an outer perimeter of the third sense element 306 and an inner perimeter of the third sense element 306 is disposed to surround the outer perimeter of the second sense element 304.These sense elements 302, 304, 306 are connected to three sense pins (or terminals or inputs) of a capacitive touch controller (not illustrated in FIG.\",\n \"3).\",\n \"The middle sense element 306 can be used by the touch controller as a transmit (TX) electrode for a TX drive signal and the outer sense element 302 and the inner sense element 304 can be used by the touch controller as receive (RX) electrodes to measure RX signals on the RX electrodes caused by the TX signal applied to the TX electrode.\",\n \"As described in more detail below, a signal produced by the outer sense element 302 is used detect size of a touch object, as well as to dynamically modify one or more tuning parameters used by the capacitive touch controller to measure signals on the inner sense element 304.The inner sense element 304 is used to detect touches from a larger conductive object like a finger.\",\n \"Then, based on the signal produced by the outer sense element 302, the one or more tuning parameters of the capacitive touch controller to measure signals on the inner sense element 302 are dynamically modified to detect and differentiate touches by larger and smaller conductive objects, such as fingers and styli.\",\n \"In other embodiments, both sense elements 302, 304 can be used together to track touches by the larger conductive objects once a large conductive object is differentiated from a smaller conductive object.\",\n \"Similarly, once a smaller object is differentiated, both sense elements 302, 304 can be used together to track touches by the smaller conductive object.\",\n \"The outer sense element 302, inner sense element 304, and middle sense element 306 can be conductive materials like copper, ITO, carbon, silver or the like.\",\n \"The outer sense element 302, inner sense element 304, and middle sense element 306 can be constructed on a PCB, a touch screen, plexi-glass, or the like.\",\n \"Using the capacitive button 300, the touch controller can measure a mutual capacitance between the middle sense element 306 and outer sense element 302 and a mutual capacitance between the middle sense element 306 and inner sense element 304.In other embodiments where two sense elements (instead of three sense elements) are used, the touch controller can also measure a mutual capacitance between the two sense elements in connection with measuring the self-capacitance of the two sense elements.\",\n \"There are two types of capacitive sensing methods, mutual capacitive sensing and self-capacitance sensing, that can be used for measuring capacitance(s) of the capacitive buttons 200, 300.When implementing the capacitive button solution using self-capacitance sensing, only two electrodes are used (inner and outer).\",\n \"The outer sense element may be big in size, as compared to the inner sense element.\",\n \"When a finger (big finger) approaches the button touch area, the outer sense element produces a large signal as finger covers the complete area of outer sense element electrode.\",\n \"When button is touched using smaller conductive object, like a smaller finger or a stylus, no area of the outer sense element is covered by the small finger (or stylus); therefore, no signal or a smaller signal is produced on the outer sense element when the capacitive button is touched by small finger.\",\n \"The tuning properties of inner sense element are modified based on the signal produced by outer sense element to detect a touch.\",\n \"When there is no signal or a small signal produced by outer sense element electrode, the inner sense element is tuned to detect touches from the smaller finger (or stylus).\",\n \"When the outer sense element produces a large signal, the large signal indicates a presence of larger finger; therefore, tuning properties of inner sense element is modified to detect touches of big finger.\",\n \"When implementing the capacitive button solution using mutual capacitance sensing, three electrodes are used for sensing, including one transmit electrode and two receive electrodes.\",\n \"In some embodiments, such as illustrated in FIG.\",\n \"3, the transmit electrode is a middle electrode disposed between an outer electrode and an inner electrode.\",\n \"The outer electrode is placed around the transmit electrode and the transmit electrode is placed around the inner electrode.\",\n \"The embodiments described herein implement detection of different size conductive objects, such as different sizes of fingers.\",\n \"The embodiments described herein implement detection of different types of conductive objects based on size.\",\n \"That is the embodiments implement detection and differentiation of a finger touch from a stylus touch as described herein.\",\n \"Touches from a small finger may be detected by tuning at least one of the sense elements to a higher sensitivity.\",\n \"Tuning the sense element makes the sense element more sensitive to touches by conductive objects proximate to the capacitive button.\",\n \"A sense element with very high sensitivity can detect the touches from smaller objects, such as a smaller finger or a stylus.\",\n \"The embodiments described herein can provide various advantages or benefits as the conventional solutions.\",\n \"For example, the touches from stylus and touches from smaller human fingers can be detected without making the sense element overly sensitive for touches from larger human fingers.\",\n \"The embodiments may also avoid a “hover” effect on a capacitive button while implementing stylus and finger touches.\",\n \"The embodiments may avoid or greatly reduces the probability for false touches from a capacitive button when it is tuned for higher sensitivity to detect smaller fingers.\",\n \"The embodiments may enable detection of touches from multiple sizes of fingers, like 10 mm or larger human finger, 3 mm stylus and 1 mm stylus.\",\n \"The embodiments can be used to not only detect touches by big and small fingers, but also differentiate between touches by big and small fingers and report that detected touch on the capacitive button was by a big or small finger.\",\n \"There is no additional material cost for the embodiments described herein to detect touches and differentiate those touches as being by a stylus and a finger.\",\n \"Also, the embodiments described herein can be implemented using existing touch controllers.\",\n \"It should be noted that touch controllers in the embodiments above measure capacitance(s) of the capacitive button.\",\n \"In other embodiments, other circuitry can be used to measure the capacitance(s) of the capacitive button.\",\n \"In one embodiment, a processing device, including a capacitance-sensing circuit and processing logic, can be used to measure capacitances as described herein and differentiate between touches by larger conductive objects and smaller conductive objects.\",\n \"The embodiment described herein, as compared to conventional solutions, can offer finger and passive stylus touch detection on capacitive buttons without additional cost or system-level implementation complications.\",\n \"Providing the passive stylus detection and on capacitive button may provide seamless user interface experience for users.\",\n \"The embodiments described herein can be used in touch screen applications, as well as in other touch sensitive interfaces.\",\n \"For example, the capacitive buttons and corresponding method of operating the same can be implemented in products that are operated using finger and stylus.\",\n \"Examples for such products may include touchscreen smart phones, tablets, mobile phones, media devices, game consoles, or other consumer electronics.\",\n \"The embodiments described herein may also be used in control panels of various devices, including appliances.\",\n \"For example, a control panel can differentiate between a smaller finger, such as that of a child, from a larger finger for safety purposes.\",\n \"Also, the ability to differentiate between different size touches can be used in other applications, where a device performs different operations based on the different size of touches detected.\",\n \"These embodiments can be used in any device to enable the stylus and finger detection on one or more capacitive buttons.\",\n \"This may permit the devices to have a better, intuitive user interface experience, as well as create more design possibilities for these types of devices, especially mobile devices.\",\n \"In other embodiments, the self-capacitance measurement and mutual-capacitance measurements, such as described with respect to FIGS.\",\n \"2 and 3, can be used to implement a water tolerance solution.\",\n \"For example, each sense element (inner and outer) can be configured as self-capacitance sense elements to be used to detect finger or stylus.\",\n \"Then one of the two sense elements can be configured as a TX electrode (inner or outer) and the other one of the two sense elements can be configured to be an RX electrode and a mutual capacitance between the TX electrode and the RX electrode can be measured.\",\n \"The self-capacitance measurement can be used to detect different size fingers and stylus.\",\n \"A water droplet (which is an ungrounded conductor) has different signal profiles for self-capacitance measurement and for mutual capacitance measurement.\",\n \"This difference in signal profile can be used to detect and differentiate between whether water or finger is present on the sense elements, and the self-capacitance measurements can be used to identify whether the object is a finger or a stylus as described herein.\",\n \"The embodiments described herein may also be used to detect and differentiate touches from different types of touch objects, such as a touch from a bare finger and a touch from a finger covered in a glove.\",\n \"For example, a stylus has small tip and touches the sensor on very limited area, as compared to a gloved finger that has as large area.\",\n \"However, the glove finger produces a smaller signal than the finger without a glove.\",\n \"So the signal amplitude and pattern for a stylus, gloved finger and finger (without glove) will be different for each.\",\n \"The stylus may also result in a small amount of signal on the inner sense element and very small or no signal on the outer sense element.\",\n \"A gloved finger, however, results in a small amount of signal on both inner and outer sense elements because the gloved finger covers both the inner and outer sense elements, as compared to a stylus that does not cover both.\",\n \"A finger without a glove results in a larger amount of signal on inner sense element, as well as on the outer sense element, as compared to the signal produced by the gloved finger.\",\n \"Also, in other embodiments, two or more sense elements can be ganged together to form one larger sense element for different purposes.\",\n \"FIG.\",\n \"4 illustrates a block diagram of one embodiment of an electronic system 400 including a processing device 410 that may be configured to measure capacitances of a capacitive button 421.The electronic system 400 includes a capacitive button 421 coupled to the processing device 410.The capacitive button 421 may be the capacitive button 200 or the capacitive button 300.The processing device is coupled to a host 450.In one embodiment, a multiplexer circuit may be used to connect a capacitance-sensing circuit 401 of the processing device 410 with a capacitive button 421.In one embodiment, the capacitive button 421 is disposed in connection a touch-sensing surface 416 of the electronic system 400.The electrodes of the capacitive button 421 can be disposed beneath an overlay, cover of the device, or the like.\",\n \"As described herein, the capacitive button 421 can include two electrodes, such as for self-capacitance sensing embodiments, or can include three electrodes, such as for mutual capacitance sensing embodiments.\",\n \"The capacitive button 421 may also be one of many capacitive buttons.\",\n \"The electrodes of the capacitive button 421 are coupled to pins 413(1)-413(N) of the processing device 410 via one or more analog buses 415 transporting multiple signals.\",\n \"In an alternative embodiment without an analog bus, each pin may instead be connected either to a circuit that generates a transmit (TX) signal or to an individual receive (RX) channel of the capacitance-sensing circuit.\",\n \"The capacitive button 421 may be disposed to have a flat surface profile.\",\n \"Alternatively, the capacitive button 421 may have non-flat surface profiles.\",\n \"Alternatively, other configurations, layout, combinations of one or more capacitive buttons may be used.\",\n \"In one embodiment, the capacitive button 421 may be included in an ITO panel or a touch screen panel.\",\n \"In other embodiments, the capacitive button 421 can be implemented separate from the ITO panel or touch screen.\",\n \"In one embodiment, the capacitance-sensing circuit 401 may include a relaxation oscillator or other means to convert a capacitance into a measured value.\",\n \"The capacitance-sensing circuit 401 may also include a counter or timer to measure the oscillator output.\",\n \"The processing device 410 may further include software components to convert the count value (e.g., capacitance value) into a touch detection decision (also referred to as switch detection decision) or relative magnitude.\",\n \"It should be noted that there are various known methods for measuring capacitance, such as current versus voltage phase shift measurement, resistor-capacitor charge timing, capacitive bridge divider, charge transfer, successive approximation, sigma-delta modulators, charge-accumulation circuits, field effect, mutual capacitance, frequency shift, or other capacitance measurement algorithms.\",\n \"It should be noted however, instead of evaluating the raw counts relative to a threshold, the capacitance-sensing circuit 401 may be evaluating other measurements to determine the user interaction.\",\n \"For example, in the capacitance-sensing circuit 401 having a sigma-delta modulator, the capacitance-sensing circuit 401 is evaluating the ratio of pulse widths of the output (i.e., density domain), instead of the raw counts being over or under a certain threshold.\",\n \"In another embodiment, the capacitance-sensing circuit 401 includes a TX signal generator to generate a TX signal to be applied to the TX electrode and a receiver (also referred to as a sensing channel), such as an integrator, coupled to measure an RX signal on the RX electrode.\",\n \"In a further embodiment, the capacitance-sensing circuit includes an analog-to-digital converter (ADC) coupled to an output of the receiver to convert the measured RX signal to a digital value (capacitance value).\",\n \"The processing device 410, the host 450 or both, can further process the digital value.\",\n \"The processing device 410 is configured to detect one or more touches on one or more of the capacitive button(s) 421.The processing device 410 can detect conductive objects, such as touch objects (fingers or passive styluses, an active stylus, or any combination thereof).\",\n \"The capacitance-sensing circuit 401 can measure touch data on the capacitive button 421.In some cases, the capacitive button 421 can be considered a unit cell of one or more electrodes.\",\n \"In some cases, a unit cell is the electrode itself.\",\n \"In other cases, a unit cell is an intersection between two or more electrodes.\",\n \"For example, when multiple electrodes are measured, the touch data may be represented as multiple cells, each cell representing an intersection of sense elements (e.g., electrodes) of the capacitive button 421.An intersection between two sense elements may be understood as a location at which one sense electrode crosses over or overlaps another, while maintaining galvanic isolation from each other.\",\n \"The capacitive sense elements are electrodes of conductive material, such as copper.\",\n \"The sense elements may also be part of an ITO panel.\",\n \"The capacitive sense elements can be configurable to allow the capacitance-sensing circuit 401 to measure self-capacitance, mutual capacitance, or any combination thereof.\",\n \"In another embodiment, the processing device 410 is a microcontroller that obtains a capacitance touch signal data set, and finger detection firmware executing on the microcontroller identifies data set areas that indicate touches, detects and processes peaks, calculates the coordinates, differentiates between smaller and larger touches, or any combination therefore.\",\n \"The microcontroller can report the precise coordinates to a host processor 450, as well as other information.\",\n \"In one embodiment, the processing device 410 further includes processing logic 402.Operations of the processing logic 402 may be implemented in firmware; alternatively, they may be implemented in hardware or software.\",\n \"The processing logic 402 may receive signals from the capacitance-sensing circuit 401, and determine the state of the capacitive button 421, such as whether an object (e.g., a finger) is detected on or in proximity to the capacitive button 421 (e.g., determining the presence of the object), or other information related to an object detected at the capacitive button 421.For example, the processing logic 402 can differentiate between touches by smaller and larger conductive objects as described herein.\",\n \"In one embodiment, the processing logic 402 is processing logic that can be programmed to perform various functions.\",\n \"In another embodiment, instead of performing the operations of the processing logic 402 in the processing device 410, the processing device 410 may send the raw data or partially processed data to the host 450.The host 450, as illustrated in FIG.\",\n \"4, may include decision logic 451 that performs some or all of the operations of the processing logic 402.Operations of the decision logic 451 may be implemented in firmware, hardware, software, or a combination thereof.\",\n \"The host 450 may include a high-level Application Programming Interface (API) in applications 452 that perform routines on the received data, such as compensating for sensitivity differences, other compensation algorithms, baseline update routines, start-up and/or initialization routines, interpolation operations, or scaling operations.\",\n \"The operations described with respect to the processing logic 402 may be implemented in the decision logic 451, the applications 452, or in other hardware, software, and/or firmware external to the processing device 410.In some other embodiments, the processing device 410 is the host 450.In another embodiment, the processing device 410 may also include a non-sensing actions block 403.This block 403 may be used to process and/or receive/transmit data to and from the host 450.For example, additional components may be implemented to operate with the processing device 410 along with the capacitive button 421 (e.g., keyboard, keypad, mouse, trackball, LEDs, displays, or other peripheral devices).\",\n \"As illustrated, capacitance-sensing circuit 401 may be integrated into processing device 410.Capacitance-sensing circuit 401 may include analog I/O for coupling to an external component, such the capacitive button 421, and/or touch-sensor pad (not shown), touch-sensor slider (not shown), touch-sensor buttons (not shown), touch screen and/or other devices.\",\n \"The capacitance-sensing circuit 401 may be configurable to measure capacitance using mutual-capacitance sensing techniques, self-capacitance sensing technique, charge coupling techniques, or the like.\",\n \"In one embodiment, capacitance-sensing circuit 401 operates using a charge accumulation circuit, a capacitance modulation circuit, or other capacitance sensing methods known by those skilled in the art.\",\n \"In an embodiment, the capacitance-sensing circuit 401 is of the Cypress TMA-3xx, TMA-4xx, or TMA-xx families of touch screen controllers.\",\n \"Alternatively, other capacitance-sensing circuits may be used.\",\n \"The capacitive button 42 may include may include a portion (or all) that is transparent and disposed on, in, or under either a visual display itself (e.g.\",\n \"LCD monitor), or a transparent substrate in front of the display.\",\n \"When a touch object, such as a finger or stylus, approaches the capacitive button 421, the object causes a decrease in mutual capacitance between some of the TX/RX electrodes.\",\n \"In another embodiment, the presence of a finger increases the coupling capacitance of the electrodes.\",\n \"For example, in self-capacitance sensing, the self-capacitance may increase when a touch object approaches the capacitive button 42a.\",\n \"It should also be noted that the embodiments described herein are not limited to having a configuration of a processing device coupled to a host, but may include a system that measures the capacitance on the sensing device and sends the raw data to a host computer where it is analyzed by an application.\",\n \"In effect, the processing that is done by processing device 410 may also be done in the host.\",\n \"The processing device 410 may reside on a common carrier substrate such as, for example, an integrated circuit (IC) die substrate, or a multi-chip module substrate.\",\n \"Alternatively, the components of the processing device 410 may be one or more separate integrated circuits and/or discrete components.\",\n \"In one embodiment, the processing device 410 may be the Programmable System on a Chip (PSoC®) processing device, developed by Cypress Semiconductor Corporation, San Jose, Calif. Alternatively, the processing device 410 may be one or more other processing devices known by those of ordinary skill in the art, such as a microprocessor or central processing unit, a controller, special-purpose processor, digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other programmable device.\",\n \"In an alternative embodiment, for example, the processing device 410 may be a network processor having multiple processors including a core unit and multiple micro-engines.\",\n \"Additionally, the processing device 410 may include any combination of general-purpose processing device(s) and special-purpose processing device(s).\",\n \"Capacitance-sensing circuit 401 may be integrated into the IC of the processing device 410, or alternatively, in a separate IC.\",\n \"Alternatively, descriptions of capacitance-sensing circuit 401 may be generated and compiled for incorporation into other integrated circuits.\",\n \"For example, behavioral level code describing the capacitance-sensing circuit 401, or portions thereof, may be generated using a hardware descriptive language, such as VHDL or Verilog, and stored to a machine-accessible medium (e.g., CD-ROM, hard disk, floppy disk, etc.).\",\n \"Furthermore, the behavioral level code can be compiled into register transfer level (“RTL”) code, a netlist, or even a circuit layout and stored to a machine-accessible medium.\",\n \"The behavioral level code, the RTL code, the netlist, and the circuit layout may represent various levels of abstraction to describe capacitance-sensing circuit 404.It should be noted that the components of electronic system 400 may include all the components described above.\",\n \"Alternatively, electronic system 400 may include some of the components described above.\",\n \"In one embodiment, the electronic system 400 is used in a tablet computer.\",\n \"Alternatively, the electronic device may be used in other applications, such as a notebook computer, a mobile handset, a personal data assistant (“PDA”), a keyboard, a television, a remote control, a monitor, a handheld multi-media device, a handheld media (audio and/or video) player, a handheld gaming device, a signature input device for point of sale transactions, an eBook reader, global position system (“GPS”) or a control panel.\",\n \"The embodiments described herein are not limited to capacitive buttons in touch-sensitive interfaces, but can be used in other capacitive sensing implementations.\",\n \"For example, the capacitive button can be used in connection with any sensing device, such as a touch screen, touch pad, touch-sensor slider (not shown) or a panel of touch-sensor buttons.\",\n \"In one embodiment, these sensing devices include one or more capacitive sensors or other types of capacitance-sensing circuitry.\",\n \"The operations described herein are not limited to device button operations, but can include other operations, such as lighting control (dimmer), volume control, graphic equalizer control, speed control, or other control operations requiring gradual or discrete adjustments.\",\n \"It should also be noted that these embodiments of capacitive sensing implementations may be used in conjunction with non-capacitive sensing elements, including but not limited to pick buttons, sliders (ex.\",\n \"display brightness and contrast), scroll-wheels, multi-media control (ex.\",\n \"volume, track advance, etc.)\",\n \"handwriting recognition, and numeric keypad operation.\",\n \"In another embodiment, the processing device 410 is coupled to a capacitive button 421 includes at least two electrodes disposed such that an inner perimeter of a first electrode of the at least two electrodes at least partially surrounds an outer perimeter of a second electrode of the at least two electrodes.\",\n \"The processing device 410 is operative to detect a combination of activations of the first electrode and the second electrode caused by a conductive object proximate to the capacitive button 421.The processing device 410 distinguishes between a first type of conductive object and a second type of conductive object based on the combination of activations.\",\n \"The combination of activations may include a combination of measured signals from the first electrode and the second electrode.\",\n \"The combination of measured signals may be the result of self-capacitance measurements of the first electrode and the second electrode.\",\n \"In another embodiment, the processing device is further operative to apply a first drive signal to a third electrode of the at least two electrodes of the capacitive button.\",\n \"In this case, the combination of activations includes a combination of measured signals from the first electrode and the second electrode.\",\n \"The combination of measured receive signals may be the result of mutual-capacitance measurements between the third electrode and the first electrode and between the third electrode and the second electrode.\",\n \"In one embodiment, an inner perimeter of the third electrode at least partially surrounds the outer perimeter of the second electrode and the inner perimeter of the first electrode at least partially surrounds an outer perimeter of the third electrode.\",\n \"In one embodiment, the processing device includes a capacitance-sensing circuit coupled to the first electrode and the second electrode, such as capacitance-sensing circuit 401.The capacitance-sensing circuit is operative to measure a first self-capacitance of the first electrode and a second self-capacitance of the second electrode.\",\n \"The processing device 410 is operative to compare the first and second self-capacitances against one or more thresholds to detect the combination of activations.\",\n \"In another embodiment, the processing device 410 is coupled to the three electrodes and the capacitance-sensing circuit is operative to measure a first mutual capacitance between the third electrode and the first electrode and a second mutual capacitance between the third electrode and the second electrode.\",\n \"The processing device 410 is operative to compare the first and second mutual capacitances against one or more thresholds to detect the combination of activations.\",\n \"FIG.\",\n \"5 is a block diagram illustrating another embodiment of an electronic system 500 that processed touch data of a capacitive button in a capacitive sense array 521.The capacitive sense array 521 include NXM electrode matrix including multiple capacitive buttons.\",\n \"A capacitance-sensing circuit 501 may measure mutual capacitances for intersections between the transmit and receive electrodes in the respective capacitive buttons of the sense array 521.The activations of the capacitive buttons are calculated based on changes in the measured capacitances relative to the capacitances of the same touch capacitive button in an un-touched state.\",\n \"In one embodiment, capacitive sense array 521 and capacitance-sensing circuit 501 are implemented in a system or device such as electronic system 400.Capacitive sense array 521 includes a matrix 525 of NxM capacitive buttons, with each capacitive button including and one TX electrode 522 and two RX electrodes 523.The electrodes in the matrix are connected with capacitance sensing circuit 501 through demultiplexer 512 and multiplexer 513.That is the TX electrodes can be connected to the demultiplexer 512 and the RX electrodes can be coupled to the multiplexer 513 to permit multiple electrodes to be driven or sensed by the capacitance-sensing circuit 501.Capacitance-sensing circuit 501 includes multiplexer control 511, demultiplexer 512, multiplexer 513, clock generator 514, signal generator 515, demodulation circuit 516, and analog to digital converter (ADC) 517.ADC 517 is further coupled with touch coordinate converter 518.Touch coordinate converter 518 may be implemented in the processing logic 402.The transmit and receive electrodes in the electrode matrix 525 may be arranged so that each of the transmit electrodes overlap and cross each of the receive electrodes such as to form an array of intersections, while maintaining galvanic isolation from each other.\",\n \"Thus, each transmit electrode may be capacitively coupled with each of the receive electrodes.\",\n \"For example, transmit electrode 522 is capacitively coupled with two receive electrode 523 at the point where transmit electrode 522 and receive electrodes 523 overlap.\",\n \"Clock generator 514 supplies a clock signal to signal generator 515, which produces a TX signal 524 to be supplied to the transmit electrode 522 of touch capacitive button.\",\n \"In one embodiment, the signal generator 515 includes a set of switches that operate according to the clock signal from clock generator 514.The switches may generate a TX signal 524 by periodically connecting the output of signal generator 515 to a first voltage and then to a second voltage, where said first and second voltages are different.\",\n \"The output of signal generator 515 is connected with demultiplexer 512, which allows the TX signal 524 to be applied to any of the M transmit electrodes of capacitive buttons.\",\n \"In one embodiment, multiplexer control 511 controls demultiplexer 512 so that the TX signal 524 is applied to each transmit electrode 522 in a controlled sequence.\",\n \"Demultiplexer 512 may also be used to ground, float, or connect an alternate signal to the other transmit electrodes to which the TX signal 524 is not currently being applied.\",\n \"In an alternate embodiment the TX signal 524 may be presented in a true form to a subset of the transmit electrodes 522 and in complement form to a second subset of the transmit electrodes 522.There may be no overlap in members of the first and second subset of transmit electrodes 522.Because of the capacitive coupling between the transmit and receive electrodes, the TX signal 524 applied to each transmit electrode induces a current within each of the receive electrodes.\",\n \"For instance, when the TX signal 524 is applied to transmit electrode 252 through demultiplexer 512, the TX signal 524 induces an RX signal 527 on the receive electrodes in matrix 525.The RX signal 527 on each of the receive electrodes can then be measured in sequence by using multiplexer 513 to connect each of the N receive electrodes to demodulation circuit 516 in sequence.\",\n \"The mutual capacitance associated with the intersections of all TX electrodes and RX electrodes can be measured by selecting every available combination of TX electrode and an RX electrode using demultiplexer 512 and multiplexer 513.To improve performance, multiplexer 513 may also be segmented to allow more than one of the receive electrodes in matrix 525 to be routed to additional demodulation circuits 516.In an optimized configuration, wherein there is a 1-to-1 correspondence of instances of demodulation circuit 516 with receive electrodes, multiplexer 513 may not be present in the system.\",\n \"When a conductive object, such as a finger, approaches the electrode matrix 525, the object causes a decrease in the measured mutual capacitance between only some of the electrodes.\",\n \"For example, if a finger is placed near the intersection of transmit electrode 522 and receive electrode 523, the presence of the finger will decrease the charge coupled between electrodes 522 and 523.Thus, the location of the finger on the touchpad can be determined by identifying the one or more receive electrodes having a decrease in measured mutual capacitance in addition to identifying the transmit electrode to which the TX signal 524 was applied at the time the decrease in capacitance was measured on the one or more receive electrodes.\",\n \"By determining changes in the mutual capacitances associated with each intersection of electrodes in the matrix 525, the presence and locations of one or more conductive objects may be determined.\",\n \"The determination may be sequential, in parallel, or may occur more frequently at commonly used electrodes.\",\n \"In alternative embodiments, other methods for detecting the presence of a finger or other conductive object may be used where the finger or conductive object causes an increase in measured capacitance at one or more electrodes, which may be arranged in a grid or other pattern.\",\n \"For example, a finger placed near an electrode of a capacitance-sensing circuit may introduce an additional capacitance to ground that increases the total capacitance between the electrode and ground.\",\n \"The location of the finger can be determined based on the locations of one or more electrodes at which a change in measured capacitance is detected, and the associated magnitude of capacitance change at each respective electrode.\",\n \"Demodulation circuit 516 integrates the induced current signal 527.The rectified current output by demodulation circuit 516 can then be filtered and converted to a digital code by ADC 517.A series of such digital codes measured from adjacent electrode intersections, when compared to or offset by the associated codes of these same electrodes in an un-touched state, may be converted to touch coordinates indicating a position of an input on touch capacitive button by touch coordinate converter 518.The touch coordinates may then be used to detect gestures or perform other functions by the processing logic 402.For self-capacitance sensing, a sense element has capacitance associated with the sense element, which is referred as parasitic capacitance CP.\",\n \"When finger touches sensing area, an additional capacitance is added to circuit due to the presence of human finger.\",\n \"This capacitance is referred as finger capacitance CF.\",\n \"The total capacitance of sense element without finger presence is equal to CP of sense element and with presence, it is sum of CP and CF.\",\n \"A capacitance-sensing circuit, such as a touch controller, implements a Capacitance-to-Digital Converter to convert the measured capacitances to digital values (also called digital counts).\",\n \"When there is a finger touch, there is an increase in the output of capacitance to count converter as illustrated in FIG.\",\n \"6.FIG.\",\n \"6 illustrates capacitance output 600 of digital converter with a finger touch according to one embodiment.\",\n \"The raw counts are the digital values corresponding to the measured capacitances on the sense element.\",\n \"The baseline is initialized to raw counts at system start.\",\n \"Later, it slowly tracks raw counts if variation in raw counts is less than noise threshold.\",\n \"This feature helps to adapt to different environment conditions and avoid false touch detection.\",\n \"A signal is calculated by subtracting the baseline from raw counts.\",\n \"This represents capacitance added by finger touch.\",\n \"The finger threshold defines the increase in capacitance on sense element, which can be qualified as a valid touch.\",\n \"The finger threshold value can be changed dynamically as one of the tuning parameters as described herein.\",\n \"The output of capacitance to ‘digital count converter’ is passed through a simple signal processing algorithms to detect increase in sense element capacitance due to finger touch.\",\n \"Firmware algorithms use this information to differentiate between an actual finger touch and spurious noise, such as any minimal capacitances induced by variance in temperature, pressure or other environmental factors.\",\n \"If the increase in sense element capacitance is more than a predetermined value (also called finger threshold), the touch controller declares presence of finger on the sense element.\",\n \"Capacitive sensing devices may use charge transfer and delta-sigma modulator based capacitance to digital conversion (referred as CSD) and charge transfer and successive approximation based sensing methods (referred as CSA).\",\n \"Alternatively, other methods of measuring capacitance can be used to convert capacitance to digital counts.\",\n \"Regardless of the conversion method, the embodiments described herein detect and differentiate touches from big and small fingers or stylus.\",\n \"For mutual capacitance sensing, the capacitance that exists between two electrodes are measured using a capacitance to digital count converter sensing method.\",\n \"With finger presence, there is decrease in capacitance between two electrodes and the algorithm to detect finger presence measures the difference in capacitance.\",\n \"Described bellow is a method that enables detection of small and big finger touches without the capacitive button being overly sensitive to big finger touches.\",\n \"This method requires different types of sense element construction and decision logic.\",\n \"A touch by small finger (e.g.\",\n \"touches from a stylus) and big finger (human finger) touch surface area of sense element shall produce a combination of signals from sense elements.\",\n \"The combination of signals can be used to differentiate or otherwise identify small and big finger touches.\",\n \"In the following method, it is assumed that 8 mm represents a big finger and 3 mm represents a stylus or a small finger.\",\n \"FIG.\",\n \"7 is a flow diagram of a method of sensing a capacitive button according to one embodiment.\",\n \"The method 700 may be performed by processing logic that may include hardware (circuitry, dedicated logic, etc.\",\n \"), software (such as is run on a general purpose computing system or a dedicated machine), firmware (embedded software), or any combination thereof.\",\n \"In one embodiment, the processing device 410 of FIG.\",\n \"4 performs some or all of method 700.In another embodiment, the processing logic 402 of FIG.\",\n \"4 or FIG.\",\n \"5 performs some or all of the operations of method 700.In other embodiments, the capacitance-sensing circuit 401 of FIG.\",\n \"4, or the capacitance-sensing circuit 501 of FIG.\",\n \"5, performs some of the operations of method 700.Alternatively, other components of the electronic system 400 of FIG.\",\n \"4 perform some or all of the operations of method 700.In FIG.\",\n \"7, method 700 begins with the processing logic initializing sense elements and setting default finger thresholds (e.g., 3 mm stylus threshold for inner sense element) (block 702).\",\n \"The processing logic scans an inner sense element and an outer sense element and updates a baseline for both sense elements (block 704).\",\n \"The processing logic determines if the outer sense element is active (block 706).\",\n \"When the outer sense element is not active at block 706, the processing logic sets the 3 mm stylus threshold for the inner sensor element (block 708).\",\n \"However, when the outer sense element is active at block 706, the processing logic sets 8 mm finger threshold for inner sense element (block 710).\",\n \"At block 712, the processing logic determines if both inner and outer sense elements are active.\",\n \"When the processing logic determines that both inner and outer sense elements are active at block 712, the processing logic detects the 8 mm finger on the capacitive button (block 714) and returns to block 704.When the processing logic determines that both inner and outer sense elements are not active at block 712, the processing logic determines if only the inner sense element is active (block 716).\",\n \"If the inner sense element is active at block 716, the processing logic increments a 3 mm stylus delay counter (block 718).\",\n \"However, if the inner sense element is not active at block 716, the processing logic determines if a 3 mm stylus mode timeout happened (block 724).\",\n \"If the 3 mm stylus mode timeout did happen at block 724, the processing logic resets the 3 mm stylus delay counter and continues back to block 704.When the 3 mm stylus mode timeout happened, the processing logic continues to block 704.When the 3 mm stylus delay counter is incremented, the processing logic determines if the 3 mm stylus delay counter is in an overflow condition (block 720).\",\n \"When in overflow at block 720, the processing logic detects the 3 mm finger on the capacitive button (block 722); otherwise, the method 700 continues back to block 704.In this embodiment, two sense elements can be used.\",\n \"In another embodiment, the method 700 scans three sense elements as described herein.\",\n \"In another embodiment of a method, the processing logic measures signals from a first sense element and a second sense element of a capacitive button using a capacitance-sensing circuit programmed with a sensing parameter set to a first value.\",\n \"The signals correspond to capacitances of the first sense element and the second sense element.\",\n \"An inner perimeter of the first sense element is disposed to surround an outer perimeter of the second sense element.\",\n \"The processing logic detects, by processing logic whether a conductive object proximate to the capacitive button activates the first sense element based on the measured signals.\",\n \"The processing logic detects, by the processing logic, whether the conductive object proximate to the capacitive button activates the second sense element based on the measured signals.\",\n \"The processing logic adjusts, by the processing logic, the sensing parameter set to the first value to a second value when the second sense element is activated and the first sense element is not activated.\",\n \"The processing logic measures an additional signal from the second sense element using the capacitance-sensing circuit with the sensing parameter set to the second value when the second sense element is activated and the first sense element is not activated.\",\n \"In a further embodiment, the processing logic measuring, by the capacitance-sensing circuit with the sensing parameter set to the first value, additional signals from the first sense element and the second sense element when the second sense element and the first sense element are activated.\",\n \"In another embodiment, the measuring with the sensing parameter set to the first value or the second value includes measuring self-capacitances of the first sense element and the second sense element.\",\n \"Alternatively, the processing logic, by the capacitance-sensing circuit, applies or drives a first drive signal on a third sense element of the capacitive button.\",\n \"The measuring may be done with the sensing parameter set to the first value or the second value to measure a first mutual capacitance between the third sense element and the first sense element and a second mutual capacitance between the third sense element and the second sense element.\",\n \"The processing logic distinguishes between a first type of conductive object and a second type of conductive object using the processing logic based on the signals measured with the sensing parameter set to the first value.\",\n \"The conductive object is the first type when the second sense element is activated and the first sense element is not activated and the conductive object is the second type when the first sense element and the second sense element are activated.\",\n \"In another embodiment, the processing logic distinguishes between a stylus and a finger as the conductive object.\",\n \"The conductive object is the stylus when the second sense element is activated and the first sense element is not activated and the conductive object is the finger when the first sense element and the second sense element are activated.\",\n \"In another embodiment, the processing logic measures the signals from the first sense element and the second sense element using a first sensitivity and measures the additional signal using a second sensitivity.\",\n \"The first sensitivity is less than the second sensitivity.\",\n \"Alternatively, multiple activation thresholds can be used as the tuning parameters.\",\n \"Instead of changing the sensitivity of the capacitance-sensing circuit, the finger or stylus thresholds can be adjusted.\",\n \"In another embodiment, the processing logic measures the signals from the first sense element and the second sense element and compares the signals against a first activation threshold and measures the additional signal and compares the additional signal against a second activation threshold.\",\n \"The first activation threshold is higher than the second activation threshold.\",\n \"FIG.\",\n \"8 illustrates two capacitive buttons 800 according to another embodiment.\",\n \"The two capacitive buttons 800 may be used as buttons on a mobile phone, as illustrated in FIG.\",\n \"10.FIG.\",\n \"9 is a block diagram of a mobile device 900 with a touchscreen 902 and two capacitive buttons 904, 906 according to one embodiment.\",\n \"The mobile device 900 also includes a host processor 950 and a processing device 910.The processing device 910 can be a touch controller that controls the touchscreen 902 in connection with the host processor 950.In addition, the processing device 910 can detect touches on capacitive buttons 904 and 906 as described herein.\",\n \"Described herein is a new sense element layout for detecting and differentiating touches from big and small fingers or styli.\",\n \"The old sense element layout is illustrated in FIG.\",\n \"1 and embodiments of the news sense element layout is illustrated in FIGS.\",\n \"2, 3 and 8.Also, described herein is a new data processing algorithm for detecting and differentiating touches from big and small fingers or styli.\",\n \"One embodiment of this new data processing algorithm is illustrated in FIG.\",\n \"7.The embodiments described herein have the ability to detect and differentiate touches from finger with smaller diameter and touches from finger with bigger diameter on a capacitive button, without making capacitive button overly sensitive to false touches from bigger fingers.\",\n \"The embodiments also have the ability to detect and differentiate human finger touch and passive stylus touch on a capacitive button.\",\n \"These embodiments can also avoid false touches caused by the hover effect on sense element when operating with big finger.\",\n \"The embodiments described herein may also have the ability to reject touches when human finger is not exactly on button.\",\n \"For example, an algorithm can accurately accept/reject when human finger is overlapping with button below certain percentage set in firmware, such as illustrated in Table 1 below.\",\n \"Table 1 includes signal measurements from inner and outer sense elements: Signal from Signal from outer sense inner sense Output of decision # Input element element logic/algorithm 1 Big Finger, 75 20 Reject - low signal 25% touch on inner sense element (8 mm finger) 2 Big Finger, 105 40 Accept - good signal 50% touch on inner and outer (8 mm finger) sense elements 3 Big Finger, 120 90 Accept - good signal 100% touch on inner and outer (8 mm finger) sense elements 4 Small Finger 45 20 Reject - low signal on outer sense from inner sense element (3 mm element stylus) 5 Small Finger 30 30 Accept - good signal on inner sense on inner and outer element (3 mm sense elements stylus) 6 Small Finger 35 30 Accept - good signal at center (3 mm on inner and outer stylus) sense elements In some embodiments, the tuning parameter can be dynamically changed to detect small and big fingers based on a host command.\",\n \"In this case, the end product of application needs “somehow need to know” whether user is operating the product with small of big finger.\",\n \"In other embodiments, the processing logic can automatically detect and differentiate the big and small finger touches without a command from host.\",\n \"The processing logic can be implemented in a capacitive touch screen controller.\",\n \"In one embodiment, the capacitive touch screen controller is the TrueTouch® capacitive touchscreen controllers, such as the CY8CTMA3xx family of TrueTouch® Multi-Touch All-Points touchscreen controllers, developed by Cypress Semiconductor Corporation of San Jose, Calif.\",\n \"The TrueTouch® capacitive touchscreen controllers sensing technology to resolve touch locations of multiple fingers and a stylus on the touch-screens, supports leading operating systems, and is optimized for low-power multi-touch gesture and all-point touchscreen functionality.\",\n \"Alternatively, the touch position calculation features may be implemented in other touchscreen controllers, or other touch controllers of touch-sensing devices.\",\n \"In one embodiment, the touch position calculation features may be implemented with other touch filtering algorithms as would be appreciated by one of ordinary skill in the art having the benefit of this disclosure.\",\n \"The embodiments described herein may be used in various designs of mutual-capacitance sensing arrays of the capacitance sensing system, or in self-capacitance sensing arrays.\",\n \"In one embodiment, the capacitance sensing system detects multiple sense elements that are activated in the array, and can analyze a signal pattern on the neighboring sense elements to separate noise from actual signal.\",\n \"The embodiments described herein are not tied to a particular capacitive sensing solution and can be used as well with other sensing solutions, including optical sensing solutions, as would be appreciated by one of ordinary skill in the art having the benefit of this disclosure.\",\n \"In the above description, numerous details are set forth.\",\n \"It will be apparent, however, to one of ordinary skill in the art having the benefit of this disclosure, that embodiments of the present invention may be practiced without these specific details.\",\n \"In some instances, well-known structures and devices are shown in block diagram form, rather than in detail, in order to avoid obscuring the description.\",\n \"Some portions of the detailed description are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory.\",\n \"These algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art.\",\n \"An algorithm is here and generally, conceived to be a self-consistent sequence of steps leading to a desired result.\",\n \"The steps are those requiring physical manipulations of physical quantities.\",\n \"Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared and otherwise manipulated.\",\n \"It has proven convenient at times, principally for reasons of common usage, to refer to these signals as bits, values, elements, symbols, characters, terms, numbers or the like.\",\n \"It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities.\",\n \"Unless specifically stated otherwise as apparent from the above discussion, it is appreciated that throughout the description, discussions utilizing terms such as “encrypting,” “decrypting,” “storing,” “providing.” “deriving,” “obtaining,” “receiving,” “authenticating.” “deleting,” “executing,” “requesting.” “communicating,” or the like, refer to the actions and processes of a computing system, or similar electronic computing device, that manipulates and transforms data represented as physical (e.g., electronic) quantities within the computing system's registers and memories into other data similarly represented as physical quantities within the computing system memories or registers or other such information storage, transmission or display devices.\",\n \"The words “example” or “exemplary” are used herein to mean serving as an example, instance or illustration.\",\n \"Any aspect or design described herein as “example’ or “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs.\",\n \"Rather, use of the words “example” or “exemplary” is intended to present concepts in a concrete fashion.\",\n \"As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or.” That is, unless specified otherwise, or clear from context, “X includes A or B” is intended to mean any of the natural inclusive permutations.\",\n \"That is, if X includes A; X includes B; or X includes both A and B, then “X includes A or B” is satisfied under any of the foregoing instances.\",\n \"In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form.\",\n \"Moreover, use of the term “an embodiment” or “one embodiment” or “an implementation” or “one implementation” throughout is not intended to mean the same embodiment or implementation unless described as such.\",\n \"Embodiments descried herein may also relate to an apparatus for performing the operations herein.\",\n \"This apparatus may be specially constructed for the required purposes, or it may comprise a general-purpose computer selectively activated or reconfigured by a computer program stored in the computer.\",\n \"Such a computer program may be stored in a non-transitory computer-readable storage medium, such as, but not limited to, any type of disk including floppy disks, optical disks, CD-ROMs and magnetic-optical disks, read-only memories (ROMs), random access memories (RAMs), EPROMs, EEPROMs, magnetic or optical cards, flash memory, or any type of media suitable for storing electronic instructions.\",\n \"The term “computer-readable storage medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database and/or associated caches and servers) that store one or more sets of instructions.\",\n \"The term “computer-readable medium” shall also be taken to include any medium that is capable of storing, encoding or carrying a set of instructions for execution by the machine and that causes the machine to perform any one or more of the methodologies of the present embodiments.\",\n \"The term “computer-readable storage medium” shall accordingly be taken to include, but not be limited to, solid-state memories, optical media, magnetic media, any medium that is capable of storing a set of instructions for execution by the machine and that causes the machine to perform any one or more of the methodologies of the present embodiments.\",\n \"The algorithms and displays presented herein are not inherently related to any particular computer or other apparatus.\",\n \"Various general-purpose systems may be used with programs in accordance with the teachings herein, or it may prove convenient to construct a more specialized apparatus to perform the required method steps.\",\n \"The required structure for a variety of these systems will appear from the description below.\",\n \"In addition, the present embodiments are not described with reference to any particular programming language.\",\n \"It will be appreciated that a variety of programming languages may be used to implement the teachings of the embodiments as described herein.\",\n \"The above description sets forth numerous specific details such as examples of specific systems, components, methods and so forth, in order to provide a good understanding of several embodiments of the present invention.\",\n \"It will be apparent to one skilled in the art, however, that at least some embodiments of the present invention may be practiced without these specific details.\",\n \"In other instances, well-known components or methods are not described in detail or are presented in simple block diagram format in order to avoid unnecessarily obscuring the present invention.\",\n \"Thus, the specific details set forth above are merely exemplary.\",\n \"Particular implementations may vary from these exemplary details and still be contemplated to be within the scope of the present invention.\",\n \"It is to be understood that the above description is intended to be illustrative and not restrictive.\",\n \"Many other embodiments will be apparent to those of skill in the art upon reading and understanding the above description.\",\n \"The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874705"}}},{"rowIdx":4494673,"cells":{"text":{"kind":"list like","value":[["Service Takeover Method, Storage Device, And Service Takeover Apparatus","The present disclosure describes example service takeover methods, storage devices, and service takeover apparatuses.","In one example, when a communication fault occurs between two storage devices in a storage system, the two storage devices respectively obtain running statuses of the two storage devices.","A running status can reflect current usage of one or more system resources of a particular storage device.","Then, a delay duration is determined according to the running statuses, where the delay duration is a duration for which the storage device waits before sending an arbitration request to a quorum server.","The two storage devices respectively send, after the delay duration, arbitration requests to the quorum server to request to take over a service.","The quorum server then can select a storage device in a relatively better running status to take over a host service."],["1.A service takeover method in a storage system, wherein the storage system comprises a first storage device, a second storage device, and a quorum server, wherein data communication is performed between the first storage device and the second storage device by using a link, and wherein the method being performed by the first storage device comprises: obtaining a running status of the first storage device when a communication fault occurs between the first storage device and the second storage device, wherein the running status reflects current usage of a system resource of the first storage device, and wherein the system resource comprises at least one of: a processor resource, a hard disk resource, a cache resource, and a host bandwidth resource; determining a delay duration according to the running status, wherein the delay duration is a duration for which the first storage device waits before sending an arbitration request to the quorum server; and sending, after the delay duration, the arbitration request to the quorum server to request to take over a service.","2.The method according to claim 1, wherein the obtaining a running status of the first storage device comprises: reading a running status value of the first storage device, wherein the running status value is a sum of status values of all system resources, wherein a status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and wherein the correspondence comprises at least one of a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.","3.The method according to claim 2, wherein the determining the delay duration according to the running status comprises: determining the delay duration according to the running status value and a formula T=k*S, wherein T is the delay duration, S is the running status value, and k is any value.","4.The method according to claim 3, wherein k=1.5.The method according to claim 2, wherein the storage system further comprises a host, wherein the first storage device communicates with the host by using a front-end port, and wherein, before the reading the running status value of the first storage device, the method further comprises: detecting a status of the front-end port; determining that the status of the front-end port is valid; and in response to determining that the status of the front-end port is valid, reading the running status value of the first storage device.","6.A storage device, wherein the storage device is located in a storage system, and the storage device comprises: a communications interface, the communications interface configured to communicate with another storage device and a quorum server in the storage system; and at least one processor, the at least one processor configured to: obtain a running status of the storage device when determining that a communication fault occurs between the storage device and the another storage device, wherein the running status reflects current usage of a system resource of the storage device, and wherein the system resource comprises at least one of: a processor resource, a hard disk resource, a cache resource, and a host bandwidth resource; determine a delay duration according to the running status, wherein the delay duration is a duration for which the storage device waits before sending an arbitration request to the quorum server; and send, using the communications interface and after the delay duration, the arbitration request to the quorum server to request to take over a service.","7.The storage device according to claim 6, wherein the at least one processor is configured to read a running status value of the storage device, wherein the running status value is a sum of status values of all system resources, wherein a status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and wherein the correspondence comprises at least one of a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.","8.The storage device according to claim 7, wherein the at least one processor is configured to determine the delay duration according to the running status value and a formula T=k*S, wherein T is the delay duration, S is the running status value, and k is any value.","9.The storage device according to claim 8, wherein k=1.10.The storage device according to claim 7, wherein the storage system further comprises a host, wherein the storage device further comprises a front-end port, and wherein the storage device communicates with the host by using the front-end port; and the at least one processor is further configured to, before reading the running status value of the storage device: detect a status of the front-end port; determine that the status of the front-end port is valid; and in response to determining that the status of the front-end port is valid, read the running status value of the storage device."],["<SOH> BACKGROUND <EOH>For protecting data security and for a purpose of redundancy (Disaster Recovery), storage vendors establish a geographic redundancy center to implement remote backup of data, so that original data is not lost or damaged after a disaster (such as a fire or an earthquake) occurs, and a key service can resume running in an allowable time range, to minimize a loss brought by the disaster.","Currently, a main storage system is a two-center storage system.","The two-center storage system implements redundancy by establishing two data centers.","Both the two data centers can receive a service request from a host, and store service data in respective storage devices.","Then, data synchronization is implemented by using a link between the data centers.","However, once a fault occurs on the link, the data synchronization is interrupted.","Therefore, a data center needs to be designated to bear a data service of the host, and after fault recovery of the link, data received before the fault recovery is backed up to another data center.","Generally, when a fault occurs on the link, the two data centers immediately and respectively send arbitration requests to a quorum server, and the quorum server determines, according to an arbitration request receiving sequence, the data center that is to bear the data service."],["<SOH> SUMMARY <EOH>Embodiments of the present invention provide a service takeover method, a storage device, and a service takeover apparatus.","When a communication fault occurs between a storage device and another storage device, an arbitration request can be submitted to a quorum server after delay duration according to current usage of a respective system resource, so that the quorum server can select a storage device in a better running status to take over a host service.","A first aspect of the embodiments provides a service takeover method.","A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.","Data communication is performed between the first storage device and the second storage device by using a link.","The first storage device obtains a running status of the first storage device when a communication fault occurs between the first storage device and the second storage device.","The running status reflects current usage of a system resource of the first storage device.","The system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.","The first storage device determines delay duration according to the running status, where the delay duration is duration for which the first storage device waits before sending an arbitration request to the quorum server.","The first storage device sends, after the delay duration, the arbitration request to the quorum server to request to take over a service.","Similarly, when determining that a communication fault occurs between the second storage device and the first storage device, the second storage device obtains a running status of the second storage device, and determines delay duration according to the running status.","The second storage device sends, after the delay duration, an arbitration request to the quorum server to request to take over a service.","After receiving the arbitration requests sent by the two storage devices, the quorum server determines, based on a first received arbitration request, a storage device that is to take over a host service.","A storage device needs to wait for a period of time before sending an arbitration request to the quorum server.","Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","With reference to the first aspect, in a first implementation, the first storage device reads a running status value of the first storage device, where the running status value is a sum of status values of all system resources.","A status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and the correspondence includes a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.","In this implementation, usage of each system resource may be reflected by a running status value.","Therefore, the current usage of the system resource of the first storage device is better reflected, so that more proper delay duration may be obtained according to the running status value.","With reference to the first implementation, in a second implementation, the delay duration may be obtained according to the running status value and a formula T=k*S, where T is the delay duration, S is the running status value, and k is any value.","This implementation provides a specific algorithm to associate the delay duration with the running status value.","In general, the delay duration may be directly proportional to the running status value, that is, a greater running status value leads to longer waiting duration.","With reference to the second implementation, in a third implementation, k=1.The quorum server generally determines, based on a first received arbitration request, a storage device that is to take over a host service.","Therefore, the delay duration is set, so that the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","Excessively short delay duration is improper, because excessively short waiting duration is unfavorable to distinguishing a sequence in which storage devices send arbitration requests.","Excessively long delay duration is also improper, because excessively long waiting duration is unfavorable to processing a host service.","Therefore, k is set to 1 in this implementation.","With reference to any one of the foregoing implementations of the first aspect, in a fourth implementation, the storage system further includes a host.","The first storage device communicates with the host by using a front-end port.","The first storage device may detect a status of the front-end port, and when determining that the status of the front-end port is valid, read the running status value of the first storage device.","If the status of the front-end port is invalid, it indicates that communication between the first storage device and the host is interrupted, and the first storage device cannot take over a host service.","Therefore, in this case, the first storage device does not need to send an arbitration request to the quorum server.","With reference to any one of the foregoing implementations, in a fifth implementation, the arbitration request sent by the first storage device to the quorum server includes an arbitration ID and a device identifier of first storage device.","After receiving the arbitration request, the quorum server determines whether the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, and if the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, determines that the first storage device is in an arbitration scope of the quorum server.","In addition, if the quorum server does not receive, before receiving the arbitration request sent by the first storage device, an arbitration request sent by another storage device, the quorum server may determine that the first storage device is to take over a host service.","In this case, the quorum server may find a corresponding identifier of the device identifier according to the device identifier of the first storage device, and add the corresponding identifier to a response message to send to the first storage device.","With reference to the fifth implementation, in a sixth implementation, the quorum server obtains a device identifier of the second storage device according to the device identifier of the first storage device, an arbitration ID, and a correspondence between the arbitration ID and the device identifier of the second storage device, further obtains a corresponding identifier of the device identifier of the second storage device according to a correspondence between the device identifier of the second storage device and the corresponding identifier, and deletes the corresponding identifier.","Even if the second storage device subsequently sends an arbitration request to the quorum server, the quorum server does not respond to the arbitration request because the corresponding identifier of the device identifier of the second storage device is deleted.","No request response is received, and consequently, the second storage device cannot take over a host service.","A second aspect of the embodiments provides another service takeover method.","A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.","Data communication is performed between the first storage device and the second storage device by using a link.","When a communication fault occurs between the first storage device and the second storage device, the first storage device sends a first arbitration request to the quorum server, and the second storage device sends a second arbitration request to the quorum server.","After receiving the arbitration requests sent by the two storage devices, the quorum server separately queries statuses of front-end ports of the two storage devices.","If the statuses of the front-end ports are valid, the quorum server continues to receive running statuses of the two storage devices, after comparing the running statuses of the two storage devices, selects a storage device in a better running status to take over a host service, and sends a request response to the storage device.","In the service takeover method provided in the second aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","Compared with the first aspect of the embodiments, the service takeover method provided in the second aspect is mainly performed by the quorum server.","Therefore, load of the storage device may be reduced to some extent.","A third aspect of the embodiments provides a storage device, configured to perform at least one method described in the first aspect.","A fourth aspect of the embodiments provides a service takeover apparatus, and the service takeover apparatus is located in a storage device, and configured to perform at least one method described in the first aspect.","According to the storage device provided in the third aspect and the service takeover apparatus provided in the fourth aspect of the embodiments, a storage device may wait for a period of time before sending an arbitration request to the quorum server.","Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","A fifth aspect of the embodiments provides a quorum server, configured to perform the method described in the second aspect.","According to the quorum server provided in the fifth aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","Compared with the first aspect of the embodiments, the quorum server provided in the fifth aspect can reduce load of the storage device to some extent.","A sixth aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the storage device of the foregoing third aspect, and used to perform at least one method of the foregoing first aspect.","According to the computer program product provided in the sixth aspect of the embodiments of the present invention, a storage device may wait for a period of time before sending an arbitration request to a quorum server.","Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","A seventh aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the quorum server of the foregoing fifth aspect, and used to perform the method of the foregoing second aspect."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No.","PCT/CN2015/098487, filed on Dec. 23, 2015, which is hereby incorporated by reference in their entireties.","TECHNICAL FIELD Embodiments of the present invention relate to the field of storage technologies, and in particular, to a service takeover method, a storage device, and a service takeover apparatus.","BACKGROUND For protecting data security and for a purpose of redundancy (Disaster Recovery), storage vendors establish a geographic redundancy center to implement remote backup of data, so that original data is not lost or damaged after a disaster (such as a fire or an earthquake) occurs, and a key service can resume running in an allowable time range, to minimize a loss brought by the disaster.","Currently, a main storage system is a two-center storage system.","The two-center storage system implements redundancy by establishing two data centers.","Both the two data centers can receive a service request from a host, and store service data in respective storage devices.","Then, data synchronization is implemented by using a link between the data centers.","However, once a fault occurs on the link, the data synchronization is interrupted.","Therefore, a data center needs to be designated to bear a data service of the host, and after fault recovery of the link, data received before the fault recovery is backed up to another data center.","Generally, when a fault occurs on the link, the two data centers immediately and respectively send arbitration requests to a quorum server, and the quorum server determines, according to an arbitration request receiving sequence, the data center that is to bear the data service.","SUMMARY Embodiments of the present invention provide a service takeover method, a storage device, and a service takeover apparatus.","When a communication fault occurs between a storage device and another storage device, an arbitration request can be submitted to a quorum server after delay duration according to current usage of a respective system resource, so that the quorum server can select a storage device in a better running status to take over a host service.","A first aspect of the embodiments provides a service takeover method.","A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.","Data communication is performed between the first storage device and the second storage device by using a link.","The first storage device obtains a running status of the first storage device when a communication fault occurs between the first storage device and the second storage device.","The running status reflects current usage of a system resource of the first storage device.","The system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.","The first storage device determines delay duration according to the running status, where the delay duration is duration for which the first storage device waits before sending an arbitration request to the quorum server.","The first storage device sends, after the delay duration, the arbitration request to the quorum server to request to take over a service.","Similarly, when determining that a communication fault occurs between the second storage device and the first storage device, the second storage device obtains a running status of the second storage device, and determines delay duration according to the running status.","The second storage device sends, after the delay duration, an arbitration request to the quorum server to request to take over a service.","After receiving the arbitration requests sent by the two storage devices, the quorum server determines, based on a first received arbitration request, a storage device that is to take over a host service.","A storage device needs to wait for a period of time before sending an arbitration request to the quorum server.","Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","With reference to the first aspect, in a first implementation, the first storage device reads a running status value of the first storage device, where the running status value is a sum of status values of all system resources.","A status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and the correspondence includes a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.","In this implementation, usage of each system resource may be reflected by a running status value.","Therefore, the current usage of the system resource of the first storage device is better reflected, so that more proper delay duration may be obtained according to the running status value.","With reference to the first implementation, in a second implementation, the delay duration may be obtained according to the running status value and a formula T=k*S, where T is the delay duration, S is the running status value, and k is any value.","This implementation provides a specific algorithm to associate the delay duration with the running status value.","In general, the delay duration may be directly proportional to the running status value, that is, a greater running status value leads to longer waiting duration.","With reference to the second implementation, in a third implementation, k=1.The quorum server generally determines, based on a first received arbitration request, a storage device that is to take over a host service.","Therefore, the delay duration is set, so that the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","Excessively short delay duration is improper, because excessively short waiting duration is unfavorable to distinguishing a sequence in which storage devices send arbitration requests.","Excessively long delay duration is also improper, because excessively long waiting duration is unfavorable to processing a host service.","Therefore, k is set to 1 in this implementation.","With reference to any one of the foregoing implementations of the first aspect, in a fourth implementation, the storage system further includes a host.","The first storage device communicates with the host by using a front-end port.","The first storage device may detect a status of the front-end port, and when determining that the status of the front-end port is valid, read the running status value of the first storage device.","If the status of the front-end port is invalid, it indicates that communication between the first storage device and the host is interrupted, and the first storage device cannot take over a host service.","Therefore, in this case, the first storage device does not need to send an arbitration request to the quorum server.","With reference to any one of the foregoing implementations, in a fifth implementation, the arbitration request sent by the first storage device to the quorum server includes an arbitration ID and a device identifier of first storage device.","After receiving the arbitration request, the quorum server determines whether the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, and if the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, determines that the first storage device is in an arbitration scope of the quorum server.","In addition, if the quorum server does not receive, before receiving the arbitration request sent by the first storage device, an arbitration request sent by another storage device, the quorum server may determine that the first storage device is to take over a host service.","In this case, the quorum server may find a corresponding identifier of the device identifier according to the device identifier of the first storage device, and add the corresponding identifier to a response message to send to the first storage device.","With reference to the fifth implementation, in a sixth implementation, the quorum server obtains a device identifier of the second storage device according to the device identifier of the first storage device, an arbitration ID, and a correspondence between the arbitration ID and the device identifier of the second storage device, further obtains a corresponding identifier of the device identifier of the second storage device according to a correspondence between the device identifier of the second storage device and the corresponding identifier, and deletes the corresponding identifier.","Even if the second storage device subsequently sends an arbitration request to the quorum server, the quorum server does not respond to the arbitration request because the corresponding identifier of the device identifier of the second storage device is deleted.","No request response is received, and consequently, the second storage device cannot take over a host service.","A second aspect of the embodiments provides another service takeover method.","A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.","Data communication is performed between the first storage device and the second storage device by using a link.","When a communication fault occurs between the first storage device and the second storage device, the first storage device sends a first arbitration request to the quorum server, and the second storage device sends a second arbitration request to the quorum server.","After receiving the arbitration requests sent by the two storage devices, the quorum server separately queries statuses of front-end ports of the two storage devices.","If the statuses of the front-end ports are valid, the quorum server continues to receive running statuses of the two storage devices, after comparing the running statuses of the two storage devices, selects a storage device in a better running status to take over a host service, and sends a request response to the storage device.","In the service takeover method provided in the second aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","Compared with the first aspect of the embodiments, the service takeover method provided in the second aspect is mainly performed by the quorum server.","Therefore, load of the storage device may be reduced to some extent.","A third aspect of the embodiments provides a storage device, configured to perform at least one method described in the first aspect.","A fourth aspect of the embodiments provides a service takeover apparatus, and the service takeover apparatus is located in a storage device, and configured to perform at least one method described in the first aspect.","According to the storage device provided in the third aspect and the service takeover apparatus provided in the fourth aspect of the embodiments, a storage device may wait for a period of time before sending an arbitration request to the quorum server.","Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","A fifth aspect of the embodiments provides a quorum server, configured to perform the method described in the second aspect.","According to the quorum server provided in the fifth aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","Compared with the first aspect of the embodiments, the quorum server provided in the fifth aspect can reduce load of the storage device to some extent.","A sixth aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the storage device of the foregoing third aspect, and used to perform at least one method of the foregoing first aspect.","According to the computer program product provided in the sixth aspect of the embodiments of the present invention, a storage device may wait for a period of time before sending an arbitration request to a quorum server.","Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.","The running status reflects current usage of a system resource of the storage device.","Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.","A seventh aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the quorum server of the foregoing fifth aspect, and used to perform the method of the foregoing second aspect.","BRIEF DESCRIPTION OF DRAWINGS To describe the technical solutions in the embodiments of the present invention more clearly, the following briefly describes the accompanying drawings required for describing the embodiments.","FIG.","1 is an application scenario diagram according to an embodiment of the present invention; FIG.","2 is a structural diagram of a storage device according to an embodiment of the present invention; FIG.","3 is a structural diagram of a quorum server according to an embodiment of the present invention; FIG.","4 is a schematic flowchart of a service takeover method according to an embodiment of the present invention; FIG.","5 is a schematic flowchart of another service takeover method according to an embodiment of the present invention; and FIG.","6 is a structural diagram of a service takeover apparatus according to an embodiment of the present invention.","DESCRIPTION OF EMBODIMENTS A service takeover method provided in an embodiment of the present invention is mainly applied to a storage system with two data centers.","The storage system with two data centers in this embodiment of the present invention is a storage system including two or more data centers.","For ease of description, in this embodiment of the present invention, the storage system with two data centers is used as an example for description.","As shown in FIG.","1, FIG.","1 is a schematic diagram of an application scenario according to an embodiment of the present invention.","A storage system shown in FIG.","1 includes at least two hosts 100 and two data centers.","For ease of description, in this embodiment of the present invention, the two data centers shown in FIG.","1 are respectively referred to as a first station 11 and a second station 12.Data transmission may be performed between the two data centers by using the Internet Protocol (IP) or a Fiber Channel (FC).","In this embodiment of the present invention, communication may be performed between the host 100 and the first station 11 or between the host 100 and the second station 12 by using the FC or the Small Computer Systems Interface (SCSI) protocol and based on the Internet Small Computer Systems Interface (iSCSI) protocol.","This is not limited herein.","The first station 11 includes a first storage device 110, and the second station 12 includes a second storage device 120.The first storage device 110 and the second storage device 120 may be any known storage device in the prior art, such as a storage array or a server.","For example, the first storage device 110 and the second storage device 120 may include a storage area network (SAN) array, or may include a network attached storage (NAS) array.","In this embodiment of the present invention, a specific form of the storage device in the data center is not limited.","It should be noted that all methods in embodiments of the present invention are performed by the storage devices in these stations.","For ease of description, in this embodiment of the present invention, unless otherwise stated, the first station 11 is the first storage device 110 in the first station 11, and the second station 12 is the second storage device 120 in the second station 12.In the application scenario shown in FIG.","1, there is a relatively short distance between the first station 11 and the second station 12.Generally, a distance between the first station 11 and the second station 12 may be less than 100 km.","For example, the first station 11 and the second station 12 may be located in two different positions of a same city.","Certainly, in this embodiment of the present invention, the first station 11 and the second station 12 may be not in a same city as long as synchronous replication of data can be implemented between the first station 11 and the second station 12.The host 100 may include any known computing device in the prior art, such as a server, a desktop computer, or an application server.","An operating system and another application program are installed in the host 100.There may be multiple hosts 100.In the application scenario shown in FIG.","1, both the first station 11 and the second station 12 may accept access of the host 100.In a case, some hosts 100 write data into the first station 11, and some hosts 100 write data into the second station 12.In another case, one host 100 may separately write different data into the first station 11 and the second station 12.In another case, different hosts 100 may respectively write data into the first station 11 and the second station 12.For example, a host A writes data into the first station 11, and a host B writes data into the second station 12; or a host A writes data A into the first station 11, and writes data B into the second station 12.It may be understood that the first station 11 and the second station 12 may simultaneously bear a service of the host 100, and therefore, efficiency of reading and writing data can be improved.","In addition, in this embodiment of the present invention, synchronous replication can be implemented between the first station 11 and the second station 12, to ensure real-time data synchronization between the first station 11 and the second station 12.It should be noted that in the storage system shown in FIG.","1, both the first station 11 and the second station 12 may accept access of the host 100, and the first station 11 and the second station 12 maintain consistency of stored data by means of synchronous replication, and therefore the first station 11 and the second station 12 may be interchanged.","In this embodiment of the present invention, data stored in the first station 11 and the second station 12 may maintain synchronized in real time by means of a synchronous replication technology.","For example, when the host 100 writes data into the first station 11, the first station 11 may simultaneously back up the data onto the second station 12.When the data is written into both the first station 11 and the second station 12, the first station 11 returns a write success response to the host 100, to maintain data synchronization between the first station 11 and the second station 12.It should be noted that in this embodiment of the present invention, that data is written into the first station 11 may be that data is written into a cache of the first station 11, or may be that data is written into a memory of the first station 11, and this is not limited herein.","In addition, the storage system in this embodiment may further include at least one quorum server 130.Data transmission is performed between the first storage device 110 and the quorum server 130 or between the second storage device 120 and the quorum server 130 by using the IP.","Data synchronization is implemented between the first storage device 110 and the second storage device 120 by using a link.","Therefore, if a fault occurs on the link in actual application, data synchronization cannot be implemented between the first storage device 110 and the second storage device 120, and the quorum server 130 needs to determine a storage device that is to take over all host services.","The quorum server 130 may include any known computing device in the prior art, such as a server, a desktop computer, or an application server.","Generally, the two storage devices may detect whether a fault occurs on the link or on each other by means of a heartbeat between the two storage devices.","For example, when the second storage device 120 does not receive a heartbeat signal of the first storage device 110 in a specified time, the second storage device 120 may determine that a fault occurs on the link or on the first storage device 110.In this case, the second storage device 120 may send an arbitration request to the quorum server 130 to request to take over all host services.","Similarly, when the first storage device 110 does not receive a heartbeat signal of the second storage device 120 in a specified time, the first storage device 110 may determine that a fault occurs on the link or on the second storage device 120.In this case, the first storage device 110 may send an arbitration request to the quorum server 130 to request to take over all host services.","In the storage system shown in FIG.","1, the first storage device 110, the second storage device 120, and the quorum server 130 belong to a HyperMetro domain.","The HyperMetro domain is a domain in which when a service conflict occurs between two or more storage devices, one quorum server 130 coordinates a storage device that is to take over a host service.","Each HyperMetro domain may be identified by using an arbitration ID, and the first storage device 110, the second storage device 120, and the quorum server 130 store the arbitration ID.","When the first storage device 110 and the second storage device 120 send arbitration requests to the quorum server 130, the arbitration ID may be carried in the arbitration requests.","After receiving an arbitration request, the quorum server 130 determines whether an arbitration ID carried in the arbitration request is consistent with the arbitration ID stored in the quorum server 130.If the arbitration ID carried in the arbitration request is consistent with the arbitration ID stored in the quorum server 130, the quorum server 130 performs processing; or if the arbitration ID carried in the arbitration request is not consistent with the arbitration ID stored in the quorum server 130, the quorum server 130 does not perform processing.","In addition, the first storage device 110 and the second storage device 120 may register device information (such as a device identifier) of the first storage device 110 and the second storage device 120 in the quorum server 130.For example, the first storage device 110 sends a device identifier (for example, A) of the first storage device 110 to the quorum server 130, and the quorum server 130 receives the device identifier A of the first storage device 110, generates an identifier A′ corresponding to the identifier A, and stores a correspondence between the identifier A and the identifier A′ in the quorum server 130, so as to complete registration of the first storage device 110.Similarly, the second storage device 120 sends a device identifier (for example, B) of the second storage device 120 to the quorum server 130, and the quorum server 130 receives the device identifier B of the second storage device 120, generates an identifier B′ corresponding to the identifier B, and stores a correspondence between the identifier B and the identifier B′ in the quorum server 130, so as to complete registration of the second storage device 120.In addition, in this embodiment, the first storage device 110 and the second storage device 120 belong to a HyperMetro domain.","Therefore, the first storage device 110 and the second storage device 120 have a same arbitration ID.","The arbitration ID, a correspondence between the arbitration ID and the identifier A, a correspondence between the arbitration ID and the identifier A′, a correspondence between the arbitration ID and the identifier B, and a correspondence between the arbitration ID and the identifier B′ need to be stored in the quorum server 130, and are used by the quorum server 130 to determine a storage device that is to take over a host service.","A correspondence between the arbitration ID and each identifier may be shown in the following table.","Arbitration ID Device identifier A Device identifier A′ Device identifier B Device identifier B′ Structures of the first storage device 110 and the second storage device 120 shown in FIG.","1 may be that shown in FIG.","2.FIG.","2 is a schematic structural diagram of a storage device 20 according to an embodiment of the present invention.","The storage device 20 shown in FIG.","2 is a storage array.","As shown in FIG.","2, the storage device 20 may include a controller 200 and a disk array 214.The disk array 214 herein is configured to provide storage space, and may include a redundant array of independent disks (RAID), or a disk chassis including multiple disks.","There may be multiple disk arrays 214, and the disk array 214 includes multiple disks 216.The disk 216 is configured to store data.","The disk array 214 may be in communication connection with the controller 200 by using a communication protocol such as the Small Computer System Interface (Small Computer System Interface, SCSI) protocol, and this is not limited herein.","It may be understood that the disk array 214 is only an example of a memory in the storage system.","In this embodiment of the present invention, data may also be stored by using a memory such as a tape library.","It should be noted that the disk 216 is also only an example of a memory constructing the disk array 214.In actual application, there is an implementation such as constructing a disk array between cabinets including multiple disks.","Therefore, in this embodiment of the present invention, the disk array 214 may further include a memory including a non-volatile storage medium, such as a cabinet or a server that includes a solid state drive (SSD) and multiple disks.","This is not limited herein.","The controller 200 is a “brain” of the storage device 20, and mainly includes a processor 202, a cache 204, a memory 206, a communications bus (which is referred to as a bus for short) 210, and a communications interface 212.The processor 202, the cache 204, the memory 206, and the communications interface 212 complete mutual communication by using the communications bus 210.It should be noted that in this embodiment of the present invention, there may be one or more controllers 200 in the storage device 20.It may be understood that when the storage device 20 includes at least two controllers 200, stability of the storage device 20 may be improved.","There may be multiple communications interfaces 212, and are respectively configured to communicate with the host 100, the disk 216, and another storage device.","The communications interface 212 that communicates with the host 100 may also be referred to as a front-end port.","The memory 206 is configured to store a program 208.The memory 206 may include a high-speed RAM memory, and may further include a non-volatile memory, for example, at least one magnetic disk memory.","It may be understood that the memory 206 may be a non-transitory machine-readable medium capable of storing program code, such as a random-access memory (RAM), a magnetic disk, a hard disk, an optical disc, a solid state disk (SSD), or a non-volatile memory.","The program 208 may include program code, and the program code includes a computer operation instruction.","The following provides a detailed description.","The cache 204 is a memory between the controller and a hard disk, and a capacity of the cache 204 is less than that of the hard disk, but a speed of the cache 204 is faster than that of the hard disk.","The cache 204 is configured to cache data received from the host 100 and another storage device, and cache data read from the disk 216, so as to improve performance and reliability of an array.","The cache 204 may be a non-transitory machine-readable medium capable of storing data, such as a RAM, a ROM, a flash memory, or a solid state disk (SSD).","This is not limited herein.","In some scenarios, the cache 204 and the memory 206 may be integrated into a same physical device.","That is, the memory 204 may provide a function of the memory 206.Therefore, in this embodiment, a cache and a memory may not be distinguished, and a cache resource is a memory resource.","The processor 202 may include one or more central processing units CPU, or an application-specific integrated circuit (ASIC), or one or more integrated circuits configured to implement this embodiment of the present invention.","The processor 202 may process an input/output (I/O) request for the disk 216, process data in the disk 216, and so on.","In this embodiment of the present invention, the processor 202 is configured to execute the program 208, and specifically, may execute related steps in the following method embodiment.","It may be understood that in this embodiment of the present invention, the first storage device 110 and the second storage device 120 have similar hardware structures.","A hardware structure of the quorum server 130 is described below.","As shown in FIG.","3, the quorum server 130 is a server, and includes at least a processor 301, a memory 302, and a communications interface 303.The processor 301 may include one or more central processing units CPU, or an application-specific integrated circuit (ASIC), or one or more integrated circuits configured to implement this embodiment of the present invention.","In this embodiment, after receiving arbitration requests sent by the first storage device 110 and the second storage device 120, the processor 301 may determine, according to an arbitration rule, a storage device that is to take a host service.","The memory 302 is configured to store a program, and may include a high-speed RAM memory, and may further include a non-volatile memory.","It may be understood that the memory 302 may be a non-transitory machine-readable medium capable of storing program code, such as a random-access memory (RAM), a magnetic disk, a hard disk, an optical disc, a solid state disk (SSD), or a non-volatile memory.","In this embodiment, the memory 302 may be configured to store software code such as the arbitration rule, and may be further configured to store data or information sent by the first storage device 110 and the second storage device 120.There may be one or more communications interfaces 303, configured to communicate with the first storage device 110 and the second storage device 120.Service takeover methods specifically implemented by storage devices in embodiments of the present invention are described below in detail.","FIG.","4 is a flowchart of a service takeover method according to an embodiment of the present invention.","The method may be applied to an application scenario shown in FIG.","1.In addition, hardware structures of a first storage device 110 and a second storage device 120 in this embodiment of the present invention may be that shown in FIG.","2.Specifically, the method shown in FIG.","4 may be jointly performed by processors of the first storage device 110 and the second storage device 120.Step S101 to step S105 are performed by a processor 202 of the first storage device 110, step S106 and step S107 are performed by a processor 301 of a quorum server 130, and step S108 to step S112 are performed by a processor of the second storage device 120.The service takeover method shown in FIG.","4 is described with reference to FIG.","1 and FIG.","2.As shown in FIG.","4, the method may include the following steps.","STEP S101.The first storage device 110 detects whether a communication fault occurs between the first storage device 110 and the second storage device 120.This embodiment is applied to a HyperMetro scenario.","In this scenario, both the first storage device 110 and the second storage device 120 may process a service request of a host 100, for example, receive a write data request sent by the host 100, and write data carried in the write data request into the storage device (if the first storage device processes the service request, the data is written into the first storage device; or if the second storage device processes the service request, the data is written into the second storage device); or receive a read data request sent by the host 100, and send data that needs to be read according to the read data request to the host 100.Because both the first storage device 110 and the second storage device 120 may process a service request of the host 100, the first storage device 110 and the second storage device 120 separately store a part of data from the host 100.To maintain data consistency between the two storage devices, the first storage device 110 needs to synchronize data stored in the first storage device 110 to the second storage device 120.Similarly, the second storage device 120 also needs to synchronize data stored in the second storage device 120 to the first storage device 110.Therefore, the two storage devices need to synchronize data by using a link between the two storage devices.","If a fault occurs on the link, a data synchronization operation is interrupted.","Specifically, the first storage device 110 may detect, according to a heartbeat signal between the first storage device 110 and the second storage device 120, whether a fault occurs on the link or on the second storage device 120.For example, when the first storage device 110 does not receive a heartbeat signal of the second storage device 120 in a specified time, the first storage device 110 may determine that a fault occurs on the link or on the second storage device 120.In this way, the first storage device 110 determines whether a communication fault occurs between the first storage device 110 and the second storage device 120.It should be noted that if the first storage device 110 detects that a communication fault occurs between the first storage device 110 and the second storage device 120, a fault may occur on the link, or a fault may occur in the second storage device, and consequently, communication cannot be performed.","Alternatively, the first storage device 110 may not use a heartbeat signal between the first storage device 110 and the second storage device 120 to detect whether a fault occurs on the link.","For example, when the link is physically disconnected, the first storage device 110 receives a notification message indicating that the link is disconnected.","Step S102: The first storage device 110 detects a status of a front-end port of the first storage device 110.The front-end port herein is a communications interface used by the first storage device 110 to communicate with the host 100, for example, a communications interface 212 shown in FIG.","2.The status of the front-end port may be valid or invalid.","When the status is valid, it indicates that a connection between the first storage device 110 and the host 100 is in a normal state, and the first storage device 110 can receive a service request of the host 100.When the status is invalid, it indicates that the connection between the first storage device 110 and the host 100 is in an abnormal state, and the first storage device 110 cannot receive a service request of the host 100.When the front-end port is in an invalid state, it indicates that the first storage device 110 is not capable of taking over a host service.","Therefore, the first storage device 110 gives up sending an arbitration request to the quorum server 130.In some scenarios, if the front-end port becomes abnormal, a system automatically reports an error.","Therefore, the first storage device 110 does not need to actively detect the status of the front-end port.","The status of the front-end port is valid by default as long as no error alert occurs.","Step S103: When determining that the status of the front-end port is valid, the first storage device 110 obtains a running status of the first storage device 110.The running status reflects current usage of a system resource of the first storage device 110.The system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.","For example, in this embodiment, the running status of the first storage device 110 may be reflected by a running status value of the first storage device, which is represented by S. The running status value is obtained according to the current usage ratio of the system resource of the first storage device and a correspondence between a usage ratio of the system resource and a status value of the system resource.","The correspondence is preset.","The first storage device 110 has a setting interface.","After collecting statistics about running statuses of the first storage device 110, a system administrator may set the correspondence by using the setting interface.","The running status value may be stored in a cache 204 of the first storage device 110.Current usage of these system resources may be respectively reflected by parameters such as a processor usage ratio, a hard disk usage ratio, a cache usage ratio, and a host bandwidth usage ratio.","The processor usage ratio (which is also referred to as a CPU usage ratio) is a CPU resource occupied by a running program, and represents a program running situation of a storage device at a time point.","A high usage ratio indicates that the storage device runs many programs at this time point, and on the contrary, a low usage ratio indicates that the storage device runs few programs at this time point.","In addition, in this embodiment, a processor usage ratio in an interval is corresponding to a processor status value.","In this embodiment, Q1 represents a current processor status value corresponding to a current processor usage ratio.","The hard disk usage ratio (which is also referred to as a disk usage ratio) is a ratio of a used capacity to a total available capacity in a disk.","A hard disk usage ratio in an interval is corresponding to a hard disk status value.","In this embodiment, Q2 represents a current hard disk status value corresponding to a current hard disk usage ratio.","The cache usage ratio (which is also referred to as a cache water mark) is a ratio of used pages to total available pages in a cache.","A cache usage ratio in an interval is corresponding to a cache status value.","In this embodiment, Q3 represents a current cache status value corresponding to a current cache usage ratio.","The host bandwidth usage ratio is a ratio of used bandwidth to total bandwidth in bandwidth between the host and the storage device.","A host bandwidth usage ratio in an interval is corresponding to a host bandwidth status value.","In this embodiment, Q4 represents a current host bandwidth status value corresponding to a current host bandwidth usage ratio.","The following describes how to obtain the running status value S of the first storage device.","In this embodiment, S=Q1+Q2+Q3+Q4.In this embodiment, a current running status of each system resource may be monitored, so as to obtain a current usage ratio of each system resource.","In addition, the cache 204 or a memory 206 in the first storage device 110 further stores the correspondence between the usage ratio of the system resource and the status value of the system resource.","For example, Table 1 reflects a correspondence between a processor usage ratio and a processor status value.","TABLE 1 Processor Status Value Processor Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .",".",".",".",".",".","Therefore, after obtaining a current processor usage ratio by means of monitoring, the first storage device 110 may obtain a current processor status value Q1 according to the current processor usage ratio and the correspondence between the processor usage ratio and the processor status value.","Table 2 reflects a correspondence between a hard disk usage ratio and a hard disk status value.","TABLE 2 Hard Disk Status Value Hard Disk Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .",".",".",".",".",".","Therefore, after obtaining a current hard disk usage ratio by means of monitoring, the first storage device 110 may obtain a current hard disk status value Q2 according to the current hard disk usage ratio and the correspondence between the hard disk usage ratio and the hard disk status value.","Table 3 reflects a correspondence between a cache usage ratio and a cache status value.","TABLE 3 Cache Status Value Cache Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .",".",".",".",".",".","Therefore, after obtaining a current cache usage ratio by means of monitoring, the first storage device 110 may obtain a current cache status value Q3 according to the current cache usage ratio and the correspondence between the cache usage ratio and the cache status value.","Table 4 reflects a correspondence between a host bandwidth usage ratio and a host bandwidth status value.","TABLE 4 Host Bandwidth Status Value Host Bandwidth Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .",".",".",".",".",".","Therefore, after obtaining a current host bandwidth usage ratio by means of monitoring, the first storage device 110 may obtain a current host bandwidth status value Q4 according to the current host bandwidth usage ratio and the correspondence between the host bandwidth usage ratio and the host bandwidth status value.","It should be noted that the running status value S may be a sum of Q1, Q2, Q3, and Q4, or may be a sum of a part of Q1, Q2, Q3, and Q4 (for example, S=Q1+Q3), or may even be equal to one status value (for example, S=Q1).","In addition, S may also be a sum of weighted values of Q1, Q2, Q3, and Q4.For example, if a weight is set for each system resource, for example, a weight of the processor resource is 40%, a weight of the hard disk resource is 30%, a weight of the cache resource is 20%, and a weight of the host bandwidth resource is 10%, S=Q1*40%+Q2*30%+Q3*20%+Q4*10%.","It may be understood that the weight of each system resource may be adjusted according to an importance degree of the resource.","The weight of each system resource is not limited in this embodiment.","In general, the running status value is obtained according to a status value reflecting a current running status of each system resource, and is used to reflect a current overall running status of the storage device.","An algorithm for obtaining the running status value according to each status value is not limited in this embodiment.","The running status value may be obtained by means of periodic calculation, and be stored in the first storage device 110.In addition, in the correspondences of Table 1 to Table 4, each usage ratio interval and a corresponding status value may be adjusted according to an actual running status of the storage device, and are not limited in this embodiment.","In addition, it may be understood that the foregoing system resource is only an example of this embodiment of the present invention.","The storage device may further include another system resource, and a status value of the another system resource may also reflect the running status value.","Step S104: The first storage device 110 determines delay duration according to the running status.","In this embodiment, after detecting that a communication fault occurs between the first storage device 110 and the second storage device 120, the first storage device 110 does not immediately send an arbitration request to the quorum server 130, but sends an arbitration request to the quorum server 130 after waiting for a period of time.","The delay duration is duration for which the first storage device waits before sending the arbitration request to the quorum server.","Specifically, in this embodiment, the first storage device 110 may determine the delay duration according to the running status value.","The delay duration is represented by T, and is in a unit of second(s).","The delay duration T=k*S, where S is the running status value, and k is any value.","In an implementation, k=1, because neither excessively long nor excessively short delay duration is proper.","For example, when S=3, T=3s.","In addition, in this embodiment, T cannot exceed a preset threshold because excessively long delay duration is improper.","The preset threshold may be set to any value in [20, 30].","Step S105: The first storage device 110 sends an arbitration request to the quorum server 130 after the delay duration.","Before performing steps S101 to S105, the first storage device 110 may register device information of the first storage device 110 in the quorum server 130.For example, the first storage device 110 sends a device identifier A of the first storage device 110 to the quorum server 130.After receiving the identifier of the first storage device 110, the quorum server 130 generates and stores an identifier A′ corresponding to the identifier A, so as to complete registration of the first storage device 110.In step S105, the arbitration request sent by the first storage device 110 to the quorum server 130 includes an arbitration ID and the identifier of the first storage device 110.To be distinguished from delay duration of the second storage device 120, in this embodiment, the delay duration of the first storage device 110 is referred to as first delay duration, and the delay duration of the second storage device 120 is referred to as second delay duration.","To be distinguished from an arbitration request sent by the second storage device 120, in this embodiment, the arbitration request sent by the first storage device is referred to as a first arbitration request, and the arbitration request sent by the second storage device is referred to as a second arbitration request.","After receiving the first arbitration request, the quorum server 130 performs matching between the arbitration ID carried in the first arbitration request and a pre-stored arbitration ID, and when determining that the arbitration ID carried in the first arbitration request is consistent with the pre-stored arbitration ID, determines that the first storage device 110 is in an arbitration scope of the quorum server 130.In addition, the quorum server 130 does not receive the second arbitration request of the second storage device 120 before step S111.The quorum server 130 may determine, according to a principle of first receiving, that the first storage device 110 is to take over a host service.","Step S106: The quorum server 130 deletes a corresponding identifier, for example, B′ described above, of an identifier of the second storage device 120 stored in the quorum server 130.Specifically, the quorum server 130 obtains, according to a correspondence between an arbitration ID and a device identifier B and a correspondence between the device identifier B and a corresponding identifier B′, the identifier B′ corresponding to the device identifier B, and deletes the identifier B′.","Step S107: The quorum server 130 sends a response message of the first arbitration request to the first storage device 110.The response message includes the corresponding identifier of the device identifier of the first storage device 110, for example, A′ described above.","When receiving A′, the first storage device 110 may learn that the first storage device 110 wins in an arbitration and can take over a host service.","Step S108: The second storage device 120 detects whether a communication fault occurs between the second storage device 120 and the first storage device 110.Similarly, the second storage device 120 also needs to detect whether a communication fault occurs between the second storage device 120 and the first storage device 110.When detecting that a communication fault occurs, the second storage device 120 also needs to send an arbitration request to the quorum server 130.Step S108 and step S101 are similar, and are only performed by different execution bodies.","For details, refer to the description in step S101.Details are not described herein again.","Step S109: The second storage device 120 detects a status of a front-end port of the second storage device 120.In step S109, the front-end port is a communications interface used by the second storage device 120 to communicate with the host 100, and similarly has a valid state and an invalid state.","For details, refer to the description in step S102.Details are not described herein again.","Step S110: When determining that the status of the front-end port is valid, the second storage device 120 obtains a running status of the second storage device 120.In this embodiment, a running status value of the second storage device may be represented by S′, and is used to reflect a running status of a system resource of the second storage device 120.Compared with step S103, this step is only performed by a different execution body.","For details, refer to the description in step S103.Details are not described herein again.","Step S111: The second storage device 120 determines delay duration according to the running status.","Compared with step S104, this step is only performed by a different execution body.","For details, refer to the description in step S104.Details are not described herein again.","Step S112: The second storage device 120 sends an arbitration request to the quorum server 130 after the delay duration.","Before performing steps S108 to S112, the second storage device 120 may register device information of the second storage device 120 in the quorum server 130.For example, the second storage device 120 sends a device identifier B of the second storage device 120 to the quorum server 130.After receiving the identifier of the second storage device 120, the quorum server 130 generates and stores an identifier B′ corresponding to the identifier B, so as to complete registration of the second storage device 120.In step S112, the arbitration request sent by the second storage device 120 to the quorum server 130 includes an arbitration ID and the identifier of the second storage device 120.After receiving the second arbitration request, the quorum server 130 performs matching between the arbitration ID carried in the second arbitration request and a pre-stored arbitration ID, and when determining that the arbitration ID carried in the second arbitration request is consistent with the pre-stored arbitration ID, determines that the second storage device 120 is in an arbitration scope of the quorum server 130.However, because the first arbitration request arrives at the quorum server 130 earlier than the second arbitration request, and after receiving the first arbitration request, the quorum server 130 deletes the corresponding identifier of the identifier of the second storage device 120 stored in the quorum server 130.Therefore, in this case, the quorum server 130 does not send the corresponding identifier of the device identifier of the second storage device 120 to the second storage device 120, and the second storage device 120 does not receive the corresponding identifier, and therefore cannot take over a host service.","In the prior art, when detecting that a fault occurs in communication with each other, the first storage device 110 and the second storage device 120 generally send arbitration requests directly to the quorum server 130 to request to take over a host service.","The quorum server 130 generally determines, based on a first received arbitration request, a storage device that is to take over a host service.","However, in some cases, the first received arbitration request is sent by a storage device that is in a relatively poor running status.","The relatively poor running status means that a usage ratio of a part or all of system resources of the storage device reaches a threshold.","In this case, if the host service is still taken over by the storage device, service processing efficiency is relatively low.","However, in this embodiment, the first storage device 110 and the second storage device 120 do not immediately send arbitration requests to the quorum server 130, but send arbitration requests to the quorum server 130 after waiting for a period of time.","The quorum server 130 determines, based on a first received arbitration request, a storage device that is to take over a host service.","If the first received arbitration request is sent by the first storage device 110, the quorum server 130 determines that the first storage device 110 is to take over a host service.","If the first received arbitration request is sent by the second storage device 120, the quorum server 130 determines that the second storage device 120 is to take over a host service.","In this embodiment, both the delay duration of the first storage device 110 and the delay duration of the second storage device 120 are obtained according to respective running statuses, and the running statuses reflect current usage of system resources of the storage devices.","Therefore, the quorum server 130 can select a storage device in a best running status from storage devices that send arbitration requests to take over a host service.","In addition, as shown in FIG.","5, this embodiment further provides another implementation.","A difference from the implementation shown in FIG.","4 is that, in the implementation shown in FIG.","5, after a quorum server 130 receives arbitration requests of a first storage device 110 and a second storage device 120, the quorum server 130 collects information about running statuses of the two storage devices from the first storage device 110 and the second storage device 120, and then makes arbitration determining.","Specifically, this implementation may be performed by a processor 301 of a quorum server shown in FIG.","3.It should be noted that the implementation shown in FIG.","5 is different from the implementation shown in FIG.","4 only in an execution body and an execution sequence of some steps.","For specific implementation of steps, refer to the description of FIG.","4.This implementation includes the following steps.","Step S201: The first storage device 110 detects whether a communication fault occurs between the first storage device 110 and the second storage device 120.For a specific implementation process, refer to the description of S101 shown in FIG.","4.Details are not described herein again.","Step S202: After determining that a communication fault occurs between the first storage device 110 and the second storage device 120, the first storage device 110 sends a first arbitration request to the quorum server 130.For a specific implementation process, refer to the description of S105 shown in FIG.","4.Details are not described herein again.","Step S203: The second storage device 120 detects whether a communication fault occurs between the second storage device 120 and the first storage device 110.In step S203, a manner in which the second storage device 120 detects whether a communication fault occurs is similar to that in step S201, and only an execution body is different.","For a specific implementation process, refer to the description of S101 shown in FIG.","4.Details are not described herein again.","Step S204: After determining that a communication fault occurs between the second storage device 120 and the first storage device 110, the second storage device 120 sends a second arbitration request to the quorum server 130.In step S204, a manner in which the second storage device 120 sends the second arbitration request to the quorum server 130 is similar to that in step S202, and content of the arbitration request is similar to that in step S202.For a specific implementation process, refer to the description of S112 shown in FIG.","4.Details are not described herein again.","Step S205: The quorum server 130 sends a query request to the first storage device 110, to query a status of a front-end port of the first storage device 110.Step S206: After receiving the query request, the first storage device 110 detects the status of the front-end port of the first storage device 110, and reports the status of the front-end port of the first storage device 110 to the quorum server 130 (step S207).","When the status of the front-end port of the first storage device 110 is invalid, the quorum server 130 may determine that the first storage device 110 cannot take over a host service, that is, reject the first arbitration request.","When the status of the front-end port of the first storage device 110 is valid, the quorum server 130 continues to perform step S208.It may be understood that in actual application, after sending the arbitration request to the quorum server 130, the first storage device 110 may actively report the status of the front-end port of the first storage device 110, instead of waiting for a query request sent by the quorum server 130.Step S208: The quorum server 130 sends a query request to the first storage device 110, to query a running status of the first storage device 110.Step S209: After receiving the query request, the first storage device 110 reports the running status of the first storage device 110 to the quorum server 130.In an optional implementation, the first storage device 110 directly reports a usage ratio of each system resource to the quorum server 130, for example, directly reports a current processor usage ratio, a current hard disk usage ratio, a current cache usage ratio, and a current host bandwidth usage ratio to the quorum server 130.The quorum server 130 performs arbitration after receiving a running status sent by the second storage device 120.In this implementation, the quorum server 130 may pre-store correspondences between a usage ratio of system resources and status values (content of Table 1 to Table 4), and after receiving a current usage ratio of system resources sent by the first storage device 110, obtains, according to the foregoing correspondences, a status value corresponding to each usage ratio, so as to obtain a running status value that reflects an overall running status of the first storage device 110.In another optional implementation, the first storage device 110 obtains, according to a current usage ratio of system resources and the foregoing correspondences, a status value corresponding to each usage ratio, and reports the status value corresponding to each usage ratio to the quorum server 130.The quorum server 130 obtains, according to the status value corresponding to each usage ratio, a running status value that reflects an overall running status of the first storage device 110.In this implementation, the quorum server 130 does not need to pre-store correspondences between usage ratios of system resources and status values.","In still another optional implementation, based on one of the foregoing implementations, the first storage device 110 may further obtain a running status value that reflects an overall running status of the first storage device 110, and report the running status value to the quorum server 130.It may be understood that, in addition to the foregoing three implementations, the first storage device 110 may further report a running status of the first storage device 110 to the quorum server 130 by using an implementation.","A manner in which the first storage device 110 reports the running status to the quorum server 130 and content of the running status are not limited in this embodiment.","Step S210 to step S214 are similar to step S205 to step S209.A difference is that step S210 to step S214 describe a process in which the quorum server 130 queries a front-end port status and a running status of the second storage device 120.An implementation process is similar to that of the first storage device 110, and details are not described herein again.","Step S215: The quorum server 130 determines, according to the running statuses of the two storage devices, that the first storage device 110 wins.","Specifically, the quorum server 130 may determine a victorious storage device according to a current usage ratio of each system resource reported by the first storage device 110 and a current usage ratio of each system resource reported by the second storage device 120.For example, after comprehensively considering a current usage ratio of system resources reported by the two storage devices, the quorum server 130 may determine that the first storage device 110 wins when determining that the current usage ratio of each system resource of the first storage device 110 is less than the current usage ratio of each system resource of the second storage device 120, or a current usage ratio of most system resources of the first storage device 110 is less than the current usage ratio of each system resource of the second storage device 120.Alternatively, the quorum server 130 may determine a victorious storage device according to a status value of each system resource reported by the first storage device 110 and a status value of each system resource reported by the second storage device 120.For example, after comprehensively considering status values of system resources reported by the two storage devices, the quorum server 130 may determine that the first storage device 110 wins when determining that the status value of each system resource of the first storage device 110 is less than the status value of each system resource of the second storage device 120, or determining that a sum of status values of all system resources of the first storage device 110 is less than a sum of status values of all system resources of the second storage device 120.Alternatively, the quorum server 130 may determine a victorious storage device according to a running status value that is reported by the first storage device 110 and that reflects an overall running status of the first storage device 110 and a running status value that is reported by the second storage device 120 and that reflects an overall running status of the second storage device 120.For example, the quorum server 130 may determine that the first storage device 110 wins when the running status value of the first storage device 110 is less than the running status value of the second storage device 120.Step S216: The quorum server 130 deletes a corresponding identifier of an identifier of the second storage device 120 stored in the quorum server 130.Step S216 is similar to step S106 shown in FIG.","4, and details are not described herein again.","Step S217: The quorum server 130 sends a response message of the first arbitration request to the first storage device 110.Step S217 is similar to step S107 shown in FIG.","4, and details are not described herein again.","In the implementation shown in FIG.","5, when detecting that a communication fault occurs between the first storage device 110 and the second storage device 120, the first storage device 110 and the second storage device 120 respectively send arbitration requests to the quorum server 130.After receiving the arbitration requests sent by the two storage devices, the quorum server 130 separately queries front-end port statuses and running statuses of the two storage devices, so as to select a storage device in a best running status to take over a host service.","Referring to FIG.","6, FIG.","6 is a service takeover apparatus according to an embodiment of the present invention.","The apparatus is located in a first storage device, and data communication is performed between the first storage device and a second storage device by using a link.","The service takeover apparatus includes a reading module 401, a calculation module 402, and a transceiver module 403.The reading module 401 is configured to obtain a running status of the first storage device when determining that a communication fault occurs between the first storage device and the second storage device, where the running status reflects current usage of a system resource of the first storage device, and the system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.","The calculation module 402 is configured to determine delay duration according to the running status, where the delay duration is duration for which the first storage device waits before sending an arbitration request to the quorum server.","The transceiver module 403 is configured to send, after the delay duration, the arbitration request to the quorum server to request to take over a service.","The reading module 401 is specifically configured to read a running status value of the first storage device, the running status value is a sum of status values of all system resources, a status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and the correspondence includes a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.","The calculation module 402 is specifically configured to determine the delay duration according to the running status value and a formula T=k*S, where T is the delay duration, S is the running status value, and k is any value.","Optionally, k=1.In addition, the first storage device communicates with a host by using a front-end port, and the reading module 401 is further configured to: detect a status of the front-end port, determine that the status of the front-end port is valid, and when determining that the status of the front end is valid, read the running status value of the first storage device.","For specific function implementation of the modules, refer to the method steps shown in FIG.","4.Details are not described herein again.","An ordinary person skilled in the art may understand that the foregoing storage medium may include any non-transitory machine-readable medium capable of storing program code, such as a USB flash drive, a removable hard disk, a magnetic disk, an optical disc, a random-access memory (RAM), a solid state disk (SSD), or a non-volatile memory.","Finally, it should be noted that the foregoing embodiments are merely intended for describing the technical solutions of the present invention, rather than limiting the present invention."]],"string":"[\n [\n \"Service Takeover Method, Storage Device, And Service Takeover Apparatus\",\n \"The present disclosure describes example service takeover methods, storage devices, and service takeover apparatuses.\",\n \"In one example, when a communication fault occurs between two storage devices in a storage system, the two storage devices respectively obtain running statuses of the two storage devices.\",\n \"A running status can reflect current usage of one or more system resources of a particular storage device.\",\n \"Then, a delay duration is determined according to the running statuses, where the delay duration is a duration for which the storage device waits before sending an arbitration request to a quorum server.\",\n \"The two storage devices respectively send, after the delay duration, arbitration requests to the quorum server to request to take over a service.\",\n \"The quorum server then can select a storage device in a relatively better running status to take over a host service.\"\n ],\n [\n \"1.A service takeover method in a storage system, wherein the storage system comprises a first storage device, a second storage device, and a quorum server, wherein data communication is performed between the first storage device and the second storage device by using a link, and wherein the method being performed by the first storage device comprises: obtaining a running status of the first storage device when a communication fault occurs between the first storage device and the second storage device, wherein the running status reflects current usage of a system resource of the first storage device, and wherein the system resource comprises at least one of: a processor resource, a hard disk resource, a cache resource, and a host bandwidth resource; determining a delay duration according to the running status, wherein the delay duration is a duration for which the first storage device waits before sending an arbitration request to the quorum server; and sending, after the delay duration, the arbitration request to the quorum server to request to take over a service.\",\n \"2.The method according to claim 1, wherein the obtaining a running status of the first storage device comprises: reading a running status value of the first storage device, wherein the running status value is a sum of status values of all system resources, wherein a status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and wherein the correspondence comprises at least one of a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.\",\n \"3.The method according to claim 2, wherein the determining the delay duration according to the running status comprises: determining the delay duration according to the running status value and a formula T=k*S, wherein T is the delay duration, S is the running status value, and k is any value.\",\n \"4.The method according to claim 3, wherein k=1.5.The method according to claim 2, wherein the storage system further comprises a host, wherein the first storage device communicates with the host by using a front-end port, and wherein, before the reading the running status value of the first storage device, the method further comprises: detecting a status of the front-end port; determining that the status of the front-end port is valid; and in response to determining that the status of the front-end port is valid, reading the running status value of the first storage device.\",\n \"6.A storage device, wherein the storage device is located in a storage system, and the storage device comprises: a communications interface, the communications interface configured to communicate with another storage device and a quorum server in the storage system; and at least one processor, the at least one processor configured to: obtain a running status of the storage device when determining that a communication fault occurs between the storage device and the another storage device, wherein the running status reflects current usage of a system resource of the storage device, and wherein the system resource comprises at least one of: a processor resource, a hard disk resource, a cache resource, and a host bandwidth resource; determine a delay duration according to the running status, wherein the delay duration is a duration for which the storage device waits before sending an arbitration request to the quorum server; and send, using the communications interface and after the delay duration, the arbitration request to the quorum server to request to take over a service.\",\n \"7.The storage device according to claim 6, wherein the at least one processor is configured to read a running status value of the storage device, wherein the running status value is a sum of status values of all system resources, wherein a status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and wherein the correspondence comprises at least one of a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.\",\n \"8.The storage device according to claim 7, wherein the at least one processor is configured to determine the delay duration according to the running status value and a formula T=k*S, wherein T is the delay duration, S is the running status value, and k is any value.\",\n \"9.The storage device according to claim 8, wherein k=1.10.The storage device according to claim 7, wherein the storage system further comprises a host, wherein the storage device further comprises a front-end port, and wherein the storage device communicates with the host by using the front-end port; and the at least one processor is further configured to, before reading the running status value of the storage device: detect a status of the front-end port; determine that the status of the front-end port is valid; and in response to determining that the status of the front-end port is valid, read the running status value of the storage device.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>For protecting data security and for a purpose of redundancy (Disaster Recovery), storage vendors establish a geographic redundancy center to implement remote backup of data, so that original data is not lost or damaged after a disaster (such as a fire or an earthquake) occurs, and a key service can resume running in an allowable time range, to minimize a loss brought by the disaster.\",\n \"Currently, a main storage system is a two-center storage system.\",\n \"The two-center storage system implements redundancy by establishing two data centers.\",\n \"Both the two data centers can receive a service request from a host, and store service data in respective storage devices.\",\n \"Then, data synchronization is implemented by using a link between the data centers.\",\n \"However, once a fault occurs on the link, the data synchronization is interrupted.\",\n \"Therefore, a data center needs to be designated to bear a data service of the host, and after fault recovery of the link, data received before the fault recovery is backed up to another data center.\",\n \"Generally, when a fault occurs on the link, the two data centers immediately and respectively send arbitration requests to a quorum server, and the quorum server determines, according to an arbitration request receiving sequence, the data center that is to bear the data service.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>Embodiments of the present invention provide a service takeover method, a storage device, and a service takeover apparatus.\",\n \"When a communication fault occurs between a storage device and another storage device, an arbitration request can be submitted to a quorum server after delay duration according to current usage of a respective system resource, so that the quorum server can select a storage device in a better running status to take over a host service.\",\n \"A first aspect of the embodiments provides a service takeover method.\",\n \"A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.\",\n \"Data communication is performed between the first storage device and the second storage device by using a link.\",\n \"The first storage device obtains a running status of the first storage device when a communication fault occurs between the first storage device and the second storage device.\",\n \"The running status reflects current usage of a system resource of the first storage device.\",\n \"The system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.\",\n \"The first storage device determines delay duration according to the running status, where the delay duration is duration for which the first storage device waits before sending an arbitration request to the quorum server.\",\n \"The first storage device sends, after the delay duration, the arbitration request to the quorum server to request to take over a service.\",\n \"Similarly, when determining that a communication fault occurs between the second storage device and the first storage device, the second storage device obtains a running status of the second storage device, and determines delay duration according to the running status.\",\n \"The second storage device sends, after the delay duration, an arbitration request to the quorum server to request to take over a service.\",\n \"After receiving the arbitration requests sent by the two storage devices, the quorum server determines, based on a first received arbitration request, a storage device that is to take over a host service.\",\n \"A storage device needs to wait for a period of time before sending an arbitration request to the quorum server.\",\n \"Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"With reference to the first aspect, in a first implementation, the first storage device reads a running status value of the first storage device, where the running status value is a sum of status values of all system resources.\",\n \"A status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and the correspondence includes a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.\",\n \"In this implementation, usage of each system resource may be reflected by a running status value.\",\n \"Therefore, the current usage of the system resource of the first storage device is better reflected, so that more proper delay duration may be obtained according to the running status value.\",\n \"With reference to the first implementation, in a second implementation, the delay duration may be obtained according to the running status value and a formula T=k*S, where T is the delay duration, S is the running status value, and k is any value.\",\n \"This implementation provides a specific algorithm to associate the delay duration with the running status value.\",\n \"In general, the delay duration may be directly proportional to the running status value, that is, a greater running status value leads to longer waiting duration.\",\n \"With reference to the second implementation, in a third implementation, k=1.The quorum server generally determines, based on a first received arbitration request, a storage device that is to take over a host service.\",\n \"Therefore, the delay duration is set, so that the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"Excessively short delay duration is improper, because excessively short waiting duration is unfavorable to distinguishing a sequence in which storage devices send arbitration requests.\",\n \"Excessively long delay duration is also improper, because excessively long waiting duration is unfavorable to processing a host service.\",\n \"Therefore, k is set to 1 in this implementation.\",\n \"With reference to any one of the foregoing implementations of the first aspect, in a fourth implementation, the storage system further includes a host.\",\n \"The first storage device communicates with the host by using a front-end port.\",\n \"The first storage device may detect a status of the front-end port, and when determining that the status of the front-end port is valid, read the running status value of the first storage device.\",\n \"If the status of the front-end port is invalid, it indicates that communication between the first storage device and the host is interrupted, and the first storage device cannot take over a host service.\",\n \"Therefore, in this case, the first storage device does not need to send an arbitration request to the quorum server.\",\n \"With reference to any one of the foregoing implementations, in a fifth implementation, the arbitration request sent by the first storage device to the quorum server includes an arbitration ID and a device identifier of first storage device.\",\n \"After receiving the arbitration request, the quorum server determines whether the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, and if the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, determines that the first storage device is in an arbitration scope of the quorum server.\",\n \"In addition, if the quorum server does not receive, before receiving the arbitration request sent by the first storage device, an arbitration request sent by another storage device, the quorum server may determine that the first storage device is to take over a host service.\",\n \"In this case, the quorum server may find a corresponding identifier of the device identifier according to the device identifier of the first storage device, and add the corresponding identifier to a response message to send to the first storage device.\",\n \"With reference to the fifth implementation, in a sixth implementation, the quorum server obtains a device identifier of the second storage device according to the device identifier of the first storage device, an arbitration ID, and a correspondence between the arbitration ID and the device identifier of the second storage device, further obtains a corresponding identifier of the device identifier of the second storage device according to a correspondence between the device identifier of the second storage device and the corresponding identifier, and deletes the corresponding identifier.\",\n \"Even if the second storage device subsequently sends an arbitration request to the quorum server, the quorum server does not respond to the arbitration request because the corresponding identifier of the device identifier of the second storage device is deleted.\",\n \"No request response is received, and consequently, the second storage device cannot take over a host service.\",\n \"A second aspect of the embodiments provides another service takeover method.\",\n \"A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.\",\n \"Data communication is performed between the first storage device and the second storage device by using a link.\",\n \"When a communication fault occurs between the first storage device and the second storage device, the first storage device sends a first arbitration request to the quorum server, and the second storage device sends a second arbitration request to the quorum server.\",\n \"After receiving the arbitration requests sent by the two storage devices, the quorum server separately queries statuses of front-end ports of the two storage devices.\",\n \"If the statuses of the front-end ports are valid, the quorum server continues to receive running statuses of the two storage devices, after comparing the running statuses of the two storage devices, selects a storage device in a better running status to take over a host service, and sends a request response to the storage device.\",\n \"In the service takeover method provided in the second aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"Compared with the first aspect of the embodiments, the service takeover method provided in the second aspect is mainly performed by the quorum server.\",\n \"Therefore, load of the storage device may be reduced to some extent.\",\n \"A third aspect of the embodiments provides a storage device, configured to perform at least one method described in the first aspect.\",\n \"A fourth aspect of the embodiments provides a service takeover apparatus, and the service takeover apparatus is located in a storage device, and configured to perform at least one method described in the first aspect.\",\n \"According to the storage device provided in the third aspect and the service takeover apparatus provided in the fourth aspect of the embodiments, a storage device may wait for a period of time before sending an arbitration request to the quorum server.\",\n \"Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"A fifth aspect of the embodiments provides a quorum server, configured to perform the method described in the second aspect.\",\n \"According to the quorum server provided in the fifth aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"Compared with the first aspect of the embodiments, the quorum server provided in the fifth aspect can reduce load of the storage device to some extent.\",\n \"A sixth aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the storage device of the foregoing third aspect, and used to perform at least one method of the foregoing first aspect.\",\n \"According to the computer program product provided in the sixth aspect of the embodiments of the present invention, a storage device may wait for a period of time before sending an arbitration request to a quorum server.\",\n \"Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"A seventh aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the quorum server of the foregoing fifth aspect, and used to perform the method of the foregoing second aspect.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No.\",\n \"PCT/CN2015/098487, filed on Dec. 23, 2015, which is hereby incorporated by reference in their entireties.\",\n \"TECHNICAL FIELD Embodiments of the present invention relate to the field of storage technologies, and in particular, to a service takeover method, a storage device, and a service takeover apparatus.\",\n \"BACKGROUND For protecting data security and for a purpose of redundancy (Disaster Recovery), storage vendors establish a geographic redundancy center to implement remote backup of data, so that original data is not lost or damaged after a disaster (such as a fire or an earthquake) occurs, and a key service can resume running in an allowable time range, to minimize a loss brought by the disaster.\",\n \"Currently, a main storage system is a two-center storage system.\",\n \"The two-center storage system implements redundancy by establishing two data centers.\",\n \"Both the two data centers can receive a service request from a host, and store service data in respective storage devices.\",\n \"Then, data synchronization is implemented by using a link between the data centers.\",\n \"However, once a fault occurs on the link, the data synchronization is interrupted.\",\n \"Therefore, a data center needs to be designated to bear a data service of the host, and after fault recovery of the link, data received before the fault recovery is backed up to another data center.\",\n \"Generally, when a fault occurs on the link, the two data centers immediately and respectively send arbitration requests to a quorum server, and the quorum server determines, according to an arbitration request receiving sequence, the data center that is to bear the data service.\",\n \"SUMMARY Embodiments of the present invention provide a service takeover method, a storage device, and a service takeover apparatus.\",\n \"When a communication fault occurs between a storage device and another storage device, an arbitration request can be submitted to a quorum server after delay duration according to current usage of a respective system resource, so that the quorum server can select a storage device in a better running status to take over a host service.\",\n \"A first aspect of the embodiments provides a service takeover method.\",\n \"A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.\",\n \"Data communication is performed between the first storage device and the second storage device by using a link.\",\n \"The first storage device obtains a running status of the first storage device when a communication fault occurs between the first storage device and the second storage device.\",\n \"The running status reflects current usage of a system resource of the first storage device.\",\n \"The system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.\",\n \"The first storage device determines delay duration according to the running status, where the delay duration is duration for which the first storage device waits before sending an arbitration request to the quorum server.\",\n \"The first storage device sends, after the delay duration, the arbitration request to the quorum server to request to take over a service.\",\n \"Similarly, when determining that a communication fault occurs between the second storage device and the first storage device, the second storage device obtains a running status of the second storage device, and determines delay duration according to the running status.\",\n \"The second storage device sends, after the delay duration, an arbitration request to the quorum server to request to take over a service.\",\n \"After receiving the arbitration requests sent by the two storage devices, the quorum server determines, based on a first received arbitration request, a storage device that is to take over a host service.\",\n \"A storage device needs to wait for a period of time before sending an arbitration request to the quorum server.\",\n \"Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"With reference to the first aspect, in a first implementation, the first storage device reads a running status value of the first storage device, where the running status value is a sum of status values of all system resources.\",\n \"A status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and the correspondence includes a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.\",\n \"In this implementation, usage of each system resource may be reflected by a running status value.\",\n \"Therefore, the current usage of the system resource of the first storage device is better reflected, so that more proper delay duration may be obtained according to the running status value.\",\n \"With reference to the first implementation, in a second implementation, the delay duration may be obtained according to the running status value and a formula T=k*S, where T is the delay duration, S is the running status value, and k is any value.\",\n \"This implementation provides a specific algorithm to associate the delay duration with the running status value.\",\n \"In general, the delay duration may be directly proportional to the running status value, that is, a greater running status value leads to longer waiting duration.\",\n \"With reference to the second implementation, in a third implementation, k=1.The quorum server generally determines, based on a first received arbitration request, a storage device that is to take over a host service.\",\n \"Therefore, the delay duration is set, so that the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"Excessively short delay duration is improper, because excessively short waiting duration is unfavorable to distinguishing a sequence in which storage devices send arbitration requests.\",\n \"Excessively long delay duration is also improper, because excessively long waiting duration is unfavorable to processing a host service.\",\n \"Therefore, k is set to 1 in this implementation.\",\n \"With reference to any one of the foregoing implementations of the first aspect, in a fourth implementation, the storage system further includes a host.\",\n \"The first storage device communicates with the host by using a front-end port.\",\n \"The first storage device may detect a status of the front-end port, and when determining that the status of the front-end port is valid, read the running status value of the first storage device.\",\n \"If the status of the front-end port is invalid, it indicates that communication between the first storage device and the host is interrupted, and the first storage device cannot take over a host service.\",\n \"Therefore, in this case, the first storage device does not need to send an arbitration request to the quorum server.\",\n \"With reference to any one of the foregoing implementations, in a fifth implementation, the arbitration request sent by the first storage device to the quorum server includes an arbitration ID and a device identifier of first storage device.\",\n \"After receiving the arbitration request, the quorum server determines whether the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, and if the arbitration ID carried in the arbitration request is consistent with a pre-stored arbitration ID, determines that the first storage device is in an arbitration scope of the quorum server.\",\n \"In addition, if the quorum server does not receive, before receiving the arbitration request sent by the first storage device, an arbitration request sent by another storage device, the quorum server may determine that the first storage device is to take over a host service.\",\n \"In this case, the quorum server may find a corresponding identifier of the device identifier according to the device identifier of the first storage device, and add the corresponding identifier to a response message to send to the first storage device.\",\n \"With reference to the fifth implementation, in a sixth implementation, the quorum server obtains a device identifier of the second storage device according to the device identifier of the first storage device, an arbitration ID, and a correspondence between the arbitration ID and the device identifier of the second storage device, further obtains a corresponding identifier of the device identifier of the second storage device according to a correspondence between the device identifier of the second storage device and the corresponding identifier, and deletes the corresponding identifier.\",\n \"Even if the second storage device subsequently sends an arbitration request to the quorum server, the quorum server does not respond to the arbitration request because the corresponding identifier of the device identifier of the second storage device is deleted.\",\n \"No request response is received, and consequently, the second storage device cannot take over a host service.\",\n \"A second aspect of the embodiments provides another service takeover method.\",\n \"A storage system to which the method is applied includes a first storage device, a second storage device, and a quorum server.\",\n \"Data communication is performed between the first storage device and the second storage device by using a link.\",\n \"When a communication fault occurs between the first storage device and the second storage device, the first storage device sends a first arbitration request to the quorum server, and the second storage device sends a second arbitration request to the quorum server.\",\n \"After receiving the arbitration requests sent by the two storage devices, the quorum server separately queries statuses of front-end ports of the two storage devices.\",\n \"If the statuses of the front-end ports are valid, the quorum server continues to receive running statuses of the two storage devices, after comparing the running statuses of the two storage devices, selects a storage device in a better running status to take over a host service, and sends a request response to the storage device.\",\n \"In the service takeover method provided in the second aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"Compared with the first aspect of the embodiments, the service takeover method provided in the second aspect is mainly performed by the quorum server.\",\n \"Therefore, load of the storage device may be reduced to some extent.\",\n \"A third aspect of the embodiments provides a storage device, configured to perform at least one method described in the first aspect.\",\n \"A fourth aspect of the embodiments provides a service takeover apparatus, and the service takeover apparatus is located in a storage device, and configured to perform at least one method described in the first aspect.\",\n \"According to the storage device provided in the third aspect and the service takeover apparatus provided in the fourth aspect of the embodiments, a storage device may wait for a period of time before sending an arbitration request to the quorum server.\",\n \"Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"A fifth aspect of the embodiments provides a quorum server, configured to perform the method described in the second aspect.\",\n \"According to the quorum server provided in the fifth aspect, whether a storage device takes over a host service is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"Compared with the first aspect of the embodiments, the quorum server provided in the fifth aspect can reduce load of the storage device to some extent.\",\n \"A sixth aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the storage device of the foregoing third aspect, and used to perform at least one method of the foregoing first aspect.\",\n \"According to the computer program product provided in the sixth aspect of the embodiments of the present invention, a storage device may wait for a period of time before sending an arbitration request to a quorum server.\",\n \"Waiting duration is also referred to as delay duration, and is determined according to a running status of the storage device.\",\n \"The running status reflects current usage of a system resource of the storage device.\",\n \"Therefore, the quorum server can select a storage device in a better running status from storage devices that send arbitration requests to take over a host service.\",\n \"A seventh aspect of the embodiments of the present invention provides a computer program product, including a computer-readable storage medium that stores program code, where an instruction included in the program code may be executed by the quorum server of the foregoing fifth aspect, and used to perform the method of the foregoing second aspect.\",\n \"BRIEF DESCRIPTION OF DRAWINGS To describe the technical solutions in the embodiments of the present invention more clearly, the following briefly describes the accompanying drawings required for describing the embodiments.\",\n \"FIG.\",\n \"1 is an application scenario diagram according to an embodiment of the present invention; FIG.\",\n \"2 is a structural diagram of a storage device according to an embodiment of the present invention; FIG.\",\n \"3 is a structural diagram of a quorum server according to an embodiment of the present invention; FIG.\",\n \"4 is a schematic flowchart of a service takeover method according to an embodiment of the present invention; FIG.\",\n \"5 is a schematic flowchart of another service takeover method according to an embodiment of the present invention; and FIG.\",\n \"6 is a structural diagram of a service takeover apparatus according to an embodiment of the present invention.\",\n \"DESCRIPTION OF EMBODIMENTS A service takeover method provided in an embodiment of the present invention is mainly applied to a storage system with two data centers.\",\n \"The storage system with two data centers in this embodiment of the present invention is a storage system including two or more data centers.\",\n \"For ease of description, in this embodiment of the present invention, the storage system with two data centers is used as an example for description.\",\n \"As shown in FIG.\",\n \"1, FIG.\",\n \"1 is a schematic diagram of an application scenario according to an embodiment of the present invention.\",\n \"A storage system shown in FIG.\",\n \"1 includes at least two hosts 100 and two data centers.\",\n \"For ease of description, in this embodiment of the present invention, the two data centers shown in FIG.\",\n \"1 are respectively referred to as a first station 11 and a second station 12.Data transmission may be performed between the two data centers by using the Internet Protocol (IP) or a Fiber Channel (FC).\",\n \"In this embodiment of the present invention, communication may be performed between the host 100 and the first station 11 or between the host 100 and the second station 12 by using the FC or the Small Computer Systems Interface (SCSI) protocol and based on the Internet Small Computer Systems Interface (iSCSI) protocol.\",\n \"This is not limited herein.\",\n \"The first station 11 includes a first storage device 110, and the second station 12 includes a second storage device 120.The first storage device 110 and the second storage device 120 may be any known storage device in the prior art, such as a storage array or a server.\",\n \"For example, the first storage device 110 and the second storage device 120 may include a storage area network (SAN) array, or may include a network attached storage (NAS) array.\",\n \"In this embodiment of the present invention, a specific form of the storage device in the data center is not limited.\",\n \"It should be noted that all methods in embodiments of the present invention are performed by the storage devices in these stations.\",\n \"For ease of description, in this embodiment of the present invention, unless otherwise stated, the first station 11 is the first storage device 110 in the first station 11, and the second station 12 is the second storage device 120 in the second station 12.In the application scenario shown in FIG.\",\n \"1, there is a relatively short distance between the first station 11 and the second station 12.Generally, a distance between the first station 11 and the second station 12 may be less than 100 km.\",\n \"For example, the first station 11 and the second station 12 may be located in two different positions of a same city.\",\n \"Certainly, in this embodiment of the present invention, the first station 11 and the second station 12 may be not in a same city as long as synchronous replication of data can be implemented between the first station 11 and the second station 12.The host 100 may include any known computing device in the prior art, such as a server, a desktop computer, or an application server.\",\n \"An operating system and another application program are installed in the host 100.There may be multiple hosts 100.In the application scenario shown in FIG.\",\n \"1, both the first station 11 and the second station 12 may accept access of the host 100.In a case, some hosts 100 write data into the first station 11, and some hosts 100 write data into the second station 12.In another case, one host 100 may separately write different data into the first station 11 and the second station 12.In another case, different hosts 100 may respectively write data into the first station 11 and the second station 12.For example, a host A writes data into the first station 11, and a host B writes data into the second station 12; or a host A writes data A into the first station 11, and writes data B into the second station 12.It may be understood that the first station 11 and the second station 12 may simultaneously bear a service of the host 100, and therefore, efficiency of reading and writing data can be improved.\",\n \"In addition, in this embodiment of the present invention, synchronous replication can be implemented between the first station 11 and the second station 12, to ensure real-time data synchronization between the first station 11 and the second station 12.It should be noted that in the storage system shown in FIG.\",\n \"1, both the first station 11 and the second station 12 may accept access of the host 100, and the first station 11 and the second station 12 maintain consistency of stored data by means of synchronous replication, and therefore the first station 11 and the second station 12 may be interchanged.\",\n \"In this embodiment of the present invention, data stored in the first station 11 and the second station 12 may maintain synchronized in real time by means of a synchronous replication technology.\",\n \"For example, when the host 100 writes data into the first station 11, the first station 11 may simultaneously back up the data onto the second station 12.When the data is written into both the first station 11 and the second station 12, the first station 11 returns a write success response to the host 100, to maintain data synchronization between the first station 11 and the second station 12.It should be noted that in this embodiment of the present invention, that data is written into the first station 11 may be that data is written into a cache of the first station 11, or may be that data is written into a memory of the first station 11, and this is not limited herein.\",\n \"In addition, the storage system in this embodiment may further include at least one quorum server 130.Data transmission is performed between the first storage device 110 and the quorum server 130 or between the second storage device 120 and the quorum server 130 by using the IP.\",\n \"Data synchronization is implemented between the first storage device 110 and the second storage device 120 by using a link.\",\n \"Therefore, if a fault occurs on the link in actual application, data synchronization cannot be implemented between the first storage device 110 and the second storage device 120, and the quorum server 130 needs to determine a storage device that is to take over all host services.\",\n \"The quorum server 130 may include any known computing device in the prior art, such as a server, a desktop computer, or an application server.\",\n \"Generally, the two storage devices may detect whether a fault occurs on the link or on each other by means of a heartbeat between the two storage devices.\",\n \"For example, when the second storage device 120 does not receive a heartbeat signal of the first storage device 110 in a specified time, the second storage device 120 may determine that a fault occurs on the link or on the first storage device 110.In this case, the second storage device 120 may send an arbitration request to the quorum server 130 to request to take over all host services.\",\n \"Similarly, when the first storage device 110 does not receive a heartbeat signal of the second storage device 120 in a specified time, the first storage device 110 may determine that a fault occurs on the link or on the second storage device 120.In this case, the first storage device 110 may send an arbitration request to the quorum server 130 to request to take over all host services.\",\n \"In the storage system shown in FIG.\",\n \"1, the first storage device 110, the second storage device 120, and the quorum server 130 belong to a HyperMetro domain.\",\n \"The HyperMetro domain is a domain in which when a service conflict occurs between two or more storage devices, one quorum server 130 coordinates a storage device that is to take over a host service.\",\n \"Each HyperMetro domain may be identified by using an arbitration ID, and the first storage device 110, the second storage device 120, and the quorum server 130 store the arbitration ID.\",\n \"When the first storage device 110 and the second storage device 120 send arbitration requests to the quorum server 130, the arbitration ID may be carried in the arbitration requests.\",\n \"After receiving an arbitration request, the quorum server 130 determines whether an arbitration ID carried in the arbitration request is consistent with the arbitration ID stored in the quorum server 130.If the arbitration ID carried in the arbitration request is consistent with the arbitration ID stored in the quorum server 130, the quorum server 130 performs processing; or if the arbitration ID carried in the arbitration request is not consistent with the arbitration ID stored in the quorum server 130, the quorum server 130 does not perform processing.\",\n \"In addition, the first storage device 110 and the second storage device 120 may register device information (such as a device identifier) of the first storage device 110 and the second storage device 120 in the quorum server 130.For example, the first storage device 110 sends a device identifier (for example, A) of the first storage device 110 to the quorum server 130, and the quorum server 130 receives the device identifier A of the first storage device 110, generates an identifier A′ corresponding to the identifier A, and stores a correspondence between the identifier A and the identifier A′ in the quorum server 130, so as to complete registration of the first storage device 110.Similarly, the second storage device 120 sends a device identifier (for example, B) of the second storage device 120 to the quorum server 130, and the quorum server 130 receives the device identifier B of the second storage device 120, generates an identifier B′ corresponding to the identifier B, and stores a correspondence between the identifier B and the identifier B′ in the quorum server 130, so as to complete registration of the second storage device 120.In addition, in this embodiment, the first storage device 110 and the second storage device 120 belong to a HyperMetro domain.\",\n \"Therefore, the first storage device 110 and the second storage device 120 have a same arbitration ID.\",\n \"The arbitration ID, a correspondence between the arbitration ID and the identifier A, a correspondence between the arbitration ID and the identifier A′, a correspondence between the arbitration ID and the identifier B, and a correspondence between the arbitration ID and the identifier B′ need to be stored in the quorum server 130, and are used by the quorum server 130 to determine a storage device that is to take over a host service.\",\n \"A correspondence between the arbitration ID and each identifier may be shown in the following table.\",\n \"Arbitration ID Device identifier A Device identifier A′ Device identifier B Device identifier B′ Structures of the first storage device 110 and the second storage device 120 shown in FIG.\",\n \"1 may be that shown in FIG.\",\n \"2.FIG.\",\n \"2 is a schematic structural diagram of a storage device 20 according to an embodiment of the present invention.\",\n \"The storage device 20 shown in FIG.\",\n \"2 is a storage array.\",\n \"As shown in FIG.\",\n \"2, the storage device 20 may include a controller 200 and a disk array 214.The disk array 214 herein is configured to provide storage space, and may include a redundant array of independent disks (RAID), or a disk chassis including multiple disks.\",\n \"There may be multiple disk arrays 214, and the disk array 214 includes multiple disks 216.The disk 216 is configured to store data.\",\n \"The disk array 214 may be in communication connection with the controller 200 by using a communication protocol such as the Small Computer System Interface (Small Computer System Interface, SCSI) protocol, and this is not limited herein.\",\n \"It may be understood that the disk array 214 is only an example of a memory in the storage system.\",\n \"In this embodiment of the present invention, data may also be stored by using a memory such as a tape library.\",\n \"It should be noted that the disk 216 is also only an example of a memory constructing the disk array 214.In actual application, there is an implementation such as constructing a disk array between cabinets including multiple disks.\",\n \"Therefore, in this embodiment of the present invention, the disk array 214 may further include a memory including a non-volatile storage medium, such as a cabinet or a server that includes a solid state drive (SSD) and multiple disks.\",\n \"This is not limited herein.\",\n \"The controller 200 is a “brain” of the storage device 20, and mainly includes a processor 202, a cache 204, a memory 206, a communications bus (which is referred to as a bus for short) 210, and a communications interface 212.The processor 202, the cache 204, the memory 206, and the communications interface 212 complete mutual communication by using the communications bus 210.It should be noted that in this embodiment of the present invention, there may be one or more controllers 200 in the storage device 20.It may be understood that when the storage device 20 includes at least two controllers 200, stability of the storage device 20 may be improved.\",\n \"There may be multiple communications interfaces 212, and are respectively configured to communicate with the host 100, the disk 216, and another storage device.\",\n \"The communications interface 212 that communicates with the host 100 may also be referred to as a front-end port.\",\n \"The memory 206 is configured to store a program 208.The memory 206 may include a high-speed RAM memory, and may further include a non-volatile memory, for example, at least one magnetic disk memory.\",\n \"It may be understood that the memory 206 may be a non-transitory machine-readable medium capable of storing program code, such as a random-access memory (RAM), a magnetic disk, a hard disk, an optical disc, a solid state disk (SSD), or a non-volatile memory.\",\n \"The program 208 may include program code, and the program code includes a computer operation instruction.\",\n \"The following provides a detailed description.\",\n \"The cache 204 is a memory between the controller and a hard disk, and a capacity of the cache 204 is less than that of the hard disk, but a speed of the cache 204 is faster than that of the hard disk.\",\n \"The cache 204 is configured to cache data received from the host 100 and another storage device, and cache data read from the disk 216, so as to improve performance and reliability of an array.\",\n \"The cache 204 may be a non-transitory machine-readable medium capable of storing data, such as a RAM, a ROM, a flash memory, or a solid state disk (SSD).\",\n \"This is not limited herein.\",\n \"In some scenarios, the cache 204 and the memory 206 may be integrated into a same physical device.\",\n \"That is, the memory 204 may provide a function of the memory 206.Therefore, in this embodiment, a cache and a memory may not be distinguished, and a cache resource is a memory resource.\",\n \"The processor 202 may include one or more central processing units CPU, or an application-specific integrated circuit (ASIC), or one or more integrated circuits configured to implement this embodiment of the present invention.\",\n \"The processor 202 may process an input/output (I/O) request for the disk 216, process data in the disk 216, and so on.\",\n \"In this embodiment of the present invention, the processor 202 is configured to execute the program 208, and specifically, may execute related steps in the following method embodiment.\",\n \"It may be understood that in this embodiment of the present invention, the first storage device 110 and the second storage device 120 have similar hardware structures.\",\n \"A hardware structure of the quorum server 130 is described below.\",\n \"As shown in FIG.\",\n \"3, the quorum server 130 is a server, and includes at least a processor 301, a memory 302, and a communications interface 303.The processor 301 may include one or more central processing units CPU, or an application-specific integrated circuit (ASIC), or one or more integrated circuits configured to implement this embodiment of the present invention.\",\n \"In this embodiment, after receiving arbitration requests sent by the first storage device 110 and the second storage device 120, the processor 301 may determine, according to an arbitration rule, a storage device that is to take a host service.\",\n \"The memory 302 is configured to store a program, and may include a high-speed RAM memory, and may further include a non-volatile memory.\",\n \"It may be understood that the memory 302 may be a non-transitory machine-readable medium capable of storing program code, such as a random-access memory (RAM), a magnetic disk, a hard disk, an optical disc, a solid state disk (SSD), or a non-volatile memory.\",\n \"In this embodiment, the memory 302 may be configured to store software code such as the arbitration rule, and may be further configured to store data or information sent by the first storage device 110 and the second storage device 120.There may be one or more communications interfaces 303, configured to communicate with the first storage device 110 and the second storage device 120.Service takeover methods specifically implemented by storage devices in embodiments of the present invention are described below in detail.\",\n \"FIG.\",\n \"4 is a flowchart of a service takeover method according to an embodiment of the present invention.\",\n \"The method may be applied to an application scenario shown in FIG.\",\n \"1.In addition, hardware structures of a first storage device 110 and a second storage device 120 in this embodiment of the present invention may be that shown in FIG.\",\n \"2.Specifically, the method shown in FIG.\",\n \"4 may be jointly performed by processors of the first storage device 110 and the second storage device 120.Step S101 to step S105 are performed by a processor 202 of the first storage device 110, step S106 and step S107 are performed by a processor 301 of a quorum server 130, and step S108 to step S112 are performed by a processor of the second storage device 120.The service takeover method shown in FIG.\",\n \"4 is described with reference to FIG.\",\n \"1 and FIG.\",\n \"2.As shown in FIG.\",\n \"4, the method may include the following steps.\",\n \"STEP S101.The first storage device 110 detects whether a communication fault occurs between the first storage device 110 and the second storage device 120.This embodiment is applied to a HyperMetro scenario.\",\n \"In this scenario, both the first storage device 110 and the second storage device 120 may process a service request of a host 100, for example, receive a write data request sent by the host 100, and write data carried in the write data request into the storage device (if the first storage device processes the service request, the data is written into the first storage device; or if the second storage device processes the service request, the data is written into the second storage device); or receive a read data request sent by the host 100, and send data that needs to be read according to the read data request to the host 100.Because both the first storage device 110 and the second storage device 120 may process a service request of the host 100, the first storage device 110 and the second storage device 120 separately store a part of data from the host 100.To maintain data consistency between the two storage devices, the first storage device 110 needs to synchronize data stored in the first storage device 110 to the second storage device 120.Similarly, the second storage device 120 also needs to synchronize data stored in the second storage device 120 to the first storage device 110.Therefore, the two storage devices need to synchronize data by using a link between the two storage devices.\",\n \"If a fault occurs on the link, a data synchronization operation is interrupted.\",\n \"Specifically, the first storage device 110 may detect, according to a heartbeat signal between the first storage device 110 and the second storage device 120, whether a fault occurs on the link or on the second storage device 120.For example, when the first storage device 110 does not receive a heartbeat signal of the second storage device 120 in a specified time, the first storage device 110 may determine that a fault occurs on the link or on the second storage device 120.In this way, the first storage device 110 determines whether a communication fault occurs between the first storage device 110 and the second storage device 120.It should be noted that if the first storage device 110 detects that a communication fault occurs between the first storage device 110 and the second storage device 120, a fault may occur on the link, or a fault may occur in the second storage device, and consequently, communication cannot be performed.\",\n \"Alternatively, the first storage device 110 may not use a heartbeat signal between the first storage device 110 and the second storage device 120 to detect whether a fault occurs on the link.\",\n \"For example, when the link is physically disconnected, the first storage device 110 receives a notification message indicating that the link is disconnected.\",\n \"Step S102: The first storage device 110 detects a status of a front-end port of the first storage device 110.The front-end port herein is a communications interface used by the first storage device 110 to communicate with the host 100, for example, a communications interface 212 shown in FIG.\",\n \"2.The status of the front-end port may be valid or invalid.\",\n \"When the status is valid, it indicates that a connection between the first storage device 110 and the host 100 is in a normal state, and the first storage device 110 can receive a service request of the host 100.When the status is invalid, it indicates that the connection between the first storage device 110 and the host 100 is in an abnormal state, and the first storage device 110 cannot receive a service request of the host 100.When the front-end port is in an invalid state, it indicates that the first storage device 110 is not capable of taking over a host service.\",\n \"Therefore, the first storage device 110 gives up sending an arbitration request to the quorum server 130.In some scenarios, if the front-end port becomes abnormal, a system automatically reports an error.\",\n \"Therefore, the first storage device 110 does not need to actively detect the status of the front-end port.\",\n \"The status of the front-end port is valid by default as long as no error alert occurs.\",\n \"Step S103: When determining that the status of the front-end port is valid, the first storage device 110 obtains a running status of the first storage device 110.The running status reflects current usage of a system resource of the first storage device 110.The system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.\",\n \"For example, in this embodiment, the running status of the first storage device 110 may be reflected by a running status value of the first storage device, which is represented by S. The running status value is obtained according to the current usage ratio of the system resource of the first storage device and a correspondence between a usage ratio of the system resource and a status value of the system resource.\",\n \"The correspondence is preset.\",\n \"The first storage device 110 has a setting interface.\",\n \"After collecting statistics about running statuses of the first storage device 110, a system administrator may set the correspondence by using the setting interface.\",\n \"The running status value may be stored in a cache 204 of the first storage device 110.Current usage of these system resources may be respectively reflected by parameters such as a processor usage ratio, a hard disk usage ratio, a cache usage ratio, and a host bandwidth usage ratio.\",\n \"The processor usage ratio (which is also referred to as a CPU usage ratio) is a CPU resource occupied by a running program, and represents a program running situation of a storage device at a time point.\",\n \"A high usage ratio indicates that the storage device runs many programs at this time point, and on the contrary, a low usage ratio indicates that the storage device runs few programs at this time point.\",\n \"In addition, in this embodiment, a processor usage ratio in an interval is corresponding to a processor status value.\",\n \"In this embodiment, Q1 represents a current processor status value corresponding to a current processor usage ratio.\",\n \"The hard disk usage ratio (which is also referred to as a disk usage ratio) is a ratio of a used capacity to a total available capacity in a disk.\",\n \"A hard disk usage ratio in an interval is corresponding to a hard disk status value.\",\n \"In this embodiment, Q2 represents a current hard disk status value corresponding to a current hard disk usage ratio.\",\n \"The cache usage ratio (which is also referred to as a cache water mark) is a ratio of used pages to total available pages in a cache.\",\n \"A cache usage ratio in an interval is corresponding to a cache status value.\",\n \"In this embodiment, Q3 represents a current cache status value corresponding to a current cache usage ratio.\",\n \"The host bandwidth usage ratio is a ratio of used bandwidth to total bandwidth in bandwidth between the host and the storage device.\",\n \"A host bandwidth usage ratio in an interval is corresponding to a host bandwidth status value.\",\n \"In this embodiment, Q4 represents a current host bandwidth status value corresponding to a current host bandwidth usage ratio.\",\n \"The following describes how to obtain the running status value S of the first storage device.\",\n \"In this embodiment, S=Q1+Q2+Q3+Q4.In this embodiment, a current running status of each system resource may be monitored, so as to obtain a current usage ratio of each system resource.\",\n \"In addition, the cache 204 or a memory 206 in the first storage device 110 further stores the correspondence between the usage ratio of the system resource and the status value of the system resource.\",\n \"For example, Table 1 reflects a correspondence between a processor usage ratio and a processor status value.\",\n \"TABLE 1 Processor Status Value Processor Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .\",\n \".\",\n \".\",\n \".\",\n \".\",\n \".\",\n \"Therefore, after obtaining a current processor usage ratio by means of monitoring, the first storage device 110 may obtain a current processor status value Q1 according to the current processor usage ratio and the correspondence between the processor usage ratio and the processor status value.\",\n \"Table 2 reflects a correspondence between a hard disk usage ratio and a hard disk status value.\",\n \"TABLE 2 Hard Disk Status Value Hard Disk Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .\",\n \".\",\n \".\",\n \".\",\n \".\",\n \".\",\n \"Therefore, after obtaining a current hard disk usage ratio by means of monitoring, the first storage device 110 may obtain a current hard disk status value Q2 according to the current hard disk usage ratio and the correspondence between the hard disk usage ratio and the hard disk status value.\",\n \"Table 3 reflects a correspondence between a cache usage ratio and a cache status value.\",\n \"TABLE 3 Cache Status Value Cache Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .\",\n \".\",\n \".\",\n \".\",\n \".\",\n \".\",\n \"Therefore, after obtaining a current cache usage ratio by means of monitoring, the first storage device 110 may obtain a current cache status value Q3 according to the current cache usage ratio and the correspondence between the cache usage ratio and the cache status value.\",\n \"Table 4 reflects a correspondence between a host bandwidth usage ratio and a host bandwidth status value.\",\n \"TABLE 4 Host Bandwidth Status Value Host Bandwidth Usage ratio 0 <50% 1 [50%-60%) 2 [60%-70%) .\",\n \".\",\n \".\",\n \".\",\n \".\",\n \".\",\n \"Therefore, after obtaining a current host bandwidth usage ratio by means of monitoring, the first storage device 110 may obtain a current host bandwidth status value Q4 according to the current host bandwidth usage ratio and the correspondence between the host bandwidth usage ratio and the host bandwidth status value.\",\n \"It should be noted that the running status value S may be a sum of Q1, Q2, Q3, and Q4, or may be a sum of a part of Q1, Q2, Q3, and Q4 (for example, S=Q1+Q3), or may even be equal to one status value (for example, S=Q1).\",\n \"In addition, S may also be a sum of weighted values of Q1, Q2, Q3, and Q4.For example, if a weight is set for each system resource, for example, a weight of the processor resource is 40%, a weight of the hard disk resource is 30%, a weight of the cache resource is 20%, and a weight of the host bandwidth resource is 10%, S=Q1*40%+Q2*30%+Q3*20%+Q4*10%.\",\n \"It may be understood that the weight of each system resource may be adjusted according to an importance degree of the resource.\",\n \"The weight of each system resource is not limited in this embodiment.\",\n \"In general, the running status value is obtained according to a status value reflecting a current running status of each system resource, and is used to reflect a current overall running status of the storage device.\",\n \"An algorithm for obtaining the running status value according to each status value is not limited in this embodiment.\",\n \"The running status value may be obtained by means of periodic calculation, and be stored in the first storage device 110.In addition, in the correspondences of Table 1 to Table 4, each usage ratio interval and a corresponding status value may be adjusted according to an actual running status of the storage device, and are not limited in this embodiment.\",\n \"In addition, it may be understood that the foregoing system resource is only an example of this embodiment of the present invention.\",\n \"The storage device may further include another system resource, and a status value of the another system resource may also reflect the running status value.\",\n \"Step S104: The first storage device 110 determines delay duration according to the running status.\",\n \"In this embodiment, after detecting that a communication fault occurs between the first storage device 110 and the second storage device 120, the first storage device 110 does not immediately send an arbitration request to the quorum server 130, but sends an arbitration request to the quorum server 130 after waiting for a period of time.\",\n \"The delay duration is duration for which the first storage device waits before sending the arbitration request to the quorum server.\",\n \"Specifically, in this embodiment, the first storage device 110 may determine the delay duration according to the running status value.\",\n \"The delay duration is represented by T, and is in a unit of second(s).\",\n \"The delay duration T=k*S, where S is the running status value, and k is any value.\",\n \"In an implementation, k=1, because neither excessively long nor excessively short delay duration is proper.\",\n \"For example, when S=3, T=3s.\",\n \"In addition, in this embodiment, T cannot exceed a preset threshold because excessively long delay duration is improper.\",\n \"The preset threshold may be set to any value in [20, 30].\",\n \"Step S105: The first storage device 110 sends an arbitration request to the quorum server 130 after the delay duration.\",\n \"Before performing steps S101 to S105, the first storage device 110 may register device information of the first storage device 110 in the quorum server 130.For example, the first storage device 110 sends a device identifier A of the first storage device 110 to the quorum server 130.After receiving the identifier of the first storage device 110, the quorum server 130 generates and stores an identifier A′ corresponding to the identifier A, so as to complete registration of the first storage device 110.In step S105, the arbitration request sent by the first storage device 110 to the quorum server 130 includes an arbitration ID and the identifier of the first storage device 110.To be distinguished from delay duration of the second storage device 120, in this embodiment, the delay duration of the first storage device 110 is referred to as first delay duration, and the delay duration of the second storage device 120 is referred to as second delay duration.\",\n \"To be distinguished from an arbitration request sent by the second storage device 120, in this embodiment, the arbitration request sent by the first storage device is referred to as a first arbitration request, and the arbitration request sent by the second storage device is referred to as a second arbitration request.\",\n \"After receiving the first arbitration request, the quorum server 130 performs matching between the arbitration ID carried in the first arbitration request and a pre-stored arbitration ID, and when determining that the arbitration ID carried in the first arbitration request is consistent with the pre-stored arbitration ID, determines that the first storage device 110 is in an arbitration scope of the quorum server 130.In addition, the quorum server 130 does not receive the second arbitration request of the second storage device 120 before step S111.The quorum server 130 may determine, according to a principle of first receiving, that the first storage device 110 is to take over a host service.\",\n \"Step S106: The quorum server 130 deletes a corresponding identifier, for example, B′ described above, of an identifier of the second storage device 120 stored in the quorum server 130.Specifically, the quorum server 130 obtains, according to a correspondence between an arbitration ID and a device identifier B and a correspondence between the device identifier B and a corresponding identifier B′, the identifier B′ corresponding to the device identifier B, and deletes the identifier B′.\",\n \"Step S107: The quorum server 130 sends a response message of the first arbitration request to the first storage device 110.The response message includes the corresponding identifier of the device identifier of the first storage device 110, for example, A′ described above.\",\n \"When receiving A′, the first storage device 110 may learn that the first storage device 110 wins in an arbitration and can take over a host service.\",\n \"Step S108: The second storage device 120 detects whether a communication fault occurs between the second storage device 120 and the first storage device 110.Similarly, the second storage device 120 also needs to detect whether a communication fault occurs between the second storage device 120 and the first storage device 110.When detecting that a communication fault occurs, the second storage device 120 also needs to send an arbitration request to the quorum server 130.Step S108 and step S101 are similar, and are only performed by different execution bodies.\",\n \"For details, refer to the description in step S101.Details are not described herein again.\",\n \"Step S109: The second storage device 120 detects a status of a front-end port of the second storage device 120.In step S109, the front-end port is a communications interface used by the second storage device 120 to communicate with the host 100, and similarly has a valid state and an invalid state.\",\n \"For details, refer to the description in step S102.Details are not described herein again.\",\n \"Step S110: When determining that the status of the front-end port is valid, the second storage device 120 obtains a running status of the second storage device 120.In this embodiment, a running status value of the second storage device may be represented by S′, and is used to reflect a running status of a system resource of the second storage device 120.Compared with step S103, this step is only performed by a different execution body.\",\n \"For details, refer to the description in step S103.Details are not described herein again.\",\n \"Step S111: The second storage device 120 determines delay duration according to the running status.\",\n \"Compared with step S104, this step is only performed by a different execution body.\",\n \"For details, refer to the description in step S104.Details are not described herein again.\",\n \"Step S112: The second storage device 120 sends an arbitration request to the quorum server 130 after the delay duration.\",\n \"Before performing steps S108 to S112, the second storage device 120 may register device information of the second storage device 120 in the quorum server 130.For example, the second storage device 120 sends a device identifier B of the second storage device 120 to the quorum server 130.After receiving the identifier of the second storage device 120, the quorum server 130 generates and stores an identifier B′ corresponding to the identifier B, so as to complete registration of the second storage device 120.In step S112, the arbitration request sent by the second storage device 120 to the quorum server 130 includes an arbitration ID and the identifier of the second storage device 120.After receiving the second arbitration request, the quorum server 130 performs matching between the arbitration ID carried in the second arbitration request and a pre-stored arbitration ID, and when determining that the arbitration ID carried in the second arbitration request is consistent with the pre-stored arbitration ID, determines that the second storage device 120 is in an arbitration scope of the quorum server 130.However, because the first arbitration request arrives at the quorum server 130 earlier than the second arbitration request, and after receiving the first arbitration request, the quorum server 130 deletes the corresponding identifier of the identifier of the second storage device 120 stored in the quorum server 130.Therefore, in this case, the quorum server 130 does not send the corresponding identifier of the device identifier of the second storage device 120 to the second storage device 120, and the second storage device 120 does not receive the corresponding identifier, and therefore cannot take over a host service.\",\n \"In the prior art, when detecting that a fault occurs in communication with each other, the first storage device 110 and the second storage device 120 generally send arbitration requests directly to the quorum server 130 to request to take over a host service.\",\n \"The quorum server 130 generally determines, based on a first received arbitration request, a storage device that is to take over a host service.\",\n \"However, in some cases, the first received arbitration request is sent by a storage device that is in a relatively poor running status.\",\n \"The relatively poor running status means that a usage ratio of a part or all of system resources of the storage device reaches a threshold.\",\n \"In this case, if the host service is still taken over by the storage device, service processing efficiency is relatively low.\",\n \"However, in this embodiment, the first storage device 110 and the second storage device 120 do not immediately send arbitration requests to the quorum server 130, but send arbitration requests to the quorum server 130 after waiting for a period of time.\",\n \"The quorum server 130 determines, based on a first received arbitration request, a storage device that is to take over a host service.\",\n \"If the first received arbitration request is sent by the first storage device 110, the quorum server 130 determines that the first storage device 110 is to take over a host service.\",\n \"If the first received arbitration request is sent by the second storage device 120, the quorum server 130 determines that the second storage device 120 is to take over a host service.\",\n \"In this embodiment, both the delay duration of the first storage device 110 and the delay duration of the second storage device 120 are obtained according to respective running statuses, and the running statuses reflect current usage of system resources of the storage devices.\",\n \"Therefore, the quorum server 130 can select a storage device in a best running status from storage devices that send arbitration requests to take over a host service.\",\n \"In addition, as shown in FIG.\",\n \"5, this embodiment further provides another implementation.\",\n \"A difference from the implementation shown in FIG.\",\n \"4 is that, in the implementation shown in FIG.\",\n \"5, after a quorum server 130 receives arbitration requests of a first storage device 110 and a second storage device 120, the quorum server 130 collects information about running statuses of the two storage devices from the first storage device 110 and the second storage device 120, and then makes arbitration determining.\",\n \"Specifically, this implementation may be performed by a processor 301 of a quorum server shown in FIG.\",\n \"3.It should be noted that the implementation shown in FIG.\",\n \"5 is different from the implementation shown in FIG.\",\n \"4 only in an execution body and an execution sequence of some steps.\",\n \"For specific implementation of steps, refer to the description of FIG.\",\n \"4.This implementation includes the following steps.\",\n \"Step S201: The first storage device 110 detects whether a communication fault occurs between the first storage device 110 and the second storage device 120.For a specific implementation process, refer to the description of S101 shown in FIG.\",\n \"4.Details are not described herein again.\",\n \"Step S202: After determining that a communication fault occurs between the first storage device 110 and the second storage device 120, the first storage device 110 sends a first arbitration request to the quorum server 130.For a specific implementation process, refer to the description of S105 shown in FIG.\",\n \"4.Details are not described herein again.\",\n \"Step S203: The second storage device 120 detects whether a communication fault occurs between the second storage device 120 and the first storage device 110.In step S203, a manner in which the second storage device 120 detects whether a communication fault occurs is similar to that in step S201, and only an execution body is different.\",\n \"For a specific implementation process, refer to the description of S101 shown in FIG.\",\n \"4.Details are not described herein again.\",\n \"Step S204: After determining that a communication fault occurs between the second storage device 120 and the first storage device 110, the second storage device 120 sends a second arbitration request to the quorum server 130.In step S204, a manner in which the second storage device 120 sends the second arbitration request to the quorum server 130 is similar to that in step S202, and content of the arbitration request is similar to that in step S202.For a specific implementation process, refer to the description of S112 shown in FIG.\",\n \"4.Details are not described herein again.\",\n \"Step S205: The quorum server 130 sends a query request to the first storage device 110, to query a status of a front-end port of the first storage device 110.Step S206: After receiving the query request, the first storage device 110 detects the status of the front-end port of the first storage device 110, and reports the status of the front-end port of the first storage device 110 to the quorum server 130 (step S207).\",\n \"When the status of the front-end port of the first storage device 110 is invalid, the quorum server 130 may determine that the first storage device 110 cannot take over a host service, that is, reject the first arbitration request.\",\n \"When the status of the front-end port of the first storage device 110 is valid, the quorum server 130 continues to perform step S208.It may be understood that in actual application, after sending the arbitration request to the quorum server 130, the first storage device 110 may actively report the status of the front-end port of the first storage device 110, instead of waiting for a query request sent by the quorum server 130.Step S208: The quorum server 130 sends a query request to the first storage device 110, to query a running status of the first storage device 110.Step S209: After receiving the query request, the first storage device 110 reports the running status of the first storage device 110 to the quorum server 130.In an optional implementation, the first storage device 110 directly reports a usage ratio of each system resource to the quorum server 130, for example, directly reports a current processor usage ratio, a current hard disk usage ratio, a current cache usage ratio, and a current host bandwidth usage ratio to the quorum server 130.The quorum server 130 performs arbitration after receiving a running status sent by the second storage device 120.In this implementation, the quorum server 130 may pre-store correspondences between a usage ratio of system resources and status values (content of Table 1 to Table 4), and after receiving a current usage ratio of system resources sent by the first storage device 110, obtains, according to the foregoing correspondences, a status value corresponding to each usage ratio, so as to obtain a running status value that reflects an overall running status of the first storage device 110.In another optional implementation, the first storage device 110 obtains, according to a current usage ratio of system resources and the foregoing correspondences, a status value corresponding to each usage ratio, and reports the status value corresponding to each usage ratio to the quorum server 130.The quorum server 130 obtains, according to the status value corresponding to each usage ratio, a running status value that reflects an overall running status of the first storage device 110.In this implementation, the quorum server 130 does not need to pre-store correspondences between usage ratios of system resources and status values.\",\n \"In still another optional implementation, based on one of the foregoing implementations, the first storage device 110 may further obtain a running status value that reflects an overall running status of the first storage device 110, and report the running status value to the quorum server 130.It may be understood that, in addition to the foregoing three implementations, the first storage device 110 may further report a running status of the first storage device 110 to the quorum server 130 by using an implementation.\",\n \"A manner in which the first storage device 110 reports the running status to the quorum server 130 and content of the running status are not limited in this embodiment.\",\n \"Step S210 to step S214 are similar to step S205 to step S209.A difference is that step S210 to step S214 describe a process in which the quorum server 130 queries a front-end port status and a running status of the second storage device 120.An implementation process is similar to that of the first storage device 110, and details are not described herein again.\",\n \"Step S215: The quorum server 130 determines, according to the running statuses of the two storage devices, that the first storage device 110 wins.\",\n \"Specifically, the quorum server 130 may determine a victorious storage device according to a current usage ratio of each system resource reported by the first storage device 110 and a current usage ratio of each system resource reported by the second storage device 120.For example, after comprehensively considering a current usage ratio of system resources reported by the two storage devices, the quorum server 130 may determine that the first storage device 110 wins when determining that the current usage ratio of each system resource of the first storage device 110 is less than the current usage ratio of each system resource of the second storage device 120, or a current usage ratio of most system resources of the first storage device 110 is less than the current usage ratio of each system resource of the second storage device 120.Alternatively, the quorum server 130 may determine a victorious storage device according to a status value of each system resource reported by the first storage device 110 and a status value of each system resource reported by the second storage device 120.For example, after comprehensively considering status values of system resources reported by the two storage devices, the quorum server 130 may determine that the first storage device 110 wins when determining that the status value of each system resource of the first storage device 110 is less than the status value of each system resource of the second storage device 120, or determining that a sum of status values of all system resources of the first storage device 110 is less than a sum of status values of all system resources of the second storage device 120.Alternatively, the quorum server 130 may determine a victorious storage device according to a running status value that is reported by the first storage device 110 and that reflects an overall running status of the first storage device 110 and a running status value that is reported by the second storage device 120 and that reflects an overall running status of the second storage device 120.For example, the quorum server 130 may determine that the first storage device 110 wins when the running status value of the first storage device 110 is less than the running status value of the second storage device 120.Step S216: The quorum server 130 deletes a corresponding identifier of an identifier of the second storage device 120 stored in the quorum server 130.Step S216 is similar to step S106 shown in FIG.\",\n \"4, and details are not described herein again.\",\n \"Step S217: The quorum server 130 sends a response message of the first arbitration request to the first storage device 110.Step S217 is similar to step S107 shown in FIG.\",\n \"4, and details are not described herein again.\",\n \"In the implementation shown in FIG.\",\n \"5, when detecting that a communication fault occurs between the first storage device 110 and the second storage device 120, the first storage device 110 and the second storage device 120 respectively send arbitration requests to the quorum server 130.After receiving the arbitration requests sent by the two storage devices, the quorum server 130 separately queries front-end port statuses and running statuses of the two storage devices, so as to select a storage device in a best running status to take over a host service.\",\n \"Referring to FIG.\",\n \"6, FIG.\",\n \"6 is a service takeover apparatus according to an embodiment of the present invention.\",\n \"The apparatus is located in a first storage device, and data communication is performed between the first storage device and a second storage device by using a link.\",\n \"The service takeover apparatus includes a reading module 401, a calculation module 402, and a transceiver module 403.The reading module 401 is configured to obtain a running status of the first storage device when determining that a communication fault occurs between the first storage device and the second storage device, where the running status reflects current usage of a system resource of the first storage device, and the system resource includes at least one or any combination of the following resources: a processor resource, a hard disk resource, a cache resource, or a host bandwidth resource.\",\n \"The calculation module 402 is configured to determine delay duration according to the running status, where the delay duration is duration for which the first storage device waits before sending an arbitration request to the quorum server.\",\n \"The transceiver module 403 is configured to send, after the delay duration, the arbitration request to the quorum server to request to take over a service.\",\n \"The reading module 401 is specifically configured to read a running status value of the first storage device, the running status value is a sum of status values of all system resources, a status value of each system resource is obtained according to a current usage ratio of each system resource and a preset correspondence, and the correspondence includes a correspondence between a current usage ratio of the processor resource and a status value of the processor resource, a correspondence between a current usage ratio of the hard disk resource and a status value of the hard disk resource, a correspondence between a current usage ratio of the cache resource and a status value of the cache resource, and a correspondence between a current usage ratio of the host bandwidth resource and a status value of the host bandwidth resource.\",\n \"The calculation module 402 is specifically configured to determine the delay duration according to the running status value and a formula T=k*S, where T is the delay duration, S is the running status value, and k is any value.\",\n \"Optionally, k=1.In addition, the first storage device communicates with a host by using a front-end port, and the reading module 401 is further configured to: detect a status of the front-end port, determine that the status of the front-end port is valid, and when determining that the status of the front end is valid, read the running status value of the first storage device.\",\n \"For specific function implementation of the modules, refer to the method steps shown in FIG.\",\n \"4.Details are not described herein again.\",\n \"An ordinary person skilled in the art may understand that the foregoing storage medium may include any non-transitory machine-readable medium capable of storing program code, such as a USB flash drive, a removable hard disk, a magnetic disk, an optical disc, a random-access memory (RAM), a solid state disk (SSD), or a non-volatile memory.\",\n \"Finally, it should be noted that the foregoing embodiments are merely intended for describing the technical solutions of the present invention, rather than limiting the present invention.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874722"}}},{"rowIdx":4494674,"cells":{"text":{"kind":"list like","value":[["Decoding Instructions That Are Modified By One Or More Other Instructions","Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions include one or more base instructions that are subject to modification by one or more other instructions.","A decoder determines whether a first received instruction was arrived at by a non-incremental change to a program counter (i.e.","a jump in the program).","If the first instruction was arrived at by a non-incremental change to the program counter the decoder decodes the immediately preceding instruction to determine if the original instruction is a base instruction subject to modification by one or more other instructions.","If the preceding instruction indicates that the original instruction is a base instruction an error has occurred and exception handling code is invoked."],["1.A method of storing a computer program in a program memory, the computer program comprising a plurality of instructions, the method comprising: receiving the plurality of instructions at a compiler, the plurality of instructions comprising one or more base instructions and at least one modifier instruction for each base instruction; analyzing, at the compiler, the plurality of instructions to identify each base instruction and the at least one modifier instruction for each identified base instruction; and storing each identified base instruction on a same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.","2.The method of claim 1, wherein a boundary within the program memory comprises one or more of a beginning of a cache line, an end of a cache line and a memory management unit page.","3.The method of claim 1, wherein each modifier instruction is a postfix instruction.","4.The method of claim 1, wherein each modifier instruction is a prefix instruction.","5.The method of claim 1, wherein storing an identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that base instruction comprises inserting one or more No Operation instructions in the computer program before the identified base instruction or the at least one modifier instruction for the identified base instruction so that the identified base instruction and the at least one modifier instruction for that identified base instruction are stored on the same side of a boundary within the program memory.","6.The method of claim 1, wherein storing each identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction comprises reordering the plurality of instructions so that each identified base instruction is stored on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.","7.The method of claim 1, wherein the plurality of instructions comprises at least two modifier instructions for a base instruction, the method further comprising storing the base instruction on the same side of a boundary of the program memory as the at least two modifier instructions for that base instruction.","8.A device arranged to store a computer program, the computer program comprising a plurality of instructions, the device comprising: a program memory; and a processor configured to: receive the plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one modifier instruction for each base instruction, analyze the plurality of instructions to identify each base instruction and the at least one modifier instruction for each identified base instruction, and store each identified base instruction on a same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.","9.The device of claim 8, wherein a boundary within the program memory comprises one or more of a beginning of a cache line, an end of a cache line and a memory management unit page.","10.The device of claim 8, wherein each modifier instruction is a postfix instruction.","11.The device of claim 8, wherein each modifier instruction is a prefix instruction.","12.The device of claim 8, wherein the processor is configured to store an identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction by inserting one or more No Operation instructions in the computer program before the identified base instruction or the at least one modifier instruction for the identified base instruction so that the identified base instruction and the at least one modifier instruction for that base instruction are stored on the same side of a boundary within the program memory.","13.The device of claim 8, wherein the processor is configured to store each identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction by reordering the plurality of instructions so that each identified instruction is stored on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.","14.The device of claim 8, wherein the plurality of instructions comprises at least two modifier instructions for a base instruction, and the processor is configured to store that base instruction on the same side of a boundary of the program memory as the at least two modifier instructions for that base instruction.","15.A data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one modifier instruction for each base instruction, the plurality of instructions stored in the program memory so that each base instruction is stored on a same side of a boundary within the program memory as the at least one modifier instruction for that base instruction; a program counter configured to identify a first instruction in the program memory; a fetch unit configured to retrieve the first instruction in the program memory identified by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit, and request an additional instruction from the fetch unit to look for a modifier instruction for the first instruction, the additional instruction being an instruction immediately preceding the first instruction in the program memory or an instruction immediately following the first instruction in the program memory; wherein the fetch unit is further configured to determine whether the additional instruction is on the same side of a boundary of the program memory as the first instruction, and in response to determining that the additional instruction is not on the same side of the boundary of the program memory, avoid fetching the additional instruction from the program memory."],["<SOH> BACKGROUND <EOH>Computer instruction sets are used to encode the set of operations that a central processing unit (CPU) executes within a program.","It is desirable to minimize the amount of memory used to store these instructions.","For example, one instruction set may use 32 bits to encode instructions.","The use of 32 bits provides for the encoding of a rich instruction set but does not allow more common operations to be encoded using fewer bits.","Another instruction set may use 16 bits to encode instructions.","The use of 16 bits provides for high code density but limits the number of instructions that can be encoded.","One solution to the limited number of instructions that can be encoded using smaller instructions (e.g.","16 bits) is to allow a previous instruction to modify the meaning of the current instruction.","The previous modifying instruction is known as a prefix instruction.","In this way, common operations use a single instruction (e.g.","16 bits) whereas less common instructions use two instructions (one prefix instruction and one base instruction with, for example, 32 bits total).","This provides a good compromise between code density and richness of instruction.","The embodiments described below are provided by way of example only and are not limiting of implementations which solve any or all of the disadvantages of known computers."],["<SOH> SUMMARY <EOH>This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.","This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.","Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions comprise one or more base instructions that are subject to modification by one or more other instructions.","In an example, a first instruction is received at a decoder.","The decoder determines whether the first instruction was arrived at by a non-incremental change to the program counter (i.e.","a jump in the program).","If the first instruction was arrived at by a non-incremental change to the program counter the decoder decodes the immediately preceding instruction to determine if the original instruction is a base instruction (i.e.","an instruction subject to modification by one or more other instructions).","If the preceding instruction indicates that the original instruction is a base instruction an error has occurred and exception handling code is invoked.","A first aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; determining, at the decode unit, if the first instruction was invoked by a non-incremental change to a program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, requesting a second instruction from a fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program; receiving the second instruction at the decode unit from the fetch unit; analyzing the second instruction at the decode unit to determine if the first instruction is a base instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.","A second aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving an instruction at a decode unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by one or more other instructions; analyzing the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining that the received instruction is a base instruction, determining at the decode unit if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining that there are not the predetermined number of stored prefix instructions for the base instruction, invoking exception handler code.","A third aspect provides a method of decoding instructions in a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; requesting at least one additional instruction from a fetch unit, each of the at least one additional instruction following the first instruction in the program; receiving the at least one additional instruction at the decode unit, the at least one additional instruction comprising a first additional instruction; determining if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modifying the first instruction at the decode unit using the first additional instruction; and in response to determining the first additional instruction is not a postfix instruction, providing the first instruction and the at last one additional instruction to an execute unit for execution.","A fourth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify a first instruction in the program memory; a fetch unit configured to retrieve the first instruction in the program memory identified by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; determine if the first instruction was invoked by a non-incremental change to the program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, request a second instruction from the fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program memory; receive the second instruction from the fetch unit; analyze the second instruction to determine if the first instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.","A fifth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify an instruction in the program memory; a fetch unit configured to retrieve the instruction from the program memory identified by the program counter; and a decode unit configured to: receive the instruction from the fetch unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and analyze the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining the received instruction is a base instruction, determine if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining there are not the predetermined number of stored prefix instruction for the base instruction, invoke exception handler code.","A sixth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to indicate a first instruction in the program memory; a fetch unit configured to retrieve the first instruction from the program memory as indicated by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; request at least one additional instruction from the fetch unit, each of the at least one additional instruction following the first instruction in the program memory; receive the at least one additional instruction, the at least one additional instruction comprising a first additional instruction; determine if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modify the first instruction using the first postfix instruction; and in response to determining the first additional instruction is not a postfix instruction, provide the first instruction and the at least one additional instruction to an execute unit for execution.","A seventh aspect provides a compiler to store a plurality of instructions in a program memory, the compiler comprising a processor configure to: receive the plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one corresponding modifier for each base instruction; analyze the plurality of instructions to identify each base instruction and its at least one corresponding modifier; and store each base instruction and its corresponding at least one modifier in the program memory so that each base instruction and its corresponding modifiers are on the same side of a boundary within the program memory.","An eighth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fourth aspect.","A ninth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the first aspect.","A tenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fifth aspect.","An eleventh aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the second aspect.","A twelfth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the sixth aspect.","A thirteenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the third aspect.","A fourteenth aspect provides a method to decode instructions substantially as described with reference to FIG.","3 .","A fifteenth aspect provides a method to decode instructions substantially as described with reference to FIG.","5 .","A sixteenth aspect provides a method to decode instructions substantially as described with reference to FIG.","8 A seventeenth aspect provides a method to decode instructions substantially as described with reference to FIG.","10 .","The preferred features may be combined as appropriate, as would be apparent to a skilled person, and may be combined with any of the aspects of the invention."],["BACKGROUND Computer instruction sets are used to encode the set of operations that a central processing unit (CPU) executes within a program.","It is desirable to minimize the amount of memory used to store these instructions.","For example, one instruction set may use 32 bits to encode instructions.","The use of 32 bits provides for the encoding of a rich instruction set but does not allow more common operations to be encoded using fewer bits.","Another instruction set may use 16 bits to encode instructions.","The use of 16 bits provides for high code density but limits the number of instructions that can be encoded.","One solution to the limited number of instructions that can be encoded using smaller instructions (e.g.","16 bits) is to allow a previous instruction to modify the meaning of the current instruction.","The previous modifying instruction is known as a prefix instruction.","In this way, common operations use a single instruction (e.g.","16 bits) whereas less common instructions use two instructions (one prefix instruction and one base instruction with, for example, 32 bits total).","This provides a good compromise between code density and richness of instruction.","The embodiments described below are provided by way of example only and are not limiting of implementations which solve any or all of the disadvantages of known computers.","SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.","This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.","Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions comprise one or more base instructions that are subject to modification by one or more other instructions.","In an example, a first instruction is received at a decoder.","The decoder determines whether the first instruction was arrived at by a non-incremental change to the program counter (i.e.","a jump in the program).","If the first instruction was arrived at by a non-incremental change to the program counter the decoder decodes the immediately preceding instruction to determine if the original instruction is a base instruction (i.e.","an instruction subject to modification by one or more other instructions).","If the preceding instruction indicates that the original instruction is a base instruction an error has occurred and exception handling code is invoked.","A first aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; determining, at the decode unit, if the first instruction was invoked by a non-incremental change to a program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, requesting a second instruction from a fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program; receiving the second instruction at the decode unit from the fetch unit; analyzing the second instruction at the decode unit to determine if the first instruction is a base instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.","A second aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving an instruction at a decode unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by one or more other instructions; analyzing the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining that the received instruction is a base instruction, determining at the decode unit if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining that there are not the predetermined number of stored prefix instructions for the base instruction, invoking exception handler code.","A third aspect provides a method of decoding instructions in a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; requesting at least one additional instruction from a fetch unit, each of the at least one additional instruction following the first instruction in the program; receiving the at least one additional instruction at the decode unit, the at least one additional instruction comprising a first additional instruction; determining if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modifying the first instruction at the decode unit using the first additional instruction; and in response to determining the first additional instruction is not a postfix instruction, providing the first instruction and the at last one additional instruction to an execute unit for execution.","A fourth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify a first instruction in the program memory; a fetch unit configured to retrieve the first instruction in the program memory identified by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; determine if the first instruction was invoked by a non-incremental change to the program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, request a second instruction from the fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program memory; receive the second instruction from the fetch unit; analyze the second instruction to determine if the first instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.","A fifth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify an instruction in the program memory; a fetch unit configured to retrieve the instruction from the program memory identified by the program counter; and a decode unit configured to: receive the instruction from the fetch unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and analyze the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining the received instruction is a base instruction, determine if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining there are not the predetermined number of stored prefix instruction for the base instruction, invoke exception handler code.","A sixth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to indicate a first instruction in the program memory; a fetch unit configured to retrieve the first instruction from the program memory as indicated by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; request at least one additional instruction from the fetch unit, each of the at least one additional instruction following the first instruction in the program memory; receive the at least one additional instruction, the at least one additional instruction comprising a first additional instruction; determine if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modify the first instruction using the first postfix instruction; and in response to determining the first additional instruction is not a postfix instruction, provide the first instruction and the at least one additional instruction to an execute unit for execution.","A seventh aspect provides a compiler to store a plurality of instructions in a program memory, the compiler comprising a processor configure to: receive the plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one corresponding modifier for each base instruction; analyze the plurality of instructions to identify each base instruction and its at least one corresponding modifier; and store each base instruction and its corresponding at least one modifier in the program memory so that each base instruction and its corresponding modifiers are on the same side of a boundary within the program memory.","An eighth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fourth aspect.","A ninth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the first aspect.","A tenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fifth aspect.","An eleventh aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the second aspect.","A twelfth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the sixth aspect.","A thirteenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the third aspect.","A fourteenth aspect provides a method to decode instructions substantially as described with reference to FIG.","3.A fifteenth aspect provides a method to decode instructions substantially as described with reference to FIG.","5.A sixteenth aspect provides a method to decode instructions substantially as described with reference to FIG.","8 A seventeenth aspect provides a method to decode instructions substantially as described with reference to FIG.","10.The preferred features may be combined as appropriate, as would be apparent to a skilled person, and may be combined with any of the aspects of the invention.","BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention will be described, by way of example, with reference to the following drawings, in which: FIG.","1 is a schematic diagram of an example data processing apparatus; FIG.","2 shows an example of a method of decoding instructions in accordance with a first embodiment; FIG.","3 is a flowchart of the method of FIG.","2; FIG.","4 shows an example of a method of decoding instructions in accordance with a second embodiment; FIG.","5 is a flowchart of the method of FIG.","4; FIG.","6 shows an example of a method of decoding instructions in accordance with a third embodiment; FIG.","7 shows a second example of the method of FIG.","6; FIG.","8 is a flowchart of the method of FIGS.","6 and 7; FIG.","9 shows an example of a method of decoding instructions in accordance with a fourth embodiment; FIG.","10 is a flowchart of the method of FIG.","9; and FIG.","11 shows an example of a method of arranging instructions in a program memory.","Common reference numerals are used throughout the figures to indicate similar features.","DETAILED DESCRIPTION Embodiments of the present invention are described below by way of example only.","These examples represent the best ways of putting the invention into practice that are currently known to the Applicant although they are not the only ways in which this could be achieved.","The description sets forth the functions of the example and the sequence of steps for constructing and operating the example.","However, the same or equivalent functions and sequences may be accomplished by different examples.","One problem with the prefix instruction approach described above is that there exists the possibility of ambiguity in the program code.","If a machine (or an observer) starts reading from an arbitrary point, it is not apparent whether the instruction at that point should be subject to modification from a previous prefix instruction.","The widespread use of computed branches or branch instructions in program code offers the possibility that code execution could commence at any offset into the code.","This ambiguity therefore means that the effect of the program code becomes very difficult to predict.","This could lead to unexpected errors or possible methods to attack code used in secure applications.","For example, if a branch erroneously jumps to an instruction that should be modified by a prefix, the program will continue from this point without the instruction being modified.","The unpredictable nature of this can be catastrophic to the program operation.","The program may continue running for some time reading further instructions and generating outputs until something happens that causes an error or halt in the program.","This makes debugging this type of error difficult, as the source of the error is the branch to the prefixed instruction that may have occurred some time ago.","In the case of security or safety-critical applications, then it is important to know rapidly that something has gone wrong in the program, so that the error can be contained.","In the case of a branch to a prefixed instruction, the error can take some time to manifest itself, leading to an uncertain period in which the program operation is unpredictable.","This would potentially be very damaging in the case of a program controlling a nuclear power plant or a banking system, for example.","This type of error can also occur in situations other than an illegal branch.","For example, in the case of space applications, such as satellites, one or more bits within a CPU can be flipped by a high-energy particle (i.e.","from cosmic rays) passing through the spacecraft.","If an instruction address is subject to such a bit-flip, then the instruction fetched is not the one intended.","Any change to the program counter other than an increment to the next instruction will be referred to herein as a “jump” in the program.","As described above, jumps may be caused, for example, by a branch in the program or external factors, such as high-energy particles passing through the computer.","An “illegal jump” is a jump which takes the program to an instruction that cannot be legally executed.","For example, a branch instruction which takes the program directly to a prefixed base instruction causes an illegal jump since the base instruction cannot be legally executed without its prefix(es).","An “illegal branch” is a branch instruction which causes an illegal jump.","Embodiments described herein relate to methods and data processing apparatus for decoding instructions that comprise base instructions, which allow illegal jumps to base instructions to be easily identified.","In a first embodiment, one or more bits of an instruction are used to indicate whether the current instruction is subject to modification by another instruction.","In a second embodiment, both the current instruction and the previous instruction are fetched and decoded to determine if the current instruction is subject to modification by the previous instruction.","In a third embodiment, instructions are modified by a postfix instruction (i.e.","an instruction following the current instruction) instead of by a prefix instruction (i.e.","an instruction preceding the current instruction) and both the current instruction and the following instruction are fetched and decoded to determine if the current instruction is subject to modification by the following instruction.","In a fourth embodiment, instructions are modified by a postfix instruction and one or more bits of an instruction are used to indicate whether the current instruction is subject to modification by another instruction.","An instruction that is subject to modification by another instruction will be referred to herein as a “base instruction” and an instruction that modifies a subsequent instruction will be referred to herein as a “prefix instruction”.","Reference is now made to FIG.","1 which illustrates a data processing unit 100, such as a processor, that executes a computer program.","The data processing unit 100 comprises a program memory 102 configured to store a sequence of instructions forming the computer program.","In the example, shown in FIG.","1, the instructions are denoted II to In.","The data processing unit 100 further comprises a fetch unit 104 configured to fetch instructions from the program memory 102 (in program order) as indicated by a program counter (PC) 112 and a decode unit 106 arranged to interpret the instructions.","If there is no error or exception in decoding the instruction then the decode unit 106 forwards the instruction to an execute unit 108 for execution (which may include reading and/or writing to one or more registers 110) and updates the program counter 112 to point to the next instruction.","If, however, there is an error in decoding the instruction (e.g.","the instruction is invalid) then the decode unit 106 notifies an exception handler unit 114 which updates the program counter 112 so that the fetch unit 104 fetches exception handling code from the program memory 102.In this way, the exception can be handled predictably, without causing the data processing unit 100 to execute invalid code.","If prefix modifiers are used, then there may be situations where the program counter 112 is updated to point to an instruction that is to be modified by a prefix (i.e.","a base instruction).","For example, in the case of an illegal branch instruction the target base instruction will be fetched, decoded and executed unmodified, which will cause the program to operate unpredictably.","The decode unit 106 will not detect that the instruction should have been prefixed and hence will not call the exception handler unit 114.Accordingly, there is a need for the decode unit 106 to be able to identify base instructions so that it can call the exception handler unit 114 when an illegal jump to a base instruction has occurred.","Described below are methods for decoding instructions that may be implemented by the decode unit 106 which allows the decode unit 106 to identify base instructions.","One or more of the functions performed by the units (e.g.","fetch unit 104, decode unit 106, and the execute unit 108) of FIG.","1 may be performed in parallel, for example, via pipelining.","Reference is now made to FIGS.","2 and 3 which illustrate a first embodiment of a method for decoding instructions.","In this embodiment, one or more bits of the instruction are used to indicate whether there is at least one modifier for the current instruction (e.g.","whether there is a prefix instruction).","FIG.","2 illustrates an example of the first embodiment.","Specifically, FIG.","2 illustrates two instructions 202 and 204.The first instruction 202 corresponds to I4 of FIG.","1 and the second instruction 204 corresponds to I5 of FIG.","1 where I4 is the prefix for I5.Each instruction 202 and 204 has a reserved bit 206 and 208, referred to as the modifier bit, for indicating whether the instruction is subject to modification by another instruction (i.e.","that there is a prefix instruction for the instruction).","In this example, since I5 is to be modified by I4, the modifier bit 208 for I5 is set to one to indicate that I5 is to be modified by another instruction.","Since I4 is the prefix to be used to modify I5, the modifier bit 206 is set to zero to indicate that I4 is not itself to be modified by another instruction.","When the decode unit 106 decodes an instruction it checks the modifier bit 206 or 208 of the instruction 202 or 204 to determine whether the instruction is to be modified by another instruction (i.e.","whether the instruction is a base instruction).","If the modifier bit 206 or 208 indicates that the instruction 202 or 204 is to be modified and the decode unit 106 has not decoded the modifier instruction (e.g.","the prefix instruction) then the decode unit 106 detects an error (e.g.","an illegal branch) and invokes the exception handler unit 114.The exception handler unit 114 then updates the program counter 112 so that the fetch unit 104 fetches exception handling code from the program memory 102.In some cases the exception handler unit 114 may also save the state and/or flush an associated pipeline.","For example, as shown in FIG.","2, if the previous instruction was I2 (a branch instruction) which caused the program counter 112 to be updated to point to I5, the decode unit 106 would decode I5 and check the modifier bit 208.Since the modifier bit 208 for I5 is set to one indicating the instruction is to be modified and the previous instruction (I2) was not a prefix instruction, the decode unit 106 knows an error has occurred and calls the exception handler unit 114.Although, in FIG.","2, the modifier bit 206 or 208 is shown as the most significant bit of the instruction 202 or 204, it could be located at any predetermined position.","Furthermore, although, in FIG.","2, there is single modifier bit 206 or 208, in other cases there may be more than one modifier bit.","This may be used, for example, in cases where instructions can be modified by more than one modifier instruction to indicate the number of modifier instructions.","This would allow the decode unit 106 to not only catch illegal jumps (e.g.","illegal branch instructions) to instructions that should be modified, but also catch illegal jumps to instructions that are not the first modifier instructions (e.g.","the first prefix instruction).","Using one or more bits of the instruction to indicate whether the instruction is subject to modification by one or more other instructions (i.e.","the instruction is a base instruction) allows illegal jumps (e.g.","illegal branch instructions) to base instructions to be quickly and easily identified.","The trade-off, however, is that reserving one or more of the bits of the instruction for this purpose reduces the number of bits available for encoding instructions and thus reduces the number of different types of instructions that can be encoded in a single instruction.","FIG.","3 is a flowchart of an example method 300 in accordance with the first embodiment which may be executed by a decode unit (e.g.","decode unit 106).","At step 302 the decode unit 106 receives an instruction fetched by the fetch unit 104.The instruction comprises at least one modifier bit.","As described above the modifier bit indicates whether the instruction is a base instruction subject to modification by at one or more other instructions and, optionally, how many modifier instructions there are.","Once the fetched instruction has been received the method 300 proceeds to step 304.At step 304, the decode unit 106 decodes the fetched instruction to identify particular bit patterns in the fetched instruction.","Once the fetched instruction is decoded the method 300 proceeds to step 306.At step 306, the decode unit 106 determines whether the decoded instruction is a prefix for another instruction.","Determining whether the decoded instruction is a prefix for another instruction may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.","As it known to those of skill in the art an instruction may comprises an opcode (operation code) which specifies the operation to be performed.","In some cases there is a special opcode for prefix instructions.","Accordingly, determining whether the instruction is a prefix for another instruction may comprise reading the instruction's opcode.","If the decoded instruction is determined to be a prefix then the instruction is stored at step 308 so that it can be used to modify a subsequent base instruction.","In some cases the prefix instruction may be stored in a local storage unit, such as memory or registers, of the decode unit 106 or the fetch unit 104.The amount of data stored for each prefix instruction may be reduced by only storing enough information to allow the base instruction to be modified.","For example the full 16 bits of a 16 bit instruction may not be stored.","In some cases, instead of storing the prefix instruction the prefix instruction may be discarded and re-fetched after decoding a base instruction.","Once the prefix instruction is stored the method 300 proceeds back to step 302.If, however, it is determined that the decoded instruction is not a prefix, then the method 300 proceeds to step 310.At step 310, the decode unit 106 determines whether the decoded instruction is a base instruction (i.e.","that it is subject to modification by another instruction).","Determining whether the decoded instruction is a base instruction comprises analyzing the modifier bit(s) to determine if they indicate that the instruction is subject to modification.","As described above, the modifier bit(s) are one or more reserved bits in the instruction that are used to indicate whether the instruction is subject to modification by one or more other instructions and, optionally, how many modifier instructions there are.","If the modifier bit(s) indicate that the instruction is not subject to modification then at step 312 the decode unit 106 passes the unmodified instruction (i.e.","the instruction decoded in step 304) to the execute unit 108 for execution.","If, however, the modifier bit(s) indicate that the instruction is subject to modification by one or more other instructions (i.e.","that the instruction is a base instruction) then the method proceeds to step 314.At step 314, the decode unit 106 determines whether there are a predetermined number of stored prefix instructions for the base instruction.","A stored prefix instruction is a prefix instruction that has been previously decoded and stored by the decode unit as per steps 306 and 308.In cases where there is only a single modifier bit then the predetermined number may be one (i.e.","the decode unit 106 checks to see if there is a stored prefix for the base instruction).","In cases where there is more than one modifier bit indicating the number of modifiers then the decode unit 106 may analyze the modifier bits to determine the number of prefix instructions for the base instruction.","In these cases the predetermined number is the number of prefix instructions specified in the modifier bits.","For example, if the modifier bits indicate there are two prefix modifiers for the base instruction then the predetermined number is two and the decode unit 106 determines if it has two stored prefix instructions for the base instruction.","If there are the predetermined number of stored prefix instructions for the base instruction then in step 316 the decode unit 106 uses the stored prefix instruction(s) to modify the received instruction (i.e.","the instruction received in step 302).","For example, a MOV instruction (an instruction that copies data from one location to another), when unmodified, may use a 16 bit operand or address.","If the MOV instruction was preceded by a prefix instruction then the MOV instruction may be modified to use 32 bit operations or addresses instead.","In step 318 the modified instruction is provided to the execute unit 108 for execution.","If, however, there are not the predetermined number of stored prefix instructions (i.e.","there are no stored prefix instructions or less stored prefix instructions than specified in the modifier bits) then an error has occurred (e.g.","an illegal branch instruction has occurred) and at step 320, the decode unit 106 invokes the exception handler unit 114.Reference is now made to FIGS.","4 and 5 which illustrate a second embodiment of a method for decoding instructions.","In this embodiment the current instruction and the preceding instruction (i.e.","the instruction immediately preceding the current instruction in the program code) are both fetched and decoded to determine if the current instruction is subject to modification by the preceding instruction.","While more than one preceding instruction may be fetched, the decoder can determine the current instruction is a base instruction from only the immediately preceding instruction.","FIG.","4 illustrates an example of the second embodiment.","Specifically, FIG.","4 illustrates two instructions 402 and 404.The first instruction 402 corresponds to I4 of FIG.","1 and the second instruction 404 corresponds to I5 of FIG.","1 where I4 is the prefix for I5.If the previous instruction was I2 (a branch instruction) which caused the program counter 112 to be updated to point to I5, then both I5 and I4 are fetched and decoded.","I4 will be identified to be the prefix for I5.This indicates an error has occurred (e.g.","an illegal branch) and the exception handler unit 114 is called.","In some cases, both the current instruction and the preceding instruction are only fetched and decoded after a jump in the program (i.e.","a change to the program counter other than an increment to the next instruction, e.g.","a change to the program counter 112 caused by a branch instruction).","Where there is a simple increment of the program counter to the next instruction only the current instruction is fetched and decoded.","In these cases resources are not wasted fetching the preceding instruction again since it will have already been fetched and decoded in the previous cycle.","Fetching and decoding both the current and preceding instructions allows illegal jumps (e.g.","illegal branch instructions) to base instructions to be quickly and easily identified.","The trade-off is the delay caused by fetching the preceding instruction after a branch.","However, this is mitigated significantly by the fact that many processors are now highly parallel, which means that many instructions are generally issued at the same time, reducing the impact of waiting for the previous instruction.","FIG.","5 is a flowchart of an example method 500 in accordance with the second embodiment which may be executed by a decode unit (e.g.","decode unit 106).","At step 502 the decode unit 106 receives a first instruction fetched by the fetch unit 104.Once the fetched instruction has been received the method 500 proceeds to step 504.At step 504, the decode unit 106 decodes the first instruction to identify particular bit patterns in the first instruction.","Once the first instruction has been decoded the method 500 proceeds to step 506.At step 506, the decode unit 106 determines whether the first instruction is an instruction that was invoked (i.e.","arrived at) by a jump in the program.","As described above, a jump in the program is any change to the program counter other than an increment to the next instruction (i.e.","a non-incremental change to the program counter).","In some cases the execute unit 108 may be configured to send an indication or a signal to the decode unit 106 if it makes a change to the program counter other than an increment to the next instruction.","In these cases the decode unit 106 may determine that the first instruction was invoked by a jump in the program when it receives such an indication or signal from the execute unit 108.In other cases the program counter 112 itself may comprise hardware that monitors changes and provides an indication or a signal to the decode unit 106 if it detects a non-incremental change.","In these cases when the decode unit 106 receives such an indication or signal from the program counter 112 it can relate this signal to a future instruction it will receive (e.g.","it will know how many cycles it will be until it gets the instruction the indication or signal relates to).","Then when the decode unit 106 subsequently receives that instruction for decoding the decode unit 106 will know that the instruction was invoked by a jump in the program.","If the decode unit 106 determines that the first instruction was not invoked by a jump in the program then the method 500 proceeds to step 508.If, however, the decode unit 106 determines that the first instruction was invoked by a jump in the program then the method 500 proceeds to step 520.At step 508, the decode unit 106 determines whether the first instruction is a prefix for another instruction.","Determining whether the first instruction is a prefix for another instruction may comprise comparing the first instruction to one or more predetermined bit patterns to determine if there is a match.","For example, as described above, determining whether an instruction is a prefix for another instruction may comprises analyzing the opcode of the instruction.","If the first instruction is determined to be a prefix then the instruction is stored at step 510 so that it can be used later to modify a subsequent base instruction.","The method 500 then proceeds back to step 502.If, however, it is determined that the first instruction is not a prefix, then the method 500 proceeds to step 512.At step 512 the decode unit 106 determines whether there is at least one stored prefix for the first instruction.","If there is at least one prefix stored for the first instruction then in step 514 the decode unit 106 uses the stored prefix instruction(s) to modify the first instruction (i.e.","the instruction received in step 502) and in step 516 passes the modified first instruction to the execute unit 108 for execution.","If, however, there are no prefixes stored for the first instruction, then the decode unit 106 passes the unmodified first instruction (i.e.","the instruction decoded in step 504) to the execution unit 108 for execution at step 518.At step 520, the decode unit 106 requests a second instruction from the fetch unit 104.The second instruction is the instruction immediately preceding the first instruction in the program (i.e.","the instruction located at the program counter value for the first instruction minus one instruction).","At step 522 the decode unit 106 receives and decodes the second instruction.","At step 524 the decode unit 106 determines whether the second instruction is a prefix.","If the decode unit 106 determines that the second instruction is a prefix then an error has occurred (e.g.","an illegal branch instruction has occurred) and at step 526 the decode unit 106 invokes the exception handler unit 114.If, however, the decode unit 106 determines that the second instruction is not a prefix then in step 528 the decode unit 106 determines whether the first instruction is a prefix instruction.","If the decode unit 106 determines that the first instruction is a prefix then at step 510 the prefix instruction is stored for further use.","If, however, the decode unit 106 determines that the first instruction is not a prefix instruction then at step 518 the unmodified first instruction is passed to the execute unit 108 for execution.","Reference is now made to FIGS.","6 to 8 which illustrate a third embodiment of a method for decoding instructions.","In this embodiment, instead of instructions being modified by a prefix, they are modified by a postfix and both the current instruction and the following instruction are fetched and decoded to determine if the current instruction is subject to modification by the following instruction.","In other words, instead, of instructions being modified by one or more preceding instructions, instructions are modified by one or more following instructions.","Postfix modifiers were not feasible in the past because of the delay caused by waiting for the fetch and decode of the following instruction before the current instruction is sent for execution.","However, because modern multiple-issue processors have multiple instructions under consideration at the same time, the efficiency loss due to having to check for postfixes is minimized.","FIG.","6 illustrates a first example of the third embodiment where a base instruction is modified by a following instruction (i.e.","a postfix instruction).","Specifically, FIG.","6 illustrates two instructions 602 and 604.The first instruction 602 corresponds to I4 of FIG.","1 and the second instruction 604 corresponds to I5 of FIG.","1 where I5 is the postfix for I4.In this example, when I4 is fetched and decoded the decode unit 106 waits until I5 is fetched and decoded to determine whether I4 is subject to modification.","FIG.","7 illustrates a second example of the third embodiment where an illegal branch instruction occurs.","Specifically, FIG.","7 illustrates two instructions 702 and 704.The first instruction 702 corresponds to I4 of FIG.","1 and the second instruction 704 corresponds to I5 of FIG.","1 where I5 is the postfix for I4.In this example, the previous instruction I2 was a branch instruction that caused the program counter 112 to point to I5.When I5 is decoded it will be determined that I5 is a postfix for an earlier instruction.","Since a postfix cannot validly follow a branch instruction the decode unit 106 will know an error has occurred and will invoke the exception handler unit 114.FIG.","8 is a flowchart of an example method 800 in accordance with the third embodiment which may be executed by a decode unit (e.g.","decode unit 106).","At step 802 the decode unit 106 receives a first instruction fetched by the fetch unit 104.Once the first instruction has been received the method 800 proceeds to step 804.At step 804, the decode unit 106 decodes the first instruction to identify particular bit patterns in the fetched instruction.","Once the first instruction has been decoded the method 800 proceeds to step 806.At step 806, the decode unit 106 determines whether the first instruction is a postfix for another instruction.","Determining whether the decoded instruction is a postfix for another instruction may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.","As described above, instructions may comprise an opcode that describes what operation is to be performed by the instruction.","Postfix instructions may be assigned a special opcode which allows them to be identified as postfix instructions by their opcode.","This is in contrast to base instructions which cannot typically be identified as base instructions from their opcode alone.","For example, a MOV instruction has a MOV opcode.","It is only with additional information (e.g.","subsequently decoding a postfix instruction) that the decoder knows that the MOV instruction is a base instruction subject to modification by another instruction.","If the first instruction is determined to be a postfix then an error has occurred and at step 808 the decode unit 106 invokes the exception handler unit 114.If, however, it is determined that the first instruction is not a postfix then the method 800 proceeds to step 810.At step 810, the decode unit 106 requests one or more additional instructions from the fetch unit 104.The additional instructions immediately follow the first instruction in the program.","In cases where there may only be a single postfix instruction for any base instruction then the decode unit 106 may only fetch one additional instruction (i.e.","the instruction immediately following the first instruction).","In cases, however, where there may be more than one postfix instruction for any base instruction then the decode unit 106 may request multiple additional instructions (e.g.","the two instructions immediately following the first instruction).","In some cases the maximum number of modifiers is hardcoded in the decode unit 106 based on the instruction set used.","In these cases the decode unit 106 may use this hardcoded information to determine how many additional instructions to request.","For example, if the decode unit 106 is hardcoded with information specifying that the maximum number of modifiers is three then the decode unit 106 may request three additional instructions.","Once the additional instructions have been requested, the method 800 proceeds to step 812.At step 812, the decode unit 106 receives and decodes the additional instructions.","Once the additional instructions have been received and decoded, the method 800 proceeds to step 814.At step 814, the decode unit 106 determines whether the first additional instruction (i.e.","the instruction immediately following the first instruction) is a postfix.","Determining whether an additional instruction is a postfix may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.","For example, the decode unit 106 may determine an additional instruction is a postfix instruction by analyzing the opcode of the instruction.","If the first additional instruction is a postfix then the method 800 proceeds to step 816.If, however, it is determined that the first additional instruction is not a postfix then at step 820 the decode unit 106 provides both the first instruction and the additional instructions, unmodified, to the execute unit 108 for execution.","At step 816, any additional instructions that are postfix instructions are used to modify the first instruction (i.e.","the instruction received in step 802).","For example, if three additional instructions are requested and the first two additional instructions are identified as postfix instructions then the two postfix instructions are used to modify the first instruction.","Once the first instruction has been modified then in step 818 the decode unit 106 forwards the modified first instruction and any non-postfix additional instructions to the execute unit 108 for execution.","Reference is now made to FIGS.","9 and 10 which illustrate a fourth embodiment of a method for decoding instructions.","This embodiment is a combination of the first and third embodiments.","In particular, instructions are modified by postfixes (e.g.","subsequent instructions) instead of prefixes (i.e.","preceding instructions) and one or more bits of each instruction is reserved for indicating whether the instruction is subject to modification by one or more other instructions.","FIG.","9 illustrates an example of the fourth embodiment.","Specifically, FIG.","9 illustrates two instructions 902 and 904.The first instruction 902 corresponds to I4 of FIG.","1 and the second instruction 904 corresponds to I5 of FIG.","1 where I5 is the postfix for I4.As described with respect to FIG.","6, when I4 is fetched and decoded the decode unit 106 waits until I5 is fetched and decoded to determine whether I4 should be modified.","Each instruction also has a reserved bit 906 or 908, referred to as the modifier bit, for indicating whether or not the instruction is subject to modification by another instruction.","In this example, since I4 is to be modified by I5, the modifier bit 906 for I4 is set to one to indicate that I4 is subject to modification by another instruction.","Similarly since I5 is the postfix to be used to modify I4, the modifier bit 908 is set to zero to indicate that I5 is not itself subject to modification.","When the decode unit 106 decodes an instruction 902 or 904 it checks the modifier bit 906 or 908 to determine whether the instruction is subject to modification (e.g.","it is a base instruction).","If the modifier bit 906 or 908 indicates that the instruction 902 or 904 is subject to modification then the decode unit 106 knows it should wait for the next instruction to be fetched and decoded before proceeding.","If, however, the modifier bit 906 or 908 indicates that the instruction is not subject to modification then the instruction 906 or 908 can be immediately sent to the execute unit 108 for execution without having to wait for the next instruction to be fetched and decoded.","For example, when the decode unit 106 decodes I4 the modifier bit 906 tells the decode unit 106 to wait and fetch and decode I5 so that it can be used to modify I4.Although, in FIG.","9, the modifier bit 906 or 908 is shown as the most significant bit, it could be located at any predetermined position.","Furthermore, although, in FIG.","9, there is a single modifier bit 906 or 908, in other cases there may be more than one modifier bit.","This may be used, for example, in cases where instructions can be modified by more than one modifier to indicate the number of modifiers.","This tells the decode unit 106 how many instructions should be fetched and decoded before the current instruction is dispatched to the execute unit 108.Not only can the modifier bit 906 or 908 be used to tell the decode unit 106 when it should wait for the next instruction, it can also be used to identify errors in the scenario where a postfix modifier is supposed to be present, but the next instruction is not a valid modifier.","For example, if the modifier bit 906 or 908 indicates that the instruction is subject to modification but the next instruction is not a valid modifier then the decode unit 106 knows an error has occurred and can invoke the exception handler unit 114.FIG.","10 is a flowchart of an example method 1000 in accordance with the fourth embodiment which may be executed by a decode unit (e.g.","decode unit 106).","At step 1002 the decode unit 106 receives a first instruction fetched by the fetch unit 104.The first instruction comprises at least one modifier bit indicating whether the first instruction is a base instruction, and, optionally, how many modifiers there are for the first instruction.","Once the first instruction has been received the method 1000 proceeds to step 1004.At step 1004, the decode unit 106 decodes the first instruction to identify particular bit patterns in the fetched instruction.","Once the first instruction has been decoded the method 1000 proceeds to step 1006.At step 1006, the decode unit 106 determines whether the first instruction is a postfix for another instruction.","Determining whether the first instruction is a postfix for another instruction may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.","For example, the decode unit 106 may determine the first instruction is a postfix instruction by analyzing the instruction's opcode.","If the first instruction is determined to be a postfix then an error has occurred and at step 1008 the decode unit 106 invokes the exception handler unit 114.If, however, it is determined that the first instruction is not a postfix then the method 1000 proceeds to step 1010.At step 1010, the decode unit 106 determines whether the first instruction is a base instruction (i.e.","subject to modification by one or more other instructions).","Determining whether the first instruction is a base instruction comprises analyzing the modifier bit(s) to determine if they have a predetermined bit pattern indicating that the instruction is a base instruction.","If the first instruction is not a base instruction then at step 1012 the unmodified first instruction is dispatched to the execute unit 108 for execution.","If, however, the decoded instruction is a base instruction the method 1000 proceeds to step 1014.At step 1014, the decode unit 106 requests at least one additional instruction in the program.","The additional instructions immediately follow the first instruction in the program.","In cases where there can only be one postfix for any base instruction, then the decode unit 106 may only request one additional instruction.","If, however, a base instruction can be modified by more than one postfix then the decode unit 106 may decode the modifier bits to determine the number of modifiers for the first instruction and the number of additional instructions requested is equal to the number of modifiers determined from the modifier bits.","Once the additional instructions have been requested the method 1000 proceeds to step 1016.Then at step 1016 the decode unit 106 receives and decodes the additional instructions.","Once the next instruction has been received and decoded, the method 1000 proceeds to step 1018.At step 1018, it is determined whether each of the additional instructions is a valid postfix for the first instruction.","Determining whether an additional instruction is a valid postfix for the first instruction may comprise comparing the additional instruction to one or more predetermined bit patterns to determine if there is a match.","If each of the additional instructions is a valid postfix for the first instruction then the method 1000 proceeds to step 1020.If, however, it is determined that at least one of the additional instructions is not a valid postfix then an error has occurred and at step 1008 the exception handler unit 114 is invoked.","At step 1020, the received and decoded postfix instruction(s) is/are used to modify the first instruction (i.e.","the instruction received in step 1002) and in step 1022 the modified first instruction is sent to the execute unit 108 for execution.","The second and third embodiments described above, which involve fetching and decoding multiple consecutive instructions (i.e.","fetching the preceding instruction to look for a prefix, or fetching the following instruction to look for a postfix), may be further enhanced by controlling the layout of instructions in the program memory 102.In particular, the program memory 102 may have fixed boundaries which can be expensive to cross.","This can include, for example, cache line boundaries or transition page boundaries in the memory management unit (MMU).","For example, the MMU page size may be 4K.","It may therefore be undesirable to delay executing an instruction while waiting to fetch an instruction from across one of these boundaries, as it is much slower due to the cost of having to fetch an extra cache line or virtual memory page.","To address this, boundaries can be defined in the program memory 102 over which prefixing and/or postfixing are not allowed.","Specifically, a prefix or postfix instructions should not be separated from their corresponding base instruction by such a boundary.","This can avoid the cost of having to fetch an extra cache line or virtual memory page for checking a preceding or following instruction since it is known that it is not legal for a prefix or postfix to extend across the boundary.","A compiler can deal with this exception by, for example inserting a No Operation (NOP) instruction, which is an instruction that effectively does nothing at all, in order to pad a prefix or postfix instruction from its base instruction so they do not straddle the boundary.","Other, more sophisticated compilers may avoid the use of NOPs by reordering instructions.","If the instruction set permits multiple prefixes or postfixes then the positioning would be limited so the whole group of prefixes and corresponding base, or postfixes and corresponding base, is not allowed to cross the boundary.","Reference is now made to FIG.","11 which illustrates the insertion of a NOP in a program to ensure that a postfix instruction and its corresponding base instruction do not straddle a boundary.","In particular, as illustrated at (a) a program consists of four instructions 1102, 1104, 1106 and 1108.The instructions correspond to instructions I3, I4, I5 and I6 of FIG.","1 respectively where I4 is the prefix for I5 and I4 and I5 straddle a cache line 1110 boundary or an MMU page boundary.","As illustrated at (b) in FIG.","11 an NOP 1112 is inserted between I3 and I4 so that I4 is pushed to the other side of the boundary 1110 so that the prefix I4 and its base instruction I5 are on the same side of the boundary 1110.The method described in reference to FIG.","11 may be executed by a compiler or similar device.","Another example includes a non-transitory computer readable storage medium having stored thereon computer readable instructions that, when processed at a computer system for generating a manifestation of an integrated circuit, cause the computer system to generate a manifestation of an integrated circuit to perform the method of: receiving a first instruction; determining if the first instruction was invoked by a non-incremental change to a program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, requesting a second instruction, the second instruction being an instruction immediately preceding the first instruction in a computer program; receiving the second instruction; analyzing the second instruction to determine if the first instruction is a base instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.","A further example includes a non-transitory computer readable storage medium having stored thereon computer readable instructions that, when processed at a computer system for generating a manifestation of an integrated circuit, cause the computer system to generate a manifestation of an integrated circuit to perform the method of: receiving an instruction, the instruction comprising at least one modifier bit, the at least one modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by one or more other instructions; analyzing the at least one modifier bit to determine if the received instruction is a base instruction; in response to determining that the received instruction is not a base instruction, determining if the received instruction is a prefix instruction, a prefix instruction being an instruction that modifies a subsequent instruction; in response to determining the received instruction is a prefix instruction, storing the received instruction; in response to determining that the received instruction is a base instruction, determining if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining that there are not the predetermined number of stored prefix instructions for the base instruction, invoking exception handling code.","Yet another example includes a non-transitory computer readable storage medium having stored thereon computer readable instructions that, when processed at a computer system for generating a manifestation of an integrated circuit, cause the computer system to generate a manifestation of an integrated circuit to perform the method of: receiving a first instruction; determining whether the first instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first instruction is a postfix instruction, determining whether the first instruction was invoked by a non-incremental change to a program counter; and in response to determining the first instruction was invoked by a non-incremental change to the program counter, invoking exception handling code.","One of the effects of the embodiments described above is a more efficient computer.","Specifically, by enabling the data processing apparatus to more quickly and efficiently identify illegal jumps the apparatus does not have to waste resources executing erroneous code.","A further effect of the embodiments described above is the use of static analysis (also called static code analysis or SCA).","This is an automated program analysis performed on the source or object code, without executing the program.","Because it is performed without execution, static analysis must consider every possible outcome of a branch in the program.","This results in many permutations, and the analysis quickly becomes complex and slow.","Because the methods described above eliminate certain branch destinations as illegal (because they branch to the wrong part of an instruction or modifier), this cuts down on the number of branch permutations that the static analysis need to consider.","As a result, the static analysis speed is increased.","The term ‘processor’ and ‘computer’ are used herein to refer to any device, or portion thereof, with processing capability such that it can execute instructions.","The term ‘processor’ may, for example, include central processing units (CPUs), graphics processing units (GPUs or VPUs), physics processing units (PPUs), radio processing units (RPUs), digital signal processors (DSPs), general purpose processors (e.g.","a general purpose GPU), microprocessors, any processing unit which is designed to accelerate tasks outside of a CPU, etc.","Those skilled in the art will realize that such processing capabilities are incorporated into many different devices and therefore the term ‘computer’ includes set top boxes, media players, digital radios, PCs, servers, mobile telephones, personal digital assistants and many other devices.","Those skilled in the art will realize that storage devices utilized to store program instructions can be distributed across a network.","For example, a remote computer may store an example of the process described as software.","A local or terminal computer may access the remote computer and download a part or all of the software to run the program.","Alternatively, the local computer may download pieces of the software as needed, or execute some software instructions at the local terminal and some at the remote computer (or computer network).","Those skilled in the art will also realize that by utilizing conventional techniques known to those skilled in the art that all, or a portion of the software instructions may be carried out by a dedicated circuit, such as a DSP, programmable logic array, or the like.","The methods described herein may be performed by a computer configured with software in machine readable form stored on a tangible storage medium e.g.","in the form of a computer program comprising computer readable program code for configuring a computer to perform the constituent portions of described methods or in the form of a computer program comprising computer program code means adapted to perform all the steps of any of the methods described herein when the program is run on a computer and where the computer program may be embodied on a computer readable storage medium.","Examples of tangible (or non-transitory) storage media include disks, thumb drives, memory cards etc.","and do not include propagated signals.","The software can be suitable for execution on a parallel processor or a serial processor such that the method steps may be carried out in any suitable order, or simultaneously.","The hardware components described herein may be generated by a non-transitory computer readable storage medium having encoded thereon computer readable program code.","It is also intended to encompass software which “describes” or defines the configuration of hardware that implements a module, functionality, component or logic described above, such as HDL (hardware description language) software, as is used for designing integrated circuits, or for configuring programmable chips, to carry out desired functions.","That is, there may be provided a computer readable storage medium having encoded thereon computer readable program code for generating a processing unit configured to perform any of the methods described herein, or for generating a processing unit comprising any apparatus described herein.","That is, a computer system may be configured to generate a representation of a digital circuit from definitions of circuit elements and data defining rules for combining those circuit elements, wherein a non-transitory computer readable storage medium may have stored thereon processor executable instructions that when executed at such a computer system, cause the computer system to generate a processing unit as described herein.","Memories storing machine executable data for use in implementing disclosed aspects can be non-transitory media.","Non-transitory media can be volatile or non-volatile.","Examples of volatile non-transitory media include semiconductor-based memory, such as SRAM or DRAM.","Examples of technologies that can be used to implement non-volatile memory include optical and magnetic memory technologies, flash memory, phase change memory, resistive RAM.","A particular reference to “logic” refers to structure that performs a function or functions.","An example of logic includes circuitry that is arranged to perform those function(s).","For example, such circuitry may include transistors and/or other hardware elements available in a manufacturing process.","Such transistors and/or other elements may be used to form circuitry or structures that implement and/or contain memory, such as registers, flip flops, or latches, logical operators, such as Boolean operations, mathematical operators, such as adders, multipliers, or shifters, and interconnect, by way of example.","Such elements may be provided as custom circuits or standard cell libraries, macros, or at other levels of abstraction.","Such elements may be interconnected in a specific arrangement.","Logic may include circuitry that is fixed function and circuitry can be programmed to perform a function or functions; such programming may be provided from a firmware or software update or control mechanism.","Logic identified to perform one function may also include logic that implements a constituent function or sub-process.","In an example, hardware logic has circuitry that implements a fixed function operation, or operations, state machine or process.","Any range or device value given herein may be extended or altered without losing the effect sought, as will be apparent to the skilled person.","It will be understood that the benefits and advantages described above may relate to one embodiment or may relate to several embodiments.","The embodiments are not limited to those that solve any or all of the stated problems or those that have any or all of the stated benefits and advantages.","Any reference to ‘an’ item refers to one or more of those items.","The term ‘comprising’ is used herein to mean including the method blocks or elements identified, but that such blocks or elements do not comprise an exclusive list and an apparatus may contain additional blocks or elements and a method may contain additional operations or elements.","Furthermore, the blocks, elements and operations are themselves not impliedly closed.","The steps of the methods described herein may be carried out in any suitable order, or simultaneously where appropriate.","The arrows between boxes in the figures show one example sequence of method steps but are not intended to exclude other sequences or the performance of multiple steps in parallel.","Additionally, individual blocks may be deleted from any of the methods without departing from the spirit and scope of the subject matter described herein.","Aspects of any of the examples described above may be combined with aspects of any of the other examples described to form further examples without losing the effect sought.","Where elements of the figures are shown connected by arrows, it will be appreciated that these arrows show just one example flow of communications (including data and control messages) between elements.","The flow between elements may be in either direction or in both directions.","It will be understood that the above description of a preferred embodiment is given by way of example only and that various modifications may be made by those skilled in the art.","Although various embodiments have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this invention."]],"string":"[\n [\n \"Decoding Instructions That Are Modified By One Or More Other Instructions\",\n \"Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions include one or more base instructions that are subject to modification by one or more other instructions.\",\n \"A decoder determines whether a first received instruction was arrived at by a non-incremental change to a program counter (i.e.\",\n \"a jump in the program).\",\n \"If the first instruction was arrived at by a non-incremental change to the program counter the decoder decodes the immediately preceding instruction to determine if the original instruction is a base instruction subject to modification by one or more other instructions.\",\n \"If the preceding instruction indicates that the original instruction is a base instruction an error has occurred and exception handling code is invoked.\"\n ],\n [\n \"1.A method of storing a computer program in a program memory, the computer program comprising a plurality of instructions, the method comprising: receiving the plurality of instructions at a compiler, the plurality of instructions comprising one or more base instructions and at least one modifier instruction for each base instruction; analyzing, at the compiler, the plurality of instructions to identify each base instruction and the at least one modifier instruction for each identified base instruction; and storing each identified base instruction on a same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.\",\n \"2.The method of claim 1, wherein a boundary within the program memory comprises one or more of a beginning of a cache line, an end of a cache line and a memory management unit page.\",\n \"3.The method of claim 1, wherein each modifier instruction is a postfix instruction.\",\n \"4.The method of claim 1, wherein each modifier instruction is a prefix instruction.\",\n \"5.The method of claim 1, wherein storing an identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that base instruction comprises inserting one or more No Operation instructions in the computer program before the identified base instruction or the at least one modifier instruction for the identified base instruction so that the identified base instruction and the at least one modifier instruction for that identified base instruction are stored on the same side of a boundary within the program memory.\",\n \"6.The method of claim 1, wherein storing each identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction comprises reordering the plurality of instructions so that each identified base instruction is stored on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.\",\n \"7.The method of claim 1, wherein the plurality of instructions comprises at least two modifier instructions for a base instruction, the method further comprising storing the base instruction on the same side of a boundary of the program memory as the at least two modifier instructions for that base instruction.\",\n \"8.A device arranged to store a computer program, the computer program comprising a plurality of instructions, the device comprising: a program memory; and a processor configured to: receive the plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one modifier instruction for each base instruction, analyze the plurality of instructions to identify each base instruction and the at least one modifier instruction for each identified base instruction, and store each identified base instruction on a same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.\",\n \"9.The device of claim 8, wherein a boundary within the program memory comprises one or more of a beginning of a cache line, an end of a cache line and a memory management unit page.\",\n \"10.The device of claim 8, wherein each modifier instruction is a postfix instruction.\",\n \"11.The device of claim 8, wherein each modifier instruction is a prefix instruction.\",\n \"12.The device of claim 8, wherein the processor is configured to store an identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction by inserting one or more No Operation instructions in the computer program before the identified base instruction or the at least one modifier instruction for the identified base instruction so that the identified base instruction and the at least one modifier instruction for that base instruction are stored on the same side of a boundary within the program memory.\",\n \"13.The device of claim 8, wherein the processor is configured to store each identified base instruction on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction by reordering the plurality of instructions so that each identified instruction is stored on the same side of a boundary within the program memory as the at least one modifier instruction for that identified base instruction.\",\n \"14.The device of claim 8, wherein the plurality of instructions comprises at least two modifier instructions for a base instruction, and the processor is configured to store that base instruction on the same side of a boundary of the program memory as the at least two modifier instructions for that base instruction.\",\n \"15.A data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one modifier instruction for each base instruction, the plurality of instructions stored in the program memory so that each base instruction is stored on a same side of a boundary within the program memory as the at least one modifier instruction for that base instruction; a program counter configured to identify a first instruction in the program memory; a fetch unit configured to retrieve the first instruction in the program memory identified by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit, and request an additional instruction from the fetch unit to look for a modifier instruction for the first instruction, the additional instruction being an instruction immediately preceding the first instruction in the program memory or an instruction immediately following the first instruction in the program memory; wherein the fetch unit is further configured to determine whether the additional instruction is on the same side of a boundary of the program memory as the first instruction, and in response to determining that the additional instruction is not on the same side of the boundary of the program memory, avoid fetching the additional instruction from the program memory.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Computer instruction sets are used to encode the set of operations that a central processing unit (CPU) executes within a program.\",\n \"It is desirable to minimize the amount of memory used to store these instructions.\",\n \"For example, one instruction set may use 32 bits to encode instructions.\",\n \"The use of 32 bits provides for the encoding of a rich instruction set but does not allow more common operations to be encoded using fewer bits.\",\n \"Another instruction set may use 16 bits to encode instructions.\",\n \"The use of 16 bits provides for high code density but limits the number of instructions that can be encoded.\",\n \"One solution to the limited number of instructions that can be encoded using smaller instructions (e.g.\",\n \"16 bits) is to allow a previous instruction to modify the meaning of the current instruction.\",\n \"The previous modifying instruction is known as a prefix instruction.\",\n \"In this way, common operations use a single instruction (e.g.\",\n \"16 bits) whereas less common instructions use two instructions (one prefix instruction and one base instruction with, for example, 32 bits total).\",\n \"This provides a good compromise between code density and richness of instruction.\",\n \"The embodiments described below are provided by way of example only and are not limiting of implementations which solve any or all of the disadvantages of known computers.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.\",\n \"This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.\",\n \"Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions comprise one or more base instructions that are subject to modification by one or more other instructions.\",\n \"In an example, a first instruction is received at a decoder.\",\n \"The decoder determines whether the first instruction was arrived at by a non-incremental change to the program counter (i.e.\",\n \"a jump in the program).\",\n \"If the first instruction was arrived at by a non-incremental change to the program counter the decoder decodes the immediately preceding instruction to determine if the original instruction is a base instruction (i.e.\",\n \"an instruction subject to modification by one or more other instructions).\",\n \"If the preceding instruction indicates that the original instruction is a base instruction an error has occurred and exception handling code is invoked.\",\n \"A first aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; determining, at the decode unit, if the first instruction was invoked by a non-incremental change to a program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, requesting a second instruction from a fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program; receiving the second instruction at the decode unit from the fetch unit; analyzing the second instruction at the decode unit to determine if the first instruction is a base instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.\",\n \"A second aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving an instruction at a decode unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by one or more other instructions; analyzing the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining that the received instruction is a base instruction, determining at the decode unit if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining that there are not the predetermined number of stored prefix instructions for the base instruction, invoking exception handler code.\",\n \"A third aspect provides a method of decoding instructions in a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; requesting at least one additional instruction from a fetch unit, each of the at least one additional instruction following the first instruction in the program; receiving the at least one additional instruction at the decode unit, the at least one additional instruction comprising a first additional instruction; determining if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modifying the first instruction at the decode unit using the first additional instruction; and in response to determining the first additional instruction is not a postfix instruction, providing the first instruction and the at last one additional instruction to an execute unit for execution.\",\n \"A fourth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify a first instruction in the program memory; a fetch unit configured to retrieve the first instruction in the program memory identified by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; determine if the first instruction was invoked by a non-incremental change to the program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, request a second instruction from the fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program memory; receive the second instruction from the fetch unit; analyze the second instruction to determine if the first instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.\",\n \"A fifth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify an instruction in the program memory; a fetch unit configured to retrieve the instruction from the program memory identified by the program counter; and a decode unit configured to: receive the instruction from the fetch unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and analyze the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining the received instruction is a base instruction, determine if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining there are not the predetermined number of stored prefix instruction for the base instruction, invoke exception handler code.\",\n \"A sixth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to indicate a first instruction in the program memory; a fetch unit configured to retrieve the first instruction from the program memory as indicated by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; request at least one additional instruction from the fetch unit, each of the at least one additional instruction following the first instruction in the program memory; receive the at least one additional instruction, the at least one additional instruction comprising a first additional instruction; determine if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modify the first instruction using the first postfix instruction; and in response to determining the first additional instruction is not a postfix instruction, provide the first instruction and the at least one additional instruction to an execute unit for execution.\",\n \"A seventh aspect provides a compiler to store a plurality of instructions in a program memory, the compiler comprising a processor configure to: receive the plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one corresponding modifier for each base instruction; analyze the plurality of instructions to identify each base instruction and its at least one corresponding modifier; and store each base instruction and its corresponding at least one modifier in the program memory so that each base instruction and its corresponding modifiers are on the same side of a boundary within the program memory.\",\n \"An eighth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fourth aspect.\",\n \"A ninth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the first aspect.\",\n \"A tenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fifth aspect.\",\n \"An eleventh aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the second aspect.\",\n \"A twelfth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the sixth aspect.\",\n \"A thirteenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the third aspect.\",\n \"A fourteenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"3 .\",\n \"A fifteenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"5 .\",\n \"A sixteenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"8 A seventeenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"10 .\",\n \"The preferred features may be combined as appropriate, as would be apparent to a skilled person, and may be combined with any of the aspects of the invention.\"\n ],\n [\n \"BACKGROUND Computer instruction sets are used to encode the set of operations that a central processing unit (CPU) executes within a program.\",\n \"It is desirable to minimize the amount of memory used to store these instructions.\",\n \"For example, one instruction set may use 32 bits to encode instructions.\",\n \"The use of 32 bits provides for the encoding of a rich instruction set but does not allow more common operations to be encoded using fewer bits.\",\n \"Another instruction set may use 16 bits to encode instructions.\",\n \"The use of 16 bits provides for high code density but limits the number of instructions that can be encoded.\",\n \"One solution to the limited number of instructions that can be encoded using smaller instructions (e.g.\",\n \"16 bits) is to allow a previous instruction to modify the meaning of the current instruction.\",\n \"The previous modifying instruction is known as a prefix instruction.\",\n \"In this way, common operations use a single instruction (e.g.\",\n \"16 bits) whereas less common instructions use two instructions (one prefix instruction and one base instruction with, for example, 32 bits total).\",\n \"This provides a good compromise between code density and richness of instruction.\",\n \"The embodiments described below are provided by way of example only and are not limiting of implementations which solve any or all of the disadvantages of known computers.\",\n \"SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.\",\n \"This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.\",\n \"Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions comprise one or more base instructions that are subject to modification by one or more other instructions.\",\n \"In an example, a first instruction is received at a decoder.\",\n \"The decoder determines whether the first instruction was arrived at by a non-incremental change to the program counter (i.e.\",\n \"a jump in the program).\",\n \"If the first instruction was arrived at by a non-incremental change to the program counter the decoder decodes the immediately preceding instruction to determine if the original instruction is a base instruction (i.e.\",\n \"an instruction subject to modification by one or more other instructions).\",\n \"If the preceding instruction indicates that the original instruction is a base instruction an error has occurred and exception handling code is invoked.\",\n \"A first aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; determining, at the decode unit, if the first instruction was invoked by a non-incremental change to a program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, requesting a second instruction from a fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program; receiving the second instruction at the decode unit from the fetch unit; analyzing the second instruction at the decode unit to determine if the first instruction is a base instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.\",\n \"A second aspect provides a method of decoding instructions of a computer program at a decode unit, the method comprising: receiving an instruction at a decode unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by one or more other instructions; analyzing the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining that the received instruction is a base instruction, determining at the decode unit if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining that there are not the predetermined number of stored prefix instructions for the base instruction, invoking exception handler code.\",\n \"A third aspect provides a method of decoding instructions in a computer program at a decode unit, the method comprising: receiving a first instruction at the decode unit; requesting at least one additional instruction from a fetch unit, each of the at least one additional instruction following the first instruction in the program; receiving the at least one additional instruction at the decode unit, the at least one additional instruction comprising a first additional instruction; determining if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modifying the first instruction at the decode unit using the first additional instruction; and in response to determining the first additional instruction is not a postfix instruction, providing the first instruction and the at last one additional instruction to an execute unit for execution.\",\n \"A fourth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify a first instruction in the program memory; a fetch unit configured to retrieve the first instruction in the program memory identified by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; determine if the first instruction was invoked by a non-incremental change to the program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, request a second instruction from the fetch unit, the second instruction being an instruction immediately preceding the first instruction in the program memory; receive the second instruction from the fetch unit; analyze the second instruction to determine if the first instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.\",\n \"A fifth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to identify an instruction in the program memory; a fetch unit configured to retrieve the instruction from the program memory identified by the program counter; and a decode unit configured to: receive the instruction from the fetch unit, the instruction comprising at least one modifier bit, the modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by at least one other instruction; and analyze the at least one modifier bit at the decode unit to determine if the received instruction is a base instruction; in response to determining the received instruction is a base instruction, determine if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining there are not the predetermined number of stored prefix instruction for the base instruction, invoke exception handler code.\",\n \"A sixth aspect provides a data processing apparatus arranged to execute a computer program, the data processing apparatus comprising: a program memory configured to store the computer program, the computer program comprising a plurality of instructions; a program counter configured to indicate a first instruction in the program memory; a fetch unit configured to retrieve the first instruction from the program memory as indicated by the program counter; and a decode unit configured to: receive the first instruction from the fetch unit; request at least one additional instruction from the fetch unit, each of the at least one additional instruction following the first instruction in the program memory; receive the at least one additional instruction, the at least one additional instruction comprising a first additional instruction; determine if the first additional instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first additional instruction is a postfix instruction, modify the first instruction using the first postfix instruction; and in response to determining the first additional instruction is not a postfix instruction, provide the first instruction and the at least one additional instruction to an execute unit for execution.\",\n \"A seventh aspect provides a compiler to store a plurality of instructions in a program memory, the compiler comprising a processor configure to: receive the plurality of instructions, the plurality of instructions comprising one or more base instructions and at least one corresponding modifier for each base instruction; analyze the plurality of instructions to identify each base instruction and its at least one corresponding modifier; and store each base instruction and its corresponding at least one modifier in the program memory so that each base instruction and its corresponding modifiers are on the same side of a boundary within the program memory.\",\n \"An eighth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fourth aspect.\",\n \"A ninth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the first aspect.\",\n \"A tenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the fifth aspect.\",\n \"An eleventh aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the second aspect.\",\n \"A twelfth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating the data processing apparatus of the sixth aspect.\",\n \"A thirteenth aspect provides a computer readable storage medium having encoded thereon computer readable program code for generating a data processing apparatus configured to perform the method of the third aspect.\",\n \"A fourteenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"3.A fifteenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"5.A sixteenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"8 A seventeenth aspect provides a method to decode instructions substantially as described with reference to FIG.\",\n \"10.The preferred features may be combined as appropriate, as would be apparent to a skilled person, and may be combined with any of the aspects of the invention.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention will be described, by way of example, with reference to the following drawings, in which: FIG.\",\n \"1 is a schematic diagram of an example data processing apparatus; FIG.\",\n \"2 shows an example of a method of decoding instructions in accordance with a first embodiment; FIG.\",\n \"3 is a flowchart of the method of FIG.\",\n \"2; FIG.\",\n \"4 shows an example of a method of decoding instructions in accordance with a second embodiment; FIG.\",\n \"5 is a flowchart of the method of FIG.\",\n \"4; FIG.\",\n \"6 shows an example of a method of decoding instructions in accordance with a third embodiment; FIG.\",\n \"7 shows a second example of the method of FIG.\",\n \"6; FIG.\",\n \"8 is a flowchart of the method of FIGS.\",\n \"6 and 7; FIG.\",\n \"9 shows an example of a method of decoding instructions in accordance with a fourth embodiment; FIG.\",\n \"10 is a flowchart of the method of FIG.\",\n \"9; and FIG.\",\n \"11 shows an example of a method of arranging instructions in a program memory.\",\n \"Common reference numerals are used throughout the figures to indicate similar features.\",\n \"DETAILED DESCRIPTION Embodiments of the present invention are described below by way of example only.\",\n \"These examples represent the best ways of putting the invention into practice that are currently known to the Applicant although they are not the only ways in which this could be achieved.\",\n \"The description sets forth the functions of the example and the sequence of steps for constructing and operating the example.\",\n \"However, the same or equivalent functions and sequences may be accomplished by different examples.\",\n \"One problem with the prefix instruction approach described above is that there exists the possibility of ambiguity in the program code.\",\n \"If a machine (or an observer) starts reading from an arbitrary point, it is not apparent whether the instruction at that point should be subject to modification from a previous prefix instruction.\",\n \"The widespread use of computed branches or branch instructions in program code offers the possibility that code execution could commence at any offset into the code.\",\n \"This ambiguity therefore means that the effect of the program code becomes very difficult to predict.\",\n \"This could lead to unexpected errors or possible methods to attack code used in secure applications.\",\n \"For example, if a branch erroneously jumps to an instruction that should be modified by a prefix, the program will continue from this point without the instruction being modified.\",\n \"The unpredictable nature of this can be catastrophic to the program operation.\",\n \"The program may continue running for some time reading further instructions and generating outputs until something happens that causes an error or halt in the program.\",\n \"This makes debugging this type of error difficult, as the source of the error is the branch to the prefixed instruction that may have occurred some time ago.\",\n \"In the case of security or safety-critical applications, then it is important to know rapidly that something has gone wrong in the program, so that the error can be contained.\",\n \"In the case of a branch to a prefixed instruction, the error can take some time to manifest itself, leading to an uncertain period in which the program operation is unpredictable.\",\n \"This would potentially be very damaging in the case of a program controlling a nuclear power plant or a banking system, for example.\",\n \"This type of error can also occur in situations other than an illegal branch.\",\n \"For example, in the case of space applications, such as satellites, one or more bits within a CPU can be flipped by a high-energy particle (i.e.\",\n \"from cosmic rays) passing through the spacecraft.\",\n \"If an instruction address is subject to such a bit-flip, then the instruction fetched is not the one intended.\",\n \"Any change to the program counter other than an increment to the next instruction will be referred to herein as a “jump” in the program.\",\n \"As described above, jumps may be caused, for example, by a branch in the program or external factors, such as high-energy particles passing through the computer.\",\n \"An “illegal jump” is a jump which takes the program to an instruction that cannot be legally executed.\",\n \"For example, a branch instruction which takes the program directly to a prefixed base instruction causes an illegal jump since the base instruction cannot be legally executed without its prefix(es).\",\n \"An “illegal branch” is a branch instruction which causes an illegal jump.\",\n \"Embodiments described herein relate to methods and data processing apparatus for decoding instructions that comprise base instructions, which allow illegal jumps to base instructions to be easily identified.\",\n \"In a first embodiment, one or more bits of an instruction are used to indicate whether the current instruction is subject to modification by another instruction.\",\n \"In a second embodiment, both the current instruction and the previous instruction are fetched and decoded to determine if the current instruction is subject to modification by the previous instruction.\",\n \"In a third embodiment, instructions are modified by a postfix instruction (i.e.\",\n \"an instruction following the current instruction) instead of by a prefix instruction (i.e.\",\n \"an instruction preceding the current instruction) and both the current instruction and the following instruction are fetched and decoded to determine if the current instruction is subject to modification by the following instruction.\",\n \"In a fourth embodiment, instructions are modified by a postfix instruction and one or more bits of an instruction are used to indicate whether the current instruction is subject to modification by another instruction.\",\n \"An instruction that is subject to modification by another instruction will be referred to herein as a “base instruction” and an instruction that modifies a subsequent instruction will be referred to herein as a “prefix instruction”.\",\n \"Reference is now made to FIG.\",\n \"1 which illustrates a data processing unit 100, such as a processor, that executes a computer program.\",\n \"The data processing unit 100 comprises a program memory 102 configured to store a sequence of instructions forming the computer program.\",\n \"In the example, shown in FIG.\",\n \"1, the instructions are denoted II to In.\",\n \"The data processing unit 100 further comprises a fetch unit 104 configured to fetch instructions from the program memory 102 (in program order) as indicated by a program counter (PC) 112 and a decode unit 106 arranged to interpret the instructions.\",\n \"If there is no error or exception in decoding the instruction then the decode unit 106 forwards the instruction to an execute unit 108 for execution (which may include reading and/or writing to one or more registers 110) and updates the program counter 112 to point to the next instruction.\",\n \"If, however, there is an error in decoding the instruction (e.g.\",\n \"the instruction is invalid) then the decode unit 106 notifies an exception handler unit 114 which updates the program counter 112 so that the fetch unit 104 fetches exception handling code from the program memory 102.In this way, the exception can be handled predictably, without causing the data processing unit 100 to execute invalid code.\",\n \"If prefix modifiers are used, then there may be situations where the program counter 112 is updated to point to an instruction that is to be modified by a prefix (i.e.\",\n \"a base instruction).\",\n \"For example, in the case of an illegal branch instruction the target base instruction will be fetched, decoded and executed unmodified, which will cause the program to operate unpredictably.\",\n \"The decode unit 106 will not detect that the instruction should have been prefixed and hence will not call the exception handler unit 114.Accordingly, there is a need for the decode unit 106 to be able to identify base instructions so that it can call the exception handler unit 114 when an illegal jump to a base instruction has occurred.\",\n \"Described below are methods for decoding instructions that may be implemented by the decode unit 106 which allows the decode unit 106 to identify base instructions.\",\n \"One or more of the functions performed by the units (e.g.\",\n \"fetch unit 104, decode unit 106, and the execute unit 108) of FIG.\",\n \"1 may be performed in parallel, for example, via pipelining.\",\n \"Reference is now made to FIGS.\",\n \"2 and 3 which illustrate a first embodiment of a method for decoding instructions.\",\n \"In this embodiment, one or more bits of the instruction are used to indicate whether there is at least one modifier for the current instruction (e.g.\",\n \"whether there is a prefix instruction).\",\n \"FIG.\",\n \"2 illustrates an example of the first embodiment.\",\n \"Specifically, FIG.\",\n \"2 illustrates two instructions 202 and 204.The first instruction 202 corresponds to I4 of FIG.\",\n \"1 and the second instruction 204 corresponds to I5 of FIG.\",\n \"1 where I4 is the prefix for I5.Each instruction 202 and 204 has a reserved bit 206 and 208, referred to as the modifier bit, for indicating whether the instruction is subject to modification by another instruction (i.e.\",\n \"that there is a prefix instruction for the instruction).\",\n \"In this example, since I5 is to be modified by I4, the modifier bit 208 for I5 is set to one to indicate that I5 is to be modified by another instruction.\",\n \"Since I4 is the prefix to be used to modify I5, the modifier bit 206 is set to zero to indicate that I4 is not itself to be modified by another instruction.\",\n \"When the decode unit 106 decodes an instruction it checks the modifier bit 206 or 208 of the instruction 202 or 204 to determine whether the instruction is to be modified by another instruction (i.e.\",\n \"whether the instruction is a base instruction).\",\n \"If the modifier bit 206 or 208 indicates that the instruction 202 or 204 is to be modified and the decode unit 106 has not decoded the modifier instruction (e.g.\",\n \"the prefix instruction) then the decode unit 106 detects an error (e.g.\",\n \"an illegal branch) and invokes the exception handler unit 114.The exception handler unit 114 then updates the program counter 112 so that the fetch unit 104 fetches exception handling code from the program memory 102.In some cases the exception handler unit 114 may also save the state and/or flush an associated pipeline.\",\n \"For example, as shown in FIG.\",\n \"2, if the previous instruction was I2 (a branch instruction) which caused the program counter 112 to be updated to point to I5, the decode unit 106 would decode I5 and check the modifier bit 208.Since the modifier bit 208 for I5 is set to one indicating the instruction is to be modified and the previous instruction (I2) was not a prefix instruction, the decode unit 106 knows an error has occurred and calls the exception handler unit 114.Although, in FIG.\",\n \"2, the modifier bit 206 or 208 is shown as the most significant bit of the instruction 202 or 204, it could be located at any predetermined position.\",\n \"Furthermore, although, in FIG.\",\n \"2, there is single modifier bit 206 or 208, in other cases there may be more than one modifier bit.\",\n \"This may be used, for example, in cases where instructions can be modified by more than one modifier instruction to indicate the number of modifier instructions.\",\n \"This would allow the decode unit 106 to not only catch illegal jumps (e.g.\",\n \"illegal branch instructions) to instructions that should be modified, but also catch illegal jumps to instructions that are not the first modifier instructions (e.g.\",\n \"the first prefix instruction).\",\n \"Using one or more bits of the instruction to indicate whether the instruction is subject to modification by one or more other instructions (i.e.\",\n \"the instruction is a base instruction) allows illegal jumps (e.g.\",\n \"illegal branch instructions) to base instructions to be quickly and easily identified.\",\n \"The trade-off, however, is that reserving one or more of the bits of the instruction for this purpose reduces the number of bits available for encoding instructions and thus reduces the number of different types of instructions that can be encoded in a single instruction.\",\n \"FIG.\",\n \"3 is a flowchart of an example method 300 in accordance with the first embodiment which may be executed by a decode unit (e.g.\",\n \"decode unit 106).\",\n \"At step 302 the decode unit 106 receives an instruction fetched by the fetch unit 104.The instruction comprises at least one modifier bit.\",\n \"As described above the modifier bit indicates whether the instruction is a base instruction subject to modification by at one or more other instructions and, optionally, how many modifier instructions there are.\",\n \"Once the fetched instruction has been received the method 300 proceeds to step 304.At step 304, the decode unit 106 decodes the fetched instruction to identify particular bit patterns in the fetched instruction.\",\n \"Once the fetched instruction is decoded the method 300 proceeds to step 306.At step 306, the decode unit 106 determines whether the decoded instruction is a prefix for another instruction.\",\n \"Determining whether the decoded instruction is a prefix for another instruction may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.\",\n \"As it known to those of skill in the art an instruction may comprises an opcode (operation code) which specifies the operation to be performed.\",\n \"In some cases there is a special opcode for prefix instructions.\",\n \"Accordingly, determining whether the instruction is a prefix for another instruction may comprise reading the instruction's opcode.\",\n \"If the decoded instruction is determined to be a prefix then the instruction is stored at step 308 so that it can be used to modify a subsequent base instruction.\",\n \"In some cases the prefix instruction may be stored in a local storage unit, such as memory or registers, of the decode unit 106 or the fetch unit 104.The amount of data stored for each prefix instruction may be reduced by only storing enough information to allow the base instruction to be modified.\",\n \"For example the full 16 bits of a 16 bit instruction may not be stored.\",\n \"In some cases, instead of storing the prefix instruction the prefix instruction may be discarded and re-fetched after decoding a base instruction.\",\n \"Once the prefix instruction is stored the method 300 proceeds back to step 302.If, however, it is determined that the decoded instruction is not a prefix, then the method 300 proceeds to step 310.At step 310, the decode unit 106 determines whether the decoded instruction is a base instruction (i.e.\",\n \"that it is subject to modification by another instruction).\",\n \"Determining whether the decoded instruction is a base instruction comprises analyzing the modifier bit(s) to determine if they indicate that the instruction is subject to modification.\",\n \"As described above, the modifier bit(s) are one or more reserved bits in the instruction that are used to indicate whether the instruction is subject to modification by one or more other instructions and, optionally, how many modifier instructions there are.\",\n \"If the modifier bit(s) indicate that the instruction is not subject to modification then at step 312 the decode unit 106 passes the unmodified instruction (i.e.\",\n \"the instruction decoded in step 304) to the execute unit 108 for execution.\",\n \"If, however, the modifier bit(s) indicate that the instruction is subject to modification by one or more other instructions (i.e.\",\n \"that the instruction is a base instruction) then the method proceeds to step 314.At step 314, the decode unit 106 determines whether there are a predetermined number of stored prefix instructions for the base instruction.\",\n \"A stored prefix instruction is a prefix instruction that has been previously decoded and stored by the decode unit as per steps 306 and 308.In cases where there is only a single modifier bit then the predetermined number may be one (i.e.\",\n \"the decode unit 106 checks to see if there is a stored prefix for the base instruction).\",\n \"In cases where there is more than one modifier bit indicating the number of modifiers then the decode unit 106 may analyze the modifier bits to determine the number of prefix instructions for the base instruction.\",\n \"In these cases the predetermined number is the number of prefix instructions specified in the modifier bits.\",\n \"For example, if the modifier bits indicate there are two prefix modifiers for the base instruction then the predetermined number is two and the decode unit 106 determines if it has two stored prefix instructions for the base instruction.\",\n \"If there are the predetermined number of stored prefix instructions for the base instruction then in step 316 the decode unit 106 uses the stored prefix instruction(s) to modify the received instruction (i.e.\",\n \"the instruction received in step 302).\",\n \"For example, a MOV instruction (an instruction that copies data from one location to another), when unmodified, may use a 16 bit operand or address.\",\n \"If the MOV instruction was preceded by a prefix instruction then the MOV instruction may be modified to use 32 bit operations or addresses instead.\",\n \"In step 318 the modified instruction is provided to the execute unit 108 for execution.\",\n \"If, however, there are not the predetermined number of stored prefix instructions (i.e.\",\n \"there are no stored prefix instructions or less stored prefix instructions than specified in the modifier bits) then an error has occurred (e.g.\",\n \"an illegal branch instruction has occurred) and at step 320, the decode unit 106 invokes the exception handler unit 114.Reference is now made to FIGS.\",\n \"4 and 5 which illustrate a second embodiment of a method for decoding instructions.\",\n \"In this embodiment the current instruction and the preceding instruction (i.e.\",\n \"the instruction immediately preceding the current instruction in the program code) are both fetched and decoded to determine if the current instruction is subject to modification by the preceding instruction.\",\n \"While more than one preceding instruction may be fetched, the decoder can determine the current instruction is a base instruction from only the immediately preceding instruction.\",\n \"FIG.\",\n \"4 illustrates an example of the second embodiment.\",\n \"Specifically, FIG.\",\n \"4 illustrates two instructions 402 and 404.The first instruction 402 corresponds to I4 of FIG.\",\n \"1 and the second instruction 404 corresponds to I5 of FIG.\",\n \"1 where I4 is the prefix for I5.If the previous instruction was I2 (a branch instruction) which caused the program counter 112 to be updated to point to I5, then both I5 and I4 are fetched and decoded.\",\n \"I4 will be identified to be the prefix for I5.This indicates an error has occurred (e.g.\",\n \"an illegal branch) and the exception handler unit 114 is called.\",\n \"In some cases, both the current instruction and the preceding instruction are only fetched and decoded after a jump in the program (i.e.\",\n \"a change to the program counter other than an increment to the next instruction, e.g.\",\n \"a change to the program counter 112 caused by a branch instruction).\",\n \"Where there is a simple increment of the program counter to the next instruction only the current instruction is fetched and decoded.\",\n \"In these cases resources are not wasted fetching the preceding instruction again since it will have already been fetched and decoded in the previous cycle.\",\n \"Fetching and decoding both the current and preceding instructions allows illegal jumps (e.g.\",\n \"illegal branch instructions) to base instructions to be quickly and easily identified.\",\n \"The trade-off is the delay caused by fetching the preceding instruction after a branch.\",\n \"However, this is mitigated significantly by the fact that many processors are now highly parallel, which means that many instructions are generally issued at the same time, reducing the impact of waiting for the previous instruction.\",\n \"FIG.\",\n \"5 is a flowchart of an example method 500 in accordance with the second embodiment which may be executed by a decode unit (e.g.\",\n \"decode unit 106).\",\n \"At step 502 the decode unit 106 receives a first instruction fetched by the fetch unit 104.Once the fetched instruction has been received the method 500 proceeds to step 504.At step 504, the decode unit 106 decodes the first instruction to identify particular bit patterns in the first instruction.\",\n \"Once the first instruction has been decoded the method 500 proceeds to step 506.At step 506, the decode unit 106 determines whether the first instruction is an instruction that was invoked (i.e.\",\n \"arrived at) by a jump in the program.\",\n \"As described above, a jump in the program is any change to the program counter other than an increment to the next instruction (i.e.\",\n \"a non-incremental change to the program counter).\",\n \"In some cases the execute unit 108 may be configured to send an indication or a signal to the decode unit 106 if it makes a change to the program counter other than an increment to the next instruction.\",\n \"In these cases the decode unit 106 may determine that the first instruction was invoked by a jump in the program when it receives such an indication or signal from the execute unit 108.In other cases the program counter 112 itself may comprise hardware that monitors changes and provides an indication or a signal to the decode unit 106 if it detects a non-incremental change.\",\n \"In these cases when the decode unit 106 receives such an indication or signal from the program counter 112 it can relate this signal to a future instruction it will receive (e.g.\",\n \"it will know how many cycles it will be until it gets the instruction the indication or signal relates to).\",\n \"Then when the decode unit 106 subsequently receives that instruction for decoding the decode unit 106 will know that the instruction was invoked by a jump in the program.\",\n \"If the decode unit 106 determines that the first instruction was not invoked by a jump in the program then the method 500 proceeds to step 508.If, however, the decode unit 106 determines that the first instruction was invoked by a jump in the program then the method 500 proceeds to step 520.At step 508, the decode unit 106 determines whether the first instruction is a prefix for another instruction.\",\n \"Determining whether the first instruction is a prefix for another instruction may comprise comparing the first instruction to one or more predetermined bit patterns to determine if there is a match.\",\n \"For example, as described above, determining whether an instruction is a prefix for another instruction may comprises analyzing the opcode of the instruction.\",\n \"If the first instruction is determined to be a prefix then the instruction is stored at step 510 so that it can be used later to modify a subsequent base instruction.\",\n \"The method 500 then proceeds back to step 502.If, however, it is determined that the first instruction is not a prefix, then the method 500 proceeds to step 512.At step 512 the decode unit 106 determines whether there is at least one stored prefix for the first instruction.\",\n \"If there is at least one prefix stored for the first instruction then in step 514 the decode unit 106 uses the stored prefix instruction(s) to modify the first instruction (i.e.\",\n \"the instruction received in step 502) and in step 516 passes the modified first instruction to the execute unit 108 for execution.\",\n \"If, however, there are no prefixes stored for the first instruction, then the decode unit 106 passes the unmodified first instruction (i.e.\",\n \"the instruction decoded in step 504) to the execution unit 108 for execution at step 518.At step 520, the decode unit 106 requests a second instruction from the fetch unit 104.The second instruction is the instruction immediately preceding the first instruction in the program (i.e.\",\n \"the instruction located at the program counter value for the first instruction minus one instruction).\",\n \"At step 522 the decode unit 106 receives and decodes the second instruction.\",\n \"At step 524 the decode unit 106 determines whether the second instruction is a prefix.\",\n \"If the decode unit 106 determines that the second instruction is a prefix then an error has occurred (e.g.\",\n \"an illegal branch instruction has occurred) and at step 526 the decode unit 106 invokes the exception handler unit 114.If, however, the decode unit 106 determines that the second instruction is not a prefix then in step 528 the decode unit 106 determines whether the first instruction is a prefix instruction.\",\n \"If the decode unit 106 determines that the first instruction is a prefix then at step 510 the prefix instruction is stored for further use.\",\n \"If, however, the decode unit 106 determines that the first instruction is not a prefix instruction then at step 518 the unmodified first instruction is passed to the execute unit 108 for execution.\",\n \"Reference is now made to FIGS.\",\n \"6 to 8 which illustrate a third embodiment of a method for decoding instructions.\",\n \"In this embodiment, instead of instructions being modified by a prefix, they are modified by a postfix and both the current instruction and the following instruction are fetched and decoded to determine if the current instruction is subject to modification by the following instruction.\",\n \"In other words, instead, of instructions being modified by one or more preceding instructions, instructions are modified by one or more following instructions.\",\n \"Postfix modifiers were not feasible in the past because of the delay caused by waiting for the fetch and decode of the following instruction before the current instruction is sent for execution.\",\n \"However, because modern multiple-issue processors have multiple instructions under consideration at the same time, the efficiency loss due to having to check for postfixes is minimized.\",\n \"FIG.\",\n \"6 illustrates a first example of the third embodiment where a base instruction is modified by a following instruction (i.e.\",\n \"a postfix instruction).\",\n \"Specifically, FIG.\",\n \"6 illustrates two instructions 602 and 604.The first instruction 602 corresponds to I4 of FIG.\",\n \"1 and the second instruction 604 corresponds to I5 of FIG.\",\n \"1 where I5 is the postfix for I4.In this example, when I4 is fetched and decoded the decode unit 106 waits until I5 is fetched and decoded to determine whether I4 is subject to modification.\",\n \"FIG.\",\n \"7 illustrates a second example of the third embodiment where an illegal branch instruction occurs.\",\n \"Specifically, FIG.\",\n \"7 illustrates two instructions 702 and 704.The first instruction 702 corresponds to I4 of FIG.\",\n \"1 and the second instruction 704 corresponds to I5 of FIG.\",\n \"1 where I5 is the postfix for I4.In this example, the previous instruction I2 was a branch instruction that caused the program counter 112 to point to I5.When I5 is decoded it will be determined that I5 is a postfix for an earlier instruction.\",\n \"Since a postfix cannot validly follow a branch instruction the decode unit 106 will know an error has occurred and will invoke the exception handler unit 114.FIG.\",\n \"8 is a flowchart of an example method 800 in accordance with the third embodiment which may be executed by a decode unit (e.g.\",\n \"decode unit 106).\",\n \"At step 802 the decode unit 106 receives a first instruction fetched by the fetch unit 104.Once the first instruction has been received the method 800 proceeds to step 804.At step 804, the decode unit 106 decodes the first instruction to identify particular bit patterns in the fetched instruction.\",\n \"Once the first instruction has been decoded the method 800 proceeds to step 806.At step 806, the decode unit 106 determines whether the first instruction is a postfix for another instruction.\",\n \"Determining whether the decoded instruction is a postfix for another instruction may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.\",\n \"As described above, instructions may comprise an opcode that describes what operation is to be performed by the instruction.\",\n \"Postfix instructions may be assigned a special opcode which allows them to be identified as postfix instructions by their opcode.\",\n \"This is in contrast to base instructions which cannot typically be identified as base instructions from their opcode alone.\",\n \"For example, a MOV instruction has a MOV opcode.\",\n \"It is only with additional information (e.g.\",\n \"subsequently decoding a postfix instruction) that the decoder knows that the MOV instruction is a base instruction subject to modification by another instruction.\",\n \"If the first instruction is determined to be a postfix then an error has occurred and at step 808 the decode unit 106 invokes the exception handler unit 114.If, however, it is determined that the first instruction is not a postfix then the method 800 proceeds to step 810.At step 810, the decode unit 106 requests one or more additional instructions from the fetch unit 104.The additional instructions immediately follow the first instruction in the program.\",\n \"In cases where there may only be a single postfix instruction for any base instruction then the decode unit 106 may only fetch one additional instruction (i.e.\",\n \"the instruction immediately following the first instruction).\",\n \"In cases, however, where there may be more than one postfix instruction for any base instruction then the decode unit 106 may request multiple additional instructions (e.g.\",\n \"the two instructions immediately following the first instruction).\",\n \"In some cases the maximum number of modifiers is hardcoded in the decode unit 106 based on the instruction set used.\",\n \"In these cases the decode unit 106 may use this hardcoded information to determine how many additional instructions to request.\",\n \"For example, if the decode unit 106 is hardcoded with information specifying that the maximum number of modifiers is three then the decode unit 106 may request three additional instructions.\",\n \"Once the additional instructions have been requested, the method 800 proceeds to step 812.At step 812, the decode unit 106 receives and decodes the additional instructions.\",\n \"Once the additional instructions have been received and decoded, the method 800 proceeds to step 814.At step 814, the decode unit 106 determines whether the first additional instruction (i.e.\",\n \"the instruction immediately following the first instruction) is a postfix.\",\n \"Determining whether an additional instruction is a postfix may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.\",\n \"For example, the decode unit 106 may determine an additional instruction is a postfix instruction by analyzing the opcode of the instruction.\",\n \"If the first additional instruction is a postfix then the method 800 proceeds to step 816.If, however, it is determined that the first additional instruction is not a postfix then at step 820 the decode unit 106 provides both the first instruction and the additional instructions, unmodified, to the execute unit 108 for execution.\",\n \"At step 816, any additional instructions that are postfix instructions are used to modify the first instruction (i.e.\",\n \"the instruction received in step 802).\",\n \"For example, if three additional instructions are requested and the first two additional instructions are identified as postfix instructions then the two postfix instructions are used to modify the first instruction.\",\n \"Once the first instruction has been modified then in step 818 the decode unit 106 forwards the modified first instruction and any non-postfix additional instructions to the execute unit 108 for execution.\",\n \"Reference is now made to FIGS.\",\n \"9 and 10 which illustrate a fourth embodiment of a method for decoding instructions.\",\n \"This embodiment is a combination of the first and third embodiments.\",\n \"In particular, instructions are modified by postfixes (e.g.\",\n \"subsequent instructions) instead of prefixes (i.e.\",\n \"preceding instructions) and one or more bits of each instruction is reserved for indicating whether the instruction is subject to modification by one or more other instructions.\",\n \"FIG.\",\n \"9 illustrates an example of the fourth embodiment.\",\n \"Specifically, FIG.\",\n \"9 illustrates two instructions 902 and 904.The first instruction 902 corresponds to I4 of FIG.\",\n \"1 and the second instruction 904 corresponds to I5 of FIG.\",\n \"1 where I5 is the postfix for I4.As described with respect to FIG.\",\n \"6, when I4 is fetched and decoded the decode unit 106 waits until I5 is fetched and decoded to determine whether I4 should be modified.\",\n \"Each instruction also has a reserved bit 906 or 908, referred to as the modifier bit, for indicating whether or not the instruction is subject to modification by another instruction.\",\n \"In this example, since I4 is to be modified by I5, the modifier bit 906 for I4 is set to one to indicate that I4 is subject to modification by another instruction.\",\n \"Similarly since I5 is the postfix to be used to modify I4, the modifier bit 908 is set to zero to indicate that I5 is not itself subject to modification.\",\n \"When the decode unit 106 decodes an instruction 902 or 904 it checks the modifier bit 906 or 908 to determine whether the instruction is subject to modification (e.g.\",\n \"it is a base instruction).\",\n \"If the modifier bit 906 or 908 indicates that the instruction 902 or 904 is subject to modification then the decode unit 106 knows it should wait for the next instruction to be fetched and decoded before proceeding.\",\n \"If, however, the modifier bit 906 or 908 indicates that the instruction is not subject to modification then the instruction 906 or 908 can be immediately sent to the execute unit 108 for execution without having to wait for the next instruction to be fetched and decoded.\",\n \"For example, when the decode unit 106 decodes I4 the modifier bit 906 tells the decode unit 106 to wait and fetch and decode I5 so that it can be used to modify I4.Although, in FIG.\",\n \"9, the modifier bit 906 or 908 is shown as the most significant bit, it could be located at any predetermined position.\",\n \"Furthermore, although, in FIG.\",\n \"9, there is a single modifier bit 906 or 908, in other cases there may be more than one modifier bit.\",\n \"This may be used, for example, in cases where instructions can be modified by more than one modifier to indicate the number of modifiers.\",\n \"This tells the decode unit 106 how many instructions should be fetched and decoded before the current instruction is dispatched to the execute unit 108.Not only can the modifier bit 906 or 908 be used to tell the decode unit 106 when it should wait for the next instruction, it can also be used to identify errors in the scenario where a postfix modifier is supposed to be present, but the next instruction is not a valid modifier.\",\n \"For example, if the modifier bit 906 or 908 indicates that the instruction is subject to modification but the next instruction is not a valid modifier then the decode unit 106 knows an error has occurred and can invoke the exception handler unit 114.FIG.\",\n \"10 is a flowchart of an example method 1000 in accordance with the fourth embodiment which may be executed by a decode unit (e.g.\",\n \"decode unit 106).\",\n \"At step 1002 the decode unit 106 receives a first instruction fetched by the fetch unit 104.The first instruction comprises at least one modifier bit indicating whether the first instruction is a base instruction, and, optionally, how many modifiers there are for the first instruction.\",\n \"Once the first instruction has been received the method 1000 proceeds to step 1004.At step 1004, the decode unit 106 decodes the first instruction to identify particular bit patterns in the fetched instruction.\",\n \"Once the first instruction has been decoded the method 1000 proceeds to step 1006.At step 1006, the decode unit 106 determines whether the first instruction is a postfix for another instruction.\",\n \"Determining whether the first instruction is a postfix for another instruction may comprise comparing the instruction to one or more predetermined bit patterns to determine if there is a match.\",\n \"For example, the decode unit 106 may determine the first instruction is a postfix instruction by analyzing the instruction's opcode.\",\n \"If the first instruction is determined to be a postfix then an error has occurred and at step 1008 the decode unit 106 invokes the exception handler unit 114.If, however, it is determined that the first instruction is not a postfix then the method 1000 proceeds to step 1010.At step 1010, the decode unit 106 determines whether the first instruction is a base instruction (i.e.\",\n \"subject to modification by one or more other instructions).\",\n \"Determining whether the first instruction is a base instruction comprises analyzing the modifier bit(s) to determine if they have a predetermined bit pattern indicating that the instruction is a base instruction.\",\n \"If the first instruction is not a base instruction then at step 1012 the unmodified first instruction is dispatched to the execute unit 108 for execution.\",\n \"If, however, the decoded instruction is a base instruction the method 1000 proceeds to step 1014.At step 1014, the decode unit 106 requests at least one additional instruction in the program.\",\n \"The additional instructions immediately follow the first instruction in the program.\",\n \"In cases where there can only be one postfix for any base instruction, then the decode unit 106 may only request one additional instruction.\",\n \"If, however, a base instruction can be modified by more than one postfix then the decode unit 106 may decode the modifier bits to determine the number of modifiers for the first instruction and the number of additional instructions requested is equal to the number of modifiers determined from the modifier bits.\",\n \"Once the additional instructions have been requested the method 1000 proceeds to step 1016.Then at step 1016 the decode unit 106 receives and decodes the additional instructions.\",\n \"Once the next instruction has been received and decoded, the method 1000 proceeds to step 1018.At step 1018, it is determined whether each of the additional instructions is a valid postfix for the first instruction.\",\n \"Determining whether an additional instruction is a valid postfix for the first instruction may comprise comparing the additional instruction to one or more predetermined bit patterns to determine if there is a match.\",\n \"If each of the additional instructions is a valid postfix for the first instruction then the method 1000 proceeds to step 1020.If, however, it is determined that at least one of the additional instructions is not a valid postfix then an error has occurred and at step 1008 the exception handler unit 114 is invoked.\",\n \"At step 1020, the received and decoded postfix instruction(s) is/are used to modify the first instruction (i.e.\",\n \"the instruction received in step 1002) and in step 1022 the modified first instruction is sent to the execute unit 108 for execution.\",\n \"The second and third embodiments described above, which involve fetching and decoding multiple consecutive instructions (i.e.\",\n \"fetching the preceding instruction to look for a prefix, or fetching the following instruction to look for a postfix), may be further enhanced by controlling the layout of instructions in the program memory 102.In particular, the program memory 102 may have fixed boundaries which can be expensive to cross.\",\n \"This can include, for example, cache line boundaries or transition page boundaries in the memory management unit (MMU).\",\n \"For example, the MMU page size may be 4K.\",\n \"It may therefore be undesirable to delay executing an instruction while waiting to fetch an instruction from across one of these boundaries, as it is much slower due to the cost of having to fetch an extra cache line or virtual memory page.\",\n \"To address this, boundaries can be defined in the program memory 102 over which prefixing and/or postfixing are not allowed.\",\n \"Specifically, a prefix or postfix instructions should not be separated from their corresponding base instruction by such a boundary.\",\n \"This can avoid the cost of having to fetch an extra cache line or virtual memory page for checking a preceding or following instruction since it is known that it is not legal for a prefix or postfix to extend across the boundary.\",\n \"A compiler can deal with this exception by, for example inserting a No Operation (NOP) instruction, which is an instruction that effectively does nothing at all, in order to pad a prefix or postfix instruction from its base instruction so they do not straddle the boundary.\",\n \"Other, more sophisticated compilers may avoid the use of NOPs by reordering instructions.\",\n \"If the instruction set permits multiple prefixes or postfixes then the positioning would be limited so the whole group of prefixes and corresponding base, or postfixes and corresponding base, is not allowed to cross the boundary.\",\n \"Reference is now made to FIG.\",\n \"11 which illustrates the insertion of a NOP in a program to ensure that a postfix instruction and its corresponding base instruction do not straddle a boundary.\",\n \"In particular, as illustrated at (a) a program consists of four instructions 1102, 1104, 1106 and 1108.The instructions correspond to instructions I3, I4, I5 and I6 of FIG.\",\n \"1 respectively where I4 is the prefix for I5 and I4 and I5 straddle a cache line 1110 boundary or an MMU page boundary.\",\n \"As illustrated at (b) in FIG.\",\n \"11 an NOP 1112 is inserted between I3 and I4 so that I4 is pushed to the other side of the boundary 1110 so that the prefix I4 and its base instruction I5 are on the same side of the boundary 1110.The method described in reference to FIG.\",\n \"11 may be executed by a compiler or similar device.\",\n \"Another example includes a non-transitory computer readable storage medium having stored thereon computer readable instructions that, when processed at a computer system for generating a manifestation of an integrated circuit, cause the computer system to generate a manifestation of an integrated circuit to perform the method of: receiving a first instruction; determining if the first instruction was invoked by a non-incremental change to a program counter; in response to determining the first instruction was invoked by a non-incremental change to the program counter, requesting a second instruction, the second instruction being an instruction immediately preceding the first instruction in a computer program; receiving the second instruction; analyzing the second instruction to determine if the first instruction is a base instruction; and in response to determining the first instruction is a base instruction, invoking exception handling code.\",\n \"A further example includes a non-transitory computer readable storage medium having stored thereon computer readable instructions that, when processed at a computer system for generating a manifestation of an integrated circuit, cause the computer system to generate a manifestation of an integrated circuit to perform the method of: receiving an instruction, the instruction comprising at least one modifier bit, the at least one modifier bit indicating whether the instruction is a base instruction, a base instruction being an instruction subject to modification by one or more other instructions; analyzing the at least one modifier bit to determine if the received instruction is a base instruction; in response to determining that the received instruction is not a base instruction, determining if the received instruction is a prefix instruction, a prefix instruction being an instruction that modifies a subsequent instruction; in response to determining the received instruction is a prefix instruction, storing the received instruction; in response to determining that the received instruction is a base instruction, determining if there are a predetermined number of stored prefix instructions for the base instruction; and in response to determining that there are not the predetermined number of stored prefix instructions for the base instruction, invoking exception handling code.\",\n \"Yet another example includes a non-transitory computer readable storage medium having stored thereon computer readable instructions that, when processed at a computer system for generating a manifestation of an integrated circuit, cause the computer system to generate a manifestation of an integrated circuit to perform the method of: receiving a first instruction; determining whether the first instruction is a postfix instruction, a postfix instruction being an instruction that modifies a preceding instruction; in response to determining the first instruction is a postfix instruction, determining whether the first instruction was invoked by a non-incremental change to a program counter; and in response to determining the first instruction was invoked by a non-incremental change to the program counter, invoking exception handling code.\",\n \"One of the effects of the embodiments described above is a more efficient computer.\",\n \"Specifically, by enabling the data processing apparatus to more quickly and efficiently identify illegal jumps the apparatus does not have to waste resources executing erroneous code.\",\n \"A further effect of the embodiments described above is the use of static analysis (also called static code analysis or SCA).\",\n \"This is an automated program analysis performed on the source or object code, without executing the program.\",\n \"Because it is performed without execution, static analysis must consider every possible outcome of a branch in the program.\",\n \"This results in many permutations, and the analysis quickly becomes complex and slow.\",\n \"Because the methods described above eliminate certain branch destinations as illegal (because they branch to the wrong part of an instruction or modifier), this cuts down on the number of branch permutations that the static analysis need to consider.\",\n \"As a result, the static analysis speed is increased.\",\n \"The term ‘processor’ and ‘computer’ are used herein to refer to any device, or portion thereof, with processing capability such that it can execute instructions.\",\n \"The term ‘processor’ may, for example, include central processing units (CPUs), graphics processing units (GPUs or VPUs), physics processing units (PPUs), radio processing units (RPUs), digital signal processors (DSPs), general purpose processors (e.g.\",\n \"a general purpose GPU), microprocessors, any processing unit which is designed to accelerate tasks outside of a CPU, etc.\",\n \"Those skilled in the art will realize that such processing capabilities are incorporated into many different devices and therefore the term ‘computer’ includes set top boxes, media players, digital radios, PCs, servers, mobile telephones, personal digital assistants and many other devices.\",\n \"Those skilled in the art will realize that storage devices utilized to store program instructions can be distributed across a network.\",\n \"For example, a remote computer may store an example of the process described as software.\",\n \"A local or terminal computer may access the remote computer and download a part or all of the software to run the program.\",\n \"Alternatively, the local computer may download pieces of the software as needed, or execute some software instructions at the local terminal and some at the remote computer (or computer network).\",\n \"Those skilled in the art will also realize that by utilizing conventional techniques known to those skilled in the art that all, or a portion of the software instructions may be carried out by a dedicated circuit, such as a DSP, programmable logic array, or the like.\",\n \"The methods described herein may be performed by a computer configured with software in machine readable form stored on a tangible storage medium e.g.\",\n \"in the form of a computer program comprising computer readable program code for configuring a computer to perform the constituent portions of described methods or in the form of a computer program comprising computer program code means adapted to perform all the steps of any of the methods described herein when the program is run on a computer and where the computer program may be embodied on a computer readable storage medium.\",\n \"Examples of tangible (or non-transitory) storage media include disks, thumb drives, memory cards etc.\",\n \"and do not include propagated signals.\",\n \"The software can be suitable for execution on a parallel processor or a serial processor such that the method steps may be carried out in any suitable order, or simultaneously.\",\n \"The hardware components described herein may be generated by a non-transitory computer readable storage medium having encoded thereon computer readable program code.\",\n \"It is also intended to encompass software which “describes” or defines the configuration of hardware that implements a module, functionality, component or logic described above, such as HDL (hardware description language) software, as is used for designing integrated circuits, or for configuring programmable chips, to carry out desired functions.\",\n \"That is, there may be provided a computer readable storage medium having encoded thereon computer readable program code for generating a processing unit configured to perform any of the methods described herein, or for generating a processing unit comprising any apparatus described herein.\",\n \"That is, a computer system may be configured to generate a representation of a digital circuit from definitions of circuit elements and data defining rules for combining those circuit elements, wherein a non-transitory computer readable storage medium may have stored thereon processor executable instructions that when executed at such a computer system, cause the computer system to generate a processing unit as described herein.\",\n \"Memories storing machine executable data for use in implementing disclosed aspects can be non-transitory media.\",\n \"Non-transitory media can be volatile or non-volatile.\",\n \"Examples of volatile non-transitory media include semiconductor-based memory, such as SRAM or DRAM.\",\n \"Examples of technologies that can be used to implement non-volatile memory include optical and magnetic memory technologies, flash memory, phase change memory, resistive RAM.\",\n \"A particular reference to “logic” refers to structure that performs a function or functions.\",\n \"An example of logic includes circuitry that is arranged to perform those function(s).\",\n \"For example, such circuitry may include transistors and/or other hardware elements available in a manufacturing process.\",\n \"Such transistors and/or other elements may be used to form circuitry or structures that implement and/or contain memory, such as registers, flip flops, or latches, logical operators, such as Boolean operations, mathematical operators, such as adders, multipliers, or shifters, and interconnect, by way of example.\",\n \"Such elements may be provided as custom circuits or standard cell libraries, macros, or at other levels of abstraction.\",\n \"Such elements may be interconnected in a specific arrangement.\",\n \"Logic may include circuitry that is fixed function and circuitry can be programmed to perform a function or functions; such programming may be provided from a firmware or software update or control mechanism.\",\n \"Logic identified to perform one function may also include logic that implements a constituent function or sub-process.\",\n \"In an example, hardware logic has circuitry that implements a fixed function operation, or operations, state machine or process.\",\n \"Any range or device value given herein may be extended or altered without losing the effect sought, as will be apparent to the skilled person.\",\n \"It will be understood that the benefits and advantages described above may relate to one embodiment or may relate to several embodiments.\",\n \"The embodiments are not limited to those that solve any or all of the stated problems or those that have any or all of the stated benefits and advantages.\",\n \"Any reference to ‘an’ item refers to one or more of those items.\",\n \"The term ‘comprising’ is used herein to mean including the method blocks or elements identified, but that such blocks or elements do not comprise an exclusive list and an apparatus may contain additional blocks or elements and a method may contain additional operations or elements.\",\n \"Furthermore, the blocks, elements and operations are themselves not impliedly closed.\",\n \"The steps of the methods described herein may be carried out in any suitable order, or simultaneously where appropriate.\",\n \"The arrows between boxes in the figures show one example sequence of method steps but are not intended to exclude other sequences or the performance of multiple steps in parallel.\",\n \"Additionally, individual blocks may be deleted from any of the methods without departing from the spirit and scope of the subject matter described herein.\",\n \"Aspects of any of the examples described above may be combined with aspects of any of the other examples described to form further examples without losing the effect sought.\",\n \"Where elements of the figures are shown connected by arrows, it will be appreciated that these arrows show just one example flow of communications (including data and control messages) between elements.\",\n \"The flow between elements may be in either direction or in both directions.\",\n \"It will be understood that the above description of a preferred embodiment is given by way of example only and that various modifications may be made by those skilled in the art.\",\n \"Although various embodiments have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this invention.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874724"}}},{"rowIdx":4494675,"cells":{"text":{"kind":"list like","value":[["METHOD AND DEVICE FOR SEPARATING AND TRANSFERRING PELLETS","A pellet column is formed in a metering duct.","The lowermost pellet is located in a connection point where an outlet duct is connected to the metering duct and leads transversely away therefrom.","A first duct, which opens into the metering duct via a first duct mouth above the connection point, is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is fixed thereto.","This pellet acts as a block for the pellets thereabove.","A second duct, which opens into the connection point via a second duct mouth, is impinged with positive pressure, wherein the pellet at the connection point is pneumatically ejected via the outlet duct and supplied to a container.","After the ejection of the lowermost pellet, the negative pressure in the first duct is switched off such that the pellet held at the first duct mouth advances toward the connection point."],["1.A method for separating and transferring pellets into a target container, the method comprising the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.","2.The method of claim 1 further comprising the step of impinging the second pressure differential duct with negative pressure so as to cause the lowermost pellet to be suctioned onto the second duct mouth prior to the pneumatic ejection.","3.The method of claim 2, wherein the suctioning of the pellet that acts as a block onto the first duct mouth and the suctioning of the lowermost pellet onto the second duct mouth are performed in a temporally alternating manner.","4.The method of claim 1 further comprising the step of impinging the first pressure differential duct with positive pressure for facilitating the advancement of the pellet held at the first duct mouth.","5.The method of claim 1, wherein, in the case of an impingement of at least one of the first pressure differential duct and the second pressure differential duct by positive pressure, a protective gas is directed into the corresponding one of the metering duct and the outlet duct.","6.The method of claim 1 further comprising the step of monitoring a pressure in at least one of the first pressure differential duct and the second pressure differential duct.","7.The method of claim 1 further comprising the step of monitoring a flow rate in at least one of the first pressure differential duct and the second pressure differential duct.","8.The method of claim 1 further comprising the steps of: monitoring a pressure in at least one of the first pressure differential duct and the second pressure differential duct; and, monitoring a flow rate in at least one of the first pressure differential duct and the second pressure differential duct.","9.A singularization device comprising: a storage space for pellets; a metering duct leading downward from said storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located therabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.","10.The singularization device of claim 9, wherein: said first duct mouth and said second duct mouth are arranged at a mutual height differential (AH); the pellets have a mean diameter (D); and, said mutual height differential (AH) is an integer multiple of said mean diameter (D).","11.The singularization device of claim 10, wherein said integer multiple is one.","12.The singularization device of claim 9, wherein the singularization device comprises a plurality of first pressure differential ducts each having a corresponding first duct mouth.","13.The singularization device of claim 9, wherein a plurality of singularization devices are interconnected in a modular manner.","14.The singularization device of claim 13, wherein: each singularization device has a main body; each main body has an external surface; and, at least one of said storage space, said metering duct, said outlet duct, said first pressure differential duct and said second pressure differential duct is incorporated into said external surface of said main body and is closed by a corresponding one of said main bodies of a neighboring singularization device.","15.The singularization device of claim 13, wherein the singularization devices each have a cuboid-shaped main body and are interconnected in a linear sequence.","16.The singularization device of claim 13, wherein: the singularization devices each have main bodies; said main bodies have a footprint shaped as circular segments; and, the singularization devices are interconnected in the shape of a circle or in the shape of circular segments.","17.A singularization device comprising: a storage space for pellets; a metering duct leading downward from said storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; and, said second pressure differential duct being configured to be impinged with positive pressure."],["<SOH> BACKGROUND OF THE INVENTION <EOH>Numerous pharmaceutical agents are applied as solutions but are unstable in the dissolved state.","However, the pharmaceutical agents as freeze-dried formulations can be stored in a stable manner and be dissolved again immediately prior to being used.","Examples thereof to be mentioned are biotechnological products, peptides, vaccines, and certain reagents.","More recently, such formulations are also produced in the form of more or less spherical multi-particular preparations as so-called cryo-pellets.","To this end, the source solution is brought into a drop form, wherein drops having an accurately defined volume are producible.","These drops are frozen, for example in liquid nitrogen, and are then dried by way of sublimation.","The dry cryo-pellets that are produced in this way have at least approximately a spherical configuration having a defined mean diameter.","If required, the cryo-pellets can again be dissolved in suitable quantities.","The target herein is to produce only such a limited quantity of solution as is required for covering the immediate demand, to which end corresponding quantities of cryo-pellets are kept available in suitable packaging units.","The number of cryo-pellets required for preparing a solution is typically very low.","Consequently, only a single pellet or just a few pellets are required which is why a volumetric metering in the filling of respective packaging units is precluded.","Rather, a filling of the packaging units with a specific suitable number of pellets is targeted, to which end the pellets in this very number have to be separated from a comparatively large supply and then have to be transferred into the target container.","However, the prior art does not provide any suitable method for separating and for transferring and also no device suitable for this purpose, which can be traced back to inter alia the following aspects: Cryo-pellets are extremely fragile and sensitive to abrasion.","Existing supply technologies (for example slides, vibration infeeds) lead to mechanical damage to the pellets.","The density of the pellets, being ρ<0.2 g/ml, is so minor that the weight of the pellets alone is hardly sufficient for a targeted supply.","The pellets in the case of frequent contact with one another and with other surfaces have a pronounced tendency toward electrostatic charging, this being critical in particular in the case of a vibration infeed.","Filling has in most cases to be performed at very low relative humidity or under a protective gas atmosphere."],["<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the invention to provide a method for separating and for transferring pellets into a target container, the method enabling a reliable and economical implementation also in the case of difficult materials such as in the case of cryo-pellets.","This object can, for example, be achieved by a method for separating and transferring pellets into a target container.","The method includes the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.","It is a further object of the invention to provide a singularization device for separating and transferring pellets into a target container.","This object can, for example, be achieved by a singularization device having: a storage space for pellets; a metering duct leading downward from the storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located thereabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.","Initially a supply of pellets is provided in a storage space.","The pellets are then directed in such a manner from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented, that a column of pellets that lie on top of one another is formed in the metering duct.","The lowermost pellet of this column of pellets is located in a connection point, wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct.","A first pressure differential duct which via a first duct mouth above the connection point opens into the metering duct is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is consequently locationally fixed thereto.","This suctioned pellet herein acts as a block for the pellets that are located thereabove.","Proceeding therefrom, a second pressure differential duct which via a second duct mouth opens into the connection point is impinged with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container.","After the pneumatic ejection of the lowermost pellet the holding negative pressure in the first upper pressure differential duct is switched off such that the pellet that is held at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.","By way of a method according to the invention that has been described above, and by way of the associated device, one or a plurality of pellets can be separated from the enlarged pellet supply and be supplied to the target container, wherein separating as well as supplying is performed solely by the targeted application of negative pressure and positive pressure.","The mechanical action on the pellets is very minor on account of the purely pneumatic handling.","Even mechanically critical pellets such as cryo-pellets can be reliably handled without mechanical damage to the pellets, such as abrasion or the like, is to be noted.","The density of the pellets that is insufficient for a conveyance by weight, proves to be an advantage because suctioning and fixing the pellets, as well as the transportation by pneumatic ejection, function similarly effectively in the case of the typically very low material densities herein.","Friction and other mechanical effects are reduced to a minimum such that electrostatic charging or the possible effects thereof, respectively, are largely avoided or are negligible, respectively.","The first and the second duct mouth are mutually disposed at a height differential.","In an advantageous embodiment of the singularization device, the height differential is an integral multiple of a mean diameter of the pellets.","It is ensured on account thereof that a defined number of pellets is collected below that pellet that acts as a block, the defined number being precisely blown into the target container.","The integral multiple can be two, three, four, or more, and predefines the number of the pellets that are to be in each case pneumatically ejected into one target container.","In an advantageous embodiment the integral multiple is one, as a consequence of which exactly one pellet is pneumatically ejected with each work cycle.","However, this does not necessarily mean that also exactly only one pellet is supplied to the target container.","Rather, a specific number of individual pellets can be blown into the target container by way of a specific number of cycles, on account of which a high reliability in terms of the process is provided.","In order to be able to vary the number of the pellets to be exhausted, an embodiment of the singularization device in which a plurality of first pressure differential ducts via the first duct mouths assigned thereto open into the metering duct can also be expedient.","Depending on requirements, in this instance a duct mouth that is positioned so as to be more or less higher can be activated by way of negative pressure and serve as a block, wherein in this instance, depending on the chosen position in terms of height, a more or less large number of pellets are collected therebelow and ejected into the target container.","In all cases, the separation of a specific number of pellets is based on the fact that that negative pressure is built up in the first upper pressure differential duct, as a consequence of which a pellet is suctioned and retained at the assigned first duct mouth, wherein this suctioned and retained pellet acts as a block for the pellets that are located thereabove.","It is achieved on account thereof that the one or the plurality of pellets that are collected therebelow can be exhausted in the envisaged number without further pellets prematurely moving on from above and falsifying the previously separated quantity.","Various types of handling can be considered for the pellets that are collected below the blocking pellet.","For example, it can be sufficient for the lowermost pellet to simply stand on the base of the transversely running outlet duct and to herein lie in the effective range of the second pressure differential duct as soon.","As a pulse of compressed air is exhausted by way of this second pressure differential duct, the pellet and optionally also the following pellets are conjointly carried to the target container by the compressed air or the compressed gas.","However, in an advantageous embodiment the lowermost pellet is not simply left to stand on the base.","Rather, the lowermost pellet prior to the pneumatic ejection is suctioned onto the second duct mouth in that the second pressure differential duct is temporarily impinged with negative pressure.","On account thereof, above all while considering the effective minor weights, reliable replenishing of the pellets from top to bottom is facilitated.","Moreover, the lowermost pellet is reliably fixed by way of a suction force to the duct mouth of the lower pressure differential duct, the lowermost pellet on account thereof being positioned in a locationally accurate manner.","This facilitates an accurate counting process as well as a later exhausting procedure that is reproducible.","Various temporal profiles can be considered for suctioning the pellets onto the two duct mouths.","However, the suctioning of the pellet that acts as the block onto the first duct mouth, and the suctioning of the lowermost pellet onto the second duct mouth is preferably performed in a temporally alternating manner.","Temporal overlaps are indeed permitted herein.","However, it any case, it should be ensured that there are time frames in which only one of the two pressure differential ducts is impinged with negative pressure.","It is ensured on account thereof that the suctioning onto one of the two duct mouths is not influenced in a disadvantageous manner by suctioning onto the respective other duct mouth.","As soon as the desired number of pellets has been exhausted, a corresponding number of pellets has to move on from above.","To this end, the holding negative pressure in the first pressure differential duct is switched off.","It can be sufficient for the ambient pressure or a slight but no longer holding negative pressure to remain in this instance.","In an advantageous embodiment, the first pressure differential duct is impinged in the sense of a gas pulse with positive pressure at least briefly.","A downward movement of the pellet that is initially held on the first duct mouth is supported or facilitated, respectively, even in the case of a very slight positive pressure.","It can be sufficient for the entire process management to be carried out with air as a pressure and negative medium.","A protective gas is expediently used for sensitive pellets such as cryo-pellets, wherein such a protective gas is advantageously introduced into the metering duct or into the outlet duct, respectively in the case of an impingement of the first and/or of the second pressure differential duct by positive pressure.","It is considered on account thereof that cryo-pellets are typically extremely hygroscopic.","Moreover, the protective gas can serve for rendering the pellets inert.","Pressure monitoring and/or flow-rate monitoring of the first and/or of the second pressure differential duct is preferably performed in an advantageous embodiment.","Disturbances in the process can be identified, and counter measures can be initiated, by identifying irregularities in the profile of the pressure or the flowrate, respectively.","Overall, the method that is conceived so as to be simple, in a corresponding manner also requires a singularization device that is also conceived so as to be simple, wherein the substantial elements in the form of ducts and the like can be readily incorporated into a main body.","This permits a plurality of singularization devices to be interconnected in the manner of modules and therefore to be able to be constructed in a flexible manner in the desired number and configuration.","It can be expedient for the required ducts and the like to be configured as bores in such a main body.","However, in one preferred variant, the storage space, the metering duct, the outlet duct, the first pressure differential duct, and/or the second pressure differential duct are/is incorporated into the surface of such a main body, and are/is closed by the main body of the neighboring singularization device.","The production effort is minimized on account thereof, on the one hand.","On the other hand, ready accessibility to all ducts can be achieved by way of disassembly, such that disturbances of any type can be readily remedied.","Depending on requirements, it can be expedient for cuboid-shaped main bodies to be interconnected in a linear sequence.","Alternatively, it can be expedient for main bodies that in the footprint are shaped as circular segments to be interconnected in the shape of a circle or in the shape of circular segments, such that overall compact systems of a plurality of singularization devices are constructed, and wherein such individual main bodies can be replaced, removed, or added in a modular manner."],["CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation application of international patent application PCT/EP2015/001484, filed Jul.","18, 2015, designating the United States and the entire content of which is incorporated herein by reference.","FIELD OF THE INVENTION The invention relates to a method for separating and for transferring pellets, in particular cryo-pellets, into a target container, and to a singularization device for carrying out this method.","BACKGROUND OF THE INVENTION Numerous pharmaceutical agents are applied as solutions but are unstable in the dissolved state.","However, the pharmaceutical agents as freeze-dried formulations can be stored in a stable manner and be dissolved again immediately prior to being used.","Examples thereof to be mentioned are biotechnological products, peptides, vaccines, and certain reagents.","More recently, such formulations are also produced in the form of more or less spherical multi-particular preparations as so-called cryo-pellets.","To this end, the source solution is brought into a drop form, wherein drops having an accurately defined volume are producible.","These drops are frozen, for example in liquid nitrogen, and are then dried by way of sublimation.","The dry cryo-pellets that are produced in this way have at least approximately a spherical configuration having a defined mean diameter.","If required, the cryo-pellets can again be dissolved in suitable quantities.","The target herein is to produce only such a limited quantity of solution as is required for covering the immediate demand, to which end corresponding quantities of cryo-pellets are kept available in suitable packaging units.","The number of cryo-pellets required for preparing a solution is typically very low.","Consequently, only a single pellet or just a few pellets are required which is why a volumetric metering in the filling of respective packaging units is precluded.","Rather, a filling of the packaging units with a specific suitable number of pellets is targeted, to which end the pellets in this very number have to be separated from a comparatively large supply and then have to be transferred into the target container.","However, the prior art does not provide any suitable method for separating and for transferring and also no device suitable for this purpose, which can be traced back to inter alia the following aspects: Cryo-pellets are extremely fragile and sensitive to abrasion.","Existing supply technologies (for example slides, vibration infeeds) lead to mechanical damage to the pellets.","The density of the pellets, being ρ<0.2 g/ml, is so minor that the weight of the pellets alone is hardly sufficient for a targeted supply.","The pellets in the case of frequent contact with one another and with other surfaces have a pronounced tendency toward electrostatic charging, this being critical in particular in the case of a vibration infeed.","Filling has in most cases to be performed at very low relative humidity or under a protective gas atmosphere.","SUMMARY OF THE INVENTION It is an object of the invention to provide a method for separating and for transferring pellets into a target container, the method enabling a reliable and economical implementation also in the case of difficult materials such as in the case of cryo-pellets.","This object can, for example, be achieved by a method for separating and transferring pellets into a target container.","The method includes the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.","It is a further object of the invention to provide a singularization device for separating and transferring pellets into a target container.","This object can, for example, be achieved by a singularization device having: a storage space for pellets; a metering duct leading downward from the storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located thereabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.","Initially a supply of pellets is provided in a storage space.","The pellets are then directed in such a manner from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented, that a column of pellets that lie on top of one another is formed in the metering duct.","The lowermost pellet of this column of pellets is located in a connection point, wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct.","A first pressure differential duct which via a first duct mouth above the connection point opens into the metering duct is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is consequently locationally fixed thereto.","This suctioned pellet herein acts as a block for the pellets that are located thereabove.","Proceeding therefrom, a second pressure differential duct which via a second duct mouth opens into the connection point is impinged with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container.","After the pneumatic ejection of the lowermost pellet the holding negative pressure in the first upper pressure differential duct is switched off such that the pellet that is held at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.","By way of a method according to the invention that has been described above, and by way of the associated device, one or a plurality of pellets can be separated from the enlarged pellet supply and be supplied to the target container, wherein separating as well as supplying is performed solely by the targeted application of negative pressure and positive pressure.","The mechanical action on the pellets is very minor on account of the purely pneumatic handling.","Even mechanically critical pellets such as cryo-pellets can be reliably handled without mechanical damage to the pellets, such as abrasion or the like, is to be noted.","The density of the pellets that is insufficient for a conveyance by weight, proves to be an advantage because suctioning and fixing the pellets, as well as the transportation by pneumatic ejection, function similarly effectively in the case of the typically very low material densities herein.","Friction and other mechanical effects are reduced to a minimum such that electrostatic charging or the possible effects thereof, respectively, are largely avoided or are negligible, respectively.","The first and the second duct mouth are mutually disposed at a height differential.","In an advantageous embodiment of the singularization device, the height differential is an integral multiple of a mean diameter of the pellets.","It is ensured on account thereof that a defined number of pellets is collected below that pellet that acts as a block, the defined number being precisely blown into the target container.","The integral multiple can be two, three, four, or more, and predefines the number of the pellets that are to be in each case pneumatically ejected into one target container.","In an advantageous embodiment the integral multiple is one, as a consequence of which exactly one pellet is pneumatically ejected with each work cycle.","However, this does not necessarily mean that also exactly only one pellet is supplied to the target container.","Rather, a specific number of individual pellets can be blown into the target container by way of a specific number of cycles, on account of which a high reliability in terms of the process is provided.","In order to be able to vary the number of the pellets to be exhausted, an embodiment of the singularization device in which a plurality of first pressure differential ducts via the first duct mouths assigned thereto open into the metering duct can also be expedient.","Depending on requirements, in this instance a duct mouth that is positioned so as to be more or less higher can be activated by way of negative pressure and serve as a block, wherein in this instance, depending on the chosen position in terms of height, a more or less large number of pellets are collected therebelow and ejected into the target container.","In all cases, the separation of a specific number of pellets is based on the fact that that negative pressure is built up in the first upper pressure differential duct, as a consequence of which a pellet is suctioned and retained at the assigned first duct mouth, wherein this suctioned and retained pellet acts as a block for the pellets that are located thereabove.","It is achieved on account thereof that the one or the plurality of pellets that are collected therebelow can be exhausted in the envisaged number without further pellets prematurely moving on from above and falsifying the previously separated quantity.","Various types of handling can be considered for the pellets that are collected below the blocking pellet.","For example, it can be sufficient for the lowermost pellet to simply stand on the base of the transversely running outlet duct and to herein lie in the effective range of the second pressure differential duct as soon.","As a pulse of compressed air is exhausted by way of this second pressure differential duct, the pellet and optionally also the following pellets are conjointly carried to the target container by the compressed air or the compressed gas.","However, in an advantageous embodiment the lowermost pellet is not simply left to stand on the base.","Rather, the lowermost pellet prior to the pneumatic ejection is suctioned onto the second duct mouth in that the second pressure differential duct is temporarily impinged with negative pressure.","On account thereof, above all while considering the effective minor weights, reliable replenishing of the pellets from top to bottom is facilitated.","Moreover, the lowermost pellet is reliably fixed by way of a suction force to the duct mouth of the lower pressure differential duct, the lowermost pellet on account thereof being positioned in a locationally accurate manner.","This facilitates an accurate counting process as well as a later exhausting procedure that is reproducible.","Various temporal profiles can be considered for suctioning the pellets onto the two duct mouths.","However, the suctioning of the pellet that acts as the block onto the first duct mouth, and the suctioning of the lowermost pellet onto the second duct mouth is preferably performed in a temporally alternating manner.","Temporal overlaps are indeed permitted herein.","However, it any case, it should be ensured that there are time frames in which only one of the two pressure differential ducts is impinged with negative pressure.","It is ensured on account thereof that the suctioning onto one of the two duct mouths is not influenced in a disadvantageous manner by suctioning onto the respective other duct mouth.","As soon as the desired number of pellets has been exhausted, a corresponding number of pellets has to move on from above.","To this end, the holding negative pressure in the first pressure differential duct is switched off.","It can be sufficient for the ambient pressure or a slight but no longer holding negative pressure to remain in this instance.","In an advantageous embodiment, the first pressure differential duct is impinged in the sense of a gas pulse with positive pressure at least briefly.","A downward movement of the pellet that is initially held on the first duct mouth is supported or facilitated, respectively, even in the case of a very slight positive pressure.","It can be sufficient for the entire process management to be carried out with air as a pressure and negative medium.","A protective gas is expediently used for sensitive pellets such as cryo-pellets, wherein such a protective gas is advantageously introduced into the metering duct or into the outlet duct, respectively in the case of an impingement of the first and/or of the second pressure differential duct by positive pressure.","It is considered on account thereof that cryo-pellets are typically extremely hygroscopic.","Moreover, the protective gas can serve for rendering the pellets inert.","Pressure monitoring and/or flow-rate monitoring of the first and/or of the second pressure differential duct is preferably performed in an advantageous embodiment.","Disturbances in the process can be identified, and counter measures can be initiated, by identifying irregularities in the profile of the pressure or the flowrate, respectively.","Overall, the method that is conceived so as to be simple, in a corresponding manner also requires a singularization device that is also conceived so as to be simple, wherein the substantial elements in the form of ducts and the like can be readily incorporated into a main body.","This permits a plurality of singularization devices to be interconnected in the manner of modules and therefore to be able to be constructed in a flexible manner in the desired number and configuration.","It can be expedient for the required ducts and the like to be configured as bores in such a main body.","However, in one preferred variant, the storage space, the metering duct, the outlet duct, the first pressure differential duct, and/or the second pressure differential duct are/is incorporated into the surface of such a main body, and are/is closed by the main body of the neighboring singularization device.","The production effort is minimized on account thereof, on the one hand.","On the other hand, ready accessibility to all ducts can be achieved by way of disassembly, such that disturbances of any type can be readily remedied.","Depending on requirements, it can be expedient for cuboid-shaped main bodies to be interconnected in a linear sequence.","Alternatively, it can be expedient for main bodies that in the footprint are shaped as circular segments to be interconnected in the shape of a circle or in the shape of circular segments, such that overall compact systems of a plurality of singularization devices are constructed, and wherein such individual main bodies can be replaced, removed, or added in a modular manner.","BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described with reference to the drawings wherein: FIG.","1 in a schematic sectional illustration shows a first embodiment of a singularization device for separating cryo-pellets from a comparatively large supply and for transferring the separated pellets into a target container via a vertically oriented metering duct, of an outlet duct that runs transversely to the latter, and of two pressure differential ducts, wherein in each case one pellet is suctioned at and fixed to the duct mouths of both pressure differential ducts; FIG.","2 shows the arrangement as per FIG.","1 when ejecting the lower pellet in the case of a simultaneously suctioned and fixed upper pellet; FIG.","3 shows the arrangement as per FIGS.","1 and 2 when transferring the upper pellet to the lower duct mouth; FIG.","4 shows a variant of the arrangement as per FIGS.","1 to 3, having a plurality of upper pressure differential ducts, presently in an exemplary manner three upper pressure differential ducts, for the simultaneous separation of a plurality of pellets; FIG.","5 in a perspective view shows a cuboid-shaped main body for forming the singularization device as per FIGS.","1 to 3, wherein a storage space, the metering duct, the outlet duct, the first pressure differential duct, and the second pressure differential duct are incorporated into the surface of the main body; FIG.","6 in a perspective view shows an embodiment in which a plurality of cuboid-shaped main bodies as per FIG.","5 are positioned so as to be mutually adjacent in a linear sequence, forming a linear sequence of a plurality of singularization devices; FIG.","7 in a sectional illustration shows a variant of the embodiment as per FIG.","1, having an outlet duct that discharges downward; FIG.","8 in a plan view shows the main body as per FIG.","7, having a circular-segment-shaped footprint; and, FIG.","9 in a perspective view from below shows a group of a plurality of main bodies as per FIGS.","7 and 8, arranged in a circular shape.","DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION FIG.","1 in a schematic sectional illustration shows a first embodiment of a singularization device 3 for transferring pellets 1, 1′, 1″, into a schematically indicated target container 2.The singularization device 3 shown here and the method, described hereunder and carried out by the singularization device 3, are suitable for separating and transferring almost arbitrary pellets, wherein the cryo-pellets that are particularly critical in terms of handling are the main focus and serve as examples for the pellets 1, 1′, 1″.","The singularization device 3 includes a storage space 4 for the pellets 1 and a metering duct 5 that leads out of the storage space 4 downward and is vertically oriented.","The storage space 4 here is configured as a funnel which in relation to the direction of weight tapers off in a downward manner into the metering duct 5.The vertical orientation of the metering duct 5 does not necessarily mean a precisely vertical alignment.","An inclined embodiment in which in any case a significant vertical extent is present in portions can also be expedient.","A first longitudinal axis 28 of the metering duct 5, which in the usual operating position in the embodiment shown does indeed lie parallel with the direction of weight but in relation to the direction of weight can also have an inclination of not more than 45° and in particular of not more than 30°, a serves as a yardstick.","The singularization device 3 furthermore includes an outlet duct 6 which at a connection point 7 is connected to the metering duct 5 and leads transversely away from the metering duct 5.To this end, the outlet duct 6 in the embodiment shown is horizontally disposed.","A second longitudinal axis 29 of the outlet duct 6 in the usual operating position thus lies perpendicularly to the direction of weight, or parallel with the horizontal, respectively.","The second longitudinal axis 29 in relation to the horizontal can also have an inclination of preferably not more than 45° and in particular of not more than 30°.","The singularization device 3 moreover includes at least one, presently exactly one, first pressure differential duct 8, and a second pressure differential duct 10.The first pressure differential duct 8 via a first duct mouth 9 above the connection point 7 opens into the metering duct 5.The second pressure differential duct 10 by way of a second duct mouth 11 above the first duct mouth 9 opens into the connection point 7.The first pressure differential duct 8 has a first duct axis 12, while the second pressure differential duct 10 has a second duct axis 13.The first duct axis 12 in the region of the associated duct mouth 9 lies transversely to the first longitudinal axis 28 of the metering duct 5, while the second duct axis 13 of the second pressure differential duct 10 in the region of the associated duct mouth 11 runs substantially parallel, presently even so as to be coaxial, with the second longitudinal axis 29 of the outlet duct 6.The two pressure differential ducts 8, 10 at the assigned duct mouths 9, 11 thereof are provided in each case with one retention means 18, 19 that prevents any ingress of foreign particles and in particular of the pellets 1, 1′, 1″ into the respective pressure differential ducts 8, 10.However, at the same time, the retention means 18, 19 are gas-permeable.","Filter materials with fine pores, such as sintered filters, membrane filters, or the like are suitable therefor.","In order for the method to be carried out, it is necessary for the first, upper pressure differential duct 8 to be able to be impinged with negative pressure when required, while the second, lower pressure differential duct 10 is to be able to be impinged with positive pressure when required.","However, in the embodiment shown, both pressure differential ducts 8, 10 are impingable in an alternating manner with negative pressure or else with positive pressure.","To this end, in each case one negative pressure source 14 as well as in each case also one positive pressure source 15 are provided for both pressure differential ducts 8, 10, wherein the first pressure differential duct 8, or the second pressure differential duct 10, respectively, via a respective assigned switching valve 16 can be selectively connected to the associated negative pressure source 14 or to the associated positive pressure source 15.Of course, a position of the respective switching valve 16 in which the ambient pressure is set in the respective pressure differential duct 8, 10 is also possible.","The operation of the singularization device 3 shown can be performed at atmospheric conditions, wherein compressed air via the negative pressure source 14 is fed into the system by way of the respective pressure differential duct 8, 10.Protective gas containers 17 in which protective gas is kept available under positive pressure are provided as positive pressure sources 15 in the embodiment shown.","In the context of individual method steps that are described further below, the pressurized protective gas via the first pressure differential duct 8 and/or of the second pressure differential duct 10 is directed from the respective protective gas container 17 through the respectively assigned duct mouth 9, 11 into the metering duct 5 or into the outlet duct 6, respectively.","In the interests of simplicity two protective gas containers 17 are drawn in according to FIG.","1.However, it can also be expedient to feed both pressure differential ducts 8, 10 from a collective protective gas container 17.According to ab advantageous embodiment of the method, according to FIG.","1 a comparatively large supply of a plurality of pellets 1 is first provided in the storage space 4.The pellets 1 together with the singularization device 3 form an inherently tuned system according to which the available passage cross section of the metering duct 5 as well as the available passage cross-section of the outlet duct 6 are slightly larger than a mean diameter D (FIG.","2) of the pellets 1.In a more exact definition, the passage cross-section in particular of the vertically standing metering duct 5 is larger than the mean diameter D (FIG.","2) by so much that the pellets 1 can indeed pass in an unimpeded manner from the top to the bottom through the metering duct 5 without however, on the other hand, two pellets being allowed to pass simultaneously beside one another.","Rather, the available passage cross-section of the metering duct 5 is dimensioned in such a manner that the pellets 1 drop from the storage space 4 downward into the metering duct 5, thereby forming a column of pellets 1, 1′, 1″ that lie on top of one another.","As part of this column, a lowermost pellet 1′ in the initial position shown in FIG.","1 is located in the connection point 7 of the outlet duct 6 with the metering duct 5.It can be expedient here in for the lowermost pellet 1′ to stand on the base of the outlet duct 6.In the embodiment shown, the second pressure differential duct 10 is initially impinged with negative pressure in that the second pressure differential duct 10 via the assigned switching valve 16 is connected to the associated negative pressure source 14.Consequently, the lowermost pellet 1′ is suctioned onto the second duct mouth 11 and pressed against the retention means 19, on account of which the lowermost pellet 1′ is held in position.","In the initial position mentioned according to FIG.","1, the first, upper pressure differential duct 8 is also simultaneously impinged with negative pressure, to which end the first pressure differential duct 8 likewise via the switching valve 16 thereof is connected to the associated negative pressure source 14 of the pressure differential duct 8.Consequently, that pellet 1″ that is closest to the assigned duct mouth 9 is suctioned from the column of pellets 1.This pellet 1″ is pressed against the retention means 18 and herein is locationally fixed as long as the holding negative pressure is maintained in the upper pressure differential duct 8.It is prevented on account thereof that the suctioned pellet 1 slips downward into the connection point 7, on the one hand.","On the other hand, the suctioned pellet″ acts as a block for the pellets 1 located thereabove and consequently prevents the latter from moving on downward.","In the combined view of FIGS.","1 and 2 it also becomes evident that the first duct mouth 9 of the first, upper pressure differential duct 8 is positioned above the second duct mouth 11 of the second, lower pressure differential duct 10 by way of a height differential ΔH.","This height differential ΔH is at least approximately an integral multiple of the mean diameter D of the pellets 1.It will become evident further below that a mathematically exact adherence to the integral multiple is not crucial, this here being expressed by way of the terminology “at least approximately”.","In any case, this integral multiple in the embodiment as per FIGS.","1 to 3 within the context of specific tolerances is one.","The latter and the adherence to the tolerances mentioned leads to only space for exactly one lowermost pellet 1 to remain below the pellet 1″ that has been suctioned onto the upper duct mouth 9 and acts as a block.","In an analogous manner thereto, in the case of a larger integral multiple, there remains space for a corresponding number of lower pellets 1′ below the mentioned pellet 1″ that acts as a block.","The latter case is illustrated in an exemplary manner in FIG.","4; this to be discussed in yet more detail further below.","FIGS.","2 and 3 in fragments show the arrangement as per FIG.","1 when the following method steps are being carried out.","Proceeding from the initial position as per FIG.","1, exhausting those lower pellets 1′ which are collected below the pellet 1″ that acts as a block and is fixed to the first duct mouth 9 is performed in the next method step.","This method step is shown in the schematic sectional illustration as per FIG.","2.To this end, the second pressure differential duct 10 is impinged with positive pressure over a defined period of time, to which end the second pressure differential duct 10 via the assigned switching valve 16 is connected to the positive pressure source 15 that is assigned to the second pressure differential duct 10.A gas pulse, as a consequence of which gas is blown according to an arrow 22 through the duct mouth 11 into the outlet duct 6 along the fourth duct axis 29 thereof is created in the lower pressure differential duct 10.The blown-in gas according to an arrow 23 carries the lowermost pellet 1′ that previously was suctioned at the lower duct mouth 11 through the outlet duct 6 into the provided target container 2.A single gas pulse is typically sufficient for exhausting a single lower pellet 1′ or a plurality of lower pellets 1′ that have been simultaneously collected.","In the case of a plurality of lower pellets 1′ having been separated below the pellet 1″ that serves as a block, exhausting can alternatively also be performed by way of a corresponding number of gas pulses.","In any case, the upper, first pressure differential duct 8 during exhausting is impinged with the holding negative pressure that has been described above such that the pellet 1″ that serves as a block as well as all pellets 1 that are located thereabove remain in place despite the pressure pulse that has been initiated below.","The pellets 1 are thus neither blown back into the storage space 4 nor are the pellets 1 able to prematurely move on downward into the connection point 7 that in the meantime has been vacated.","Once the one or the plurality of lower pellets 1′ have been exhausted according to FIG.","2, the next method step is carried out according to FIG.","3.The holding negative pressure in the first pressure differential duct 8 is switched off such that the pellet 1″ that is held on the first duct mouth 11 (FIG.","2) moves on toward the connection point 7, a new lowermost pellet 1′ (FIG.","3) being located in the connection point 7.This replenishment can take place solely as a result of the acting weights.","To this end, the lower, second pressure differential duct 10 in the embodiment shown is again impinged with negative pressure, on account of which the respective lowermost pellet 1′ prior to being exhausted later is suctioned onto the second duct mouth 11.The transfer of pellets from the upper, first duct mouth 9 to the lower, second duct mouth 11 according to an arrow 25, as has been described above, can also yet be supported in that the first pressure differential duct 8 is briefly impinged with positive pressure in that the first pressure differential duct 8 via the assigned switching valve 16 thereof is connected to the assigned positive pressure source 15.On account thereof, a pressure pulse via which gas according to an arrow 24 is introduced through the duct mouth 9 into the metering duct 5, thereby supporting the moving-on according to the arrow 25 of the pellet 1″ that has previously been held on the first duct mouth 9 (FIG.","2) is formed.","This positive pressure pulse simultaneously prevents premature moving-on in a downward manner of the column of pellets 1 that is located thereabove.","Air or compressed air, respectively, can be used as the process and positive pressure medium.","To the extent that a protective gas container 17 is provided as a positive pressure source 15 according to the embodiment as per FIGS.","1 to 3, the protective gas in the case of the pressure pulses that have been described above is introduced from the respective protective gas container 17 through the first and/or the second pressure differential duct 8, 10 into the metering duct 5 or into the outlet duct 6, respectively.","On account thereof, a protective gas atmosphere can be maintained in all regions of the singularization device that interact with the pellets 1, 1′, 1″.","This permits the handling of cryo-pellets that are extremely hygroscopic and, when required, also enables the pellets 1, 1′, 1″ to be rendered inert.","The impingement of the two pressure differential ducts 8, 10 with negative pressure can be mutually overlapping to a certain extent.","However, suctioning of the pellet 1″ that acts as a block onto the first duct mouth 9, and suctioning of the lowermost pellet 1′ onto the second duct mouth 11, is advantageously performed in a temporally alternating manner such that the holding negative pressure on the upper duct mouth 9 is at least temporarily switched off when the transfer and the moving-on of the lowermost pellet 1′ are performed via negative pressure at the lower, second duct mouth 11.In any case, the temporary negative pressure in the lower, second pressure differential duct 10 also supports the moving-on of the pellets 1 from the target container 2 into the metering duct 5.This can also be utilized for the initial filling of the metering duct 5 with pellets 1, 1′, 1″ for achieving the initial position as per FIG.","1.Subsequently to the method step according to FIG.","3, the upper, first pressure differential duct 8 is again impinged with negative pressure, on account of which a new pellet 1″ that serves as a block is consequently suctioned and fixed.","The initial position as per FIG.","1 is reestablished, and the previously described method cycle can restart.","It can also be derived from the illustration as per FIG.","1 that monitoring means which presently in an exemplary manner are configured as a pressure sensor 26 and/or as a flow rate sensor 27 and are connected to a suitable monitoring unit (not illustrated here for the sake of simplicity) are disposed in the region of the first and/or the second pressure differential duct 8, 10.On account thereof, pressure monitoring and/or rate flow monitoring can be performed and errors in the method sequence can be identified.","FIG.","4 in a schematic sectional illustration shows a variant of the arrangement as per FIGS.","1 to 3, wherein a plurality of, in an exemplary manner presently three, first pressure differential ducts 8, 8′, 8″ via the first duct mouths 9, 9′, 9″ assigned thereto open into the metering duct 5.The height differential between the individual duct mouths 9, 9′, 9″ here is again an integral multiple of the mean diameter D of the pellets 1, wherein the integral multiple here is 1.The uppermost first duct mouth 9 thus is at a height differential AH above the second duct mouth 11, wherein, in a manner analogous to that of the embodiment as per FIGS.","1 to 3, this height differential AH is at least approximately an integral multiple of the mean diameter D. This integral multiple in the embodiment shown is 3.To the extent of the uppermost of the plurality of first pressure differential ducts 8, 8′, 8″, presently thus the pressure differential duct 8, thus being impinged with negative pressure a block by way of an adhering or suctioned pellet 1″, respectively, is configured at the assigned duct mouth 9, exactly three lower pellets 1′ being collected therebelow and according to the method sequence as per FIGS.","1 to 3 being exhausted into the respective target container 2.Depending on requirements, however, one of the other first pressure differential ducts 8′, 8″ can also be impinged with negative pressure, this then resulting in a separation of precisely one or precisely two lower pellets 1′.","Of course, the same applies in an analogous manner also to a deviating number or positioning of first duct mouths 9, 9′, 9″.","In terms of the remaining features and reference signs as well as also method steps, the embodiment as per FIG.","4 is identical to that of FIGS.","1 to 3.FIG.","5 in a perspective view shows a cuboid-shaped main body 20 for forming an individual singularization device 3 as per FIGS.","1 to 3, and 6.It can be expedient for bores, openings, or the like, to be incorporated into such a main body 20 so as to configure therewith the various ducts as described above.","The two pressure differential ducts 8, 10 in the embodiment shown are formed by two such bores.","Deviating therefrom, the storage space 4, the metering duct 5, and the outlet duct 6 are machined as a duct-type depression into a surface 21 of the main body 20, the depressions initially being open to the outside.","However, it can also be expedient for the two pressure differential ducts 8, 10 or another part of the aforementioned elements, to be additionally configured in this one surface 21.According to the perspective illustration as per FIG.","6, a plurality of such main bodies 20 can be interconnected in a linear sequence, wherein the duct-type depressions mentioned in a main body 20 are closed by the neighboring main body 20′, and on account of which singularization devices 3, 3′ that are interconnected in the manner of modules are formed.","Deviating therefrom, FIG.","8 shows a main body 20 in a plan view, the footprint of the main body 20 being in the shape of a circular segment.","Here too, the various ducts can be configured on a lateral surface 21 in a manner analogous to that of FIG.","5.However, in an exemplary manner, the storage space 4, the metering duct 5, and also the other elements, are machined so as to be centric in the main body 20.FIG.","9 in a perspective view from below shows a group of a plurality of main bodies 20, 20′ as per FIG.","8, the main bodies 20, 20′ being interconnected in the manner of modules so as to be mutually adjacent and, by virtue of the shape of a circular segment of an individual main body 20 overall forming a group of singularization devices 3, 3′ that is disposed in the shape of a circle.","Of course, individual singularization devices 3′ which presently for the sake of simplicity are only illustrated in dashed lines can also be omitted, on account of which the overall shape of a circular segment of the group of singularization devices 3 results.","It can also be derived from the perspective illustration as per FIG.","9 that little space in the radially inward region remains of the circular or circular-segment shape chosen.","In consideration thereof, exit openings 30 of the outlet ducts 6 (FIG.","7) are disposed on the lower side of the main bodies 20.Details thereof are derived from the schematic sectional illustration of the main body 20 as per FIG.","7.In a manner deviating from the embodiment as per FIG.","1, only that part of the outlet duct 6 that is directly adjacent to the connection point 7 runs transversely to the metering duct 5, or transversely to the direction of weight, respectively, while a duct segment 6′ of the outlet duct 6 that is adjacent thereto is angled in a downward manner and via the lower exit opening 30 leads to the target container 2 that is positioned therebelow.","In as far as not explicitly described or illustrated in the drawings so as to deviate therefrom, the embodiments as per FIGS.","5 and 6 and as per FIGS.","7 to 9 in terms of the remaining features and reference signs are mutually identical as well as identical to the embodiment as per FIGS.","1 to 3.The same also applies to the assigned method steps.","Apart therefrom, features of the one embodiment can also be linked to a respective other embodiment.","It is understood that the foregoing description is that of the preferred embodiments of the invention and that various changes and modifications may be made thereto without departing from the spirit and scope of the invention as defined in the appended claims."]],"string":"[\n [\n \"METHOD AND DEVICE FOR SEPARATING AND TRANSFERRING PELLETS\",\n \"A pellet column is formed in a metering duct.\",\n \"The lowermost pellet is located in a connection point where an outlet duct is connected to the metering duct and leads transversely away therefrom.\",\n \"A first duct, which opens into the metering duct via a first duct mouth above the connection point, is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is fixed thereto.\",\n \"This pellet acts as a block for the pellets thereabove.\",\n \"A second duct, which opens into the connection point via a second duct mouth, is impinged with positive pressure, wherein the pellet at the connection point is pneumatically ejected via the outlet duct and supplied to a container.\",\n \"After the ejection of the lowermost pellet, the negative pressure in the first duct is switched off such that the pellet held at the first duct mouth advances toward the connection point.\"\n ],\n [\n \"1.A method for separating and transferring pellets into a target container, the method comprising the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.\",\n \"2.The method of claim 1 further comprising the step of impinging the second pressure differential duct with negative pressure so as to cause the lowermost pellet to be suctioned onto the second duct mouth prior to the pneumatic ejection.\",\n \"3.The method of claim 2, wherein the suctioning of the pellet that acts as a block onto the first duct mouth and the suctioning of the lowermost pellet onto the second duct mouth are performed in a temporally alternating manner.\",\n \"4.The method of claim 1 further comprising the step of impinging the first pressure differential duct with positive pressure for facilitating the advancement of the pellet held at the first duct mouth.\",\n \"5.The method of claim 1, wherein, in the case of an impingement of at least one of the first pressure differential duct and the second pressure differential duct by positive pressure, a protective gas is directed into the corresponding one of the metering duct and the outlet duct.\",\n \"6.The method of claim 1 further comprising the step of monitoring a pressure in at least one of the first pressure differential duct and the second pressure differential duct.\",\n \"7.The method of claim 1 further comprising the step of monitoring a flow rate in at least one of the first pressure differential duct and the second pressure differential duct.\",\n \"8.The method of claim 1 further comprising the steps of: monitoring a pressure in at least one of the first pressure differential duct and the second pressure differential duct; and, monitoring a flow rate in at least one of the first pressure differential duct and the second pressure differential duct.\",\n \"9.A singularization device comprising: a storage space for pellets; a metering duct leading downward from said storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located therabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.\",\n \"10.The singularization device of claim 9, wherein: said first duct mouth and said second duct mouth are arranged at a mutual height differential (AH); the pellets have a mean diameter (D); and, said mutual height differential (AH) is an integer multiple of said mean diameter (D).\",\n \"11.The singularization device of claim 10, wherein said integer multiple is one.\",\n \"12.The singularization device of claim 9, wherein the singularization device comprises a plurality of first pressure differential ducts each having a corresponding first duct mouth.\",\n \"13.The singularization device of claim 9, wherein a plurality of singularization devices are interconnected in a modular manner.\",\n \"14.The singularization device of claim 13, wherein: each singularization device has a main body; each main body has an external surface; and, at least one of said storage space, said metering duct, said outlet duct, said first pressure differential duct and said second pressure differential duct is incorporated into said external surface of said main body and is closed by a corresponding one of said main bodies of a neighboring singularization device.\",\n \"15.The singularization device of claim 13, wherein the singularization devices each have a cuboid-shaped main body and are interconnected in a linear sequence.\",\n \"16.The singularization device of claim 13, wherein: the singularization devices each have main bodies; said main bodies have a footprint shaped as circular segments; and, the singularization devices are interconnected in the shape of a circle or in the shape of circular segments.\",\n \"17.A singularization device comprising: a storage space for pellets; a metering duct leading downward from said storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; and, said second pressure differential duct being configured to be impinged with positive pressure.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>Numerous pharmaceutical agents are applied as solutions but are unstable in the dissolved state.\",\n \"However, the pharmaceutical agents as freeze-dried formulations can be stored in a stable manner and be dissolved again immediately prior to being used.\",\n \"Examples thereof to be mentioned are biotechnological products, peptides, vaccines, and certain reagents.\",\n \"More recently, such formulations are also produced in the form of more or less spherical multi-particular preparations as so-called cryo-pellets.\",\n \"To this end, the source solution is brought into a drop form, wherein drops having an accurately defined volume are producible.\",\n \"These drops are frozen, for example in liquid nitrogen, and are then dried by way of sublimation.\",\n \"The dry cryo-pellets that are produced in this way have at least approximately a spherical configuration having a defined mean diameter.\",\n \"If required, the cryo-pellets can again be dissolved in suitable quantities.\",\n \"The target herein is to produce only such a limited quantity of solution as is required for covering the immediate demand, to which end corresponding quantities of cryo-pellets are kept available in suitable packaging units.\",\n \"The number of cryo-pellets required for preparing a solution is typically very low.\",\n \"Consequently, only a single pellet or just a few pellets are required which is why a volumetric metering in the filling of respective packaging units is precluded.\",\n \"Rather, a filling of the packaging units with a specific suitable number of pellets is targeted, to which end the pellets in this very number have to be separated from a comparatively large supply and then have to be transferred into the target container.\",\n \"However, the prior art does not provide any suitable method for separating and for transferring and also no device suitable for this purpose, which can be traced back to inter alia the following aspects: Cryo-pellets are extremely fragile and sensitive to abrasion.\",\n \"Existing supply technologies (for example slides, vibration infeeds) lead to mechanical damage to the pellets.\",\n \"The density of the pellets, being ρ<0.2 g/ml, is so minor that the weight of the pellets alone is hardly sufficient for a targeted supply.\",\n \"The pellets in the case of frequent contact with one another and with other surfaces have a pronounced tendency toward electrostatic charging, this being critical in particular in the case of a vibration infeed.\",\n \"Filling has in most cases to be performed at very low relative humidity or under a protective gas atmosphere.\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the invention to provide a method for separating and for transferring pellets into a target container, the method enabling a reliable and economical implementation also in the case of difficult materials such as in the case of cryo-pellets.\",\n \"This object can, for example, be achieved by a method for separating and transferring pellets into a target container.\",\n \"The method includes the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.\",\n \"It is a further object of the invention to provide a singularization device for separating and transferring pellets into a target container.\",\n \"This object can, for example, be achieved by a singularization device having: a storage space for pellets; a metering duct leading downward from the storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located thereabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.\",\n \"Initially a supply of pellets is provided in a storage space.\",\n \"The pellets are then directed in such a manner from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented, that a column of pellets that lie on top of one another is formed in the metering duct.\",\n \"The lowermost pellet of this column of pellets is located in a connection point, wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct.\",\n \"A first pressure differential duct which via a first duct mouth above the connection point opens into the metering duct is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is consequently locationally fixed thereto.\",\n \"This suctioned pellet herein acts as a block for the pellets that are located thereabove.\",\n \"Proceeding therefrom, a second pressure differential duct which via a second duct mouth opens into the connection point is impinged with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container.\",\n \"After the pneumatic ejection of the lowermost pellet the holding negative pressure in the first upper pressure differential duct is switched off such that the pellet that is held at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.\",\n \"By way of a method according to the invention that has been described above, and by way of the associated device, one or a plurality of pellets can be separated from the enlarged pellet supply and be supplied to the target container, wherein separating as well as supplying is performed solely by the targeted application of negative pressure and positive pressure.\",\n \"The mechanical action on the pellets is very minor on account of the purely pneumatic handling.\",\n \"Even mechanically critical pellets such as cryo-pellets can be reliably handled without mechanical damage to the pellets, such as abrasion or the like, is to be noted.\",\n \"The density of the pellets that is insufficient for a conveyance by weight, proves to be an advantage because suctioning and fixing the pellets, as well as the transportation by pneumatic ejection, function similarly effectively in the case of the typically very low material densities herein.\",\n \"Friction and other mechanical effects are reduced to a minimum such that electrostatic charging or the possible effects thereof, respectively, are largely avoided or are negligible, respectively.\",\n \"The first and the second duct mouth are mutually disposed at a height differential.\",\n \"In an advantageous embodiment of the singularization device, the height differential is an integral multiple of a mean diameter of the pellets.\",\n \"It is ensured on account thereof that a defined number of pellets is collected below that pellet that acts as a block, the defined number being precisely blown into the target container.\",\n \"The integral multiple can be two, three, four, or more, and predefines the number of the pellets that are to be in each case pneumatically ejected into one target container.\",\n \"In an advantageous embodiment the integral multiple is one, as a consequence of which exactly one pellet is pneumatically ejected with each work cycle.\",\n \"However, this does not necessarily mean that also exactly only one pellet is supplied to the target container.\",\n \"Rather, a specific number of individual pellets can be blown into the target container by way of a specific number of cycles, on account of which a high reliability in terms of the process is provided.\",\n \"In order to be able to vary the number of the pellets to be exhausted, an embodiment of the singularization device in which a plurality of first pressure differential ducts via the first duct mouths assigned thereto open into the metering duct can also be expedient.\",\n \"Depending on requirements, in this instance a duct mouth that is positioned so as to be more or less higher can be activated by way of negative pressure and serve as a block, wherein in this instance, depending on the chosen position in terms of height, a more or less large number of pellets are collected therebelow and ejected into the target container.\",\n \"In all cases, the separation of a specific number of pellets is based on the fact that that negative pressure is built up in the first upper pressure differential duct, as a consequence of which a pellet is suctioned and retained at the assigned first duct mouth, wherein this suctioned and retained pellet acts as a block for the pellets that are located thereabove.\",\n \"It is achieved on account thereof that the one or the plurality of pellets that are collected therebelow can be exhausted in the envisaged number without further pellets prematurely moving on from above and falsifying the previously separated quantity.\",\n \"Various types of handling can be considered for the pellets that are collected below the blocking pellet.\",\n \"For example, it can be sufficient for the lowermost pellet to simply stand on the base of the transversely running outlet duct and to herein lie in the effective range of the second pressure differential duct as soon.\",\n \"As a pulse of compressed air is exhausted by way of this second pressure differential duct, the pellet and optionally also the following pellets are conjointly carried to the target container by the compressed air or the compressed gas.\",\n \"However, in an advantageous embodiment the lowermost pellet is not simply left to stand on the base.\",\n \"Rather, the lowermost pellet prior to the pneumatic ejection is suctioned onto the second duct mouth in that the second pressure differential duct is temporarily impinged with negative pressure.\",\n \"On account thereof, above all while considering the effective minor weights, reliable replenishing of the pellets from top to bottom is facilitated.\",\n \"Moreover, the lowermost pellet is reliably fixed by way of a suction force to the duct mouth of the lower pressure differential duct, the lowermost pellet on account thereof being positioned in a locationally accurate manner.\",\n \"This facilitates an accurate counting process as well as a later exhausting procedure that is reproducible.\",\n \"Various temporal profiles can be considered for suctioning the pellets onto the two duct mouths.\",\n \"However, the suctioning of the pellet that acts as the block onto the first duct mouth, and the suctioning of the lowermost pellet onto the second duct mouth is preferably performed in a temporally alternating manner.\",\n \"Temporal overlaps are indeed permitted herein.\",\n \"However, it any case, it should be ensured that there are time frames in which only one of the two pressure differential ducts is impinged with negative pressure.\",\n \"It is ensured on account thereof that the suctioning onto one of the two duct mouths is not influenced in a disadvantageous manner by suctioning onto the respective other duct mouth.\",\n \"As soon as the desired number of pellets has been exhausted, a corresponding number of pellets has to move on from above.\",\n \"To this end, the holding negative pressure in the first pressure differential duct is switched off.\",\n \"It can be sufficient for the ambient pressure or a slight but no longer holding negative pressure to remain in this instance.\",\n \"In an advantageous embodiment, the first pressure differential duct is impinged in the sense of a gas pulse with positive pressure at least briefly.\",\n \"A downward movement of the pellet that is initially held on the first duct mouth is supported or facilitated, respectively, even in the case of a very slight positive pressure.\",\n \"It can be sufficient for the entire process management to be carried out with air as a pressure and negative medium.\",\n \"A protective gas is expediently used for sensitive pellets such as cryo-pellets, wherein such a protective gas is advantageously introduced into the metering duct or into the outlet duct, respectively in the case of an impingement of the first and/or of the second pressure differential duct by positive pressure.\",\n \"It is considered on account thereof that cryo-pellets are typically extremely hygroscopic.\",\n \"Moreover, the protective gas can serve for rendering the pellets inert.\",\n \"Pressure monitoring and/or flow-rate monitoring of the first and/or of the second pressure differential duct is preferably performed in an advantageous embodiment.\",\n \"Disturbances in the process can be identified, and counter measures can be initiated, by identifying irregularities in the profile of the pressure or the flowrate, respectively.\",\n \"Overall, the method that is conceived so as to be simple, in a corresponding manner also requires a singularization device that is also conceived so as to be simple, wherein the substantial elements in the form of ducts and the like can be readily incorporated into a main body.\",\n \"This permits a plurality of singularization devices to be interconnected in the manner of modules and therefore to be able to be constructed in a flexible manner in the desired number and configuration.\",\n \"It can be expedient for the required ducts and the like to be configured as bores in such a main body.\",\n \"However, in one preferred variant, the storage space, the metering duct, the outlet duct, the first pressure differential duct, and/or the second pressure differential duct are/is incorporated into the surface of such a main body, and are/is closed by the main body of the neighboring singularization device.\",\n \"The production effort is minimized on account thereof, on the one hand.\",\n \"On the other hand, ready accessibility to all ducts can be achieved by way of disassembly, such that disturbances of any type can be readily remedied.\",\n \"Depending on requirements, it can be expedient for cuboid-shaped main bodies to be interconnected in a linear sequence.\",\n \"Alternatively, it can be expedient for main bodies that in the footprint are shaped as circular segments to be interconnected in the shape of a circle or in the shape of circular segments, such that overall compact systems of a plurality of singularization devices are constructed, and wherein such individual main bodies can be replaced, removed, or added in a modular manner.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation application of international patent application PCT/EP2015/001484, filed Jul.\",\n \"18, 2015, designating the United States and the entire content of which is incorporated herein by reference.\",\n \"FIELD OF THE INVENTION The invention relates to a method for separating and for transferring pellets, in particular cryo-pellets, into a target container, and to a singularization device for carrying out this method.\",\n \"BACKGROUND OF THE INVENTION Numerous pharmaceutical agents are applied as solutions but are unstable in the dissolved state.\",\n \"However, the pharmaceutical agents as freeze-dried formulations can be stored in a stable manner and be dissolved again immediately prior to being used.\",\n \"Examples thereof to be mentioned are biotechnological products, peptides, vaccines, and certain reagents.\",\n \"More recently, such formulations are also produced in the form of more or less spherical multi-particular preparations as so-called cryo-pellets.\",\n \"To this end, the source solution is brought into a drop form, wherein drops having an accurately defined volume are producible.\",\n \"These drops are frozen, for example in liquid nitrogen, and are then dried by way of sublimation.\",\n \"The dry cryo-pellets that are produced in this way have at least approximately a spherical configuration having a defined mean diameter.\",\n \"If required, the cryo-pellets can again be dissolved in suitable quantities.\",\n \"The target herein is to produce only such a limited quantity of solution as is required for covering the immediate demand, to which end corresponding quantities of cryo-pellets are kept available in suitable packaging units.\",\n \"The number of cryo-pellets required for preparing a solution is typically very low.\",\n \"Consequently, only a single pellet or just a few pellets are required which is why a volumetric metering in the filling of respective packaging units is precluded.\",\n \"Rather, a filling of the packaging units with a specific suitable number of pellets is targeted, to which end the pellets in this very number have to be separated from a comparatively large supply and then have to be transferred into the target container.\",\n \"However, the prior art does not provide any suitable method for separating and for transferring and also no device suitable for this purpose, which can be traced back to inter alia the following aspects: Cryo-pellets are extremely fragile and sensitive to abrasion.\",\n \"Existing supply technologies (for example slides, vibration infeeds) lead to mechanical damage to the pellets.\",\n \"The density of the pellets, being ρ<0.2 g/ml, is so minor that the weight of the pellets alone is hardly sufficient for a targeted supply.\",\n \"The pellets in the case of frequent contact with one another and with other surfaces have a pronounced tendency toward electrostatic charging, this being critical in particular in the case of a vibration infeed.\",\n \"Filling has in most cases to be performed at very low relative humidity or under a protective gas atmosphere.\",\n \"SUMMARY OF THE INVENTION It is an object of the invention to provide a method for separating and for transferring pellets into a target container, the method enabling a reliable and economical implementation also in the case of difficult materials such as in the case of cryo-pellets.\",\n \"This object can, for example, be achieved by a method for separating and transferring pellets into a target container.\",\n \"The method includes the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.\",\n \"It is a further object of the invention to provide a singularization device for separating and transferring pellets into a target container.\",\n \"This object can, for example, be achieved by a singularization device having: a storage space for pellets; a metering duct leading downward from the storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located thereabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.\",\n \"Initially a supply of pellets is provided in a storage space.\",\n \"The pellets are then directed in such a manner from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented, that a column of pellets that lie on top of one another is formed in the metering duct.\",\n \"The lowermost pellet of this column of pellets is located in a connection point, wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct.\",\n \"A first pressure differential duct which via a first duct mouth above the connection point opens into the metering duct is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is consequently locationally fixed thereto.\",\n \"This suctioned pellet herein acts as a block for the pellets that are located thereabove.\",\n \"Proceeding therefrom, a second pressure differential duct which via a second duct mouth opens into the connection point is impinged with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container.\",\n \"After the pneumatic ejection of the lowermost pellet the holding negative pressure in the first upper pressure differential duct is switched off such that the pellet that is held at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.\",\n \"By way of a method according to the invention that has been described above, and by way of the associated device, one or a plurality of pellets can be separated from the enlarged pellet supply and be supplied to the target container, wherein separating as well as supplying is performed solely by the targeted application of negative pressure and positive pressure.\",\n \"The mechanical action on the pellets is very minor on account of the purely pneumatic handling.\",\n \"Even mechanically critical pellets such as cryo-pellets can be reliably handled without mechanical damage to the pellets, such as abrasion or the like, is to be noted.\",\n \"The density of the pellets that is insufficient for a conveyance by weight, proves to be an advantage because suctioning and fixing the pellets, as well as the transportation by pneumatic ejection, function similarly effectively in the case of the typically very low material densities herein.\",\n \"Friction and other mechanical effects are reduced to a minimum such that electrostatic charging or the possible effects thereof, respectively, are largely avoided or are negligible, respectively.\",\n \"The first and the second duct mouth are mutually disposed at a height differential.\",\n \"In an advantageous embodiment of the singularization device, the height differential is an integral multiple of a mean diameter of the pellets.\",\n \"It is ensured on account thereof that a defined number of pellets is collected below that pellet that acts as a block, the defined number being precisely blown into the target container.\",\n \"The integral multiple can be two, three, four, or more, and predefines the number of the pellets that are to be in each case pneumatically ejected into one target container.\",\n \"In an advantageous embodiment the integral multiple is one, as a consequence of which exactly one pellet is pneumatically ejected with each work cycle.\",\n \"However, this does not necessarily mean that also exactly only one pellet is supplied to the target container.\",\n \"Rather, a specific number of individual pellets can be blown into the target container by way of a specific number of cycles, on account of which a high reliability in terms of the process is provided.\",\n \"In order to be able to vary the number of the pellets to be exhausted, an embodiment of the singularization device in which a plurality of first pressure differential ducts via the first duct mouths assigned thereto open into the metering duct can also be expedient.\",\n \"Depending on requirements, in this instance a duct mouth that is positioned so as to be more or less higher can be activated by way of negative pressure and serve as a block, wherein in this instance, depending on the chosen position in terms of height, a more or less large number of pellets are collected therebelow and ejected into the target container.\",\n \"In all cases, the separation of a specific number of pellets is based on the fact that that negative pressure is built up in the first upper pressure differential duct, as a consequence of which a pellet is suctioned and retained at the assigned first duct mouth, wherein this suctioned and retained pellet acts as a block for the pellets that are located thereabove.\",\n \"It is achieved on account thereof that the one or the plurality of pellets that are collected therebelow can be exhausted in the envisaged number without further pellets prematurely moving on from above and falsifying the previously separated quantity.\",\n \"Various types of handling can be considered for the pellets that are collected below the blocking pellet.\",\n \"For example, it can be sufficient for the lowermost pellet to simply stand on the base of the transversely running outlet duct and to herein lie in the effective range of the second pressure differential duct as soon.\",\n \"As a pulse of compressed air is exhausted by way of this second pressure differential duct, the pellet and optionally also the following pellets are conjointly carried to the target container by the compressed air or the compressed gas.\",\n \"However, in an advantageous embodiment the lowermost pellet is not simply left to stand on the base.\",\n \"Rather, the lowermost pellet prior to the pneumatic ejection is suctioned onto the second duct mouth in that the second pressure differential duct is temporarily impinged with negative pressure.\",\n \"On account thereof, above all while considering the effective minor weights, reliable replenishing of the pellets from top to bottom is facilitated.\",\n \"Moreover, the lowermost pellet is reliably fixed by way of a suction force to the duct mouth of the lower pressure differential duct, the lowermost pellet on account thereof being positioned in a locationally accurate manner.\",\n \"This facilitates an accurate counting process as well as a later exhausting procedure that is reproducible.\",\n \"Various temporal profiles can be considered for suctioning the pellets onto the two duct mouths.\",\n \"However, the suctioning of the pellet that acts as the block onto the first duct mouth, and the suctioning of the lowermost pellet onto the second duct mouth is preferably performed in a temporally alternating manner.\",\n \"Temporal overlaps are indeed permitted herein.\",\n \"However, it any case, it should be ensured that there are time frames in which only one of the two pressure differential ducts is impinged with negative pressure.\",\n \"It is ensured on account thereof that the suctioning onto one of the two duct mouths is not influenced in a disadvantageous manner by suctioning onto the respective other duct mouth.\",\n \"As soon as the desired number of pellets has been exhausted, a corresponding number of pellets has to move on from above.\",\n \"To this end, the holding negative pressure in the first pressure differential duct is switched off.\",\n \"It can be sufficient for the ambient pressure or a slight but no longer holding negative pressure to remain in this instance.\",\n \"In an advantageous embodiment, the first pressure differential duct is impinged in the sense of a gas pulse with positive pressure at least briefly.\",\n \"A downward movement of the pellet that is initially held on the first duct mouth is supported or facilitated, respectively, even in the case of a very slight positive pressure.\",\n \"It can be sufficient for the entire process management to be carried out with air as a pressure and negative medium.\",\n \"A protective gas is expediently used for sensitive pellets such as cryo-pellets, wherein such a protective gas is advantageously introduced into the metering duct or into the outlet duct, respectively in the case of an impingement of the first and/or of the second pressure differential duct by positive pressure.\",\n \"It is considered on account thereof that cryo-pellets are typically extremely hygroscopic.\",\n \"Moreover, the protective gas can serve for rendering the pellets inert.\",\n \"Pressure monitoring and/or flow-rate monitoring of the first and/or of the second pressure differential duct is preferably performed in an advantageous embodiment.\",\n \"Disturbances in the process can be identified, and counter measures can be initiated, by identifying irregularities in the profile of the pressure or the flowrate, respectively.\",\n \"Overall, the method that is conceived so as to be simple, in a corresponding manner also requires a singularization device that is also conceived so as to be simple, wherein the substantial elements in the form of ducts and the like can be readily incorporated into a main body.\",\n \"This permits a plurality of singularization devices to be interconnected in the manner of modules and therefore to be able to be constructed in a flexible manner in the desired number and configuration.\",\n \"It can be expedient for the required ducts and the like to be configured as bores in such a main body.\",\n \"However, in one preferred variant, the storage space, the metering duct, the outlet duct, the first pressure differential duct, and/or the second pressure differential duct are/is incorporated into the surface of such a main body, and are/is closed by the main body of the neighboring singularization device.\",\n \"The production effort is minimized on account thereof, on the one hand.\",\n \"On the other hand, ready accessibility to all ducts can be achieved by way of disassembly, such that disturbances of any type can be readily remedied.\",\n \"Depending on requirements, it can be expedient for cuboid-shaped main bodies to be interconnected in a linear sequence.\",\n \"Alternatively, it can be expedient for main bodies that in the footprint are shaped as circular segments to be interconnected in the shape of a circle or in the shape of circular segments, such that overall compact systems of a plurality of singularization devices are constructed, and wherein such individual main bodies can be replaced, removed, or added in a modular manner.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described with reference to the drawings wherein: FIG.\",\n \"1 in a schematic sectional illustration shows a first embodiment of a singularization device for separating cryo-pellets from a comparatively large supply and for transferring the separated pellets into a target container via a vertically oriented metering duct, of an outlet duct that runs transversely to the latter, and of two pressure differential ducts, wherein in each case one pellet is suctioned at and fixed to the duct mouths of both pressure differential ducts; FIG.\",\n \"2 shows the arrangement as per FIG.\",\n \"1 when ejecting the lower pellet in the case of a simultaneously suctioned and fixed upper pellet; FIG.\",\n \"3 shows the arrangement as per FIGS.\",\n \"1 and 2 when transferring the upper pellet to the lower duct mouth; FIG.\",\n \"4 shows a variant of the arrangement as per FIGS.\",\n \"1 to 3, having a plurality of upper pressure differential ducts, presently in an exemplary manner three upper pressure differential ducts, for the simultaneous separation of a plurality of pellets; FIG.\",\n \"5 in a perspective view shows a cuboid-shaped main body for forming the singularization device as per FIGS.\",\n \"1 to 3, wherein a storage space, the metering duct, the outlet duct, the first pressure differential duct, and the second pressure differential duct are incorporated into the surface of the main body; FIG.\",\n \"6 in a perspective view shows an embodiment in which a plurality of cuboid-shaped main bodies as per FIG.\",\n \"5 are positioned so as to be mutually adjacent in a linear sequence, forming a linear sequence of a plurality of singularization devices; FIG.\",\n \"7 in a sectional illustration shows a variant of the embodiment as per FIG.\",\n \"1, having an outlet duct that discharges downward; FIG.\",\n \"8 in a plan view shows the main body as per FIG.\",\n \"7, having a circular-segment-shaped footprint; and, FIG.\",\n \"9 in a perspective view from below shows a group of a plurality of main bodies as per FIGS.\",\n \"7 and 8, arranged in a circular shape.\",\n \"DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION FIG.\",\n \"1 in a schematic sectional illustration shows a first embodiment of a singularization device 3 for transferring pellets 1, 1′, 1″, into a schematically indicated target container 2.The singularization device 3 shown here and the method, described hereunder and carried out by the singularization device 3, are suitable for separating and transferring almost arbitrary pellets, wherein the cryo-pellets that are particularly critical in terms of handling are the main focus and serve as examples for the pellets 1, 1′, 1″.\",\n \"The singularization device 3 includes a storage space 4 for the pellets 1 and a metering duct 5 that leads out of the storage space 4 downward and is vertically oriented.\",\n \"The storage space 4 here is configured as a funnel which in relation to the direction of weight tapers off in a downward manner into the metering duct 5.The vertical orientation of the metering duct 5 does not necessarily mean a precisely vertical alignment.\",\n \"An inclined embodiment in which in any case a significant vertical extent is present in portions can also be expedient.\",\n \"A first longitudinal axis 28 of the metering duct 5, which in the usual operating position in the embodiment shown does indeed lie parallel with the direction of weight but in relation to the direction of weight can also have an inclination of not more than 45° and in particular of not more than 30°, a serves as a yardstick.\",\n \"The singularization device 3 furthermore includes an outlet duct 6 which at a connection point 7 is connected to the metering duct 5 and leads transversely away from the metering duct 5.To this end, the outlet duct 6 in the embodiment shown is horizontally disposed.\",\n \"A second longitudinal axis 29 of the outlet duct 6 in the usual operating position thus lies perpendicularly to the direction of weight, or parallel with the horizontal, respectively.\",\n \"The second longitudinal axis 29 in relation to the horizontal can also have an inclination of preferably not more than 45° and in particular of not more than 30°.\",\n \"The singularization device 3 moreover includes at least one, presently exactly one, first pressure differential duct 8, and a second pressure differential duct 10.The first pressure differential duct 8 via a first duct mouth 9 above the connection point 7 opens into the metering duct 5.The second pressure differential duct 10 by way of a second duct mouth 11 above the first duct mouth 9 opens into the connection point 7.The first pressure differential duct 8 has a first duct axis 12, while the second pressure differential duct 10 has a second duct axis 13.The first duct axis 12 in the region of the associated duct mouth 9 lies transversely to the first longitudinal axis 28 of the metering duct 5, while the second duct axis 13 of the second pressure differential duct 10 in the region of the associated duct mouth 11 runs substantially parallel, presently even so as to be coaxial, with the second longitudinal axis 29 of the outlet duct 6.The two pressure differential ducts 8, 10 at the assigned duct mouths 9, 11 thereof are provided in each case with one retention means 18, 19 that prevents any ingress of foreign particles and in particular of the pellets 1, 1′, 1″ into the respective pressure differential ducts 8, 10.However, at the same time, the retention means 18, 19 are gas-permeable.\",\n \"Filter materials with fine pores, such as sintered filters, membrane filters, or the like are suitable therefor.\",\n \"In order for the method to be carried out, it is necessary for the first, upper pressure differential duct 8 to be able to be impinged with negative pressure when required, while the second, lower pressure differential duct 10 is to be able to be impinged with positive pressure when required.\",\n \"However, in the embodiment shown, both pressure differential ducts 8, 10 are impingable in an alternating manner with negative pressure or else with positive pressure.\",\n \"To this end, in each case one negative pressure source 14 as well as in each case also one positive pressure source 15 are provided for both pressure differential ducts 8, 10, wherein the first pressure differential duct 8, or the second pressure differential duct 10, respectively, via a respective assigned switching valve 16 can be selectively connected to the associated negative pressure source 14 or to the associated positive pressure source 15.Of course, a position of the respective switching valve 16 in which the ambient pressure is set in the respective pressure differential duct 8, 10 is also possible.\",\n \"The operation of the singularization device 3 shown can be performed at atmospheric conditions, wherein compressed air via the negative pressure source 14 is fed into the system by way of the respective pressure differential duct 8, 10.Protective gas containers 17 in which protective gas is kept available under positive pressure are provided as positive pressure sources 15 in the embodiment shown.\",\n \"In the context of individual method steps that are described further below, the pressurized protective gas via the first pressure differential duct 8 and/or of the second pressure differential duct 10 is directed from the respective protective gas container 17 through the respectively assigned duct mouth 9, 11 into the metering duct 5 or into the outlet duct 6, respectively.\",\n \"In the interests of simplicity two protective gas containers 17 are drawn in according to FIG.\",\n \"1.However, it can also be expedient to feed both pressure differential ducts 8, 10 from a collective protective gas container 17.According to ab advantageous embodiment of the method, according to FIG.\",\n \"1 a comparatively large supply of a plurality of pellets 1 is first provided in the storage space 4.The pellets 1 together with the singularization device 3 form an inherently tuned system according to which the available passage cross section of the metering duct 5 as well as the available passage cross-section of the outlet duct 6 are slightly larger than a mean diameter D (FIG.\",\n \"2) of the pellets 1.In a more exact definition, the passage cross-section in particular of the vertically standing metering duct 5 is larger than the mean diameter D (FIG.\",\n \"2) by so much that the pellets 1 can indeed pass in an unimpeded manner from the top to the bottom through the metering duct 5 without however, on the other hand, two pellets being allowed to pass simultaneously beside one another.\",\n \"Rather, the available passage cross-section of the metering duct 5 is dimensioned in such a manner that the pellets 1 drop from the storage space 4 downward into the metering duct 5, thereby forming a column of pellets 1, 1′, 1″ that lie on top of one another.\",\n \"As part of this column, a lowermost pellet 1′ in the initial position shown in FIG.\",\n \"1 is located in the connection point 7 of the outlet duct 6 with the metering duct 5.It can be expedient here in for the lowermost pellet 1′ to stand on the base of the outlet duct 6.In the embodiment shown, the second pressure differential duct 10 is initially impinged with negative pressure in that the second pressure differential duct 10 via the assigned switching valve 16 is connected to the associated negative pressure source 14.Consequently, the lowermost pellet 1′ is suctioned onto the second duct mouth 11 and pressed against the retention means 19, on account of which the lowermost pellet 1′ is held in position.\",\n \"In the initial position mentioned according to FIG.\",\n \"1, the first, upper pressure differential duct 8 is also simultaneously impinged with negative pressure, to which end the first pressure differential duct 8 likewise via the switching valve 16 thereof is connected to the associated negative pressure source 14 of the pressure differential duct 8.Consequently, that pellet 1″ that is closest to the assigned duct mouth 9 is suctioned from the column of pellets 1.This pellet 1″ is pressed against the retention means 18 and herein is locationally fixed as long as the holding negative pressure is maintained in the upper pressure differential duct 8.It is prevented on account thereof that the suctioned pellet 1 slips downward into the connection point 7, on the one hand.\",\n \"On the other hand, the suctioned pellet″ acts as a block for the pellets 1 located thereabove and consequently prevents the latter from moving on downward.\",\n \"In the combined view of FIGS.\",\n \"1 and 2 it also becomes evident that the first duct mouth 9 of the first, upper pressure differential duct 8 is positioned above the second duct mouth 11 of the second, lower pressure differential duct 10 by way of a height differential ΔH.\",\n \"This height differential ΔH is at least approximately an integral multiple of the mean diameter D of the pellets 1.It will become evident further below that a mathematically exact adherence to the integral multiple is not crucial, this here being expressed by way of the terminology “at least approximately”.\",\n \"In any case, this integral multiple in the embodiment as per FIGS.\",\n \"1 to 3 within the context of specific tolerances is one.\",\n \"The latter and the adherence to the tolerances mentioned leads to only space for exactly one lowermost pellet 1 to remain below the pellet 1″ that has been suctioned onto the upper duct mouth 9 and acts as a block.\",\n \"In an analogous manner thereto, in the case of a larger integral multiple, there remains space for a corresponding number of lower pellets 1′ below the mentioned pellet 1″ that acts as a block.\",\n \"The latter case is illustrated in an exemplary manner in FIG.\",\n \"4; this to be discussed in yet more detail further below.\",\n \"FIGS.\",\n \"2 and 3 in fragments show the arrangement as per FIG.\",\n \"1 when the following method steps are being carried out.\",\n \"Proceeding from the initial position as per FIG.\",\n \"1, exhausting those lower pellets 1′ which are collected below the pellet 1″ that acts as a block and is fixed to the first duct mouth 9 is performed in the next method step.\",\n \"This method step is shown in the schematic sectional illustration as per FIG.\",\n \"2.To this end, the second pressure differential duct 10 is impinged with positive pressure over a defined period of time, to which end the second pressure differential duct 10 via the assigned switching valve 16 is connected to the positive pressure source 15 that is assigned to the second pressure differential duct 10.A gas pulse, as a consequence of which gas is blown according to an arrow 22 through the duct mouth 11 into the outlet duct 6 along the fourth duct axis 29 thereof is created in the lower pressure differential duct 10.The blown-in gas according to an arrow 23 carries the lowermost pellet 1′ that previously was suctioned at the lower duct mouth 11 through the outlet duct 6 into the provided target container 2.A single gas pulse is typically sufficient for exhausting a single lower pellet 1′ or a plurality of lower pellets 1′ that have been simultaneously collected.\",\n \"In the case of a plurality of lower pellets 1′ having been separated below the pellet 1″ that serves as a block, exhausting can alternatively also be performed by way of a corresponding number of gas pulses.\",\n \"In any case, the upper, first pressure differential duct 8 during exhausting is impinged with the holding negative pressure that has been described above such that the pellet 1″ that serves as a block as well as all pellets 1 that are located thereabove remain in place despite the pressure pulse that has been initiated below.\",\n \"The pellets 1 are thus neither blown back into the storage space 4 nor are the pellets 1 able to prematurely move on downward into the connection point 7 that in the meantime has been vacated.\",\n \"Once the one or the plurality of lower pellets 1′ have been exhausted according to FIG.\",\n \"2, the next method step is carried out according to FIG.\",\n \"3.The holding negative pressure in the first pressure differential duct 8 is switched off such that the pellet 1″ that is held on the first duct mouth 11 (FIG.\",\n \"2) moves on toward the connection point 7, a new lowermost pellet 1′ (FIG.\",\n \"3) being located in the connection point 7.This replenishment can take place solely as a result of the acting weights.\",\n \"To this end, the lower, second pressure differential duct 10 in the embodiment shown is again impinged with negative pressure, on account of which the respective lowermost pellet 1′ prior to being exhausted later is suctioned onto the second duct mouth 11.The transfer of pellets from the upper, first duct mouth 9 to the lower, second duct mouth 11 according to an arrow 25, as has been described above, can also yet be supported in that the first pressure differential duct 8 is briefly impinged with positive pressure in that the first pressure differential duct 8 via the assigned switching valve 16 thereof is connected to the assigned positive pressure source 15.On account thereof, a pressure pulse via which gas according to an arrow 24 is introduced through the duct mouth 9 into the metering duct 5, thereby supporting the moving-on according to the arrow 25 of the pellet 1″ that has previously been held on the first duct mouth 9 (FIG.\",\n \"2) is formed.\",\n \"This positive pressure pulse simultaneously prevents premature moving-on in a downward manner of the column of pellets 1 that is located thereabove.\",\n \"Air or compressed air, respectively, can be used as the process and positive pressure medium.\",\n \"To the extent that a protective gas container 17 is provided as a positive pressure source 15 according to the embodiment as per FIGS.\",\n \"1 to 3, the protective gas in the case of the pressure pulses that have been described above is introduced from the respective protective gas container 17 through the first and/or the second pressure differential duct 8, 10 into the metering duct 5 or into the outlet duct 6, respectively.\",\n \"On account thereof, a protective gas atmosphere can be maintained in all regions of the singularization device that interact with the pellets 1, 1′, 1″.\",\n \"This permits the handling of cryo-pellets that are extremely hygroscopic and, when required, also enables the pellets 1, 1′, 1″ to be rendered inert.\",\n \"The impingement of the two pressure differential ducts 8, 10 with negative pressure can be mutually overlapping to a certain extent.\",\n \"However, suctioning of the pellet 1″ that acts as a block onto the first duct mouth 9, and suctioning of the lowermost pellet 1′ onto the second duct mouth 11, is advantageously performed in a temporally alternating manner such that the holding negative pressure on the upper duct mouth 9 is at least temporarily switched off when the transfer and the moving-on of the lowermost pellet 1′ are performed via negative pressure at the lower, second duct mouth 11.In any case, the temporary negative pressure in the lower, second pressure differential duct 10 also supports the moving-on of the pellets 1 from the target container 2 into the metering duct 5.This can also be utilized for the initial filling of the metering duct 5 with pellets 1, 1′, 1″ for achieving the initial position as per FIG.\",\n \"1.Subsequently to the method step according to FIG.\",\n \"3, the upper, first pressure differential duct 8 is again impinged with negative pressure, on account of which a new pellet 1″ that serves as a block is consequently suctioned and fixed.\",\n \"The initial position as per FIG.\",\n \"1 is reestablished, and the previously described method cycle can restart.\",\n \"It can also be derived from the illustration as per FIG.\",\n \"1 that monitoring means which presently in an exemplary manner are configured as a pressure sensor 26 and/or as a flow rate sensor 27 and are connected to a suitable monitoring unit (not illustrated here for the sake of simplicity) are disposed in the region of the first and/or the second pressure differential duct 8, 10.On account thereof, pressure monitoring and/or rate flow monitoring can be performed and errors in the method sequence can be identified.\",\n \"FIG.\",\n \"4 in a schematic sectional illustration shows a variant of the arrangement as per FIGS.\",\n \"1 to 3, wherein a plurality of, in an exemplary manner presently three, first pressure differential ducts 8, 8′, 8″ via the first duct mouths 9, 9′, 9″ assigned thereto open into the metering duct 5.The height differential between the individual duct mouths 9, 9′, 9″ here is again an integral multiple of the mean diameter D of the pellets 1, wherein the integral multiple here is 1.The uppermost first duct mouth 9 thus is at a height differential AH above the second duct mouth 11, wherein, in a manner analogous to that of the embodiment as per FIGS.\",\n \"1 to 3, this height differential AH is at least approximately an integral multiple of the mean diameter D. This integral multiple in the embodiment shown is 3.To the extent of the uppermost of the plurality of first pressure differential ducts 8, 8′, 8″, presently thus the pressure differential duct 8, thus being impinged with negative pressure a block by way of an adhering or suctioned pellet 1″, respectively, is configured at the assigned duct mouth 9, exactly three lower pellets 1′ being collected therebelow and according to the method sequence as per FIGS.\",\n \"1 to 3 being exhausted into the respective target container 2.Depending on requirements, however, one of the other first pressure differential ducts 8′, 8″ can also be impinged with negative pressure, this then resulting in a separation of precisely one or precisely two lower pellets 1′.\",\n \"Of course, the same applies in an analogous manner also to a deviating number or positioning of first duct mouths 9, 9′, 9″.\",\n \"In terms of the remaining features and reference signs as well as also method steps, the embodiment as per FIG.\",\n \"4 is identical to that of FIGS.\",\n \"1 to 3.FIG.\",\n \"5 in a perspective view shows a cuboid-shaped main body 20 for forming an individual singularization device 3 as per FIGS.\",\n \"1 to 3, and 6.It can be expedient for bores, openings, or the like, to be incorporated into such a main body 20 so as to configure therewith the various ducts as described above.\",\n \"The two pressure differential ducts 8, 10 in the embodiment shown are formed by two such bores.\",\n \"Deviating therefrom, the storage space 4, the metering duct 5, and the outlet duct 6 are machined as a duct-type depression into a surface 21 of the main body 20, the depressions initially being open to the outside.\",\n \"However, it can also be expedient for the two pressure differential ducts 8, 10 or another part of the aforementioned elements, to be additionally configured in this one surface 21.According to the perspective illustration as per FIG.\",\n \"6, a plurality of such main bodies 20 can be interconnected in a linear sequence, wherein the duct-type depressions mentioned in a main body 20 are closed by the neighboring main body 20′, and on account of which singularization devices 3, 3′ that are interconnected in the manner of modules are formed.\",\n \"Deviating therefrom, FIG.\",\n \"8 shows a main body 20 in a plan view, the footprint of the main body 20 being in the shape of a circular segment.\",\n \"Here too, the various ducts can be configured on a lateral surface 21 in a manner analogous to that of FIG.\",\n \"5.However, in an exemplary manner, the storage space 4, the metering duct 5, and also the other elements, are machined so as to be centric in the main body 20.FIG.\",\n \"9 in a perspective view from below shows a group of a plurality of main bodies 20, 20′ as per FIG.\",\n \"8, the main bodies 20, 20′ being interconnected in the manner of modules so as to be mutually adjacent and, by virtue of the shape of a circular segment of an individual main body 20 overall forming a group of singularization devices 3, 3′ that is disposed in the shape of a circle.\",\n \"Of course, individual singularization devices 3′ which presently for the sake of simplicity are only illustrated in dashed lines can also be omitted, on account of which the overall shape of a circular segment of the group of singularization devices 3 results.\",\n \"It can also be derived from the perspective illustration as per FIG.\",\n \"9 that little space in the radially inward region remains of the circular or circular-segment shape chosen.\",\n \"In consideration thereof, exit openings 30 of the outlet ducts 6 (FIG.\",\n \"7) are disposed on the lower side of the main bodies 20.Details thereof are derived from the schematic sectional illustration of the main body 20 as per FIG.\",\n \"7.In a manner deviating from the embodiment as per FIG.\",\n \"1, only that part of the outlet duct 6 that is directly adjacent to the connection point 7 runs transversely to the metering duct 5, or transversely to the direction of weight, respectively, while a duct segment 6′ of the outlet duct 6 that is adjacent thereto is angled in a downward manner and via the lower exit opening 30 leads to the target container 2 that is positioned therebelow.\",\n \"In as far as not explicitly described or illustrated in the drawings so as to deviate therefrom, the embodiments as per FIGS.\",\n \"5 and 6 and as per FIGS.\",\n \"7 to 9 in terms of the remaining features and reference signs are mutually identical as well as identical to the embodiment as per FIGS.\",\n \"1 to 3.The same also applies to the assigned method steps.\",\n \"Apart therefrom, features of the one embodiment can also be linked to a respective other embodiment.\",\n \"It is understood that the foregoing description is that of the preferred embodiments of the invention and that various changes and modifications may be made thereto without departing from the spirit and scope of the invention as defined in the appended claims.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874732"}}},{"rowIdx":4494676,"cells":{"text":{"kind":"list like","value":[["POWER SUPPLY SYSTEM AND SHORT CIRCUIT AND/OR BAD CONNECTION DETECTION METHOD THEREOF, AND POWER CONVERTER THEREOF","The present invention discloses a short circuit and/or bad connection detection method for use in a power supply system.","The power supply system includes a power converter which converts an input voltage to an output voltage and supplies an output current to an electronic device.","In the short circuit detection method, the conversion from the input voltage to the output voltage is disabled in a disable time period, and whether a short circuit occurs is determined according to the decreasing speed of the output voltage.","In the bad connection detection method, an actual voltage and an actual current received by the electronic device are compared with the output voltage and the output current, to determine whether a bad connection occurs."],["1.A power converter for converting an input voltage to an output voltage, wherein the output voltage is to be supplied to an electronic device through a cable; the power converter comprising: a switch; a switch control unit for controlling the switch, to perform the conversion from the input voltage to the output voltage; and an abnormal condition detection unit, including: a temporary stop signal generation circuit for generating a temporary stop signal, to temporarily disable the switch control unit for a disable time period; and an abnormal voltage drop detection circuit for determining whether or not an abnormal condition occurs during the disable time period in which the switch control unit has been disabled according to a decreasing speed of the output voltage; wherein, after the switch control unit has been disabled, the abnormal voltage drop detection circuit subsequently determines whether the output voltage drops abnormally according to the decreasing speed of the output voltage, so as to subsequently determine whether or not the abnormal condition occurs.","2.The power converter of claim 1, wherein the abnormal voltage drop detection circuit includes: a voltage comparison circuit for determining whether or not the abnormal condition occurs according to a comparison result between the output voltage and a reference voltage.","3.The power converter of claim 2, wherein the reference voltage is adjustable.","4.The power converter of claim 3, wherein: when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.","5.The power converter of claim 1, wherein the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to the switch control unit via a feedback circuit, wherein the temporary stop signal disables the switch control unit by turning off the feedback circuit.","6.The power converter of claim 1, wherein the temporary stop signal generation circuit generates the temporary stop signal by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during or immediately after a start-up operation; generating the temporary stop signal STOP during or immediately after a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly.","7.A abnormal condition detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage to be supplied to an electronic device through a cable; the abnormal condition detection method of the power supply system comprising the steps of: stopping converting the input voltage to the output voltage for a disable time period in which a switch control unit of the power converter has been disabled; after the switch control unit has been disabled, subsequently determining whether the output voltage drops abnormally according to a decreasing speed of the output voltage, so as to subsequently determine whether or not a an abnormal condition occurs.","8.The abnormal condition detection method of the power supply system of claim 7, wherein the step of determining whether or not the abnormal condition occurs according to the decreasing speed of the output voltage includes: comparing the output voltage with a reference voltage.","9.The abnormal condition detection method of the power supply system of claim 8, wherein the reference voltage is adjustable.","10.The abnormal condition detection method of the power supply system of claim 9, wherein: when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.","11.The abnormal condition detection method of the power supply system of claim 7, wherein the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to a switch control unit via a feedback circuit, wherein the step of stopping converting the input voltage to the output voltage for a disable time period includes: disabling the switch control unit by turning off the feedback circuit.","12.The abnormal condition detection method of the power supply system of claim 7, wherein the step of stopping converting the input voltage to the output voltage for a disable time period includes: starting the disable time period during or immediately after a start-up operation; starting the disable time period during or immediately after a power-on-reset operation; starting the disable time period periodically; or starting the disable time period irregularly; or a combination of two or more of the above.","13.A power supply system, comprising: a power converter for converting an input voltage to an output voltage and supplying an output current, wherein the output voltage and the output current are supplied to an electronic device through a cable; and a bad connection detection unit, including: a voltage sensing circuit for sensing an actual voltage received by the electronic device; a current sensing circuit for sensing an actual current received by the electronic device; a first analog-to-digital converter for converting the actual voltage to a first digital signal; a second analog-to-digital converter for converting the actual current to a second digital signal; and a calculation circuit for determining whether or not a bad connection occurs according to the first digital signal, the second digital signal, the output voltage and the output current.","14.The power supply system of claim 13, wherein the calculation circuit compares the first digital signal with a desired level of the output voltage and compares the second digital signal with a desired level of the output current, to determine whether or not the bad connection occurs.","15.The power supply system of claim 13, wherein the calculation circuit compares the first digital signal with a digital signal of the output voltage converted from a sensed value of the output voltage and compares the second digital signal with a digital signal of the output current converted from a sensed value of the output current, to determine whether or not the bad connection occurs.","16.The power supply system of claim 13, wherein the bad connection detection unit is located inside the electronic device.","17.The power supply system of claim 13, wherein the bad connection detection unit has a first part inside the electronic device and a second part inside the power converter, and the first and second parts of the bad connection detection unit communicate through a signal line of the cable.","18.A bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with a desired level of the output voltage and a desired level of the output current, respectively; and when a difference between the actual voltage digital signal and the desired level of the output voltage exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the desired level of the output current exceeds a second predetermined threshold difference, determining that a bad connection occurs.","19.A bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; sensing the output voltage and the output current and converting the output voltage and the output current to an output voltage digital signal and an output current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with the output voltage digital signal and the output current digital signal, respectively; and when a difference between the actual voltage digital signal and the output voltage digital signal exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the output current digital signal exceeds a second predetermined threshold difference, determining that a bad connection occurs."],["<SOH> BACKGROUND OF THE INVENTION <EOH>"],["<SOH> SUMMARY OF THE INVENTION <EOH>From one perspective, the present invention provides a power converter for converting an input voltage to an output voltage, wherein the output voltage is to be supplied to an electronic device through a cable; the power converter comprising: a switch; a switch control unit for controlling the switch, to perform the conversion from the input voltage to the output voltage; and a short circuit detection unit, including: a timer circuit for generating a temporary stop signal, to temporarily disable the switch control unit for a disable time period; and an abnormal voltage drop detection circuit for determining whether or not a short circuit occurs during the disable time period according to a decreasing speed of the output voltage.","In one embodiment, the abnormal voltage drop detection circuit includes: a voltage comparison circuit for determining whether or not the short circuit occurs according to a comparison result between the output voltage and a reference voltage.","In one embodiment, the reference voltage is adjustable.","In one embodiment, when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.","In one embodiment, the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to the switch control unit via a feedback circuit, wherein the temporary stop signal disables the switch control unit by turning off the feedback circuit.","In one embodiment, the timer circuit generates the temporary stop signal by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during or immediately after a start-up operation; generating the temporary stop signal STOP during or immediately after a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly.","From another perspective, the present invention provides a short circuit detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage to be supplied to an electronic device through a cable; the short circuit detection method of the power supply system comprising the steps of: stopping converting the input voltage to the output voltage for a disable time period; and determining whether or not a short circuit occurs according to a decreasing speed of the output voltage.","From another perspective, the present invention provides a power supply system, comprising: a power converter for converting an input voltage to an output voltage and supplying an output current, wherein the output voltage and the output current are supplied to an electronic device through a cable; and a bad connection detection unit, including: a voltage sensing circuit for sensing an actual voltage received by the electronic device; a current sensing circuit for sensing an actual current received by the electronic device; a first analog-to-digital converter for converting the actual voltage to a first digital signal; a second analog-to-digital converter for converting the actual current to a second digital signal; and a calculation circuit for determining whether or not a bad connection occurs according to the first digital signal, the second digital signal, the output voltage and the output current.","In one embodiment, the calculation circuit compares the first digital signal with a desired level of the output voltage and compares the second digital signal with a desired level of the output current, to determine whether or not the bad connection occurs.","In one embodiment, the calculation circuit compares the first digital signal with a digital signal of the output voltage converted from a sensed value of the output voltage and compares the second digital signal with a digital signal of the output current converted from a sensed value of the output current, to determine whether or not the bad connection occurs.","In one embodiment, the bad connection detection unit is located inside the electronic device.","In one embodiment, the bad connection detection unit has a first part inside the electronic device and a second part inside the power converter, and the first and second parts of the bad connection detection unit communicate through a signal line of the cable.","From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with a desired level of the output voltage and a desired level of the output current, respectively; and when a difference between the actual voltage digital signal and the desired level of the output voltage exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the desired level of the output current exceeds a second predetermined threshold difference, determining that a bad connection occurs.","From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; sensing the output voltage and the output current and converting the output voltage and the output current to an output voltage digital signal and an output current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with the output voltage digital signal and the output current digital signal, respectively; and when a difference between the actual voltage digital signal and the output voltage digital signal exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the output current digital signal exceeds a second predetermined threshold difference, determining that a bad connection occurs.","The objectives, technical details, features, and effects of the present invention will be better understood with regard to the detailed description of the embodiments below, with reference to the attached drawings."],["CROSS REFERENCE The present invention claims priority to U.S. 62/014,305, filed on Jun.","19, 2014.BACKGROUND OF THE INVENTION Field of Invention The present invention relates to a power supply system capable of performing a short circuit detection and a bad connection detection; particularly, it relates to such a power supply system capable of detecting abnormal but not severe conditions which lead to undesirable power loss, such as weakly short circuit and weakly bad connection conditions, and a detection method and a power converter thereof.","Description of Related Art Please refer to FIGS.","1A and 1B.","FIG.","1A shows a block diagram of a conventional power supply system.","FIG.","1B explains how an abnormal but not severe condition occurs in the prior art of FIG.","1A which leads to power loss.","The conventional power supply system 10 comprises a power converter 11, a cable 12 and an electronic device 13.A port 112 of the power converter 11 is connected to a port 121 of the cable 12.A port 132 of the electronic device 13 is connected to another port 122 of the cable 12.When the power converter 11, the cable 12 and the electronic device 13 are connected in serial, power lines 17 and 18 form a loop to deliver the power.","The cable 12 further includes a signal line 14, for data transmission between the power converter 11 and the electronic device 13.The signal line 14 can be, for example but not limited to, a differential signal line.","As shown in FIG.","1B, when an unwanted material such as dust, dirt, thread, etc.","falls on or in the ports 112, 121, 122 and/or 132, the power lines 17 and 18 may be “weakly short-circuited”—i.e., a short-cut current path is formed between the power lines 17 and 18, but the electrical connection is weak, so there is not a huge amount of current flowing through this short-cut current path.","Such “weakly short circuit” is illustrated by the resistors R11, R121, R122 and R13 in the figure.","Although there is not a huge amount of current flowing through the short-cut current path, this abnormal condition still leads to power loss, and if this abnormal condition is not well controlled, it can be very dangerous.","Besides, if the power lines 17 and 18 does not have a good quality, or a bad connection occurs between the ports, even though the bad connection is not so severe to cause an open-circuit, this abnormal condition will also lead to power loss.","The bad connection is illustrated by the resistors R1′, R2′, R3′ and R4′ in the figure.","Because the “weakly short circuit” and “bad connection” usually do not lead to fully short-circuit or complete open-circuit, the prior art did not propose an effective solution to address this issue.","The prior art U.S. Pat.","No.","8,498,087 and U.S. Pat.","No.","8,339,760 provide an approach to solve the above-mentioned problem by detecting whether there is abnormal temperature increase in the cable.","However, to do so, an additional heat detection signal line is required, which is not compatible to the current standard cable, and also leads to a higher manufacturing cost.","Moreover, before an abnormal temperature increase becomes detectable, unwanted power loss and other problems have already happened for a long time.","Therefore, the above-mentioned prior art patents do not practically solve the problem.","In view of the above, to overcome the drawbacks in the prior art, the present invention proposes a power supply system capable of detecting an abnormal condition such as a weakly short circuit and a bad connection, which leads to undesirable power loss.","SUMMARY OF THE INVENTION From one perspective, the present invention provides a power converter for converting an input voltage to an output voltage, wherein the output voltage is to be supplied to an electronic device through a cable; the power converter comprising: a switch; a switch control unit for controlling the switch, to perform the conversion from the input voltage to the output voltage; and a short circuit detection unit, including: a timer circuit for generating a temporary stop signal, to temporarily disable the switch control unit for a disable time period; and an abnormal voltage drop detection circuit for determining whether or not a short circuit occurs during the disable time period according to a decreasing speed of the output voltage.","In one embodiment, the abnormal voltage drop detection circuit includes: a voltage comparison circuit for determining whether or not the short circuit occurs according to a comparison result between the output voltage and a reference voltage.","In one embodiment, the reference voltage is adjustable.","In one embodiment, when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.","In one embodiment, the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to the switch control unit via a feedback circuit, wherein the temporary stop signal disables the switch control unit by turning off the feedback circuit.","In one embodiment, the timer circuit generates the temporary stop signal by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during or immediately after a start-up operation; generating the temporary stop signal STOP during or immediately after a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly.","From another perspective, the present invention provides a short circuit detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage to be supplied to an electronic device through a cable; the short circuit detection method of the power supply system comprising the steps of: stopping converting the input voltage to the output voltage for a disable time period; and determining whether or not a short circuit occurs according to a decreasing speed of the output voltage.","From another perspective, the present invention provides a power supply system, comprising: a power converter for converting an input voltage to an output voltage and supplying an output current, wherein the output voltage and the output current are supplied to an electronic device through a cable; and a bad connection detection unit, including: a voltage sensing circuit for sensing an actual voltage received by the electronic device; a current sensing circuit for sensing an actual current received by the electronic device; a first analog-to-digital converter for converting the actual voltage to a first digital signal; a second analog-to-digital converter for converting the actual current to a second digital signal; and a calculation circuit for determining whether or not a bad connection occurs according to the first digital signal, the second digital signal, the output voltage and the output current.","In one embodiment, the calculation circuit compares the first digital signal with a desired level of the output voltage and compares the second digital signal with a desired level of the output current, to determine whether or not the bad connection occurs.","In one embodiment, the calculation circuit compares the first digital signal with a digital signal of the output voltage converted from a sensed value of the output voltage and compares the second digital signal with a digital signal of the output current converted from a sensed value of the output current, to determine whether or not the bad connection occurs.","In one embodiment, the bad connection detection unit is located inside the electronic device.","In one embodiment, the bad connection detection unit has a first part inside the electronic device and a second part inside the power converter, and the first and second parts of the bad connection detection unit communicate through a signal line of the cable.","From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with a desired level of the output voltage and a desired level of the output current, respectively; and when a difference between the actual voltage digital signal and the desired level of the output voltage exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the desired level of the output current exceeds a second predetermined threshold difference, determining that a bad connection occurs.","From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; sensing the output voltage and the output current and converting the output voltage and the output current to an output voltage digital signal and an output current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with the output voltage digital signal and the output current digital signal, respectively; and when a difference between the actual voltage digital signal and the output voltage digital signal exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the output current digital signal exceeds a second predetermined threshold difference, determining that a bad connection occurs.","The objectives, technical details, features, and effects of the present invention will be better understood with regard to the detailed description of the embodiments below, with reference to the attached drawings.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1A shows a block diagram of a conventional power supply system.","FIG.","1B explains how an abnormal condition occurs in the prior art of FIG.","1A which leads to power loss.","FIGS.","2A-2B show a block diagram of a power supply system according to a first embodiment of the present invention.","FIG.","2C shows an embodiment of a power converter.","FIGS.","3A-3B show a block diagram of a power supply system according to a second embodiment of the present invention.","FIGS.","4A-4B show a block diagram of a power supply system according to a third embodiment of the present invention.","FIG.","5A shows an embodiment of a short circuit detection unit.","FIG.","5B explains how the present invention performs the short circuit detection.","FIG.","6A shows another embodiment of a short circuit detection unit.","FIGS.","6B-6C show two embodiments as to how the present invention generates a temporary stop signal.","FIGS.","7A-7C explain an embodiment as to how the present invention performs the bad connection detection.","FIGS.","7D-7E show two embodiments as to how the present invention performs the bad connection detection.","DESCRIPTION OF THE PREFERRED EMBODIMENTS The above and other technical details, features and effects of the present invention will be will be better understood with regard to the detailed description of the embodiments below, with reference to the drawings.","The drawings as referred to throughout the description of the present invention are for illustration only, to show the interrelations between the components and devices, but not drawn according to actual scale.","Please refer to FIGS.","2A-2C, FIGS.","3A-3B and FIGS.","4A-4B.","FIG.","2A shows a block diagram of a power supply system according to a first embodiment of the present invention.","FIG.","2B shows a circuit diagram of FIG.","2A.","FIG.","2C shows an embodiment of a power converter.","In FIGS.","2A-2C, the power converter is not coupled to a cable.","FIG.","3A shows a block diagram of a power supply system according to a second embodiment of the present invention.","FIG.","3B shows a circuit diagram of FIG.","3A.","In FIGS.","3A-3B, the power converter is coupled to a cable.","FIG.","4A shows a block diagram of a power supply system according to a third embodiment of the present invention.","FIG.","4B shows a circuit diagram of FIG.","4A.","In FIGS.","4A-4B, the power converter and the electronic device are coupled to each other through a cable.","In one embodiment, the power converter 21 has not yet been connected to any other device or component (as shown by the power supply system 20 in FIG.","2B).","As shown in FIG.","2B, the power converter 21 has one port 212.In another embodiment, the power converter 21 has already been connected to a cable 22 but has not yet been connected to an electronic device (as shown by the power supply system 30 in FIG.","3B).","As shown in FIG.","3B, a port 212 of the power converter 21 is connected to a port 221 of the cable 22.In still another embodiment, the power converter 21, the cable 22 and the electronic device 23 have already been connected in serial (as shown by the power supply system 40 in FIG.","4B).","A port 212 of the power converter 21 is connected to a port 221 of the cable 22, and a port 232 of the electronic device 23 is connected to a port 222 of the cable 22.Please refer to FIG.","2C.","The power converter 21 can be, for example but not limited to, an isolated type AC-DC converter.","Note that the power converter 21 shown in FIG.","2C is for illustrative purpose only, but not for limiting the scope of the present invention.","The power converter 21 can be any other type of power converter.","In the isolated type AC-DC converter shown in FIG.","2C, the power converter 21 includes a transformer 213 having a primary side 213a and a secondary side 213b.","The primary side 213a is coupled to a switch SW which is controlled by a switch control unit 214.The secondary side 213b is coupled to an output unit 210, which generates a feedback signal FB according to an output voltage Vout, and provides the feedback signal FB through a feedback circuit 215 (e.g., an opto-coupler circuit) to the switch control unit 214.In normal operation, the switch control unit 214 controls the switch SW according to the feedback signal FB, to convert an input voltage Vin to the output voltage Vout at the secondary side 213b.","The output unit 210 includes a short circuit detection unit 211, to detect whether a short circuit or even a weakly short circuit occurs.","The details for the short circuit detection unit 211 will be described later.","The basics of an isolated type AC-DC converter are well known to those skilled in the art, so for the sake of simplicity, only the circuits relevant to the present invention are illustrated whereas other circuits irrelevant to the present invention are omitted.","Note that the power converter 21 is not limited to an isolated type AC-DC converter, yet it can also be another type of switching power converter such as a synchronous or asynchronous boost, buck, buck-boost or inverting power converter.","Among these switching power converters (including the isolated type AC-DC converter), they all have a switch control unit, which controls at least one switch according to the feedback signal, to convert the input voltage to the output voltage.","The present invention is applicable to anyone of these switching power converters.","The short circuit detection unit can be located at any appropriate location within the switching power converter, which, when detecting that a short circuit or a weakly short circuit occurs, issues an error signal Error 1 to the switch control unit.","Please refer to FIGS.","3A-3B and FIGS.","4A-4B.","Unlike the embodiment shown in FIGS.","2A-2C, the power converter 21 shown in FIGS.","3A-3B has already been connected to a cable 22.And, in embodiment shown in FIGS.","4A-4B, the power converter 21 is connected to the cable 22 and the cable 22 is connected to the electronic device 23.In the embodiment shown in FIGS.","4A-4B, in normal operation, the power lines 27 and 28 form a loop, so that power can be delivered to the electronic device 23.The cable 22 further includes a signal line 24, for data transmission between the power converter 21 and the electronic device 23.The signal line 24 can be, for example but not limited to, a differential signal line.","As shown in FIGS.","2B, 3B and 4B, when there is an unwanted material such as dust falling on or in the ports 212, 221, 222 and/or 232, a short-cut current path is formed between the power lines 17 and 18, but the electrical connection is weak, so there is not a huge amount of current flowing through this short-cut current path.","Such “weakly short circuit” is illustrated by the resistors R21, R221, R222 and R23 in the figures.","This abnormal condition leads to power loss, and if this abnormal condition is not well controlled, it can be very dangerous.","To overcome this drawback, the short circuit detection unit 211 of this embodiment can detect whether a short circuit abnormal condition occurs, so that necessary procedures can be taken as soon as possible.","FIGS.","5A-5B shows an embodiment of the short circuit detection unit 211.Regardless whether the power converter 21 is connected to the cable 22 and regardless whether the cable 22 is connected to the electronic device 23, this embodiment can be adopted to check whether a short circuit abnormal condition occurs.","Please refer to FIGS.","5A-5B.","The short circuit detection unit 211 of this embodiment includes a timer circuit 2112 and an abnormal voltage drop detection circuit 2114.The timer circuit 2112 counts time according to a clock signal CLK, to generate a temporary stop signal STOP which lasts for a period of time, i.e., the disable time period Tdis.","(“To generate a temporary stop signal STOP” means to set the level of the temporary stop signal STOP to a predefined level, such as a high level or a low level of a digital signal).","In this embodiment, the timer circuit 2112 periodically generates the temporary stop signal STOP.","In other embodiments, the temporary stop signal STOP can be triggered and generated by other mechanisms (which will be described later).","The clock signal CLK can be obtained from a clock signal inside the power converter 21; or, it can be obtained from an oscillator (not shown).","When the temporary stop signal STOP is generated, the switch control unit 214 is disabled, so that the power converter 21 does not operate to convert the input voltage Vin to the output voltage Vout.","The switch control unit 214 can be disabled by various ways, and the present invention is not limited to anyone of these ways.","This embodiment shows one example: if the power converter 21 is isolated type AC-DC converter, it usually uses a feedback circuit 215 (e.g., an opto-coupler circuit) to transmit the feedback signal FB.","The temporary stop signal STOP can be used to disable the feedback circuit 215.Because the isolated type AC-DC converter adopts a negative feedback mechanism, when the feedback circuit 215 does not operate, the switch control unit 214 will judge that the output voltage Vout is sufficient, so as not to proceed the operation to convert the input voltage Vin to the output voltage Vout, and this is equivalent to disabling the switch control unit 214.If the power converter 21 is another type of switching power converter, the switch control unit 214 can be disabled by any suitable way.","The disable time period Tdis in which the temporary stop signal STOP disables the switch control unit 214 is shown in FIG.","5B.","While the temporary stop signal STOP disables the switch control unit 214, the timer circuit 2112 enables the abnormal voltage drop detection circuit 2114 by an enable signal EN.","Therefore, the temporary stop signal STOP and the enable signal EN can be the same signal, or one being an inverted signal of the other.","Certainly, in another embodiment, the temporary stop signal STOP and the enable signal EN can be two different signals, and the enable signal EN can start slightly later than the temporary stop signal STOP.","Being enabled, the abnormal voltage drop detection circuit 2114 determines whether the output voltage Vout drops abnormally according to a decreasing speed of the output voltage Vout.","Please refer to FIG.","5B.","During the disable time period Tdis, the power converter 21 does not operate to convert the input voltage Vin to the output voltage Vout.","However, because there is a normal depletion of charges, the output voltage Vout will drop slowly.","Hence, a threshold line can be set, based upon a reasonable decreasing speed of the output voltage Vout.","If the decreasing speed of the output voltage Vout is faster and than the threshold line, it can be judged that an undesirable short circuit occurs.","Please refer to FIG.","6A in conjugation with FIG.","5B.","In one embodiment, the abnormal voltage drop detection circuit 2114 includes a voltage comparison circuit 2114a, which compare the output voltage Vout with a reference voltage Vdis (in circuit design, an equivalent approach is to compare a divided voltage of the output voltage Vout with a proportional value of the reference voltage Vdis).","In normal operation, the output voltage Vout will not drop below the reference voltage Vdis during the disable time period Tdis (as shown by the line A in FIG.","5B).","Nevertheless, if the output voltage Vout is below the reference voltage Vdis during the disable time period Tdis (as shown by the line B in FIG.","5B), it indicates that, in addition to the normal depletion of the charges, there must be a short circuit.","Under such circumstance, the voltage comparison circuit 2114a outputs the error signal Error 1 to reflect that a short circuit has occurred.","The abnormal voltage drop detection circuit 2114 can detect and calculate the decreasing speed of the output voltage Vout by any other way instead of adopting the voltage comparison circuit.","For example, the abnormal voltage drop detection circuit 2114 can detect the output voltage Vout at two different time points, to obtain a dropping slope of the output voltage Vout (i.e., the slope of line A or line B); the dropping slope can be compared with the slope of the threshold line.","Adopting the voltage comparison circuit to detect and calculate the decreasing speed of the output voltage Vout is a relatively simpler approach; however, any other approach to detect and calculate the decreasing speed of the output voltage Vout is still within the scope of the present invention.","As compared to the case wherein the power converter 21 is not connected to the electronic device 23 through the cable 22, in the case wherein the power converter 21 is connected to the electronic device 23 through the cable 22, the normal depletion of charges is relatively higher.","Under such circumstance, in one embodiment, the reference voltage Vdis can be set to a relatively lower level.","There are many ways to adjust the setting of the reference voltage Vdis, and the present invention is not limited to anyone of these ways.","For example, when the power converter 21 is connected to the electronic device 23 through the cable 22, usually, the electronic device 23 will transmit signals through the signal line 24 to confirm the connection status, or to communicate for other purposes.","Therefore, for example, the short circuit detection unit 211 can set the reference voltage Vdis to a relatively lower level when the signal line 24 transmits a signal verifying that the power converter 21 is connected to the electronic device 23 through the cable 22.On the contrary, when the signal line 24 does not transmit a signal verifying that the power converter 21 is connected to the electronic device 23 through the cable 22, the short circuit detection unit 211 can set the reference voltage Vdis to a relatively higher level.","However, that the reference voltage Vdis is adjustable is only preferred but not necessary.","Certainly, it is also practicable and within the scope of the present invention that the reference voltage Vdis is a constant.","Besides adjusting the reference voltage Vdis according to whether or not the electronic device 23 is connected to the power converter 21 through the cable 22, in another embodiment of the present invention, the duration of the disable time period Tdis can be adjusted.","For example, in the case wheren the power converter 21 is connected to the electronic device 23 through the cable 22, the normal depletion of charges is relatively higher.","Under such circumstance, the duration of the disable time period Tdis can be shortened, for example by changing the frequency of the clock signal CLK or the time count of the timer circuit.","In the embodiment shown in FIG.","6B, the temporary stop signal STOP is periodically generated, which is only one example.","In other embodiments, the temporary stop signal STOP can be generated during (or immediately after) a start-up operation or a power-on-reset operation, or, the temporary stop signal STOP can be generated irregularly during normal operation.","For example, please refer to FIG.","6C, typically, a Power On Reset (POR) signal is generated during a start-up operation or a power-on-reset operation, and the temporary stop signal STOP can be generated according to this POR signal.","For another example, the temporary stop signal STOP can be generated can be set randomly.","Thus, the present invention can generate the temporary stop signal STOP by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during (or immediately after) a start-up operation; generating the temporary stop signal STOP during (or immediately after) a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly (for example, the temporary stop signal STOP can be generated not only periodically but also irregularly).","FIGS.","7A-7C show another embodiment of the present invention, which show the bad connection detection unit and explain how the present invention performs a bad connection detection.","The bad connection needs to be detected only when the power converter 21 is connected to the cable 22 and the cable 22 is connected to the electronic device 23, so this is what is shown in FIGS.","7A-7C.","Please refer to FIG.","7B.","Although what the power converter 21 provides is the output voltage Vout, the voltage actually received by the electronic device 23 is the actual voltage Vp because of the bad connection (which is expressed by resistors R1, R2, R3 and R4).","Likewise, although what the power converter 21 provides is the output current Iout, the current actually received by the electronic device 23 is the actual current Ip because of the bad connection.","The bad connection detection unit 235 is provided to detect whether a bad connection occurs.","As shown in FIGS.","7B-7C, the bad connection detection unit 235 of this embodiment can be, for example but not limited to, located inside the electronic device 23.The bad connection detection unit 235 includes a voltage sensing circuit 2351, a current sensing circuit 2352, an analog-to-digital converter (ADC) 2353, an analog-to-digital converter (ADC) 2354, and a calculation circuit 2355.The voltage sensing circuit 2351 senses the actual voltage Vp, which is then converted to a digital signal by the ADC 2353.The current sensing circuit 2352 senses the actual current Ip, which is then converted to a digital signal by the ADC 2354.The calculation circuit 2355 performs calculation according to the outputs from the ADC 2353 and ADC 2354.In one embodiment, information of the target level of the output voltage Vout and the target level of the output current Iout is given by the electronic device 23, via the signal line 24 in the cable 22, to the power converter 21.Under such circumstance, because the electronic device 23 has already known the target levels of the output voltage Vout and the output current Iout, these levels can be pre-stored in the calculation circuit 2355.The calculation circuit 2355 can compare the outputs from the ADC 2353 and the ADC 2354 with the pre-stored target levels of the output voltage Vout and the output current Iout.","When a difference between the target level of the output voltage Vout and the actual voltage Vp is too large, and/or when a difference between the target level of the output current Iout and the actual current Ip is too large (i.e., the difference exceeds a predetermined threshold difference), the calculation circuit 2355 will issue an error signal Error 2 to indicate that a “bad connection” occurs.","Such error signal Error 2 can be transmitted via, for example, the signal line 24.Certainly, in other embodiments, the error signal Error 2 can be transmitted via other wirings (under such circumstance, the cable 22 needs to include such wirings).","Furthermore, to avoid misjudging the occurrence of a bad connection when the circuit just starts up or when the electronic device 23 is in heavily loaded condition, the determination of “bad connection” can be conducted when the circuit is stable.","FIG.","7D explains another embodiment as to how the present invention performs a bad connection detection.","In this embodiment, an ADC 2141 and an ADC 2142 are included in the power converter 21 (e.g., when the power converter 21 is an isolated type AC-DC converter, the ADC 2141 and the ADC 2142 can be located inside the output unit 210; or, when the power converter 21 is another type of power converter, the ADC 2141 and the ADC 2142 can be located inside the switch control unit 214).","The ADC 2141 and the ADC 2142 convert the output voltage Vout and the output current Iout into digital signals, respectively.","The converted digital values are outputted to the calculation circuit 2355 through a buffer circuit 2143.The calculation circuit 2355 compares the outputs from the ADC 2353 and the ADC 2354 with the information of the output voltage Vout and the output current Iout outputted from the buffer circuit 2143.When a difference between the target level of the output voltage Vout and the actual voltage Vp is too large, and/or when a difference between the target level of the output current Iout and the actual current Ip is too large (i.e., the difference exceeds a predetermined threshold difference), the calculation circuit 2355 will issue an error signal Error 2 to indicate that a “bad connection” occurs.","Because the signal line 24 can transmit signals bi-directionally, the information of the output voltage Vout, the output current Iout and the error signal Error 2 can all be transmitted via the signal line 24.FIG.","7E explains another embodiment as to how the present invention performs a bad connection detection.","In this embodiment, a calculation circuit 2144 is included in the power converter 21 (e.g., when the power converter 21 is an isolated type AC-DC converter, the calculation circuit 2144 can be located inside the output unit 210; or, when the power converter 21 is another type of power converter, the calculation circuit 2144 can be located inside the switch control unit 214).","And, in this embodiment, the bad connection detection circuit 235 further includes a buffer circuit 2356 in the electronic device 23.In other words, the bad connection detection circuit 235 can be regarded as having two separate parts, located inside the power converter 21 and inside the electronic device 23, respectively.","The bad connection detection circuit 235 outputs digital signals converted from the actual voltage Vp and the actual current Ip, which are sent to the calculation circuit 2144 of the switch control unit 214.The calculation circuit 2144 compares the converted digital signals of the actual voltage Vp and the actual current Ip with the converted digital values of the output voltage Vout and the output current Iout outputted from the ADC 2141 and the ADC 2142, respectively.","When a difference between the voltages and/or a difference between the currents is too large (i.e., the difference exceeds a predetermined threshold difference), the calculation circuit 2144 will issue an error signal Error 2 to indicate that a “bad connection” occurs.","When an abnormal condition such as a short circuit or a bad connection is detected and the error signal Error 1 or the error signal Error 2 is generated, the generated error signal Error 1 or Error 2 can be used in various ways.","For example, the error signal Error 1 or Error 2 can function as an alarm signal to the user (e.g., the error signal Error 1 or Error2 can light up an LED lamp, or trigger a buzzer to issue an alert).","Or, the error signal Error 1 or Error2 can maintain the temporary stop signal STOP at the predefined level.","Or, the error signal Error 1 or Error2 can be used to directly disable the switch control unit 214.Or, the error signal Error 1 or Error2 can be used to turn off the power converter 21.Or, if the power converter 21 is an isolated type AC-DC converter, the error signal Error 1 or Error2 can be used to open the path by which the secondary side of the transformer provides the output voltage Vout.","Or, the error signal Error 1 or Error2 is not used to turn off the power converter 21, but instead to limit the maximum of the output current of the power converter 21.Any or more of the above and other ways can be adopted, depending on practical needs.","In view of the above, the power supply system of the present invention can, on one hand, detect the abnormal short circuit through the short circuit detection unit 211 and can, on the other hand, detect the abnormal bad connection through the bad connection detection unit 235, so that power loss due to these abnormal conditions can be avoided to improve the power utilization efficiency and better protect the circuit.","The present invention has been described in considerable detail with reference to certain preferred embodiments thereof.","It should be understood that the description is for illustrative purpose, not for limiting the scope of the present invention.","An embodiment or a claim of the present invention does not need to achieve all the objectives or advantages of the present invention.","The title and abstract are provided for assisting searches but not for limiting the scope of the present invention.","Those skilled in this art can readily conceive variations and modifications within the spirit of the present invention.","For example, the definition of the high level and the low level of a digital signal are interchangeable, with corresponding amendments of the circuits processing these signals.","For another example, a device which does not substantially influence the primary function of a signal can be inserted between any two devices or circuits in the shown embodiments.","For yet another example, the cable 22 and the power converter 21 can be integrated into a single device; or, the cable 22 and the electronic device can be integrated into a single device, and the spirit of the present invention can still be applied to such configurations.","In view of the foregoing, the spirit of the present invention should cover all such and other modifications and variations, which should be interpreted to fall within the scope of the following claims and their equivalents."]],"string":"[\n [\n \"POWER SUPPLY SYSTEM AND SHORT CIRCUIT AND/OR BAD CONNECTION DETECTION METHOD THEREOF, AND POWER CONVERTER THEREOF\",\n \"The present invention discloses a short circuit and/or bad connection detection method for use in a power supply system.\",\n \"The power supply system includes a power converter which converts an input voltage to an output voltage and supplies an output current to an electronic device.\",\n \"In the short circuit detection method, the conversion from the input voltage to the output voltage is disabled in a disable time period, and whether a short circuit occurs is determined according to the decreasing speed of the output voltage.\",\n \"In the bad connection detection method, an actual voltage and an actual current received by the electronic device are compared with the output voltage and the output current, to determine whether a bad connection occurs.\"\n ],\n [\n \"1.A power converter for converting an input voltage to an output voltage, wherein the output voltage is to be supplied to an electronic device through a cable; the power converter comprising: a switch; a switch control unit for controlling the switch, to perform the conversion from the input voltage to the output voltage; and an abnormal condition detection unit, including: a temporary stop signal generation circuit for generating a temporary stop signal, to temporarily disable the switch control unit for a disable time period; and an abnormal voltage drop detection circuit for determining whether or not an abnormal condition occurs during the disable time period in which the switch control unit has been disabled according to a decreasing speed of the output voltage; wherein, after the switch control unit has been disabled, the abnormal voltage drop detection circuit subsequently determines whether the output voltage drops abnormally according to the decreasing speed of the output voltage, so as to subsequently determine whether or not the abnormal condition occurs.\",\n \"2.The power converter of claim 1, wherein the abnormal voltage drop detection circuit includes: a voltage comparison circuit for determining whether or not the abnormal condition occurs according to a comparison result between the output voltage and a reference voltage.\",\n \"3.The power converter of claim 2, wherein the reference voltage is adjustable.\",\n \"4.The power converter of claim 3, wherein: when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.\",\n \"5.The power converter of claim 1, wherein the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to the switch control unit via a feedback circuit, wherein the temporary stop signal disables the switch control unit by turning off the feedback circuit.\",\n \"6.The power converter of claim 1, wherein the temporary stop signal generation circuit generates the temporary stop signal by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during or immediately after a start-up operation; generating the temporary stop signal STOP during or immediately after a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly.\",\n \"7.A abnormal condition detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage to be supplied to an electronic device through a cable; the abnormal condition detection method of the power supply system comprising the steps of: stopping converting the input voltage to the output voltage for a disable time period in which a switch control unit of the power converter has been disabled; after the switch control unit has been disabled, subsequently determining whether the output voltage drops abnormally according to a decreasing speed of the output voltage, so as to subsequently determine whether or not a an abnormal condition occurs.\",\n \"8.The abnormal condition detection method of the power supply system of claim 7, wherein the step of determining whether or not the abnormal condition occurs according to the decreasing speed of the output voltage includes: comparing the output voltage with a reference voltage.\",\n \"9.The abnormal condition detection method of the power supply system of claim 8, wherein the reference voltage is adjustable.\",\n \"10.The abnormal condition detection method of the power supply system of claim 9, wherein: when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.\",\n \"11.The abnormal condition detection method of the power supply system of claim 7, wherein the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to a switch control unit via a feedback circuit, wherein the step of stopping converting the input voltage to the output voltage for a disable time period includes: disabling the switch control unit by turning off the feedback circuit.\",\n \"12.The abnormal condition detection method of the power supply system of claim 7, wherein the step of stopping converting the input voltage to the output voltage for a disable time period includes: starting the disable time period during or immediately after a start-up operation; starting the disable time period during or immediately after a power-on-reset operation; starting the disable time period periodically; or starting the disable time period irregularly; or a combination of two or more of the above.\",\n \"13.A power supply system, comprising: a power converter for converting an input voltage to an output voltage and supplying an output current, wherein the output voltage and the output current are supplied to an electronic device through a cable; and a bad connection detection unit, including: a voltage sensing circuit for sensing an actual voltage received by the electronic device; a current sensing circuit for sensing an actual current received by the electronic device; a first analog-to-digital converter for converting the actual voltage to a first digital signal; a second analog-to-digital converter for converting the actual current to a second digital signal; and a calculation circuit for determining whether or not a bad connection occurs according to the first digital signal, the second digital signal, the output voltage and the output current.\",\n \"14.The power supply system of claim 13, wherein the calculation circuit compares the first digital signal with a desired level of the output voltage and compares the second digital signal with a desired level of the output current, to determine whether or not the bad connection occurs.\",\n \"15.The power supply system of claim 13, wherein the calculation circuit compares the first digital signal with a digital signal of the output voltage converted from a sensed value of the output voltage and compares the second digital signal with a digital signal of the output current converted from a sensed value of the output current, to determine whether or not the bad connection occurs.\",\n \"16.The power supply system of claim 13, wherein the bad connection detection unit is located inside the electronic device.\",\n \"17.The power supply system of claim 13, wherein the bad connection detection unit has a first part inside the electronic device and a second part inside the power converter, and the first and second parts of the bad connection detection unit communicate through a signal line of the cable.\",\n \"18.A bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with a desired level of the output voltage and a desired level of the output current, respectively; and when a difference between the actual voltage digital signal and the desired level of the output voltage exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the desired level of the output current exceeds a second predetermined threshold difference, determining that a bad connection occurs.\",\n \"19.A bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; sensing the output voltage and the output current and converting the output voltage and the output current to an output voltage digital signal and an output current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with the output voltage digital signal and the output current digital signal, respectively; and when a difference between the actual voltage digital signal and the output voltage digital signal exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the output current digital signal exceeds a second predetermined threshold difference, determining that a bad connection occurs.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>From one perspective, the present invention provides a power converter for converting an input voltage to an output voltage, wherein the output voltage is to be supplied to an electronic device through a cable; the power converter comprising: a switch; a switch control unit for controlling the switch, to perform the conversion from the input voltage to the output voltage; and a short circuit detection unit, including: a timer circuit for generating a temporary stop signal, to temporarily disable the switch control unit for a disable time period; and an abnormal voltage drop detection circuit for determining whether or not a short circuit occurs during the disable time period according to a decreasing speed of the output voltage.\",\n \"In one embodiment, the abnormal voltage drop detection circuit includes: a voltage comparison circuit for determining whether or not the short circuit occurs according to a comparison result between the output voltage and a reference voltage.\",\n \"In one embodiment, the reference voltage is adjustable.\",\n \"In one embodiment, when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.\",\n \"In one embodiment, the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to the switch control unit via a feedback circuit, wherein the temporary stop signal disables the switch control unit by turning off the feedback circuit.\",\n \"In one embodiment, the timer circuit generates the temporary stop signal by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during or immediately after a start-up operation; generating the temporary stop signal STOP during or immediately after a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly.\",\n \"From another perspective, the present invention provides a short circuit detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage to be supplied to an electronic device through a cable; the short circuit detection method of the power supply system comprising the steps of: stopping converting the input voltage to the output voltage for a disable time period; and determining whether or not a short circuit occurs according to a decreasing speed of the output voltage.\",\n \"From another perspective, the present invention provides a power supply system, comprising: a power converter for converting an input voltage to an output voltage and supplying an output current, wherein the output voltage and the output current are supplied to an electronic device through a cable; and a bad connection detection unit, including: a voltage sensing circuit for sensing an actual voltage received by the electronic device; a current sensing circuit for sensing an actual current received by the electronic device; a first analog-to-digital converter for converting the actual voltage to a first digital signal; a second analog-to-digital converter for converting the actual current to a second digital signal; and a calculation circuit for determining whether or not a bad connection occurs according to the first digital signal, the second digital signal, the output voltage and the output current.\",\n \"In one embodiment, the calculation circuit compares the first digital signal with a desired level of the output voltage and compares the second digital signal with a desired level of the output current, to determine whether or not the bad connection occurs.\",\n \"In one embodiment, the calculation circuit compares the first digital signal with a digital signal of the output voltage converted from a sensed value of the output voltage and compares the second digital signal with a digital signal of the output current converted from a sensed value of the output current, to determine whether or not the bad connection occurs.\",\n \"In one embodiment, the bad connection detection unit is located inside the electronic device.\",\n \"In one embodiment, the bad connection detection unit has a first part inside the electronic device and a second part inside the power converter, and the first and second parts of the bad connection detection unit communicate through a signal line of the cable.\",\n \"From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with a desired level of the output voltage and a desired level of the output current, respectively; and when a difference between the actual voltage digital signal and the desired level of the output voltage exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the desired level of the output current exceeds a second predetermined threshold difference, determining that a bad connection occurs.\",\n \"From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; sensing the output voltage and the output current and converting the output voltage and the output current to an output voltage digital signal and an output current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with the output voltage digital signal and the output current digital signal, respectively; and when a difference between the actual voltage digital signal and the output voltage digital signal exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the output current digital signal exceeds a second predetermined threshold difference, determining that a bad connection occurs.\",\n \"The objectives, technical details, features, and effects of the present invention will be better understood with regard to the detailed description of the embodiments below, with reference to the attached drawings.\"\n ],\n [\n \"CROSS REFERENCE The present invention claims priority to U.S. 62/014,305, filed on Jun.\",\n \"19, 2014.BACKGROUND OF THE INVENTION Field of Invention The present invention relates to a power supply system capable of performing a short circuit detection and a bad connection detection; particularly, it relates to such a power supply system capable of detecting abnormal but not severe conditions which lead to undesirable power loss, such as weakly short circuit and weakly bad connection conditions, and a detection method and a power converter thereof.\",\n \"Description of Related Art Please refer to FIGS.\",\n \"1A and 1B.\",\n \"FIG.\",\n \"1A shows a block diagram of a conventional power supply system.\",\n \"FIG.\",\n \"1B explains how an abnormal but not severe condition occurs in the prior art of FIG.\",\n \"1A which leads to power loss.\",\n \"The conventional power supply system 10 comprises a power converter 11, a cable 12 and an electronic device 13.A port 112 of the power converter 11 is connected to a port 121 of the cable 12.A port 132 of the electronic device 13 is connected to another port 122 of the cable 12.When the power converter 11, the cable 12 and the electronic device 13 are connected in serial, power lines 17 and 18 form a loop to deliver the power.\",\n \"The cable 12 further includes a signal line 14, for data transmission between the power converter 11 and the electronic device 13.The signal line 14 can be, for example but not limited to, a differential signal line.\",\n \"As shown in FIG.\",\n \"1B, when an unwanted material such as dust, dirt, thread, etc.\",\n \"falls on or in the ports 112, 121, 122 and/or 132, the power lines 17 and 18 may be “weakly short-circuited”—i.e., a short-cut current path is formed between the power lines 17 and 18, but the electrical connection is weak, so there is not a huge amount of current flowing through this short-cut current path.\",\n \"Such “weakly short circuit” is illustrated by the resistors R11, R121, R122 and R13 in the figure.\",\n \"Although there is not a huge amount of current flowing through the short-cut current path, this abnormal condition still leads to power loss, and if this abnormal condition is not well controlled, it can be very dangerous.\",\n \"Besides, if the power lines 17 and 18 does not have a good quality, or a bad connection occurs between the ports, even though the bad connection is not so severe to cause an open-circuit, this abnormal condition will also lead to power loss.\",\n \"The bad connection is illustrated by the resistors R1′, R2′, R3′ and R4′ in the figure.\",\n \"Because the “weakly short circuit” and “bad connection” usually do not lead to fully short-circuit or complete open-circuit, the prior art did not propose an effective solution to address this issue.\",\n \"The prior art U.S. Pat.\",\n \"No.\",\n \"8,498,087 and U.S. Pat.\",\n \"No.\",\n \"8,339,760 provide an approach to solve the above-mentioned problem by detecting whether there is abnormal temperature increase in the cable.\",\n \"However, to do so, an additional heat detection signal line is required, which is not compatible to the current standard cable, and also leads to a higher manufacturing cost.\",\n \"Moreover, before an abnormal temperature increase becomes detectable, unwanted power loss and other problems have already happened for a long time.\",\n \"Therefore, the above-mentioned prior art patents do not practically solve the problem.\",\n \"In view of the above, to overcome the drawbacks in the prior art, the present invention proposes a power supply system capable of detecting an abnormal condition such as a weakly short circuit and a bad connection, which leads to undesirable power loss.\",\n \"SUMMARY OF THE INVENTION From one perspective, the present invention provides a power converter for converting an input voltage to an output voltage, wherein the output voltage is to be supplied to an electronic device through a cable; the power converter comprising: a switch; a switch control unit for controlling the switch, to perform the conversion from the input voltage to the output voltage; and a short circuit detection unit, including: a timer circuit for generating a temporary stop signal, to temporarily disable the switch control unit for a disable time period; and an abnormal voltage drop detection circuit for determining whether or not a short circuit occurs during the disable time period according to a decreasing speed of the output voltage.\",\n \"In one embodiment, the abnormal voltage drop detection circuit includes: a voltage comparison circuit for determining whether or not the short circuit occurs according to a comparison result between the output voltage and a reference voltage.\",\n \"In one embodiment, the reference voltage is adjustable.\",\n \"In one embodiment, when the power converter is coupled to the electronic device through the cable, the reference voltage is set to a relatively lower level; and when the power converter is not coupled to the electronic device through the cable, the reference voltage is set to a relatively higher level.\",\n \"In one embodiment, the power converter includes an isolated type AC-DC converter, and the isolated type AC-DC converter transmits a feedback signal related to the output voltage to the switch control unit via a feedback circuit, wherein the temporary stop signal disables the switch control unit by turning off the feedback circuit.\",\n \"In one embodiment, the timer circuit generates the temporary stop signal by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during or immediately after a start-up operation; generating the temporary stop signal STOP during or immediately after a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly.\",\n \"From another perspective, the present invention provides a short circuit detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage to be supplied to an electronic device through a cable; the short circuit detection method of the power supply system comprising the steps of: stopping converting the input voltage to the output voltage for a disable time period; and determining whether or not a short circuit occurs according to a decreasing speed of the output voltage.\",\n \"From another perspective, the present invention provides a power supply system, comprising: a power converter for converting an input voltage to an output voltage and supplying an output current, wherein the output voltage and the output current are supplied to an electronic device through a cable; and a bad connection detection unit, including: a voltage sensing circuit for sensing an actual voltage received by the electronic device; a current sensing circuit for sensing an actual current received by the electronic device; a first analog-to-digital converter for converting the actual voltage to a first digital signal; a second analog-to-digital converter for converting the actual current to a second digital signal; and a calculation circuit for determining whether or not a bad connection occurs according to the first digital signal, the second digital signal, the output voltage and the output current.\",\n \"In one embodiment, the calculation circuit compares the first digital signal with a desired level of the output voltage and compares the second digital signal with a desired level of the output current, to determine whether or not the bad connection occurs.\",\n \"In one embodiment, the calculation circuit compares the first digital signal with a digital signal of the output voltage converted from a sensed value of the output voltage and compares the second digital signal with a digital signal of the output current converted from a sensed value of the output current, to determine whether or not the bad connection occurs.\",\n \"In one embodiment, the bad connection detection unit is located inside the electronic device.\",\n \"In one embodiment, the bad connection detection unit has a first part inside the electronic device and a second part inside the power converter, and the first and second parts of the bad connection detection unit communicate through a signal line of the cable.\",\n \"From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with a desired level of the output voltage and a desired level of the output current, respectively; and when a difference between the actual voltage digital signal and the desired level of the output voltage exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the desired level of the output current exceeds a second predetermined threshold difference, determining that a bad connection occurs.\",\n \"From another perspective, the present invention provides a bad connection detection method of a power supply system, wherein the power supply system includes a power converter for converting an input voltage to an output voltage and supplying an output current, the output voltage and the output current being supplied to an electronic device through a cable, the bad connection detection method of the power supply system comprising the steps of: sensing a actual voltage and an actual current received by the electronic device and converting the actual voltage and the actual current to an actual voltage digital signal and an actual current digital signal, respectively; sensing the output voltage and the output current and converting the output voltage and the output current to an output voltage digital signal and an output current digital signal, respectively; comparing the actual voltage digital signal and the actual current digital signal with the output voltage digital signal and the output current digital signal, respectively; and when a difference between the actual voltage digital signal and the output voltage digital signal exceeds a first predetermined threshold difference, and/or when a difference between the actual current digital signal and the output current digital signal exceeds a second predetermined threshold difference, determining that a bad connection occurs.\",\n \"The objectives, technical details, features, and effects of the present invention will be better understood with regard to the detailed description of the embodiments below, with reference to the attached drawings.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1A shows a block diagram of a conventional power supply system.\",\n \"FIG.\",\n \"1B explains how an abnormal condition occurs in the prior art of FIG.\",\n \"1A which leads to power loss.\",\n \"FIGS.\",\n \"2A-2B show a block diagram of a power supply system according to a first embodiment of the present invention.\",\n \"FIG.\",\n \"2C shows an embodiment of a power converter.\",\n \"FIGS.\",\n \"3A-3B show a block diagram of a power supply system according to a second embodiment of the present invention.\",\n \"FIGS.\",\n \"4A-4B show a block diagram of a power supply system according to a third embodiment of the present invention.\",\n \"FIG.\",\n \"5A shows an embodiment of a short circuit detection unit.\",\n \"FIG.\",\n \"5B explains how the present invention performs the short circuit detection.\",\n \"FIG.\",\n \"6A shows another embodiment of a short circuit detection unit.\",\n \"FIGS.\",\n \"6B-6C show two embodiments as to how the present invention generates a temporary stop signal.\",\n \"FIGS.\",\n \"7A-7C explain an embodiment as to how the present invention performs the bad connection detection.\",\n \"FIGS.\",\n \"7D-7E show two embodiments as to how the present invention performs the bad connection detection.\",\n \"DESCRIPTION OF THE PREFERRED EMBODIMENTS The above and other technical details, features and effects of the present invention will be will be better understood with regard to the detailed description of the embodiments below, with reference to the drawings.\",\n \"The drawings as referred to throughout the description of the present invention are for illustration only, to show the interrelations between the components and devices, but not drawn according to actual scale.\",\n \"Please refer to FIGS.\",\n \"2A-2C, FIGS.\",\n \"3A-3B and FIGS.\",\n \"4A-4B.\",\n \"FIG.\",\n \"2A shows a block diagram of a power supply system according to a first embodiment of the present invention.\",\n \"FIG.\",\n \"2B shows a circuit diagram of FIG.\",\n \"2A.\",\n \"FIG.\",\n \"2C shows an embodiment of a power converter.\",\n \"In FIGS.\",\n \"2A-2C, the power converter is not coupled to a cable.\",\n \"FIG.\",\n \"3A shows a block diagram of a power supply system according to a second embodiment of the present invention.\",\n \"FIG.\",\n \"3B shows a circuit diagram of FIG.\",\n \"3A.\",\n \"In FIGS.\",\n \"3A-3B, the power converter is coupled to a cable.\",\n \"FIG.\",\n \"4A shows a block diagram of a power supply system according to a third embodiment of the present invention.\",\n \"FIG.\",\n \"4B shows a circuit diagram of FIG.\",\n \"4A.\",\n \"In FIGS.\",\n \"4A-4B, the power converter and the electronic device are coupled to each other through a cable.\",\n \"In one embodiment, the power converter 21 has not yet been connected to any other device or component (as shown by the power supply system 20 in FIG.\",\n \"2B).\",\n \"As shown in FIG.\",\n \"2B, the power converter 21 has one port 212.In another embodiment, the power converter 21 has already been connected to a cable 22 but has not yet been connected to an electronic device (as shown by the power supply system 30 in FIG.\",\n \"3B).\",\n \"As shown in FIG.\",\n \"3B, a port 212 of the power converter 21 is connected to a port 221 of the cable 22.In still another embodiment, the power converter 21, the cable 22 and the electronic device 23 have already been connected in serial (as shown by the power supply system 40 in FIG.\",\n \"4B).\",\n \"A port 212 of the power converter 21 is connected to a port 221 of the cable 22, and a port 232 of the electronic device 23 is connected to a port 222 of the cable 22.Please refer to FIG.\",\n \"2C.\",\n \"The power converter 21 can be, for example but not limited to, an isolated type AC-DC converter.\",\n \"Note that the power converter 21 shown in FIG.\",\n \"2C is for illustrative purpose only, but not for limiting the scope of the present invention.\",\n \"The power converter 21 can be any other type of power converter.\",\n \"In the isolated type AC-DC converter shown in FIG.\",\n \"2C, the power converter 21 includes a transformer 213 having a primary side 213a and a secondary side 213b.\",\n \"The primary side 213a is coupled to a switch SW which is controlled by a switch control unit 214.The secondary side 213b is coupled to an output unit 210, which generates a feedback signal FB according to an output voltage Vout, and provides the feedback signal FB through a feedback circuit 215 (e.g., an opto-coupler circuit) to the switch control unit 214.In normal operation, the switch control unit 214 controls the switch SW according to the feedback signal FB, to convert an input voltage Vin to the output voltage Vout at the secondary side 213b.\",\n \"The output unit 210 includes a short circuit detection unit 211, to detect whether a short circuit or even a weakly short circuit occurs.\",\n \"The details for the short circuit detection unit 211 will be described later.\",\n \"The basics of an isolated type AC-DC converter are well known to those skilled in the art, so for the sake of simplicity, only the circuits relevant to the present invention are illustrated whereas other circuits irrelevant to the present invention are omitted.\",\n \"Note that the power converter 21 is not limited to an isolated type AC-DC converter, yet it can also be another type of switching power converter such as a synchronous or asynchronous boost, buck, buck-boost or inverting power converter.\",\n \"Among these switching power converters (including the isolated type AC-DC converter), they all have a switch control unit, which controls at least one switch according to the feedback signal, to convert the input voltage to the output voltage.\",\n \"The present invention is applicable to anyone of these switching power converters.\",\n \"The short circuit detection unit can be located at any appropriate location within the switching power converter, which, when detecting that a short circuit or a weakly short circuit occurs, issues an error signal Error 1 to the switch control unit.\",\n \"Please refer to FIGS.\",\n \"3A-3B and FIGS.\",\n \"4A-4B.\",\n \"Unlike the embodiment shown in FIGS.\",\n \"2A-2C, the power converter 21 shown in FIGS.\",\n \"3A-3B has already been connected to a cable 22.And, in embodiment shown in FIGS.\",\n \"4A-4B, the power converter 21 is connected to the cable 22 and the cable 22 is connected to the electronic device 23.In the embodiment shown in FIGS.\",\n \"4A-4B, in normal operation, the power lines 27 and 28 form a loop, so that power can be delivered to the electronic device 23.The cable 22 further includes a signal line 24, for data transmission between the power converter 21 and the electronic device 23.The signal line 24 can be, for example but not limited to, a differential signal line.\",\n \"As shown in FIGS.\",\n \"2B, 3B and 4B, when there is an unwanted material such as dust falling on or in the ports 212, 221, 222 and/or 232, a short-cut current path is formed between the power lines 17 and 18, but the electrical connection is weak, so there is not a huge amount of current flowing through this short-cut current path.\",\n \"Such “weakly short circuit” is illustrated by the resistors R21, R221, R222 and R23 in the figures.\",\n \"This abnormal condition leads to power loss, and if this abnormal condition is not well controlled, it can be very dangerous.\",\n \"To overcome this drawback, the short circuit detection unit 211 of this embodiment can detect whether a short circuit abnormal condition occurs, so that necessary procedures can be taken as soon as possible.\",\n \"FIGS.\",\n \"5A-5B shows an embodiment of the short circuit detection unit 211.Regardless whether the power converter 21 is connected to the cable 22 and regardless whether the cable 22 is connected to the electronic device 23, this embodiment can be adopted to check whether a short circuit abnormal condition occurs.\",\n \"Please refer to FIGS.\",\n \"5A-5B.\",\n \"The short circuit detection unit 211 of this embodiment includes a timer circuit 2112 and an abnormal voltage drop detection circuit 2114.The timer circuit 2112 counts time according to a clock signal CLK, to generate a temporary stop signal STOP which lasts for a period of time, i.e., the disable time period Tdis.\",\n \"(“To generate a temporary stop signal STOP” means to set the level of the temporary stop signal STOP to a predefined level, such as a high level or a low level of a digital signal).\",\n \"In this embodiment, the timer circuit 2112 periodically generates the temporary stop signal STOP.\",\n \"In other embodiments, the temporary stop signal STOP can be triggered and generated by other mechanisms (which will be described later).\",\n \"The clock signal CLK can be obtained from a clock signal inside the power converter 21; or, it can be obtained from an oscillator (not shown).\",\n \"When the temporary stop signal STOP is generated, the switch control unit 214 is disabled, so that the power converter 21 does not operate to convert the input voltage Vin to the output voltage Vout.\",\n \"The switch control unit 214 can be disabled by various ways, and the present invention is not limited to anyone of these ways.\",\n \"This embodiment shows one example: if the power converter 21 is isolated type AC-DC converter, it usually uses a feedback circuit 215 (e.g., an opto-coupler circuit) to transmit the feedback signal FB.\",\n \"The temporary stop signal STOP can be used to disable the feedback circuit 215.Because the isolated type AC-DC converter adopts a negative feedback mechanism, when the feedback circuit 215 does not operate, the switch control unit 214 will judge that the output voltage Vout is sufficient, so as not to proceed the operation to convert the input voltage Vin to the output voltage Vout, and this is equivalent to disabling the switch control unit 214.If the power converter 21 is another type of switching power converter, the switch control unit 214 can be disabled by any suitable way.\",\n \"The disable time period Tdis in which the temporary stop signal STOP disables the switch control unit 214 is shown in FIG.\",\n \"5B.\",\n \"While the temporary stop signal STOP disables the switch control unit 214, the timer circuit 2112 enables the abnormal voltage drop detection circuit 2114 by an enable signal EN.\",\n \"Therefore, the temporary stop signal STOP and the enable signal EN can be the same signal, or one being an inverted signal of the other.\",\n \"Certainly, in another embodiment, the temporary stop signal STOP and the enable signal EN can be two different signals, and the enable signal EN can start slightly later than the temporary stop signal STOP.\",\n \"Being enabled, the abnormal voltage drop detection circuit 2114 determines whether the output voltage Vout drops abnormally according to a decreasing speed of the output voltage Vout.\",\n \"Please refer to FIG.\",\n \"5B.\",\n \"During the disable time period Tdis, the power converter 21 does not operate to convert the input voltage Vin to the output voltage Vout.\",\n \"However, because there is a normal depletion of charges, the output voltage Vout will drop slowly.\",\n \"Hence, a threshold line can be set, based upon a reasonable decreasing speed of the output voltage Vout.\",\n \"If the decreasing speed of the output voltage Vout is faster and than the threshold line, it can be judged that an undesirable short circuit occurs.\",\n \"Please refer to FIG.\",\n \"6A in conjugation with FIG.\",\n \"5B.\",\n \"In one embodiment, the abnormal voltage drop detection circuit 2114 includes a voltage comparison circuit 2114a, which compare the output voltage Vout with a reference voltage Vdis (in circuit design, an equivalent approach is to compare a divided voltage of the output voltage Vout with a proportional value of the reference voltage Vdis).\",\n \"In normal operation, the output voltage Vout will not drop below the reference voltage Vdis during the disable time period Tdis (as shown by the line A in FIG.\",\n \"5B).\",\n \"Nevertheless, if the output voltage Vout is below the reference voltage Vdis during the disable time period Tdis (as shown by the line B in FIG.\",\n \"5B), it indicates that, in addition to the normal depletion of the charges, there must be a short circuit.\",\n \"Under such circumstance, the voltage comparison circuit 2114a outputs the error signal Error 1 to reflect that a short circuit has occurred.\",\n \"The abnormal voltage drop detection circuit 2114 can detect and calculate the decreasing speed of the output voltage Vout by any other way instead of adopting the voltage comparison circuit.\",\n \"For example, the abnormal voltage drop detection circuit 2114 can detect the output voltage Vout at two different time points, to obtain a dropping slope of the output voltage Vout (i.e., the slope of line A or line B); the dropping slope can be compared with the slope of the threshold line.\",\n \"Adopting the voltage comparison circuit to detect and calculate the decreasing speed of the output voltage Vout is a relatively simpler approach; however, any other approach to detect and calculate the decreasing speed of the output voltage Vout is still within the scope of the present invention.\",\n \"As compared to the case wherein the power converter 21 is not connected to the electronic device 23 through the cable 22, in the case wherein the power converter 21 is connected to the electronic device 23 through the cable 22, the normal depletion of charges is relatively higher.\",\n \"Under such circumstance, in one embodiment, the reference voltage Vdis can be set to a relatively lower level.\",\n \"There are many ways to adjust the setting of the reference voltage Vdis, and the present invention is not limited to anyone of these ways.\",\n \"For example, when the power converter 21 is connected to the electronic device 23 through the cable 22, usually, the electronic device 23 will transmit signals through the signal line 24 to confirm the connection status, or to communicate for other purposes.\",\n \"Therefore, for example, the short circuit detection unit 211 can set the reference voltage Vdis to a relatively lower level when the signal line 24 transmits a signal verifying that the power converter 21 is connected to the electronic device 23 through the cable 22.On the contrary, when the signal line 24 does not transmit a signal verifying that the power converter 21 is connected to the electronic device 23 through the cable 22, the short circuit detection unit 211 can set the reference voltage Vdis to a relatively higher level.\",\n \"However, that the reference voltage Vdis is adjustable is only preferred but not necessary.\",\n \"Certainly, it is also practicable and within the scope of the present invention that the reference voltage Vdis is a constant.\",\n \"Besides adjusting the reference voltage Vdis according to whether or not the electronic device 23 is connected to the power converter 21 through the cable 22, in another embodiment of the present invention, the duration of the disable time period Tdis can be adjusted.\",\n \"For example, in the case wheren the power converter 21 is connected to the electronic device 23 through the cable 22, the normal depletion of charges is relatively higher.\",\n \"Under such circumstance, the duration of the disable time period Tdis can be shortened, for example by changing the frequency of the clock signal CLK or the time count of the timer circuit.\",\n \"In the embodiment shown in FIG.\",\n \"6B, the temporary stop signal STOP is periodically generated, which is only one example.\",\n \"In other embodiments, the temporary stop signal STOP can be generated during (or immediately after) a start-up operation or a power-on-reset operation, or, the temporary stop signal STOP can be generated irregularly during normal operation.\",\n \"For example, please refer to FIG.\",\n \"6C, typically, a Power On Reset (POR) signal is generated during a start-up operation or a power-on-reset operation, and the temporary stop signal STOP can be generated according to this POR signal.\",\n \"For another example, the temporary stop signal STOP can be generated can be set randomly.\",\n \"Thus, the present invention can generate the temporary stop signal STOP by one or a combination of two or more of the following approaches: generating the temporary stop signal STOP during (or immediately after) a start-up operation; generating the temporary stop signal STOP during (or immediately after) a power-on-reset operation; generating the temporary stop signal STOP periodically; or generating the temporary stop signal STOP irregularly (for example, the temporary stop signal STOP can be generated not only periodically but also irregularly).\",\n \"FIGS.\",\n \"7A-7C show another embodiment of the present invention, which show the bad connection detection unit and explain how the present invention performs a bad connection detection.\",\n \"The bad connection needs to be detected only when the power converter 21 is connected to the cable 22 and the cable 22 is connected to the electronic device 23, so this is what is shown in FIGS.\",\n \"7A-7C.\",\n \"Please refer to FIG.\",\n \"7B.\",\n \"Although what the power converter 21 provides is the output voltage Vout, the voltage actually received by the electronic device 23 is the actual voltage Vp because of the bad connection (which is expressed by resistors R1, R2, R3 and R4).\",\n \"Likewise, although what the power converter 21 provides is the output current Iout, the current actually received by the electronic device 23 is the actual current Ip because of the bad connection.\",\n \"The bad connection detection unit 235 is provided to detect whether a bad connection occurs.\",\n \"As shown in FIGS.\",\n \"7B-7C, the bad connection detection unit 235 of this embodiment can be, for example but not limited to, located inside the electronic device 23.The bad connection detection unit 235 includes a voltage sensing circuit 2351, a current sensing circuit 2352, an analog-to-digital converter (ADC) 2353, an analog-to-digital converter (ADC) 2354, and a calculation circuit 2355.The voltage sensing circuit 2351 senses the actual voltage Vp, which is then converted to a digital signal by the ADC 2353.The current sensing circuit 2352 senses the actual current Ip, which is then converted to a digital signal by the ADC 2354.The calculation circuit 2355 performs calculation according to the outputs from the ADC 2353 and ADC 2354.In one embodiment, information of the target level of the output voltage Vout and the target level of the output current Iout is given by the electronic device 23, via the signal line 24 in the cable 22, to the power converter 21.Under such circumstance, because the electronic device 23 has already known the target levels of the output voltage Vout and the output current Iout, these levels can be pre-stored in the calculation circuit 2355.The calculation circuit 2355 can compare the outputs from the ADC 2353 and the ADC 2354 with the pre-stored target levels of the output voltage Vout and the output current Iout.\",\n \"When a difference between the target level of the output voltage Vout and the actual voltage Vp is too large, and/or when a difference between the target level of the output current Iout and the actual current Ip is too large (i.e., the difference exceeds a predetermined threshold difference), the calculation circuit 2355 will issue an error signal Error 2 to indicate that a “bad connection” occurs.\",\n \"Such error signal Error 2 can be transmitted via, for example, the signal line 24.Certainly, in other embodiments, the error signal Error 2 can be transmitted via other wirings (under such circumstance, the cable 22 needs to include such wirings).\",\n \"Furthermore, to avoid misjudging the occurrence of a bad connection when the circuit just starts up or when the electronic device 23 is in heavily loaded condition, the determination of “bad connection” can be conducted when the circuit is stable.\",\n \"FIG.\",\n \"7D explains another embodiment as to how the present invention performs a bad connection detection.\",\n \"In this embodiment, an ADC 2141 and an ADC 2142 are included in the power converter 21 (e.g., when the power converter 21 is an isolated type AC-DC converter, the ADC 2141 and the ADC 2142 can be located inside the output unit 210; or, when the power converter 21 is another type of power converter, the ADC 2141 and the ADC 2142 can be located inside the switch control unit 214).\",\n \"The ADC 2141 and the ADC 2142 convert the output voltage Vout and the output current Iout into digital signals, respectively.\",\n \"The converted digital values are outputted to the calculation circuit 2355 through a buffer circuit 2143.The calculation circuit 2355 compares the outputs from the ADC 2353 and the ADC 2354 with the information of the output voltage Vout and the output current Iout outputted from the buffer circuit 2143.When a difference between the target level of the output voltage Vout and the actual voltage Vp is too large, and/or when a difference between the target level of the output current Iout and the actual current Ip is too large (i.e., the difference exceeds a predetermined threshold difference), the calculation circuit 2355 will issue an error signal Error 2 to indicate that a “bad connection” occurs.\",\n \"Because the signal line 24 can transmit signals bi-directionally, the information of the output voltage Vout, the output current Iout and the error signal Error 2 can all be transmitted via the signal line 24.FIG.\",\n \"7E explains another embodiment as to how the present invention performs a bad connection detection.\",\n \"In this embodiment, a calculation circuit 2144 is included in the power converter 21 (e.g., when the power converter 21 is an isolated type AC-DC converter, the calculation circuit 2144 can be located inside the output unit 210; or, when the power converter 21 is another type of power converter, the calculation circuit 2144 can be located inside the switch control unit 214).\",\n \"And, in this embodiment, the bad connection detection circuit 235 further includes a buffer circuit 2356 in the electronic device 23.In other words, the bad connection detection circuit 235 can be regarded as having two separate parts, located inside the power converter 21 and inside the electronic device 23, respectively.\",\n \"The bad connection detection circuit 235 outputs digital signals converted from the actual voltage Vp and the actual current Ip, which are sent to the calculation circuit 2144 of the switch control unit 214.The calculation circuit 2144 compares the converted digital signals of the actual voltage Vp and the actual current Ip with the converted digital values of the output voltage Vout and the output current Iout outputted from the ADC 2141 and the ADC 2142, respectively.\",\n \"When a difference between the voltages and/or a difference between the currents is too large (i.e., the difference exceeds a predetermined threshold difference), the calculation circuit 2144 will issue an error signal Error 2 to indicate that a “bad connection” occurs.\",\n \"When an abnormal condition such as a short circuit or a bad connection is detected and the error signal Error 1 or the error signal Error 2 is generated, the generated error signal Error 1 or Error 2 can be used in various ways.\",\n \"For example, the error signal Error 1 or Error 2 can function as an alarm signal to the user (e.g., the error signal Error 1 or Error2 can light up an LED lamp, or trigger a buzzer to issue an alert).\",\n \"Or, the error signal Error 1 or Error2 can maintain the temporary stop signal STOP at the predefined level.\",\n \"Or, the error signal Error 1 or Error2 can be used to directly disable the switch control unit 214.Or, the error signal Error 1 or Error2 can be used to turn off the power converter 21.Or, if the power converter 21 is an isolated type AC-DC converter, the error signal Error 1 or Error2 can be used to open the path by which the secondary side of the transformer provides the output voltage Vout.\",\n \"Or, the error signal Error 1 or Error2 is not used to turn off the power converter 21, but instead to limit the maximum of the output current of the power converter 21.Any or more of the above and other ways can be adopted, depending on practical needs.\",\n \"In view of the above, the power supply system of the present invention can, on one hand, detect the abnormal short circuit through the short circuit detection unit 211 and can, on the other hand, detect the abnormal bad connection through the bad connection detection unit 235, so that power loss due to these abnormal conditions can be avoided to improve the power utilization efficiency and better protect the circuit.\",\n \"The present invention has been described in considerable detail with reference to certain preferred embodiments thereof.\",\n \"It should be understood that the description is for illustrative purpose, not for limiting the scope of the present invention.\",\n \"An embodiment or a claim of the present invention does not need to achieve all the objectives or advantages of the present invention.\",\n \"The title and abstract are provided for assisting searches but not for limiting the scope of the present invention.\",\n \"Those skilled in this art can readily conceive variations and modifications within the spirit of the present invention.\",\n \"For example, the definition of the high level and the low level of a digital signal are interchangeable, with corresponding amendments of the circuits processing these signals.\",\n \"For another example, a device which does not substantially influence the primary function of a signal can be inserted between any two devices or circuits in the shown embodiments.\",\n \"For yet another example, the cable 22 and the power converter 21 can be integrated into a single device; or, the cable 22 and the electronic device can be integrated into a single device, and the spirit of the present invention can still be applied to such configurations.\",\n \"In view of the foregoing, the spirit of the present invention should cover all such and other modifications and variations, which should be interpreted to fall within the scope of the following claims and their equivalents.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874733"}}},{"rowIdx":4494677,"cells":{"text":{"kind":"list like","value":[["METHOD AND APPARATUS FOR RECEIVING OR TRANSMITTING DOWNLINK CONTROL SIGNAL IN WIRELESS COMMUNICATION SYSTEM","Provided is a method for receiving a downlink signal by a user equipment (UE) in a wireless communication system according to one embodiment of the present disclosure, comprising: receiving a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; receiving a downlink control information (DCI) configuring the SPS-PDSCH; and decoding the SPS-PDSCH using one of the received plurality of parameter sets, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating the parameter set to be used for decoding is included in the DCI."],["1.A method for receiving a downlink signal by a user equipment (UE) in a wireless communication system, comprising: receiving a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; receiving a downlink control information (DCI), carried by an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and decoding the SPS-PDSCH in the subframe using a parameter set from among the plurality of parameter sets, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.","2.The method according to claim 1, wherein the starting symbol position of the SPS-PDSCH is different from a starting symbol position of the EPDCCH carrying the DCI.","3.The method according to claim 1, wherein the UE is scheduled to receive two or more EPDCCHs in the subframe.","4.The method according to claim 3, wherein the two or more EPDCCHs are transmitted from different transmission points or different evolved Node B.","5.The method according to claim 1, wherein each of the plurality of parameter sets includes resource element (RE) mapping pattern information related to specific reference signal(s).","6.The method according to claim 1, wherein: if the SPS-PDSCH is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel is restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.","7.The method according to claim 1, wherein the user equipment (UE) is configured in transmission mode 10.8.The method according to claim 1, wherein the determined parameter set is used for decoding the SPS-PDSCH until receiving a new DCI configuring SPS.","9.The method according to claim 1, further comprising: if the DCI configuring SPS includes an indicator which indicates the parameter set to be used for decoding, decoding the SPS-PDSCH using a parameter set indicated by the indicator.","10.A method for transmitting a downlink signal to a user equipment (UE) in a wireless communication system, performed by an eNodeB (evolved Node B) and comprising: transmitting a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; and transmitting a downlink control information (DCI), carried by an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and wherein a parameter set from among the plurality of parameter sets is used for the UE to decode the SPS-PDSCH in the subframe, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.","11.The method according to claim 10, wherein the starting symbol position of the SPS-PDSCH is different from a starting symbol position of the EPDCCH carrying the DCI.","12.The method according to claim 10, wherein the UE is scheduled to receive two or more EPDCCHs in the subframe.","13.The method according to claim 12, wherein the two or more EPDCCHs are transmitted from different transmission points or different eNodeB.","14.The method according to claim 10, wherein each of the plurality of parameter sets includes resource element (RE) mapping pattern information related to specific reference signal(s).","15.The method according to claim 10, wherein: if the SPS-PDSCH is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel is restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.","16.The method according to claim 10, wherein the user equipment (UE) is configured in transmission mode 10.17.The method according to claim 10, wherein the determined parameter set is used for decoding the SPS-PDSCH until receiving a new DCI configuring SPS.","18.The method according to claim 10, further comprising: if the DCI configuring SPS includes an indicator which indicates the parameter set to be used for decoding, the parameter set indicated by the indicator is used for the UE to decode the SPS-PDSCH.","19.A user equipment (UE) for receiving a downlink control signal in a wireless communication system, comprising: a radio frequency (RF) unit; and a processor that controls the RF unit, wherein the processor receives a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling, receives a downlink control information (DCI), carried in an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and decodes the SPS-PDSCH in the subframe using a parameter set from among the plurality of parameter sets, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.","20.An evolved Node B (eNB) for transmitting a downlink control signal in a wireless communication system, comprising: a radio frequency (RF) unit; and a processor that controls the RF unit, wherein the processor transmits a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; and transmits a downlink control information (DCI), carried by an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and wherein a parameter set from among the plurality of parameter sets is used for the UE to decode the SPS-PDSCH in the subframe, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH."],["<SOH> BACKGROUND ART <EOH>Recently, various devices requiring machine-to-machine (M2M) communication and high data transfer rate, such as smartphones or tablet personal computers (PCs), have appeared and come into widespread use.","This has rapidly increased the quantity of data which needs to be processed in a cellular network.","In order to satisfy such rapidly increasing data throughput, recently, carrier aggregation (CA) technology which efficiently uses more frequency bands, cognitive ratio technology, multiple antenna (MIMO) technology for increasing data capacity in a restricted frequency, multiple-base-station cooperative technology, etc.","have been highlighted.","In addition, communication environments have evolved such that the density of accessible nodes is increased in the vicinity of a user equipment (UE).","Here, the node includes one or more antennas and refers to a fixed point capable of transmitting/receiving radio frequency (RF) signals to/from the user equipment (UE).","A communication system including high-density nodes may provide a communication service of higher performance to the UE by cooperation between nodes.","A multi-node coordinated communication scheme in which a plurality of nodes communicates with a user equipment (UE) using the same time-frequency resources has much higher data throughput than legacy communication scheme in which each node operates as an independent base station (BS) to communicate with the UE without cooperation.","A multi-node system performs coordinated communication using a plurality of nodes, each of which operates as a base station or an access point, an antenna, an antenna group, a remote radio head (RRH), and a remote radio unit (RRU).","Unlike the conventional centralized antenna system in which antennas are concentrated at a base station (BS), nodes are spaced apart from each other by a predetermined distance or more in the multi-node system.","The nodes can be managed by one or more base stations or base station controllers which control operations of the nodes or schedule data transmitted/received through the nodes.","Each node is connected to a base station or a base station controller which manages the node through a cable or a dedicated line.","The multi-node system can be considered as a kind of Multiple Input Multiple Output (MIMO) system since dispersed nodes can communicate with a single UE or multiple UEs by simultaneously transmitting/receiving different data streams.","However, since the multi-node system transmits signals using the dispersed nodes, a transmission area covered by each antenna is reduced compared to antennas included in the conventional centralized antenna system.","Accordingly, transmit power required for each antenna to transmit a signal in the multi-node system can be reduced compared to the conventional centralized antenna system using MIMO.","In addition, a transmission distance between an antenna and a UE is reduced to decrease in pathloss and enable rapid data transmission in the multi-node system.","This can improve transmission capacity and power efficiency of a cellular system and meet communication performance having relatively uniform quality regardless of UE locations in a cell.","Further, the multi-node system reduces signal loss generated during transmission since base station(s) or base station controller(s) connected to a plurality of nodes transmit/receive data in cooperation with each other.","When nodes spaced apart by over a predetermined distance perform coordinated communication with a UE, correlation and interference between antennas are reduced.","Therefore, a high signal to interference-plus-noise ratio (SINR) can be obtained according to the multi-node coordinated communication scheme.","Owing to the above-mentioned advantages of the multi-node system, the multi-node system is used with or replaces the conventional centralized antenna system to become a new foundation of cellular communication in order to reduce base station cost and backhaul network maintenance cost while extending service coverage and improving channel capacity and SINR in next-generation mobile communication systems."],["TECHNICAL FIELD The present invention relates to a wireless communication system, and more particularly to a method and apparatus for receiving or transmitting a downlink control signal in a wireless communication system.","BACKGROUND ART Recently, various devices requiring machine-to-machine (M2M) communication and high data transfer rate, such as smartphones or tablet personal computers (PCs), have appeared and come into widespread use.","This has rapidly increased the quantity of data which needs to be processed in a cellular network.","In order to satisfy such rapidly increasing data throughput, recently, carrier aggregation (CA) technology which efficiently uses more frequency bands, cognitive ratio technology, multiple antenna (MIMO) technology for increasing data capacity in a restricted frequency, multiple-base-station cooperative technology, etc.","have been highlighted.","In addition, communication environments have evolved such that the density of accessible nodes is increased in the vicinity of a user equipment (UE).","Here, the node includes one or more antennas and refers to a fixed point capable of transmitting/receiving radio frequency (RF) signals to/from the user equipment (UE).","A communication system including high-density nodes may provide a communication service of higher performance to the UE by cooperation between nodes.","A multi-node coordinated communication scheme in which a plurality of nodes communicates with a user equipment (UE) using the same time-frequency resources has much higher data throughput than legacy communication scheme in which each node operates as an independent base station (BS) to communicate with the UE without cooperation.","A multi-node system performs coordinated communication using a plurality of nodes, each of which operates as a base station or an access point, an antenna, an antenna group, a remote radio head (RRH), and a remote radio unit (RRU).","Unlike the conventional centralized antenna system in which antennas are concentrated at a base station (BS), nodes are spaced apart from each other by a predetermined distance or more in the multi-node system.","The nodes can be managed by one or more base stations or base station controllers which control operations of the nodes or schedule data transmitted/received through the nodes.","Each node is connected to a base station or a base station controller which manages the node through a cable or a dedicated line.","The multi-node system can be considered as a kind of Multiple Input Multiple Output (MIMO) system since dispersed nodes can communicate with a single UE or multiple UEs by simultaneously transmitting/receiving different data streams.","However, since the multi-node system transmits signals using the dispersed nodes, a transmission area covered by each antenna is reduced compared to antennas included in the conventional centralized antenna system.","Accordingly, transmit power required for each antenna to transmit a signal in the multi-node system can be reduced compared to the conventional centralized antenna system using MIMO.","In addition, a transmission distance between an antenna and a UE is reduced to decrease in pathloss and enable rapid data transmission in the multi-node system.","This can improve transmission capacity and power efficiency of a cellular system and meet communication performance having relatively uniform quality regardless of UE locations in a cell.","Further, the multi-node system reduces signal loss generated during transmission since base station(s) or base station controller(s) connected to a plurality of nodes transmit/receive data in cooperation with each other.","When nodes spaced apart by over a predetermined distance perform coordinated communication with a UE, correlation and interference between antennas are reduced.","Therefore, a high signal to interference-plus-noise ratio (SINR) can be obtained according to the multi-node coordinated communication scheme.","Owing to the above-mentioned advantages of the multi-node system, the multi-node system is used with or replaces the conventional centralized antenna system to become a new foundation of cellular communication in order to reduce base station cost and backhaul network maintenance cost while extending service coverage and improving channel capacity and SINR in next-generation mobile communication systems.","DISCLOSURE Technical Problem An object of the present invention is to provide a method for receiving or transmitting downlink control information in a wireless communication system.","It is to be understood that technical objects to be achieved by the present invention are not limited to the aforementioned technical objects and other technical objects which are not mentioned herein will be apparent from the following description to one of ordinary skill in the art to which the present invention pertains.","Technical Solution The objects of the present invention can be achieved by providing a method for receiving a downlink signal by a user equipment (UE) in a wireless communication system including: receiving Semi Persistent Scheduling (SPS)—related control information through higher layer signaling or a downlink control channel; and decoding a semi-persistently-scheduled downlink data channel based on the SPS-related control information, wherein the method further includes: if downlink control information (DCI) received through the downlink control channel is a first downlink control information (DCI) format, decoding the downlink data channel using a first parameter set from among candidate parameter sets received through higher layer signaling; and if downlink control information (DCI) received through the downlink control channel is a second DCI format, decoding the downlink data channel by using a second parameter set indicated by the downlink control information from among the candidate parameter sets received through higher layer signaling.","Additionally or alternatively, each of the candidate parameter sets may include information regarding a starting symbol position of the downlink data channel.","Additionally or alternatively, each of the candidate parameter sets may include resource element (RE) mapping pattern information related to specific reference signal(s).","Additionally or alternatively, if the semi-persistently-scheduled downlink data channel is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel may be restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.","Additionally or alternatively, the user equipment (UE) may be configured in transmission mode 10.Additionally or alternatively, the user equipment (UE) may be configured to receive downlink signal from at least two eNBs.","Additionally or alternatively, the method may further include decoding the downlink data channel by using the first parameter set or the second parameter set until new SPS-related information is received.","In accordance with another aspect of the present invention, a user equipment (UE) for receiving a downlink control signal in a wireless communication system includes: a radio frequency (RF) unit; and a processor configured to control the RF unit, wherein the processor receives Semi Persistent Scheduling (SPS)—related control information through higher layer signaling or a downlink control channel, and decodes a semi-persistently-scheduled downlink data channel based on the SPS-related control information, wherein, if downlink control information (DCI) received through the downlink control channel is a first downlink control information (DCI) format, the processor is further configured to decode the downlink data channel by using a first parameter set from among candidate parameter sets received through higher layer signaling; and, if downlink control information (DCI) received through the downlink control channel is a second DCI format, the processor is further configured to decode the downlink data channel by using a second parameter set indicated by the downlink control information from among the candidate parameter sets received through higher layer signaling.","Additionally or alternatively, each of the candidate parameter sets may include information regarding a starting symbol position of the downlink data channel.","Additionally or alternatively, each of the candidate parameter sets may include resource element (RE) mapping pattern information related to specific reference signal(s).","Additionally or alternatively, if the semi-persistently-scheduled downlink data channel is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel may be restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.","Additionally or alternatively, the user equipment (UE) may be configured in transmission mode 10.Additionally or alternatively, the user equipment (UE) may be configured to receive downlink signal from at least two eNBs.","Additionally or alternatively, the processor may be configured to decode the downlink data channel by using the first parameter set or the second parameter set until new SPS-related information is received.","It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.","Advantageous Effects According to exemplary embodiments of the present invention, the present invention can efficiently transmit and receive downlink control information in a wireless communication system.","It will be appreciated by persons skilled in the art that the effects that can be achieved with the present invention are not limited to what has been particularly described hereinabove and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings.","DESCRIPTION OF DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention, illustrate embodiments of the invention and together with the description serve to explain the principle of the invention.","FIG.","1 exemplarily shows a radio frame structure for use in a wireless communication system.","FIG.","2 exemplarily shows a downlink/uplink (DL/UL) slot structure for use in a wireless communication system.","FIG.","3 exemplarily shows a downlink (DL) subframe structure for use in a 3GPP LTE/LTE-A system.","FIG.","4 exemplarily shows an uplink (UL) subframe for use in a 3GPP LTE/LTE-A system.","FIG.","5 exemplarily shows an EPDCCH (Enhanced Physical Downlink Control Channel).","FIG.","6 exemplarily shows an EPDCCH (Enhanced Physical Downlink Control Channel).","FIG.","7 is a conceptual diagram illustrating a carrier aggregation (CA) scheme.","FIG.","8 is a conceptual diagram illustrating a cross-carrier scheduling scheme.","FIG.","9 is a conceptual diagram illustrating a wireless communication system for enabling a UE to receive a Joint Transmission (JT) service from a CoMP aggregation.","FIG.","10 is a conceptual diagram illustrating a method for deciding the start symbol position of the SPS-scheduled PDSCH (hereinafter referred to as SPS-PDSCH) according to the above mentioned embodiment.","FIG.","11 is a conceptual diagram illustrating invention method for deciding the start symbol position of SPS-PDSCH when the SPS-configured UE receives at least two EPDCCH-related parameters.","FIG.","12 is a block diagram of an apparatus for implementing embodiment(s) of the present invention.","BEST MODE Reference will now be made in detail to the preferred embodiments of the present invention, examples of which are illustrated in the accompanying drawings.","The accompanying drawings illustrate exemplary embodiments of the present invention and provide a more detailed description of the present invention.","However, the scope of the present invention should not be limited thereto.","In some cases, to prevent the concept of the present invention from being ambiguous, structures and apparatuses of the known art will be omitted, or will be shown in the form of a block diagram based on main functions of each structure and apparatus.","Also, wherever possible, the same reference numbers will be used throughout the drawings and the specification to refer to the same or like parts.","In the present invention, a user equipment (UE) is fixed or mobile.","The UE is a device that transmits and receives user data and/or control information by communicating with a base station (BS).","The term ‘UE’ may be replaced with ‘terminal equipment’, ‘Mobile Station (MS)’, ‘Mobile Terminal (MT)’, ‘User Terminal (UT)’, ‘Subscriber Station (SS)’, ‘wireless device’, ‘Personal Digital Assistant (PDA)’, ‘wireless modem’, ‘handheld device’, etc.","A BS is typically a fixed station that communicates with a UE and/or another BS.","The BS exchanges data and control information with a UE and another BS.","The term ‘BS’ may be replaced with ‘Advanced Base Station (ABS)’, ‘Node B’, ‘evolved-Node B (eNB)’, ‘Base Transceiver System (BTS)’, ‘Access Point (AP)’, ‘Processing Server (PS)’, etc.","In the following description, BS is commonly called eNB.","In the present invention, a node refers to a fixed point capable of transmitting/receiving a radio signal to/from a UE by communication with the UE.","Various eNBs can be used as nodes.","For example, a node can be a BS, NB, eNB, pico-cell eNB (PeNB), home eNB (HeNB), relay, repeater, etc.","Furthermore, a node may not be an eNB.","For example, a node can be a radio remote head (RRH) or a radio remote unit (RRU).","The RRH and RRU have power levels lower than that of the eNB.","Since the RRH or RRU (referred to as RRH/RRU hereinafter) is connected to an eNB through a dedicated line such as an optical cable in general, cooperative communication according to RRH/RRU and eNB can be smoothly performed compared to cooperative communication according to eNBs connected through a wireless link.","At least one antenna is installed per node.","An antenna may refer to an antenna port, a virtual antenna or an antenna group.","A node may also be called a point.","Unlink a conventional centralized antenna system (CAS) (i.e.","single node system) in which antennas are concentrated in an eNB and controlled an eNB controller, plural nodes are spaced apart at a predetermined distance or longer in a multi-node system.","The plural nodes can be managed by one or more eNBs or eNB controllers that control operations of the nodes or schedule data to be transmitted/received through the nodes.","Each node may be connected to an eNB or eNB controller managing the corresponding node via a cable or a dedicated line.","In the multi-node system, the same cell identity (ID) or different cell IDs may be used for signal transmission/reception through plural nodes.","When plural nodes have the same cell ID, each of the plural nodes operates as an antenna group of a cell.","If nodes have different cell IDs in the multi-node system, the multi-node system can be regarded as a multi-cell (e.g.","macro-cell/femto-cell/pico-cell) system.","When multiple cells respectively configured by plural nodes are overlaid according to coverage, a network configured by multiple cells is called a multi-tier network.","The cell ID of the RRH/RRU may be identical to or different from the cell ID of an eNB.","When the RRH/RRU and eNB use different cell IDs, both the RRH/RRU and eNB operate as independent eNBs.","In a multi-node system according to the present invention, which will be described below, one or more eNBs or eNB controllers connected to plural nodes can control the plural nodes such that signals are simultaneously transmitted to or received from a UE through some or all nodes.","While there is a difference between multi-node systems according to the nature of each node and implementation form of each node, multi-node systems are discriminated from single node systems (e.g.","CAS, conventional MIMO systems, conventional relay systems, conventional repeater systems, etc.)","since a plurality of nodes provides communication services to a UE in a predetermined time-frequency resource.","Accordingly, embodiments of the present invention with respect to a method of performing coordinated data transmission using some or all nodes can be applied to various types of multi-node systems.","For example, a node refers to an antenna group spaced apart from another node by a predetermined distance or more, in general.","However, embodiments of the present invention, which will be described below, can even be applied to a case in which a node refers to an arbitrary antenna group irrespective of node interval.","In the case of an eNB including an X-pole (cross polarized) antenna, for example, the embodiments of the preset invention are applicable on the assumption that the eNB controls a node composed of an H-pole antenna and a V-pole antenna.","A communication scheme through which signals are transmitted/received via plural transmit (Tx)/receive (Rx) nodes, signals are transmitted/received via at least one node selected from plural Tx/Rx nodes, or a node transmitting a downlink signal is discriminated from a node transmitting an uplink signal is called multi-eNB MIMO or CoMP (Coordinated Multi-Point Tx/Rx).","Coordinated transmission schemes from among CoMP communication schemes can be categorized into JP (Joint Processing) and scheduling coordination.","The former may be divided into JT (Joint Transmission)/JR (Joint Reception) and DPS (Dynamic Point Selection) and the latter may be divided into CS (Coordinated Scheduling) and CB (Coordinated Beamforming).","DPS may be called DCS (Dynamic Cell Selection).","When JP is performed, more various communication environments can be generated, compared to other CoMP schemes.","JT refers to a communication scheme by which plural nodes transmit the same stream to a UE and JR refers to a communication scheme by which plural nodes receive the same stream from the UE.","The UE/eNB combine signals received from the plural nodes to restore the stream.","In the case of JT/JR, signal transmission reliability can be improved according to transmit diversity since the same stream is transmitted from/to plural nodes.","DPS refers to a communication scheme by which a signal is transmitted/received through a node selected from plural nodes according to a specific rule.","In the case of DPS, signal transmission reliability can be improved because a node having a good channel state between the node and a UE is selected as a communication node.","In the present invention, a cell refers to a specific geographical area in which one or more nodes provide communication services.","Accordingly, communication with a specific cell may mean communication with an eNB or a node providing communication services to the specific cell.","A downlink/uplink signal of a specific cell refers to a downlink/uplink signal from/to an eNB or a node providing communication services to the specific cell.","A cell providing uplink/downlink communication services to a UE is called a serving cell.","Furthermore, channel status/quality of a specific cell refers to channel status/quality of a channel or a communication link generated between an eNB or a node providing communication services to the specific cell and a UE.","In 3GPP LTE-A systems, a UE can measure downlink channel state from a specific node using one or more CSI-RSs (Channel State Information Reference Signals) transmitted through antenna port(s) of the specific node on a CSI-RS resource allocated to the specific node.","In general, neighboring nodes transmit CSI-RS resources on orthogonal CSI-RS resources.","When CSI-RS resources are orthogonal, this means that the CSI-RS resources have different subframe configurations and/or CSI-RS sequences which specify subframes to which CSI-RSs are allocated according to CSI-RS resource configurations, subframe offsets and transmission periods, etc.","which specify symbols and subcarriers carrying the CSI RSs.","In the present invention, PDCCH (Physical Downlink Control Channel)/PCFICH (Physical Control Format Indicator Channel)/PHICH (Physical Hybrid automatic repeat request Indicator Channel)/PDSCH (Physical Downlink Shared Channel) refer to a set of time-frequency resources or resource elements respectively carrying DCI (Downlink Control Information)/CFI (Control Format Indicator)/downlink ACK/NACK (Acknowlegement/Negative ACK)/downlink data.","In addition, PUCCH (Physical Uplink Control Channel)/PUSCH (Physical Uplink Shared Channel)/PRACH (Physical Random Access Channel) refer to sets of time-frequency resources or resource elements respectively carrying UCI (Uplink Control Information)/uplink data/random access signals.","In the present invention, a time-frequency resource or a resource element (RE), which is allocated to or belongs to PDCCH/PCFICH/PHICH/PDSCH/PUCCH/PUSCH/PRACH, is referred to as a PDCCH/PCFICH/PHICH/PDSCH/PUCCH/PUSCH/PRACH RE or PDCCH/PCFICH/PHICH/PDSCH/PUCCH/PUSCH/PRACH resource.","In the following description, transmission of PUCCH/PUSCH/PRACH by a UE is equivalent to transmission of uplink control information/uplink data/random access signal through or on PUCCH/PUSCH/PRACH.","Furthermore, transmission of PDCCH/PCFICH/PHICH/PDSCH by an eNB is equivalent to transmission of downlink data/control information through or on PDCCH/PCFICH/PHICH/PDSCH.","FIG.","1 illustrates an exemplary radio frame structure used in a wireless communication system.","FIG.","1(a) illustrates a frame structure for frequency division duplex (FDD) used in 3GPP LTE/LTE-A and FIG.","1(b) illustrates a frame structure for time division duplex (TDD) used in 3GPP LTE/LTE-A.","Referring to FIG.","1, a radio frame used in 3GPP LTE/LTE-A has a length of 10 ms (307200 Ts) and includes 10 subframes in equal size.","The 10 subframes in the radio frame may be numbered.","Here, Ts denotes sampling time and is represented as Ts=1/(2048*15 kHz).","Each subframe has a length of 1 ms and includes two slots.","20 slots in the radio frame can be sequentially numbered from 0 to 19.Each slot has a length of 0.5 ms. A time for transmitting a subframe is defined as a transmission time interval (TTI).","Time resources can be discriminated by a radio frame number (or radio frame index), subframe number (or subframe index) and a slot number (or slot index).","The radio frame can be configured differently according to duplex mode.","Downlink transmission is discriminated from uplink transmission by frequency in FDD mode, and thus the radio frame includes only one of a downlink subframe and an uplink subframe in a specific frequency band.","In TDD mode, downlink transmission is discriminated from uplink transmission by time, and thus the radio frame includes both a downlink subframe and an uplink subframe in a specific frequency band.","Table 1 shows DL-UL configurations of subframes in a radio frame in the TDD mode.","TABLE 1 Downlink- to-Uplink Switch- DL-UL point Subframe number configuration periodicity 0 1 2 3 4 5 6 7 8 9 0 5 ms D S U U U D S U U U 1 5 ms D S U U D D S U U D 2 5 ms D S U D D D S U D D 3 10 ms D S U U U D D D D D 4 10 ms D S U U D D D D D D 5 10 ms D S U D D D D D D D 6 5 ms D S U U U D S U U D In Table 1, D denotes a downlink subframe, U denotes an uplink subframe and S denotes a special subframe.","The special subframe includes three fields of DwPTS (Downlink Pilot TimeSlot), GP (Guard Period), and UpPTS (Uplink Pilot TimeSlot).","DwPTS is a period reserved for downlink transmission and UpPTS is a period reserved for uplink transmission.","Table 2 shows special subframe configuration.","TABLE 2 Normal cyclic Extended cyclic prefix in downlink prefix in downlink UpPTS UpPTS Normal Extended Normal Special cyclic cyclic cyclic Extended subframe prefix in prefix prefix in cyclic prefix configuration DwPTS uplink in uplink DwPTS uplink in uplink 0 6592 · Ts 2192 · Ts 2560 · Ts 7680 · Ts 2192 · Ts 2560 · Ts 1 19760 · Ts 20480 · Ts 2 21952 · Ts 23040 · Ts 3 24144 · Ts 25600 · Ts 4 26336 · Ts 7680 · Ts 4384 · Ts 5120 · Ts 5 6592 · Ts 4384 · Ts 5120 · Ts 20480 · Ts 6 19760 · Ts 23040 · Ts 7 21952 · Ts 12800 · Ts 8 24144 · Ts — — — FIG.","2 illustrates an exemplary downlink/uplink slot structure in a wireless communication system.","Particularly, FIG.","2 illustrates a resource grid structure in 3GPP LTE/LTE-A.","A resource grid is present per antenna port.","Referring to FIG.","2, a slot includes a plurality of OFDM (Orthogonal Frequency Division Multiplexing) symbols in the time domain and a plurality of resource blocks (RBs) in the frequency domain.","An OFDM symbol may refer to a symbol period.","A signal transmitted in each slot may be represented by a resource grid composed of NRBDL/UL*NscRB subcarriers and NsymbDL/UL OFDM symbols.","Here, NRBDL denotes the number of RBs in a downlink slot and NRBUL denotes the number of RBs in an uplink slot.","NRBDL and NRBUL respectively depend on a DL transmission bandwidth and a UL transmission bandwidth.","NsymbDL denotes the number of OFDM symbols in the downlink slot and NsymbUL denotes the number of OFDM symbols in the uplink slot.","In addition, NscRB denotes the number of subcarriers constructing one RB.","An OFDM symbol may be called an SC-FDM (Single Carrier Frequency Division Multiplexing) symbol according to multiple access scheme.","The number of OFDM symbols included in a slot may depend on a channel bandwidth and the length of a cyclic prefix (CP).","For example, a slot includes 7 OFDM symbols in the case of normal CP and 6 OFDM symbols in the case of extended CP.","While FIG.","2 illustrates a subframe in which a slot includes 7 OFDM symbols for convenience, embodiments of the present invention can be equally applied to subframes having different numbers of OFDM symbols.","Referring to FIG.","2, each OFDM symbol includes NRBDL/UL*NscRB subcarriers in the frequency domain.","Subcarrier types can be classified into a data subcarrier for data transmission, a reference signal subcarrier for reference signal transmission, and null subcarriers for a guard band and a direct current (DC) component.","The null subcarrier for a DC component is a subcarrier remaining unused and is mapped to a carrier frequency (f0) during OFDM signal generation or frequency up-conversion.","The carrier frequency is also called a center frequency.","An RB is defined by NsymbDL/UL (e.g.","7) consecutive OFDM symbols in the time domain and NscRB (e.g.","12) consecutive subcarriers in the frequency domain.","For reference, a resource composed by an OFDM symbol and a subcarrier is called a resource element (RE) or a tone.","Accordingly, an RB is composed of NsymbDL/UL*NscRB REs.","Each RE in a resource grid can be uniquely defined by an index pair (k, 1) in a slot.","Here, k is an index in the range of 0 to NsymbDL/UL*NscRB−1 frequency domain and 1 is an index in the range of 0 to NsymbDL/UL−1.Two RBs, which occupy NscRB same continuous subcarriers for one subframe and are respectively located at two slots of the subframe, will be referred to as a pair of physical resource blocks (PRB).","The two RBs constituting the PRB have the same PRB number (or PRB index).","A virtual resource block (VRB) is a logical resource allocation unit for resource allocation.","The VRB has the same size as that of the PRB.","The VRB may be divided into a localized VRB and a distributed VRB depending on a mapping scheme of VRB into PRB.","The localized VRBs are mapped into the PRBs, whereby VRB number (VRB index) corresponds to PRB number.","That is, nPRB=nVRB is obtained.","Numbers are given to the localized VRBs from 0 to NDLVRB−1, and NDLVRB=NDLRB is obtained.","Accordingly, according to the localized mapping scheme, the VRBs having the same VRB number are mapped into the PRBs having the same PRB number at the first slot and the second slot.","On the other hand, the distributed VRBs are mapped into the PRBs through interleaving.","Accordingly, the VRBs having the same VRB number may be mapped into the PRBs having different PRB numbers at the first slot and the second slot.","Two PRBs, which are respectively located at two slots of the subframe and have the same VRB number, will be referred to as a pair of VRBs.","FIG.","3 illustrates a downlink (DL) subframe structure used in 3GPP LTE/LTE-A.","Referring to FIG.","3, a DL subframe is divided into a control region and a data region.","A maximum of three (four) OFDM symbols located in a front portion of a first slot within a subframe correspond to the control region to which a control channel is allocated.","A resource region available for PDCCH transmission in the DL subframe is referred to as a PDCCH region hereinafter.","The remaining OFDM symbols correspond to the data region to which a physical downlink shared chancel (PDSCH) is allocated.","A resource region available for PDSCH transmission in the DL subframe is referred to as a PDSCH region hereinafter.","Examples of downlink control channels used in 3GPP LTE include a physical control format indicator channel (PCFICH), a physical downlink control channel (PDCCH), a physical hybrid ARQ indicator channel (PHICH), etc.","The PCFICH is transmitted at a first OFDM symbol of a subframe and carries information regarding the number of OFDM symbols used for transmission of control channels within the subframe.","The PHICH is a response of uplink transmission and carries an HARQ acknowledgment (ACK)/negative acknowledgment (NACK) signal.","Control information carried on the PDCCH is called downlink control information (DCI).","The DCI contains resource allocation information and control information for a UE or a UE group.","For example, the DCI includes a transport format and resource allocation information of a downlink shared channel (DL-SCH), a transport format and resource allocation information of an uplink shared channel (UL-SCH), paging information of a paging channel (PCH), system information on the DL-SCH, information about resource allocation of an upper layer control message such as a random access response transmitted on the PDSCH, a transmit control command set with respect to individual UEs in a UE group, a transmit power control command, information on activation of a voice over IP (VoIP), downlink assignment index (DAI), etc.","The transport format and resource allocation information of the DL-SCH are also called DL scheduling information or a DL grant and the transport format and resource allocation information of the UL-SCH are also called UL scheduling information or a UL grant.","The size and purpose of DCI carried on a PDCCH depend on DCI format and the size thereof may be varied according to coding rate.","Various formats, for example, formats 0 and 4 for uplink and formats 1, 1A, 1B, 1C, 1D, 2, 2A, 2B, 2C, 3 and 3A for downlink, have been defined in 3GPP LTE.","Control information such as a hopping flag, information on RB allocation, modulation coding scheme (MCS), redundancy version (RV), new data indicator (NDI), information on transmit power control (TPC), cyclic shift demodulation reference signal (DMRS), UL index, channel quality information (CQI) request, DL assignment index, HARQ process number, transmitted precoding matrix indicator (TPMI), precoding matrix indicator (PMI), etc.","is selected and combined based on DCI format and transmitted to a UE as DCI.","In general, a DCI format for a UE depends on transmission mode (TM) set for the UE.","In other words, only a DCI format corresponding to a specific TM can be used for a UE configured in the specific TM.","A PDCCH is transmitted on an aggregation of one or several consecutive control channel elements (CCEs).","The CCE is a logical allocation unit used to provide the PDCCH with a coding rate based on a state of a radio channel.","The CCE corresponds to a plurality of resource element groups (REGs).","For example, a CCE corresponds to 9 REGs and an REG corresponds to 4 REs.","3GPP LTE defines a CCE set in which a PDCCH can be located for each UE.","A CCE set from which a UE can detect a PDCCH thereof is called a PDCCH search space, simply, search space.","An individual resource through which the PDCCH can be transmitted within the search space is called a PDCCH candidate.","A set of PDCCH candidates to be monitored by the UE is defined as the search space.","In 3GPP LTE/LTE-A, search spaces for DCI formats may have different sizes and include a dedicated search space and a common search space.","The dedicated search space is a UE-specific search space and is configured for each UE.","The common search space is configured for a plurality of UEs.","The aggregation levels defining the search space are indicated as follows: TABLE 3 Search Space Number of PDCCH Type Aggregation Level L Size [in CCEs] candidates M(L) UE- 1 6 6 specific 2 12 6 4 8 2 8 16 2 Common 4 16 4 8 16 2 A PDCCH candidate corresponds to 1, 2, 4 or 8 CCEs according to CCE aggregation level.","An eNB transmits a PDCCH (DCI) on an arbitrary PDCCH candidate with in a search space and a UE monitors the search space to detect the PDCCH (DCI).","Here, monitoring refers to attempting to decode each PDCCH in the corresponding search space according to all monitored DCI formats.","The UE can detect the PDCCH thereof by monitoring plural PDCCHs.","Since the UE does not know the position in which the PDCCH thereof is transmitted, the UE attempts to decode all PDCCHs of the corresponding DCI format for each subframe until a PDCCH having the ID thereof is detected.","This process is called blind detection (or blind decoding (BD)).","The eNB can transmit data for a UE or a UE group through the data region.","Data transmitted through the data region may be called user data.","For transmission of the user data, a physical downlink shared channel (PDSCH) may be allocated to the data region.","A paging channel (PCH) and downlink-shared channel (DL-SCH) are transmitted through the PDSCH.","The UE can read data transmitted through the PDSCH by decoding control information transmitted through a PDCCH.","Information representing a UE or a UE group to which data on the PDSCH is transmitted, how the UE or UE group receives and decodes the PDSCH data, etc.","is included in the PDCCH and transmitted.","For example, if a specific PDCCH is CRC (cyclic redundancy check)-masked having radio network temporary identify (RNTI) of “A” and information about data transmitted using a radio resource (e.g.","frequency position) of “B” and transmission format information (e.g.","transport block size, modulation scheme, coding information, etc.)","of “C” is transmitted through a specific DL subframe, the UE monitors PDCCHs using RNTI information and a UE having the RNTI of “A” detects a PDCCH and receives a PDSCH indicated by “B” and “C” using information about the PDCCH.","A reference signal (RS) to be compared with a data signal is necessary for the UE to demodulate a signal received from the eNB.","A reference signal refers to a predetermined signal having a specific waveform, which is transmitted from the eNB to the UE or from the UE to the eNB and known to both the eNB and UE.","The reference signal is also called a pilot.","Reference signals are categorized into a cell-specific RS shared by all UEs in a cell and a modulation RS (DM RS) dedicated for a specific UE.","A DM RS transmitted by the eNB for demodulation of downlink data for a specific UE is called a UE-specific RS.","Both or one of DM RS and CRS may be transmitted on downlink.","When only the DM RS is transmitted without CRS, an RS for channel measurement needs to be additionally provided because the DM RS transmitted using the same precoder as used for data can be used for demodulation only.","For example, in 3GPP LTE(-A), CSI-RS corresponding to an additional RS for measurement is transmitted to the UE such that the UE can measure channel state information.","CSI-RS is transmitted in each transmission period corresponding to a plurality of subframes based on the fact that channel state variation with time is not large, unlike CRS transmitted per subframe.","FIG.","4 illustrates an exemplary uplink subframe structure used in 3GPP LTE/LTE-A.","Referring to FIG.","4, a UL subframe can be divided into a control region and a data region in the frequency domain.","One or more PUCCHs (physical uplink control channels) can be allocated to the control region to carry uplink control information (UCI).","One or more PUSCHs (Physical uplink shared channels) may be allocated to the data region of the UL subframe to carry user data.","In the UL subframe, subcarriers spaced apart from a DC subcarrier are used as the control region.","In other words, subcarriers corresponding to both ends of a UL transmission bandwidth are assigned to UCI transmission.","The DC subcarrier is a component remaining unused for signal transmission and is mapped to the carrier frequency f0 during frequency up-conversion.","A PUCCH for a UE is allocated to an RB pair belonging to resources operating at a carrier frequency and RBs belonging to the RB pair occupy different subcarriers in two slots.","Assignment of the PUCCH in this manner is represented as frequency hopping of an RB pair allocated to the PUCCH at a slot boundary.","When frequency hopping is not applied, the RB pair occupies the same subcarrier.","The PUCCH can be used to transmit the following control information.","Scheduling Request (SR): This is information used to request a UL-SCH resource and is transmitted using On-Off Keying (OOK) scheme.","HARQ ACK/NACK: This is a response signal to a downlink data packet on a PDSCH and indicates whether the downlink data packet has been successfully received.","A 1-bit ACK/NACK signal is transmitted as a response to a single downlink codeword and a 2-bit ACK/NACK signal is transmitted as a response to two downlink codewords.","HARQ-ACK responses include positive ACK (ACK), negative ACK (NACK), discontinuous transmission (DTX) and NACK/DTX.","Here, the term HARQ-ACK is used interchangeably with the term HARQ ACK/NACK and ACK/NACK.","Channel State Indicator (CSI): This is feedback information about a downlink channel.","Feedback information regarding MIMO includes a rank indicator (RI) and a precoding matrix indicator (PMI).","The quantity of control information (UCI) that a UE can transmit through a subframe depends on the number of SC-FDMA symbols available for control information transmission.","The SC-FDMA symbols available for control information transmission correspond to SC-FDMA symbols other than SC-FDMA symbols of the subframe, which are used for reference signal transmission.","In the case of a subframe in which a sounding reference signal (SRS) is configured, the last SC-FDMA symbol of the subframe is excluded from the SC-FDMA symbols available for control information transmission.","A reference signal is used to detect coherence of the PUCCH.","The PUCCH supports various formats according to information transmitted thereon.","Table 4 shows the mapping relationship between PUCCH formats and UCI in LTE/LTE-A.","TABLE 4 Number of bits per PUCCH Modulation subframe, format scheme Mbit Usage Etc.","1 N/A N/A SR (Scheduling Request) 1a BPSK 1 ACK/NACK or One SR + ACK/NACK codeword 1b QPSK 2 ACK/NACK or Two SR + ACK/NACK codeword 2 QPSK 20 CQI/PMI/RI Joint coding ACK/NACK (extended CP) 2a QPSK + BPSK 21 CQI/PMI/RI + Normal CP ACK/NACK only 2b QPSK + QPSK 22 CQI/PMI/RI + Normal CP ACK/NACK only 3 QPSK 48 ACK/NACK or SR + ACK/NACK or CQI/PMI/RI + ACK/NACK Referring to Table 4, PUCCH formats 1/1a/1b are used to transmit ACK/NACK information, PUCCH format 2/2a/2b are used to carry CSI such as CQI/PMI/RI and PUCCH format 3 is used to transmit ACK/NACK information.","Reference Signal (RS) When a packet is transmitted in a wireless communication system, signal distortion may occur during transmission since the packet is transmitted through a radio channel.","To correctly receive a distorted signal at a receiver, the distorted signal needs to be corrected using channel information.","To detect channel information, a signal known to both a transmitter and the receiver is transmitted and channel information is detected with a degree of distortion of the signal when the signal is received through a channel.","This signal is called a pilot signal or a reference signal.","When data is transmitted/received using multiple antennas, the receiver can receive a correct signal only when the receiver is aware of a channel state between each transmit antenna and each receive antenna.","Accordingly, a reference signal needs to be provided per transmit antenna, more specifically, per antenna port.","Reference signals can be classified into an uplink reference signal and a downlink reference signal.","In LTE, the uplink reference signal includes: i) a demodulation reference signal (DMRS) for channel estimation for coherent demodulation of information transmitted through a PUSCH and a PUCCH; and ii) a sounding reference signal (SRS) used for an eNB to measure uplink channel quality at a frequency of a different network.","The downlink reference signal includes: i) a cell-specific reference signal (CRS) shared by all UEs in a cell; ii) a UE-specific reference signal for a specific UE only; iii) a DMRS transmitted for coherent demodulation when a PDSCH is transmitted; iv) a channel state information reference signal (CSI-RS) for delivering channel state information (CSI) when a downlink DMRS is transmitted; v) a multimedia broadcast single frequency network (MBSFN) reference signal transmitted for coherent demodulation of a signal transmitted in MBSFN mode; and vi) a positioning reference signal used to estimate geographic position information of a UE.","Reference signals can be classified into a reference signal for channel information acquisition and a reference signal for data demodulation.","The former needs to be transmitted in a wide band as it is used for a UE to acquire channel information on downlink transmission and received by a UE even if the UE does not receive downlink data in a specific subframe.","This reference signal is used even in a handover situation.","The latter is transmitted along with a corresponding resource by an eNB when the eNB transmits a downlink signal and is used for a UE to demodulate data through channel measurement.","This reference signal needs to be transmitted in a region in which data is transmitted.","General EPDCCH (Enhanced PDCCH) Owing to introduction of a multi-node system, although various communication schemes becomes available in a manner that channel quality improvement is achieved, introduction of a new control channel is being requested to apply the above-mentioned MIMO scheme and inter-cell coordinated communication scheme to the multi-node environment.","Due to the above necessity, introduction of a new control channel is an Enhanced PDCCH (EPDCCH) is being intensively discussed, and the new control channel can be allocated to a data region (hereinafter referred to as a PDSCH region) instead of the legacy control region (hereinafter referred to as a PDCCH region).","As a result, node control information can be transmitted per UE through EPDCCH, such that the problem of insufficiency of the legacy PDCCH region can also be solved.","For reference, EPDCCH is not applied to the legacy UE, and can be received by the LTE-A UE only.","FIG.","5 is a conceptual diagram illustrating a carrier aggregation (CA) scheme.","Referring to FIG.","5, EPDCCH may define and use some parts of the PDSCH region configured to transmit data, and the UE has to perform blind decoding for detecting the presence or absence of EPDCCH.","EPDCCH performs the same scheduling operation (i.e., PDSCH, PUSCH control) as in the legacy PDCCH.","If the number of UEs connected to the same node as in RRH increases, many more EPDCCHs are allocated to the PDSCH region, such that the number of blind decoding times to be executed by the UE increases, resulting in increased complexity.","Meanwhile, a method for multiplexing EPDCCH for a plurality of UEs needs to be considered.","In more detail, according to the multiplexing scheme proposed by the present invention, on the condition that a common resource region (i.e., a common PRB set) is configured, EPDCCHs of multiple UEs can be cross-interleaved to the frequency domain or the time domain.","FIG.","6 is a conceptual diagram illustrating a method for multiplexing EPDCCH for a plurality of UEs.","Specifically, FIG.","6(a) shows an example in which a common PRB set is configured on the basis of a PRB pair and cross increasing is performed on the basis of the common PRB set.","In contrast, FIG.","6(b) shows another example in which a common PRB set is configured on a basis of a PRB and cross interleaving is performed on the basis of the common PRB set.","The schemes of FIGS.","6(a) and 6(b) have advantages in which a diversity gain of the time/frequency domains extending a plurality of RBs can be obtained.","Carrier Aggregation (CA) Carrier aggregation will hereinafter be described in detail.","FIG.","7 is a conceptual diagram illustrating carrier aggregation (CA).","Carrier aggregation refers to a method for allowing a UE to use a plurality of frequency blocks or (logical) cells, each of which is composed of uplink resources (or CCs) and/or downlink resources (or CCs), as one large logical band so as to provide a wireless communication system with a wider frequency bandwidth.","For convenience of description and better understanding of the present invention, carrier aggregation will hereinafter be referred to as a component carrier (CC).","Referring to FIG.","7, the entire system bandwidth (System BW) includes a bandwidth of 100 MHz as a logical bandwidth.","The entire system bandwidth (system BW) includes five component carriers (CCs) and each CC has a maximum bandwidth of 20 MHz.","The CC includes one or more physically contiguous subcarriers.","Although all CCs have the same bandwidth in FIG.","7, this is only exemplary and the CCs may have different bandwidths.","Although the CCs are shown as being contiguous in the frequency domain in FIG.","8, FIG.","8 merely shows the logical concept and thus the CCs may be physically contiguous or separated.","Different center frequencies may be used for the CCs or one common center frequency may be used for physically contiguous CCs.","For example, in FIG.","7, if it is assumed that all CCs are physically contiguous, a center frequency A may be used.","If it is assumed that CCs are not physically contiguous, a center frequency A, a center frequency B and the like may be used for the respective CCs.","In the present specification, the CC may correspond to a system band of a legacy system.","By defining the CC based on the legacy system, it is possible to facilitate backward compatibility and system design in a radio communication environment in which an evolved UE and a legacy UE coexist.","For example, if the LTE-A system supports carrier aggregation, each CC may correspond to the system band of the LTE system.","In this case, the CC may have any one bandwidth such as 1.25, 2.5, 5, 10 or 20 MHz.","In the case in which the entire system band is extended by carrier aggregation, a frequency band used for communication with each UE is defined in CC units.","A UE A may use 100 MHz which is the bandwidth of the entire system band and perform communication using all five CCs.","Each of UEs B1 to B5 may only use a bandwidth of 20 MHz and perform communication using one CC.","Each of UEs C1 and C2 may use a bandwidth of 40 MHz and perform communication using two CCs.","The two CCs may be contiguous or non-contiguous.","The UE C1 uses two non-contiguous CCs and the UE C2 uses two contiguous CCs.","One downlink CC and one uplink CC may be used in the LTE system and several CCs may be used in the LTE-A system.","At this time, a method of scheduling a data channel by a control channel may be divided into a linked carrier scheduling method and a cross carrier scheduling method.","More specifically, in the linked carrier scheduling method, similarly to the LTE system using a single CC, a control channel transmitted via a specific CC schedules only a data channel via the specific CC.","In contrast, in the cross carrier scheduling method, a control channel transmitted via a primary CC using a carrier indicator field (CIF) schedules a data channel transmitted via the primary CC or another CC.","FIG.","8 is a conceptual diagram of a cross carrier scheduling scheme.","Specifically, as can be seen from FIG.","8, the number of cells (or CCs) allocated to a relay node (RN) is set to 3, cross carrier scheduling is carried out using a CIF as described above.","In this case, it is assumed that a downlink cell (or CC) #A is set to a primary downlink CC (i.e., a primary cell PCell), and the remaining CCs #B and #C are used as secondary cells (SCells).","CoMP (Coordinated Multiple Point Transmission and Reception) In accordance with the improved system throughput requirements of the 3GPP LTE-A system, CoMP transmission/reception technology (also referred to as Co-MIMO, collaborative MIMO or network MIMO) has recently been proposed.","The CoMP technology can increase throughput of a UE located at a cell edge and also increase average sector throughput.","In general, in a multi-cell environment in which a frequency reuse factor is 1, the performance of the UE located on the cell edge and average sector throughput may be reduced due to Inter-Cell Interference (ICI).","In order to reduce the ICI, in the legacy LTE system, a method of enabling the UE located at the cell edge to have appropriate throughput and performance using a simple passive method such as Fractional Frequency Reuse (FFR) through the UE-specific power control in the environment restricted by interference is applied.","However, rather than decreasing the use of frequency resources per cell, it is preferable that the ICI is reduced or the UE reuses the ICI as a desired signal.","In order to accomplish the above object, a CoMP transmission scheme may be applied.","The CoMP scheme applicable to the downlink may be largely classified into a Joint Processing (JP) scheme and a Coordinated Scheduling/Beamforming (CS/CB) scheme.","In the JP scheme, each point (eNB) of a CoMP unit may use data.","The CoMP unit refers to a set of eNBs used in the CoMP scheme.","The JP scheme may be classified into a joint transmission scheme and a dynamic cell selection scheme.","The joint transmission scheme refers to a scheme for transmitting a PDSCH from a plurality of points (a part or the whole of the CoMP unit).","That is, data transmitted to a single UE may be simultaneously transmitted from a plurality of transmission points.","According to the joint transmission scheme, it is possible to coherently or non-coherently improve the quality of the received signals and to actively eliminate interference with another UE.","The dynamic cell selection scheme refers to a scheme for transmitting a PDSCH from one point (of the CoMP unit).","That is, data transmitted to a single UE at a specific time is transmitted from one point and the other points in the cooperative unit at that time do not transmit data to the UE.","The point for transmitting the data to the UE may be dynamically selected.","According to the CS/CB scheme, the CoMP units may cooperatively perform beamforming of data transmission to a single UE.","Although only a serving cell transmits the data, user scheduling/beamforming may be determined by coordination of the cells of the CoMP unit.","In uplink, coordinated multi-point reception refers to reception of a signal transmitted by coordination of a plurality of geographically separated points.","The CoMP scheme applicable to the uplink may be classified into Joint Reception (JR) and Coordinated Scheduling/Beamforming (CS/CB).","The JR scheme indicates that a plurality of reception points receives a signal transmitted through a PUSCH, the CS/CB scheme indicates that only one point receives a PUSCH, and user scheduling/beamforming is determined by the coordination of the cells of the CoMP unit.","In addition, one case in which there are multiple UL points (i.e., multiple Rx points) is referred to as UL CoMP, and the other case in which there are multiple DL points (i.e., multiple Tx points) is referred to as DL CoMP.","Quasi Co-Located (QCL) FIG.","9 is a conceptual diagram illustrating a wireless communication system for enabling a UE to receive a Joint Transmission (JT) service from a CoMP set.","That is, FIG.","9 shows an example in which the UE is set to a Tx mode of 10.In FIG.","9, the UE receives data from all transmission points (TPs) belonging to the CoMP set, for example, TP1 and TP2 and may transmit channel state information about all TPs belonging to the CoMP set.","In this case, RSs may be transmitted to the UE from a plurality of TPs in the CoMP set.","If characteristics for channel estimation with respect to different RS ports of different TPs can be shared, then reception processing load and complexity of the UE may be reduced.","In addition, if characteristics for channel estimation with respect to different RS ports of the same TP can be shared by the RS ports, then reception processing load and complexity of the UE may be decreased.","Accordingly, an LTE-A system has proposed a method for sharing characteristics for channel estimation between RS ports.","For channel estimation between RS ports, the LTE-A system has introduced the concept of “quasi co-located (QCL)”.","With regard to two antenna ports, for example, if a large-scale property of a radio channel on which a symbol is transmitted through one of the antenna ports can be inferred from a radio channel on which a symbol is transmitted through the other antenna port, then the two antenna ports can be considered quasi-co-located.","The large-scale property includes at least one of delay spread, Doppler spread, Doppler shift, average gain and average delay.","The term “quasi co-located” will now be referred to as QCL.","That is, when two antenna ports are QCL, this means that the large-scale property of a radio channel from one antenna port corresponds to the large-scale property of a radio channel from the other antenna port.","Considering a plurality of antenna ports through which RSs are transmitted, when antenna ports through which RSs of two different types are transmitted are QCL, the large-scale property of a radio channel from one antenna port may be replaced by the large-scale property of a radio channel from the other antenna port.","According to the concept of quasi-co-location (QCL), the UE cannot assume the same large-scale property for radio channels from non-QCL antenna ports.","In this case, the UE needs to perform independent processing per non-QCL antenna port for timing acquisition and tracking, frequency offset estimation and compensation, delay estimation and Doppler estimation, etc.","For antenna ports for which QCL can be assumed, the UE can perform the following operations.","With regard to delay spread and Doppler spread, the UE may equally apply a power-delay-profile, delay spread and Doppler spectrum and Doppler spread estimation result with respect to a radio channel from one antenna port to a Wiener filter used for channel estimation with respect to a radio channel from the other antenna port.","With regard to frequency shift and received timing, the UE may perform time and frequency synchronization for one antenna port and then apply the same synchronization to demodulation with respect to the other antenna port.","For average reception power, the UE may average RSRP (reference signal received power) measurement for two or more antenna ports.","Upon reception of a specific DMRS-based DL-related DCI format through a control channel (PDCCH or ePDCCH), the UE performs channel estimation with respect to a corresponding PDSCH through a DMRS sequence and then performs data demodulation.","For example, if the UE can assume QCL between a configuration of antenna ports (referred to as “DMRS ports” hereinafter) for transmission of a DMRS, received through a DL scheduling grant, and a configuration of antenna ports (referred to as “CRS ports” hereinafter) for transmission of a CRS of the DL serving cell of the UE or another cell, then the UE may apply an estimate of the large-scale property of a radio channel, which has been estimated from the CRS ports, to channel estimation through the DMRS ports, thereby improving performance of a processor of a DMRS-based receiver.","Since the CRS is a reference signal that is broadcast with high density per subframe and over the entire band, as described above, the estimate of the large-scale property can be acquired from the CRS more stably.","On the contrary, the DMRS is UE-specifically transmitted for a specific scheduled RB and a precoding matrix used by an eNB for transmission may be changed per PRG, and thus a valid channel received by the UE may be changed per PRG.","Accordingly, performance deterioration may occur when the DMRS is used to estimate the large-scale property of a radio channel over a wide band even if a plurality of PRGs is scheduled for the UE.","The CSI-RS has a transmission period of several to ten ms and is transmitted with as low density as 1 RE (2 REs when CDM is applied) per antenna port per RB.","Thus, performance deterioration may occur when the CSI-RS is used to estimate the large-scale property of the radio channel.","That is, QCL assumption between antenna ports may be used for reception of downlink reference signals, channel estimation, channel state reporting, etc.","Semi-Persistent Scheduling (SPS) SPS (Semi-persistent scheduling) is a scheduling method for reducing overhead of control signaling and efficiently employing resources of a limited control channel.","SPS is used when the UE uses time-frequency resources within a predetermined time having a relatively long period.","According to SPS, signaling for repeatedly allocating resources within the predetermined time generates signaling overhead, so that time-frequency resources (or region) allocated to the UE can be simultaneously scheduled.","Therefore, if time-frequency resources for SPS are allocated to the UE within one subframe, the UE may use the corresponding time-frequency resources without using a separate control channel in the next periodically-repeated SPS-subframe.","SPS may be efficiently used for communication such as VoIP (Voice over Internet Protocol) in which timing or necessary resources can be estimated.","RRC and PDCCH may be used as the SPS configuration method.","An interval of radio resources being periodically allocated is indicated through RRC, and detailed resource allocation information (transmission attributes such as frequency domain RA or MCS) may be transmitted through PDCCH.","SPS may use a special ID such as SPS C-RNTI so that SPS can be distinguished from general dynamic scheduling).","The present invention relates to a method for deciding PDSCH-related parameters including a start symbol of SPS-scheduled PDSCH.","In accordance with one embodiment of the present invention, the problems encountered when two or more EPDCCHs are configured in one subframe will hereinafter be described.","As can be seen from the above description, EPDCCH may indicate a PDCCH applied to a legacy PDSCH region so as to increase capacity of a control signal, and it may be possible to obtain a beamforming gain using a UE-specific reference signal (RS).","In the case of using EPDCCH, it may be assumed that a start symbol position of PDSCH is identical to the start symbol position of EPDCCH, and the start symbol position of EPDCCH may be transmitted through higher layer signaling such as RRC.","However, the start symbol position of PDSCH may be independent of EPDCCH, may be determined according to PCFICH information (e.g., control formation indicator: CFI), or may be set to a predetermined value as necessary.","The eNB may configure EPDCCH or may reconfigure the start symbol position of EPDCCH, and the EPDCCH configuration parameter including the start symbol position of EPDCCH may be transmitted to the UE through higher layer signaling such as RRC.","After completion of SPS configuration through PDCCH, the UE may receive the EPDCCH configuration parameter.","Alternatively, after reception of the EPDCCH configuration parameter, the UE may perform SPS configuration through PDCCH.","As described above, SPS configuration and EPDCCH configuration parameter reception may be achieved simultaneously.","In this case, if the SPS-configured subframe corresponds to a subframe needed for EPDCCH monitoring, there is a need to decide the periodic resource region (i.e., the start symbol position of SPS-scheduled PDSCH) scheduled through SPS configuration in the corresponding subframe.","The start symbol position of the SPS-scheduled PDSCH may be determined from a PCFICH-indicated value (or a value derived from this indication value), because the PCFICH-indicated value may be different from the start symbol position (or from the position derived from this position) of EPDCCH contained in the EPDCCH configuration parameter received through RRC signaling.","Therefore, if the UE receives the EPDCCH configuration parameter upon completion of SPS configuration, or if the UE performs SPS configuration after reception of the EPDCCH configuration parameter, it may be assumed that the start symbol position (or the position derived from this start symbol position) of EPDCCH contained in the above EPDCCH configuration parameter, prior to the PDSCH start symbol position decided by PCFICH, is the start symbol position of the SPS-scheduled PDSCH.","In this case, it is assumed that the start symbol position of the SPS-scheduled PDSCH is identical to the start symbol position of EPDCCH, or is derived from the start symbol position of EPDCCH.","Unless the above-mentioned assumption is applied, the eNB may separately perform RRC signaling of the start symbol position of the SPS-scheduled PDSCH, and the UE having received the corresponding information may have priority over PCFICH information.","However, under the condition that the UE may receive the EPDCCH configuration parameter including the PDSCH start symbol position after completion of SPS configuration, or under the condition that SPS configuration is achieved after reception of the EPDCCH configuration parameter including the PDSCH start symbol position, if the SPS-scheduled subframe does not correspond to a subframe needed for EPDCCH monitoring, the start symbol position of the SPS-scheduled PDSCH may be based on PCFICH.","The reason why the above-mentioned assumption is achieved is that EPDCCH monitoring can be configured only in some subframes.","FIG.","10 is a conceptual diagram illustrating a method for deciding the start symbol position of the SPS-scheduled PDSCH (hereinafter referred to as SPS-PDSCH) according to the above-mentioned embodiment.","In FIG.","10, the SPS-configured UE may receive the EPDCCH configuration parameter including the EPDCCH start symbol position through RRC signaling, and the corresponding position (symbol n1) is different from the PCFICH-indicated value (symbol n0).","The start symbol position of SPS-PDSCH is based on RRC signaled information, simultaneously while having priority over the PCFICH-indicated information, so that “symbol n1” may be decided.","A method for deciding the start symbol position of SPS-PDSCH is a common promise between the eNB and the UE.","In a specific situation having a controversial issue, i.e., in a subframe in which SPS is configured and the UE has to monitor EPDCCH, the eNB must schedule or transmit the SPS-PDSCH from the beginning of the start symbol of EPDCCH, and the UE must decode the SPS-PDSCH from the beginning of the start symbol position of EPDCCH.","In the meantime, the eNB can transmit two or more EPDCCH configuration parameters to the UE.","In this case, each EPDCCH configuration parameter may include the start symbol position of each EPDCCH, and may be transmitted to the UE through higher layer signaling such as RRC signaling.","If the start symbol positions of EPDCCH contained in at least two EPDCCH configuration parameters are identical to each other, the UE may determine the start symbol position of the RRC-signaled EPDCCCH to be the start symbol position of SPS-PDSCH.","However, the start symbol positions of individual EPDCCHs contained in at least two EPDCCH configuration parameters may be different from each other.","In this case, there occurs an unexpected problem in which the start symbol position of SPS-PDSCH needs to be determined.","Therefore, the UE may assume that a higher one from among the respective EPDCCH start symbol positions (i.e., a higher OFDM symbol index from among the individual EPDCH start symbol positions) is the start symbol position of SPS-PDSCH.","Specifically, if individual EPDCCHs are transmitted from different TPS as in dynamic point scheduling (DPS), and if each TP will be configured not to use several initial OFDM symbols in consideration of an interference environment, the start symbol position of SPS-PDSCH can be conservatively configured, so that the influence of inter-cell interference can be minimized.","FIG.","11 is a conceptual diagram illustrating a method for deciding the start symbol position of SPS-PDSCH when the SPS-configured UE receives at least two EPDCCH-related parameters.","If the start symbol position of EPDCCH #1 is Symbol n1 and the start symbol position of EPDCCH #2 is Symbol n2, max(n1, n2) may indicate the start symbol position of SPS-PDSCH.","In FIG.","2, the situation of n1≥n2 is assumed so that the start symbol position of SPS-PDSCH may be set to n1.When at least two different EPDCCH configuration parameters (i.e., at least two EPDCCH start symbol positions) are signaled to the UE, a smaller one from among the individual EPDCCH start symbol positions may be set to the start symbol position of SPS-PDSCH according to another method for deciding the start symbol position of SPS-PDSCH.","In still another method, in a specific situation having a controversial issue, a predetermined position may be set to the SPS-PDSCH start symbol position, or the SPS-PDSCH start symbol position may be separately signaled to the UE through separate RRC signaling or the like.","In another method, a representative EPDCCH from among two or more EPDCCHs may be configured, and the start symbol position of the representative EPDCCH may be set to the SPS-PDSCH start symbol position.","In accordance with the method for deciding the representative EPDCCH, a first signaling one from among EPDCCHs may be set to a representative one.","In accordance with another scheme, a method for deciding the start symbol position of SPS-PDSCH in a subframe for detecting EPDCCH (i.e., in a subframe in which the UE has to monitor an EPDCCH) may be determined according to categories of a control channel needed for SPS-PDSCH scheduling.","For example, assuming that the corresponding SPS is scheduled using EPDCCH, the EPDCCH set including the corresponding scheduling EPDCCH may be determined to be a representative EPDCCH set.","In this case, whereas the EPDCCH start symbol position is determined to be the SPS-PDSCH start symbol position in the EPDCCH detection subframe, and if the corresponding SPS is scheduled by PDCCH, a higher one from among the start symbol positions of two EPDCCH sets may be selected, or a first one from among the EPDCCH set may be set to a representative one, so that the SPS-PDSCH start symbol position in the EPDCCH detection subframe may be determined.","In the meantime, the method for deciding the start symbol position may be restrictively applied only when there is no explicit indicator for the SPS-PDSCH start symbol position.","A more general embodiment of the above-mentioned embodiment will hereinafter be described.","If two or more EPDCCHs are configured in UE, the start symbol positions of individual EPDCCHs may be different from each other as previously stated above.","Meanwhile, individual EPDCCHs may be transmitted from different TPs.","In this case, individual EPDCCHs (or PDSCHs scheduled by the corresponding EPDCCH) may have different PDSCH start symbol positions, different rate matching patterns (or PDSCH RE mapping patterns) related to a specific RS (e.g., CRS or CSI-RS), different antenna port configurations (e.g., DM-RS antenna port configurations used in EPDCCH/PDSCH decoding), different seeds of the pseudo random sequence used to generate the RS (e.g., DM-RS) sequence, and/or different scrambling IDs.","Therefore, in case of the SPS-configured UE, the start symbol position of SPS-PDSCH and the above-mentioned parameters applied to SPS-PDSCH should be determined.","The UE may receive information regarding two or more applicable parameter sets (i.e., several candidate parameter sets) through higher layer signaling such as RRC signaling.","A) UE may assume that the CRS pattern of the serving cell is always applied to SPS-PDSCH, and DM-RS used for SPS-PDSCH (or EPDCCH) decoding is QCL-processed with the CRS of the serving cell.","B) A set of actually applied parameters from among parameter sets applicable to SPS-PDSCH may be signaled to the UE through higher layer signaling such as RRC signaling.","The UE having received the above set may assume that the RRC-signaled parameter sets are applied to SPS-PDSCH.","Specifically, the corresponding signaling may be transmitted while simultaneously performing SPS scheduling (SPS configuration).","C) Parameters applied to SPS-PDSCH may always be based on the serving cell as described in the above section (A), and may also be based on a control channel scheduling the corresponding SPS.","In other words, assuming that SPS is scheduled through a specific control channel at a specific time, parameters to be applied to SPS-PDSCH may be based on parameters having been applied to transmission of the above specific control channel, prior to execution of SPS configuration due to transmission of still another control channel.","For example, assuming SPS scheduling is achieved through PDCCH, the scheduling result may be based on parameters of PDCCH (i.e., parameters of the serving cell).","When SPS scheduling is achieved through EPDCCH, the scheduling result may be based on parameters used for transmission of the corresponding EPDCCH.","D) Parameters applied to SPS-PDSCH may be designated through a control channel having scheduled the corresponding SPS.","In other words, assuming that SPS is scheduled through a specific control channel at a specific time, parameters to be applied to SPS-PDSCH may be based on parameters indicated through the above specific control channel, before SPS-PDSCH is scheduled after transmission of another control channel.","Differently from the above method (C), parameters used for the above specific control channel may be different from parameters indicated by an indicator transmitted over the above specific control channel.","For example, assuming that execution of rate matching is indicated according to the CRS pattern of an adjacent cell through a PDCCH transmitted using the CRS parameter of the serving cell, the next SPS-PDSCH needs to be rate-matched according to the CRS pattern of the indicated adjacent cell, as can be seen from the above method (D).","E) If two or more EPDCCHs are configured, it may be assumed that parameters applied to SPS-PDSCH are based on a specific EPDCCH from among the corresponding EPDCCHs.","For example, if the UE receives two or more EPDCCH configuration parameters through RRC signaling, parameters applied to SPS-PDSCH may always be based on configuration parameters of a first EPDCCH.","F) Parameters applied to SPS-PDSCH may be predetermined as necessary.","In this case, the corresponding parameters may be different from those of EPDCCH.","Specifically, this scheme can be used, irrespective of whether a channel having scheduled the corresponding SPS-PDSCH is a PDCCH or an EPDCCH.","G) Parameters applied to SPS-PDSCH may be based on parameters of a dynamic PDSCH.","The dynamic PDSCH may be a PDSCH capable of being transmitted using at least two different parameter sets, and information as to which parameter set has been applied to a specific PDSCH may be contained in a DCI detected from PDCCH or EPDCCH, so that this information may be transmitted to the UE through DCI.","Therefore, the UE may recognize parameters applied to the dynamic PDSCH by interpreting DCI, and a specific rule may be assumed between the UE and the eNB.","This specific rule indicates that parameters applied to SPS-PDSCH are identical to those of the dynamic PDSCH.","Information related to the above operation may be implicitly recognized according to a predetermined rule, or the eNB may inform the UE of this information through predefined signaling (e.g., higher layer signaling or physical layer signaling).","In addition, different schemes may be applied according to the scheduling message categories (e.g., DCI format) for SPS scheduling.","Specifically, according to the presence or absence of information as to whether the indicator indicating parameters applied to PDSCH is present in the scheduling message, different operation schemes may be used.","For example, if SPS scheduling is performed using the scheduling message having the above indicator, the above method (D) may be used.","On the contrary, if the scheduling message having no indicator is used, the above methods A), B) and C) may be used.","In addition, some of various parameters applied to PDSCH may be determined according to different schemes.","For example, the SPS-PDSCH start symbol may use a control channel for scheduling the SPS according to the above method (C), CRS to be assumed in the rate matching may use the CRS of the serving cell according to the above method (A), and CSI-RS to be assumed in the rate matching may use a series of parameters pre-signaled by RRC according to the above method (B).","Specifically, the above-mentioned operations may be efficiently used when the explicit indicator is not present in the parameters related to the SPS scheduling message.","In more detail, the method for deciding parameters applied to SPS-PDSCH based on the method (D) is used in a subframe corresponding to DCI format 2D.","In a subframe corresponding to DCI format 0 or 1A, a method for deciding parameters applied to SPS-PDSCH based on the method (B) is used.","In the meantime, when deciding the start symbol position of SPS-PDSCH, the SPS-PDSCH start symbol position must be limited to Symbol #2 in a subframe in which the PDSCH start symbol index is set to a maximum of 2 in the same manner as in the MBSFN subframe.","For example, assuming that a higher one of the start symbol positions of EPDCCH configured through RRC signaling is set to the start symbol position of SPS-PDSCH, if the higher one is higher than 2, the corresponding value is used.","If the higher one is not higher than 2 (i.e., if the higher one is less than 2), it is assumed that the symbol is Symbol #2.The above-mentioned assumption can be applied not only to the case in which a higher one from among the start symbol positions of EPDCCH is set to the SPS-PDSCH start symbol position, but also to the above-mentioned methods, i.e., a PCFICH-based method, a method based on a smaller one from among the EPDCCH start symbol positions, or a method based on the start symbol position of a representative EPDCCH.","Some of the above-mentioned methods will be shown in the following table, and as such a detailed description thereof will be given below.","Before or after SPS configuration is completed, if the UE does not receive the EPDCCH configuration parameter including the EPDCCH start symbol position information (i.e., if CCH configuration is not present), it is assumed that a value indicated by PCFICH is set to the SPS-PDSCH start symbol position (index), as can be seen from ‘1’ in the following Table.","If SPS configuration is achieved before or after reception of the EPDCCH start symbol position information, it is assumed that the EPDCCH start symbol position is set to the start symbol position (as denoted by “2” in the following table).","If at least two EPDCCH start symbol positions are different from each other, a higher one from among the at least two EPDCCH start symbol positions may be set to the SPS-PDSCH start symbol position (as denoted by “3” in the following table).","In the case of the MBSFN subframe, if at least two EPDCCH start symbol positions are received, a higher one from among the at least two EPDCCH start symbols is used.","If the corresponding value is less than 2, it is assumed that the SPS-PDSCH start symbol position is set to Symbol #2 (4).","TABLE 5 1 2 3 4 PDSCH Starting symbol N0 N0 N0 N0 position indicated by PCFICH Starting symbol position of — N1 N1 N1 EPDCCH #1 Starting symbol position of — — N2 N2 EPDCCH #2 Starting symbol position of N0 N1 If N1 >= N2, N1 If N1 >= N2 SPS-scheduled PDSCH If N1 < N2, N2 & N1 > 2, N1 If N1 < N2 & N2 > 2, N2 Otherwise, 2 The above-mentioned operations may be selectively applied according to subframe configuration.","For example, in the case of the MBSFN subframe, since SPS-PDSCH is transmitted on the basis of DM-RS, the SPS-PDSCH start symbol position or information (CRS, CSI-RS, etc.)","to be assumed in the rate matching can be obtained using one of the methods based on the DMRS-based EPDCCH configuration parameter.","On the contrary, in the case of the non-MBSFN subframe, SPS-PDSCH may be transmitted on the basis of CRS.","In this case, the SPS-PDSCH start symbol position may be derived from PCFICH of the serving cell, or the rate matching is not assumed for CRS of a neighbor cell.","Even in the case of the non-MBSFN subframe, if SPS-PDSCH is transmitted on the basis of DM-RS, one of the above-mentioned methods may also be used on the basis of the DMRS-based EPDCCH configuration parameters.","The above-mentioned embodiments may also assume that the EPDCCH start symbol does not overlap with the PDCCH transmission region.","If the above assumption is not present, the start symbol positions of EPDCCHs and the PDSCH start symbol position derived by the indicator transmitted by PCFICH may be simultaneously considered in the process for deciding the start symbol position of SPS-PDSCH.","For example, according to case “3” shown in Table 5, if the PDSCH start symbol index derived by PCFICH is higher than the start symbol index of EPDCCHs, the value derived by PCFICH may be set to the SPS-PDSCH start symbol position.","In the meantime, if CA (Carrier Aggregation) is configured, the UE may simultaneously monitor a PDCCH and an EPDCCH at a specific subframe.","For example, in the case of the UE in which cross carrier scheduling (CCS) is configured, PDSCH of PCell of the corresponding UE is scheduled by EPDCCH transmitted to PCell.","PDSCH of SCell may be CCS-processed by PDCCH transmitted to PCell.","In this case, the following method may be used to determine the PDSCH start symbol position of PCell.","a) Method for assuming the start symbol position of EPDCCH In accordance with a method for assuming the corresponding subframe to be a subframe which has to monitor the EPDCCH, since PDSCH of PCell is scheduled by EPDCCH, this means that the scheduling result may follow the start symbol position of a scheduling channel.","b) Method for assuming the start symbol position derived by PCFICH In accordance with the method (b), the corresponding subframe is considered to be a subframe which monitors UE-specific Search Space (USS) at PDCCH.","Specifically, if the EPDCCH start symbol position is RRC-signaled and configured and does not overlap with the PDCCH region, the start symbol position derived by PCFICH may be identical to or less than the start symbol index of EPDCCH, resources can be more efficiently used, resulting in higher efficiency in terms of resource utilization.","In the case in which there is no explicit indicator regarding the PDSCH start symbol position of PCell in PDSCH scheduling of PCell, the above-mentioned situation may be efficiently used.","Besides the above-mentioned methods, if the above indicator is present, the start symbol position indicated by the above indicator may be determined to be the PDSCH start symbol position of PCell.","Specifically, even in the case of PDSCH of SCell, PDSCH scheduling of the corresponding SCell includes the explicit indicator, a value indicated by the above indicator may be determined to be the PDSCH start symbol position of SCell, while simultaneously having priority over a predetermined start symbol position being semi-persistently decided by RRC signaling.","In this case, it is assumed that EPDCCH configuration parameters having the EPDCCH start symbol position may be configured through higher layer signaling, or may be set to predetermined values.","If higher layer signaling is not present, the EPDCCH start symbol position may be derived from PCFICH.","In the meantime, the CCS-configured UE may be SPS activated through EPDCCH of PCell, so that it may receive the SPS-PDSCH scheduling result of PCell.","In a case in which the above-mentioned CC is not configured, the method for deciding the SPS-PDSCH start symbol position and various SPS-PDSCH parameters may be applied without change.","However, in the case of the SPS-PDSCH start symbol position of PCell, the UE may monitor a PDCCH even in the subframe needed for EPDCCH monitoring, due to the presence of CCS regarding the SCell.","As a result, another scheme for satisfying the start symbol position derived from PCFICH instead of the EPDCCH start symbol position may also be used.","In the meantime, if PDSCH of SCell is CCS-processed by PDCCH or EPDCCH applied to PCell, the PDSCH start symbol of SCell may be determined as follows.","a′) The above-mentioned PDSCH start symbol of SCell may satisfy a PDSCH start symbol position of SCell signaled by RRC.","b′) If the explicit indicator for the PDSCH start symbol position of SCell is contained in the PDSCH scheduling message of SCell transmitted in PDCCH/EPDCCH, the UE may be based on the start symbol position indicated by the above indicator.","This method (b′) is irrelevant to information as to whether the above scheduling message is transmitted over PDCCH or EPDCCH.","c′) If the explicit indicator regarding the PDSCH start symbol of SCell is not contained in the PDSCH scheduling of SCell transmitted in PDCCH/EPDCCH, the PDSCH start symbol position of SCell and/or a parameter to be applied to PDSCH of SCell may be determined using any one of the above-mentioned methods (A) to (G).","However, since the PDSCH start symbol position of the RRC-configured SCell is present, the start symbol position indicated by the corresponding RRC may be used as necessary.","FIG.","12 is a block diagram of a transmitting device 10 and a receiving device 20 configured to implement exemplary embodiments of the present invention.","Referring to FIG.","12, the transmitting device 10 and the receiving device 20 respectively include radio frequency (RF) units 13 and 23 for transmitting and receiving radio signals carrying information, data, signals, and/or messages, memories 12 and 22 for storing information related to communication in a wireless communication system, and processors 11 and 21 connected operationally to the RF units 13 and 23 and the memories 12 and 22 and configured to control the memories 12 and 22 and/or the RF units 13 and 23 so as to perform at least one of the above-described embodiments of the present invention.","The memories 12 and 22 may store programs for processing and control of the processors 11 and 21 and may temporarily storing input/output information.","The memories 12 and 22 may be used as buffers.","The processors 11 and 21 control the overall operation of various modules in the transmitting device 10 or the receiving device 20.The processors 11 and 21 may perform various control functions to implement the present invention.","The processors 11 and 21 may be controllers, microcontrollers, microprocessors, or microcomputers.","The processors 11 and 21 may be implemented by hardware, firmware, software, or a combination thereof.","In a hardware configuration, Application Specific Integrated Circuits (ASICs), Digital Signal Processors (DSPs), Digital Signal Processing Devices (DSPDs), Programmable Logic Devices (PLDs), or Field Programmable Gate Arrays (FPGAs) may be included in the processors 11 and 21.If the present invention is implemented using firmware or software, firmware or software may be configured to include modules, procedures, functions, etc.","performing the functions or operations of the present invention.","Firmware or software configured to perform the present invention may be included in the processors 11 and 21 or stored in the memories 12 and 22 so as to be driven by the processors 11 and 21.The processor 11 of the transmitting device 10 is scheduled from the processor 11 or a scheduler connected to the processor 11 and codes and modulates signals and/or data to be transmitted to the outside.","The coded and modulated signals and/or data are transmitted to the RF unit 13.For example, the processor 11 converts a data stream to be transmitted into K layers through demultiplexing, channel coding, scrambling and modulation.","The coded data stream is also referred to as a codeword and is equivalent to a transport block which is a data block provided by a MAC layer.","One transport block (TB) is coded into one codeword and each codeword is transmitted to the receiving device in the form of one or more layers.","For frequency up-conversion, the RF unit 13 may include an oscillator.","The RF unit 13 may include Nt (where Nt is a positive integer) transmit antennas.","A signal processing process of the receiving device 20 is the reverse of the signal processing process of the transmitting device 10.Under the control of the processor 21, the RF unit 23 of the receiving device 10 receives RF signals transmitted by the transmitting device 10.The RF unit 23 may include Nr receive antennas and frequency down-converts each signal received through receive antennas into a baseband signal.","The RF unit 23 may include an oscillator for frequency down-conversion.","The processor 21 decodes and demodulates the radio signals received through the receive antennas and restores data that the transmitting device 10 wishes to transmit.","The RF units 13 and 23 include one or more antennas.","An antenna performs a function of transmitting signals processed by the RF units 13 and 23 to the exterior or receiving radio signals from the exterior to transfer the radio signals to the RF units 13 and 23.The antenna may also be called an antenna port.","Each antenna may correspond to one physical antenna or may be configured by a combination of more than one physical antenna element.","A signal transmitted through each antenna cannot be decomposed by the receiving device 20.A reference signal (RS) transmitted through an antenna defines the corresponding antenna viewed from the receiving device 20 and enables the receiving device 20 to perform channel estimation for the antenna, irrespective of whether a channel is a single RF channel from one physical antenna or a composite channel from a plurality of physical antenna elements including the antenna.","That is, an antenna is defined such that a channel transmitting a symbol on the antenna may be derived from the channel transmitting another symbol on the same antenna.","An RF unit supporting a MIMO function of transmitting and receiving data using a plurality of antennas may be connected to two or more antennas.","In embodiments of the present invention, a UE serves as the transmission device 10 on uplink and as the receiving device 20 on downlink.","In embodiments of the present invention, an eNB serves as the receiving device 20 on uplink and as the transmission device 10 on downlink.","The transmitting device and/or the receiving device may be configured as a combination of one or more embodiments of the present invention.","The detailed description of the exemplary embodiments of the present invention has been given to enable those skilled in the art to implement and practice the invention.","Although the invention has been described with reference to the exemplary embodiments, those skilled in the art will appreciate that various modifications and variations can be made in the present invention without departing from scope of the invention described in the appended claims.","Accordingly, the invention should not be limited to the specific embodiments described herein, but should be accorded the broadest scope consistent with the principles and novel features disclosed herein.","INDUSTRIAL APPLICABILITY The present invention may be used for a wireless communication apparatus such as a terminal, a relay and a base station (BS)."]],"string":"[\n [\n \"METHOD AND APPARATUS FOR RECEIVING OR TRANSMITTING DOWNLINK CONTROL SIGNAL IN WIRELESS COMMUNICATION SYSTEM\",\n \"Provided is a method for receiving a downlink signal by a user equipment (UE) in a wireless communication system according to one embodiment of the present disclosure, comprising: receiving a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; receiving a downlink control information (DCI) configuring the SPS-PDSCH; and decoding the SPS-PDSCH using one of the received plurality of parameter sets, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating the parameter set to be used for decoding is included in the DCI.\"\n ],\n [\n \"1.A method for receiving a downlink signal by a user equipment (UE) in a wireless communication system, comprising: receiving a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; receiving a downlink control information (DCI), carried by an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and decoding the SPS-PDSCH in the subframe using a parameter set from among the plurality of parameter sets, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.\",\n \"2.The method according to claim 1, wherein the starting symbol position of the SPS-PDSCH is different from a starting symbol position of the EPDCCH carrying the DCI.\",\n \"3.The method according to claim 1, wherein the UE is scheduled to receive two or more EPDCCHs in the subframe.\",\n \"4.The method according to claim 3, wherein the two or more EPDCCHs are transmitted from different transmission points or different evolved Node B.\",\n \"5.The method according to claim 1, wherein each of the plurality of parameter sets includes resource element (RE) mapping pattern information related to specific reference signal(s).\",\n \"6.The method according to claim 1, wherein: if the SPS-PDSCH is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel is restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.\",\n \"7.The method according to claim 1, wherein the user equipment (UE) is configured in transmission mode 10.8.The method according to claim 1, wherein the determined parameter set is used for decoding the SPS-PDSCH until receiving a new DCI configuring SPS.\",\n \"9.The method according to claim 1, further comprising: if the DCI configuring SPS includes an indicator which indicates the parameter set to be used for decoding, decoding the SPS-PDSCH using a parameter set indicated by the indicator.\",\n \"10.A method for transmitting a downlink signal to a user equipment (UE) in a wireless communication system, performed by an eNodeB (evolved Node B) and comprising: transmitting a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; and transmitting a downlink control information (DCI), carried by an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and wherein a parameter set from among the plurality of parameter sets is used for the UE to decode the SPS-PDSCH in the subframe, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.\",\n \"11.The method according to claim 10, wherein the starting symbol position of the SPS-PDSCH is different from a starting symbol position of the EPDCCH carrying the DCI.\",\n \"12.The method according to claim 10, wherein the UE is scheduled to receive two or more EPDCCHs in the subframe.\",\n \"13.The method according to claim 12, wherein the two or more EPDCCHs are transmitted from different transmission points or different eNodeB.\",\n \"14.The method according to claim 10, wherein each of the plurality of parameter sets includes resource element (RE) mapping pattern information related to specific reference signal(s).\",\n \"15.The method according to claim 10, wherein: if the SPS-PDSCH is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel is restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.\",\n \"16.The method according to claim 10, wherein the user equipment (UE) is configured in transmission mode 10.17.The method according to claim 10, wherein the determined parameter set is used for decoding the SPS-PDSCH until receiving a new DCI configuring SPS.\",\n \"18.The method according to claim 10, further comprising: if the DCI configuring SPS includes an indicator which indicates the parameter set to be used for decoding, the parameter set indicated by the indicator is used for the UE to decode the SPS-PDSCH.\",\n \"19.A user equipment (UE) for receiving a downlink control signal in a wireless communication system, comprising: a radio frequency (RF) unit; and a processor that controls the RF unit, wherein the processor receives a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling, receives a downlink control information (DCI), carried in an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and decodes the SPS-PDSCH in the subframe using a parameter set from among the plurality of parameter sets, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.\",\n \"20.An evolved Node B (eNB) for transmitting a downlink control signal in a wireless communication system, comprising: a radio frequency (RF) unit; and a processor that controls the RF unit, wherein the processor transmits a plurality of parameter sets for Semi Persistent Scheduling (SPS)-physical downlink shared channel (PDSCH) through higher layer signaling; and transmits a downlink control information (DCI), carried by an enhanced physical downlink control channel (EPDCCH), configuring SPS in a subframe; and wherein a parameter set from among the plurality of parameter sets is used for the UE to decode the SPS-PDSCH in the subframe, wherein the parameter set to be used for decoding is determined based on whether an indicator indicating a parameter set to be used for decoding is included in the DCI, and wherein each of the plurality of parameter sets includes information regarding a starting symbol position of the SPS-PDSCH.\"\n ],\n [\n \"<SOH> BACKGROUND ART <EOH>Recently, various devices requiring machine-to-machine (M2M) communication and high data transfer rate, such as smartphones or tablet personal computers (PCs), have appeared and come into widespread use.\",\n \"This has rapidly increased the quantity of data which needs to be processed in a cellular network.\",\n \"In order to satisfy such rapidly increasing data throughput, recently, carrier aggregation (CA) technology which efficiently uses more frequency bands, cognitive ratio technology, multiple antenna (MIMO) technology for increasing data capacity in a restricted frequency, multiple-base-station cooperative technology, etc.\",\n \"have been highlighted.\",\n \"In addition, communication environments have evolved such that the density of accessible nodes is increased in the vicinity of a user equipment (UE).\",\n \"Here, the node includes one or more antennas and refers to a fixed point capable of transmitting/receiving radio frequency (RF) signals to/from the user equipment (UE).\",\n \"A communication system including high-density nodes may provide a communication service of higher performance to the UE by cooperation between nodes.\",\n \"A multi-node coordinated communication scheme in which a plurality of nodes communicates with a user equipment (UE) using the same time-frequency resources has much higher data throughput than legacy communication scheme in which each node operates as an independent base station (BS) to communicate with the UE without cooperation.\",\n \"A multi-node system performs coordinated communication using a plurality of nodes, each of which operates as a base station or an access point, an antenna, an antenna group, a remote radio head (RRH), and a remote radio unit (RRU).\",\n \"Unlike the conventional centralized antenna system in which antennas are concentrated at a base station (BS), nodes are spaced apart from each other by a predetermined distance or more in the multi-node system.\",\n \"The nodes can be managed by one or more base stations or base station controllers which control operations of the nodes or schedule data transmitted/received through the nodes.\",\n \"Each node is connected to a base station or a base station controller which manages the node through a cable or a dedicated line.\",\n \"The multi-node system can be considered as a kind of Multiple Input Multiple Output (MIMO) system since dispersed nodes can communicate with a single UE or multiple UEs by simultaneously transmitting/receiving different data streams.\",\n \"However, since the multi-node system transmits signals using the dispersed nodes, a transmission area covered by each antenna is reduced compared to antennas included in the conventional centralized antenna system.\",\n \"Accordingly, transmit power required for each antenna to transmit a signal in the multi-node system can be reduced compared to the conventional centralized antenna system using MIMO.\",\n \"In addition, a transmission distance between an antenna and a UE is reduced to decrease in pathloss and enable rapid data transmission in the multi-node system.\",\n \"This can improve transmission capacity and power efficiency of a cellular system and meet communication performance having relatively uniform quality regardless of UE locations in a cell.\",\n \"Further, the multi-node system reduces signal loss generated during transmission since base station(s) or base station controller(s) connected to a plurality of nodes transmit/receive data in cooperation with each other.\",\n \"When nodes spaced apart by over a predetermined distance perform coordinated communication with a UE, correlation and interference between antennas are reduced.\",\n \"Therefore, a high signal to interference-plus-noise ratio (SINR) can be obtained according to the multi-node coordinated communication scheme.\",\n \"Owing to the above-mentioned advantages of the multi-node system, the multi-node system is used with or replaces the conventional centralized antenna system to become a new foundation of cellular communication in order to reduce base station cost and backhaul network maintenance cost while extending service coverage and improving channel capacity and SINR in next-generation mobile communication systems.\"\n ],\n [\n \"TECHNICAL FIELD The present invention relates to a wireless communication system, and more particularly to a method and apparatus for receiving or transmitting a downlink control signal in a wireless communication system.\",\n \"BACKGROUND ART Recently, various devices requiring machine-to-machine (M2M) communication and high data transfer rate, such as smartphones or tablet personal computers (PCs), have appeared and come into widespread use.\",\n \"This has rapidly increased the quantity of data which needs to be processed in a cellular network.\",\n \"In order to satisfy such rapidly increasing data throughput, recently, carrier aggregation (CA) technology which efficiently uses more frequency bands, cognitive ratio technology, multiple antenna (MIMO) technology for increasing data capacity in a restricted frequency, multiple-base-station cooperative technology, etc.\",\n \"have been highlighted.\",\n \"In addition, communication environments have evolved such that the density of accessible nodes is increased in the vicinity of a user equipment (UE).\",\n \"Here, the node includes one or more antennas and refers to a fixed point capable of transmitting/receiving radio frequency (RF) signals to/from the user equipment (UE).\",\n \"A communication system including high-density nodes may provide a communication service of higher performance to the UE by cooperation between nodes.\",\n \"A multi-node coordinated communication scheme in which a plurality of nodes communicates with a user equipment (UE) using the same time-frequency resources has much higher data throughput than legacy communication scheme in which each node operates as an independent base station (BS) to communicate with the UE without cooperation.\",\n \"A multi-node system performs coordinated communication using a plurality of nodes, each of which operates as a base station or an access point, an antenna, an antenna group, a remote radio head (RRH), and a remote radio unit (RRU).\",\n \"Unlike the conventional centralized antenna system in which antennas are concentrated at a base station (BS), nodes are spaced apart from each other by a predetermined distance or more in the multi-node system.\",\n \"The nodes can be managed by one or more base stations or base station controllers which control operations of the nodes or schedule data transmitted/received through the nodes.\",\n \"Each node is connected to a base station or a base station controller which manages the node through a cable or a dedicated line.\",\n \"The multi-node system can be considered as a kind of Multiple Input Multiple Output (MIMO) system since dispersed nodes can communicate with a single UE or multiple UEs by simultaneously transmitting/receiving different data streams.\",\n \"However, since the multi-node system transmits signals using the dispersed nodes, a transmission area covered by each antenna is reduced compared to antennas included in the conventional centralized antenna system.\",\n \"Accordingly, transmit power required for each antenna to transmit a signal in the multi-node system can be reduced compared to the conventional centralized antenna system using MIMO.\",\n \"In addition, a transmission distance between an antenna and a UE is reduced to decrease in pathloss and enable rapid data transmission in the multi-node system.\",\n \"This can improve transmission capacity and power efficiency of a cellular system and meet communication performance having relatively uniform quality regardless of UE locations in a cell.\",\n \"Further, the multi-node system reduces signal loss generated during transmission since base station(s) or base station controller(s) connected to a plurality of nodes transmit/receive data in cooperation with each other.\",\n \"When nodes spaced apart by over a predetermined distance perform coordinated communication with a UE, correlation and interference between antennas are reduced.\",\n \"Therefore, a high signal to interference-plus-noise ratio (SINR) can be obtained according to the multi-node coordinated communication scheme.\",\n \"Owing to the above-mentioned advantages of the multi-node system, the multi-node system is used with or replaces the conventional centralized antenna system to become a new foundation of cellular communication in order to reduce base station cost and backhaul network maintenance cost while extending service coverage and improving channel capacity and SINR in next-generation mobile communication systems.\",\n \"DISCLOSURE Technical Problem An object of the present invention is to provide a method for receiving or transmitting downlink control information in a wireless communication system.\",\n \"It is to be understood that technical objects to be achieved by the present invention are not limited to the aforementioned technical objects and other technical objects which are not mentioned herein will be apparent from the following description to one of ordinary skill in the art to which the present invention pertains.\",\n \"Technical Solution The objects of the present invention can be achieved by providing a method for receiving a downlink signal by a user equipment (UE) in a wireless communication system including: receiving Semi Persistent Scheduling (SPS)—related control information through higher layer signaling or a downlink control channel; and decoding a semi-persistently-scheduled downlink data channel based on the SPS-related control information, wherein the method further includes: if downlink control information (DCI) received through the downlink control channel is a first downlink control information (DCI) format, decoding the downlink data channel using a first parameter set from among candidate parameter sets received through higher layer signaling; and if downlink control information (DCI) received through the downlink control channel is a second DCI format, decoding the downlink data channel by using a second parameter set indicated by the downlink control information from among the candidate parameter sets received through higher layer signaling.\",\n \"Additionally or alternatively, each of the candidate parameter sets may include information regarding a starting symbol position of the downlink data channel.\",\n \"Additionally or alternatively, each of the candidate parameter sets may include resource element (RE) mapping pattern information related to specific reference signal(s).\",\n \"Additionally or alternatively, if the semi-persistently-scheduled downlink data channel is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel may be restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.\",\n \"Additionally or alternatively, the user equipment (UE) may be configured in transmission mode 10.Additionally or alternatively, the user equipment (UE) may be configured to receive downlink signal from at least two eNBs.\",\n \"Additionally or alternatively, the method may further include decoding the downlink data channel by using the first parameter set or the second parameter set until new SPS-related information is received.\",\n \"In accordance with another aspect of the present invention, a user equipment (UE) for receiving a downlink control signal in a wireless communication system includes: a radio frequency (RF) unit; and a processor configured to control the RF unit, wherein the processor receives Semi Persistent Scheduling (SPS)—related control information through higher layer signaling or a downlink control channel, and decodes a semi-persistently-scheduled downlink data channel based on the SPS-related control information, wherein, if downlink control information (DCI) received through the downlink control channel is a first downlink control information (DCI) format, the processor is further configured to decode the downlink data channel by using a first parameter set from among candidate parameter sets received through higher layer signaling; and, if downlink control information (DCI) received through the downlink control channel is a second DCI format, the processor is further configured to decode the downlink data channel by using a second parameter set indicated by the downlink control information from among the candidate parameter sets received through higher layer signaling.\",\n \"Additionally or alternatively, each of the candidate parameter sets may include information regarding a starting symbol position of the downlink data channel.\",\n \"Additionally or alternatively, each of the candidate parameter sets may include resource element (RE) mapping pattern information related to specific reference signal(s).\",\n \"Additionally or alternatively, if the semi-persistently-scheduled downlink data channel is received in a MBSFN (Multimedia Broadcast multicast service Single Frequency Network) subframe, a starting symbol position of the downlink data channel may be restricted to a starting symbol position of a downlink data channel of the MBSFN subframe.\",\n \"Additionally or alternatively, the user equipment (UE) may be configured in transmission mode 10.Additionally or alternatively, the user equipment (UE) may be configured to receive downlink signal from at least two eNBs.\",\n \"Additionally or alternatively, the processor may be configured to decode the downlink data channel by using the first parameter set or the second parameter set until new SPS-related information is received.\",\n \"It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.\",\n \"Advantageous Effects According to exemplary embodiments of the present invention, the present invention can efficiently transmit and receive downlink control information in a wireless communication system.\",\n \"It will be appreciated by persons skilled in the art that the effects that can be achieved with the present invention are not limited to what has been particularly described hereinabove and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings.\",\n \"DESCRIPTION OF DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention, illustrate embodiments of the invention and together with the description serve to explain the principle of the invention.\",\n \"FIG.\",\n \"1 exemplarily shows a radio frame structure for use in a wireless communication system.\",\n \"FIG.\",\n \"2 exemplarily shows a downlink/uplink (DL/UL) slot structure for use in a wireless communication system.\",\n \"FIG.\",\n \"3 exemplarily shows a downlink (DL) subframe structure for use in a 3GPP LTE/LTE-A system.\",\n \"FIG.\",\n \"4 exemplarily shows an uplink (UL) subframe for use in a 3GPP LTE/LTE-A system.\",\n \"FIG.\",\n \"5 exemplarily shows an EPDCCH (Enhanced Physical Downlink Control Channel).\",\n \"FIG.\",\n \"6 exemplarily shows an EPDCCH (Enhanced Physical Downlink Control Channel).\",\n \"FIG.\",\n \"7 is a conceptual diagram illustrating a carrier aggregation (CA) scheme.\",\n \"FIG.\",\n \"8 is a conceptual diagram illustrating a cross-carrier scheduling scheme.\",\n \"FIG.\",\n \"9 is a conceptual diagram illustrating a wireless communication system for enabling a UE to receive a Joint Transmission (JT) service from a CoMP aggregation.\",\n \"FIG.\",\n \"10 is a conceptual diagram illustrating a method for deciding the start symbol position of the SPS-scheduled PDSCH (hereinafter referred to as SPS-PDSCH) according to the above mentioned embodiment.\",\n \"FIG.\",\n \"11 is a conceptual diagram illustrating invention method for deciding the start symbol position of SPS-PDSCH when the SPS-configured UE receives at least two EPDCCH-related parameters.\",\n \"FIG.\",\n \"12 is a block diagram of an apparatus for implementing embodiment(s) of the present invention.\",\n \"BEST MODE Reference will now be made in detail to the preferred embodiments of the present invention, examples of which are illustrated in the accompanying drawings.\",\n \"The accompanying drawings illustrate exemplary embodiments of the present invention and provide a more detailed description of the present invention.\",\n \"However, the scope of the present invention should not be limited thereto.\",\n \"In some cases, to prevent the concept of the present invention from being ambiguous, structures and apparatuses of the known art will be omitted, or will be shown in the form of a block diagram based on main functions of each structure and apparatus.\",\n \"Also, wherever possible, the same reference numbers will be used throughout the drawings and the specification to refer to the same or like parts.\",\n \"In the present invention, a user equipment (UE) is fixed or mobile.\",\n \"The UE is a device that transmits and receives user data and/or control information by communicating with a base station (BS).\",\n \"The term ‘UE’ may be replaced with ‘terminal equipment’, ‘Mobile Station (MS)’, ‘Mobile Terminal (MT)’, ‘User Terminal (UT)’, ‘Subscriber Station (SS)’, ‘wireless device’, ‘Personal Digital Assistant (PDA)’, ‘wireless modem’, ‘handheld device’, etc.\",\n \"A BS is typically a fixed station that communicates with a UE and/or another BS.\",\n \"The BS exchanges data and control information with a UE and another BS.\",\n \"The term ‘BS’ may be replaced with ‘Advanced Base Station (ABS)’, ‘Node B’, ‘evolved-Node B (eNB)’, ‘Base Transceiver System (BTS)’, ‘Access Point (AP)’, ‘Processing Server (PS)’, etc.\",\n \"In the following description, BS is commonly called eNB.\",\n \"In the present invention, a node refers to a fixed point capable of transmitting/receiving a radio signal to/from a UE by communication with the UE.\",\n \"Various eNBs can be used as nodes.\",\n \"For example, a node can be a BS, NB, eNB, pico-cell eNB (PeNB), home eNB (HeNB), relay, repeater, etc.\",\n \"Furthermore, a node may not be an eNB.\",\n \"For example, a node can be a radio remote head (RRH) or a radio remote unit (RRU).\",\n \"The RRH and RRU have power levels lower than that of the eNB.\",\n \"Since the RRH or RRU (referred to as RRH/RRU hereinafter) is connected to an eNB through a dedicated line such as an optical cable in general, cooperative communication according to RRH/RRU and eNB can be smoothly performed compared to cooperative communication according to eNBs connected through a wireless link.\",\n \"At least one antenna is installed per node.\",\n \"An antenna may refer to an antenna port, a virtual antenna or an antenna group.\",\n \"A node may also be called a point.\",\n \"Unlink a conventional centralized antenna system (CAS) (i.e.\",\n \"single node system) in which antennas are concentrated in an eNB and controlled an eNB controller, plural nodes are spaced apart at a predetermined distance or longer in a multi-node system.\",\n \"The plural nodes can be managed by one or more eNBs or eNB controllers that control operations of the nodes or schedule data to be transmitted/received through the nodes.\",\n \"Each node may be connected to an eNB or eNB controller managing the corresponding node via a cable or a dedicated line.\",\n \"In the multi-node system, the same cell identity (ID) or different cell IDs may be used for signal transmission/reception through plural nodes.\",\n \"When plural nodes have the same cell ID, each of the plural nodes operates as an antenna group of a cell.\",\n \"If nodes have different cell IDs in the multi-node system, the multi-node system can be regarded as a multi-cell (e.g.\",\n \"macro-cell/femto-cell/pico-cell) system.\",\n \"When multiple cells respectively configured by plural nodes are overlaid according to coverage, a network configured by multiple cells is called a multi-tier network.\",\n \"The cell ID of the RRH/RRU may be identical to or different from the cell ID of an eNB.\",\n \"When the RRH/RRU and eNB use different cell IDs, both the RRH/RRU and eNB operate as independent eNBs.\",\n \"In a multi-node system according to the present invention, which will be described below, one or more eNBs or eNB controllers connected to plural nodes can control the plural nodes such that signals are simultaneously transmitted to or received from a UE through some or all nodes.\",\n \"While there is a difference between multi-node systems according to the nature of each node and implementation form of each node, multi-node systems are discriminated from single node systems (e.g.\",\n \"CAS, conventional MIMO systems, conventional relay systems, conventional repeater systems, etc.)\",\n \"since a plurality of nodes provides communication services to a UE in a predetermined time-frequency resource.\",\n \"Accordingly, embodiments of the present invention with respect to a method of performing coordinated data transmission using some or all nodes can be applied to various types of multi-node systems.\",\n \"For example, a node refers to an antenna group spaced apart from another node by a predetermined distance or more, in general.\",\n \"However, embodiments of the present invention, which will be described below, can even be applied to a case in which a node refers to an arbitrary antenna group irrespective of node interval.\",\n \"In the case of an eNB including an X-pole (cross polarized) antenna, for example, the embodiments of the preset invention are applicable on the assumption that the eNB controls a node composed of an H-pole antenna and a V-pole antenna.\",\n \"A communication scheme through which signals are transmitted/received via plural transmit (Tx)/receive (Rx) nodes, signals are transmitted/received via at least one node selected from plural Tx/Rx nodes, or a node transmitting a downlink signal is discriminated from a node transmitting an uplink signal is called multi-eNB MIMO or CoMP (Coordinated Multi-Point Tx/Rx).\",\n \"Coordinated transmission schemes from among CoMP communication schemes can be categorized into JP (Joint Processing) and scheduling coordination.\",\n \"The former may be divided into JT (Joint Transmission)/JR (Joint Reception) and DPS (Dynamic Point Selection) and the latter may be divided into CS (Coordinated Scheduling) and CB (Coordinated Beamforming).\",\n \"DPS may be called DCS (Dynamic Cell Selection).\",\n \"When JP is performed, more various communication environments can be generated, compared to other CoMP schemes.\",\n \"JT refers to a communication scheme by which plural nodes transmit the same stream to a UE and JR refers to a communication scheme by which plural nodes receive the same stream from the UE.\",\n \"The UE/eNB combine signals received from the plural nodes to restore the stream.\",\n \"In the case of JT/JR, signal transmission reliability can be improved according to transmit diversity since the same stream is transmitted from/to plural nodes.\",\n \"DPS refers to a communication scheme by which a signal is transmitted/received through a node selected from plural nodes according to a specific rule.\",\n \"In the case of DPS, signal transmission reliability can be improved because a node having a good channel state between the node and a UE is selected as a communication node.\",\n \"In the present invention, a cell refers to a specific geographical area in which one or more nodes provide communication services.\",\n \"Accordingly, communication with a specific cell may mean communication with an eNB or a node providing communication services to the specific cell.\",\n \"A downlink/uplink signal of a specific cell refers to a downlink/uplink signal from/to an eNB or a node providing communication services to the specific cell.\",\n \"A cell providing uplink/downlink communication services to a UE is called a serving cell.\",\n \"Furthermore, channel status/quality of a specific cell refers to channel status/quality of a channel or a communication link generated between an eNB or a node providing communication services to the specific cell and a UE.\",\n \"In 3GPP LTE-A systems, a UE can measure downlink channel state from a specific node using one or more CSI-RSs (Channel State Information Reference Signals) transmitted through antenna port(s) of the specific node on a CSI-RS resource allocated to the specific node.\",\n \"In general, neighboring nodes transmit CSI-RS resources on orthogonal CSI-RS resources.\",\n \"When CSI-RS resources are orthogonal, this means that the CSI-RS resources have different subframe configurations and/or CSI-RS sequences which specify subframes to which CSI-RSs are allocated according to CSI-RS resource configurations, subframe offsets and transmission periods, etc.\",\n \"which specify symbols and subcarriers carrying the CSI RSs.\",\n \"In the present invention, PDCCH (Physical Downlink Control Channel)/PCFICH (Physical Control Format Indicator Channel)/PHICH (Physical Hybrid automatic repeat request Indicator Channel)/PDSCH (Physical Downlink Shared Channel) refer to a set of time-frequency resources or resource elements respectively carrying DCI (Downlink Control Information)/CFI (Control Format Indicator)/downlink ACK/NACK (Acknowlegement/Negative ACK)/downlink data.\",\n \"In addition, PUCCH (Physical Uplink Control Channel)/PUSCH (Physical Uplink Shared Channel)/PRACH (Physical Random Access Channel) refer to sets of time-frequency resources or resource elements respectively carrying UCI (Uplink Control Information)/uplink data/random access signals.\",\n \"In the present invention, a time-frequency resource or a resource element (RE), which is allocated to or belongs to PDCCH/PCFICH/PHICH/PDSCH/PUCCH/PUSCH/PRACH, is referred to as a PDCCH/PCFICH/PHICH/PDSCH/PUCCH/PUSCH/PRACH RE or PDCCH/PCFICH/PHICH/PDSCH/PUCCH/PUSCH/PRACH resource.\",\n \"In the following description, transmission of PUCCH/PUSCH/PRACH by a UE is equivalent to transmission of uplink control information/uplink data/random access signal through or on PUCCH/PUSCH/PRACH.\",\n \"Furthermore, transmission of PDCCH/PCFICH/PHICH/PDSCH by an eNB is equivalent to transmission of downlink data/control information through or on PDCCH/PCFICH/PHICH/PDSCH.\",\n \"FIG.\",\n \"1 illustrates an exemplary radio frame structure used in a wireless communication system.\",\n \"FIG.\",\n \"1(a) illustrates a frame structure for frequency division duplex (FDD) used in 3GPP LTE/LTE-A and FIG.\",\n \"1(b) illustrates a frame structure for time division duplex (TDD) used in 3GPP LTE/LTE-A.\",\n \"Referring to FIG.\",\n \"1, a radio frame used in 3GPP LTE/LTE-A has a length of 10 ms (307200 Ts) and includes 10 subframes in equal size.\",\n \"The 10 subframes in the radio frame may be numbered.\",\n \"Here, Ts denotes sampling time and is represented as Ts=1/(2048*15 kHz).\",\n \"Each subframe has a length of 1 ms and includes two slots.\",\n \"20 slots in the radio frame can be sequentially numbered from 0 to 19.Each slot has a length of 0.5 ms. A time for transmitting a subframe is defined as a transmission time interval (TTI).\",\n \"Time resources can be discriminated by a radio frame number (or radio frame index), subframe number (or subframe index) and a slot number (or slot index).\",\n \"The radio frame can be configured differently according to duplex mode.\",\n \"Downlink transmission is discriminated from uplink transmission by frequency in FDD mode, and thus the radio frame includes only one of a downlink subframe and an uplink subframe in a specific frequency band.\",\n \"In TDD mode, downlink transmission is discriminated from uplink transmission by time, and thus the radio frame includes both a downlink subframe and an uplink subframe in a specific frequency band.\",\n \"Table 1 shows DL-UL configurations of subframes in a radio frame in the TDD mode.\",\n \"TABLE 1 Downlink- to-Uplink Switch- DL-UL point Subframe number configuration periodicity 0 1 2 3 4 5 6 7 8 9 0 5 ms D S U U U D S U U U 1 5 ms D S U U D D S U U D 2 5 ms D S U D D D S U D D 3 10 ms D S U U U D D D D D 4 10 ms D S U U D D D D D D 5 10 ms D S U D D D D D D D 6 5 ms D S U U U D S U U D In Table 1, D denotes a downlink subframe, U denotes an uplink subframe and S denotes a special subframe.\",\n \"The special subframe includes three fields of DwPTS (Downlink Pilot TimeSlot), GP (Guard Period), and UpPTS (Uplink Pilot TimeSlot).\",\n \"DwPTS is a period reserved for downlink transmission and UpPTS is a period reserved for uplink transmission.\",\n \"Table 2 shows special subframe configuration.\",\n \"TABLE 2 Normal cyclic Extended cyclic prefix in downlink prefix in downlink UpPTS UpPTS Normal Extended Normal Special cyclic cyclic cyclic Extended subframe prefix in prefix prefix in cyclic prefix configuration DwPTS uplink in uplink DwPTS uplink in uplink 0 6592 · Ts 2192 · Ts 2560 · Ts 7680 · Ts 2192 · Ts 2560 · Ts 1 19760 · Ts 20480 · Ts 2 21952 · Ts 23040 · Ts 3 24144 · Ts 25600 · Ts 4 26336 · Ts 7680 · Ts 4384 · Ts 5120 · Ts 5 6592 · Ts 4384 · Ts 5120 · Ts 20480 · Ts 6 19760 · Ts 23040 · Ts 7 21952 · Ts 12800 · Ts 8 24144 · Ts — — — FIG.\",\n \"2 illustrates an exemplary downlink/uplink slot structure in a wireless communication system.\",\n \"Particularly, FIG.\",\n \"2 illustrates a resource grid structure in 3GPP LTE/LTE-A.\",\n \"A resource grid is present per antenna port.\",\n \"Referring to FIG.\",\n \"2, a slot includes a plurality of OFDM (Orthogonal Frequency Division Multiplexing) symbols in the time domain and a plurality of resource blocks (RBs) in the frequency domain.\",\n \"An OFDM symbol may refer to a symbol period.\",\n \"A signal transmitted in each slot may be represented by a resource grid composed of NRBDL/UL*NscRB subcarriers and NsymbDL/UL OFDM symbols.\",\n \"Here, NRBDL denotes the number of RBs in a downlink slot and NRBUL denotes the number of RBs in an uplink slot.\",\n \"NRBDL and NRBUL respectively depend on a DL transmission bandwidth and a UL transmission bandwidth.\",\n \"NsymbDL denotes the number of OFDM symbols in the downlink slot and NsymbUL denotes the number of OFDM symbols in the uplink slot.\",\n \"In addition, NscRB denotes the number of subcarriers constructing one RB.\",\n \"An OFDM symbol may be called an SC-FDM (Single Carrier Frequency Division Multiplexing) symbol according to multiple access scheme.\",\n \"The number of OFDM symbols included in a slot may depend on a channel bandwidth and the length of a cyclic prefix (CP).\",\n \"For example, a slot includes 7 OFDM symbols in the case of normal CP and 6 OFDM symbols in the case of extended CP.\",\n \"While FIG.\",\n \"2 illustrates a subframe in which a slot includes 7 OFDM symbols for convenience, embodiments of the present invention can be equally applied to subframes having different numbers of OFDM symbols.\",\n \"Referring to FIG.\",\n \"2, each OFDM symbol includes NRBDL/UL*NscRB subcarriers in the frequency domain.\",\n \"Subcarrier types can be classified into a data subcarrier for data transmission, a reference signal subcarrier for reference signal transmission, and null subcarriers for a guard band and a direct current (DC) component.\",\n \"The null subcarrier for a DC component is a subcarrier remaining unused and is mapped to a carrier frequency (f0) during OFDM signal generation or frequency up-conversion.\",\n \"The carrier frequency is also called a center frequency.\",\n \"An RB is defined by NsymbDL/UL (e.g.\",\n \"7) consecutive OFDM symbols in the time domain and NscRB (e.g.\",\n \"12) consecutive subcarriers in the frequency domain.\",\n \"For reference, a resource composed by an OFDM symbol and a subcarrier is called a resource element (RE) or a tone.\",\n \"Accordingly, an RB is composed of NsymbDL/UL*NscRB REs.\",\n \"Each RE in a resource grid can be uniquely defined by an index pair (k, 1) in a slot.\",\n \"Here, k is an index in the range of 0 to NsymbDL/UL*NscRB−1 frequency domain and 1 is an index in the range of 0 to NsymbDL/UL−1.Two RBs, which occupy NscRB same continuous subcarriers for one subframe and are respectively located at two slots of the subframe, will be referred to as a pair of physical resource blocks (PRB).\",\n \"The two RBs constituting the PRB have the same PRB number (or PRB index).\",\n \"A virtual resource block (VRB) is a logical resource allocation unit for resource allocation.\",\n \"The VRB has the same size as that of the PRB.\",\n \"The VRB may be divided into a localized VRB and a distributed VRB depending on a mapping scheme of VRB into PRB.\",\n \"The localized VRBs are mapped into the PRBs, whereby VRB number (VRB index) corresponds to PRB number.\",\n \"That is, nPRB=nVRB is obtained.\",\n \"Numbers are given to the localized VRBs from 0 to NDLVRB−1, and NDLVRB=NDLRB is obtained.\",\n \"Accordingly, according to the localized mapping scheme, the VRBs having the same VRB number are mapped into the PRBs having the same PRB number at the first slot and the second slot.\",\n \"On the other hand, the distributed VRBs are mapped into the PRBs through interleaving.\",\n \"Accordingly, the VRBs having the same VRB number may be mapped into the PRBs having different PRB numbers at the first slot and the second slot.\",\n \"Two PRBs, which are respectively located at two slots of the subframe and have the same VRB number, will be referred to as a pair of VRBs.\",\n \"FIG.\",\n \"3 illustrates a downlink (DL) subframe structure used in 3GPP LTE/LTE-A.\",\n \"Referring to FIG.\",\n \"3, a DL subframe is divided into a control region and a data region.\",\n \"A maximum of three (four) OFDM symbols located in a front portion of a first slot within a subframe correspond to the control region to which a control channel is allocated.\",\n \"A resource region available for PDCCH transmission in the DL subframe is referred to as a PDCCH region hereinafter.\",\n \"The remaining OFDM symbols correspond to the data region to which a physical downlink shared chancel (PDSCH) is allocated.\",\n \"A resource region available for PDSCH transmission in the DL subframe is referred to as a PDSCH region hereinafter.\",\n \"Examples of downlink control channels used in 3GPP LTE include a physical control format indicator channel (PCFICH), a physical downlink control channel (PDCCH), a physical hybrid ARQ indicator channel (PHICH), etc.\",\n \"The PCFICH is transmitted at a first OFDM symbol of a subframe and carries information regarding the number of OFDM symbols used for transmission of control channels within the subframe.\",\n \"The PHICH is a response of uplink transmission and carries an HARQ acknowledgment (ACK)/negative acknowledgment (NACK) signal.\",\n \"Control information carried on the PDCCH is called downlink control information (DCI).\",\n \"The DCI contains resource allocation information and control information for a UE or a UE group.\",\n \"For example, the DCI includes a transport format and resource allocation information of a downlink shared channel (DL-SCH), a transport format and resource allocation information of an uplink shared channel (UL-SCH), paging information of a paging channel (PCH), system information on the DL-SCH, information about resource allocation of an upper layer control message such as a random access response transmitted on the PDSCH, a transmit control command set with respect to individual UEs in a UE group, a transmit power control command, information on activation of a voice over IP (VoIP), downlink assignment index (DAI), etc.\",\n \"The transport format and resource allocation information of the DL-SCH are also called DL scheduling information or a DL grant and the transport format and resource allocation information of the UL-SCH are also called UL scheduling information or a UL grant.\",\n \"The size and purpose of DCI carried on a PDCCH depend on DCI format and the size thereof may be varied according to coding rate.\",\n \"Various formats, for example, formats 0 and 4 for uplink and formats 1, 1A, 1B, 1C, 1D, 2, 2A, 2B, 2C, 3 and 3A for downlink, have been defined in 3GPP LTE.\",\n \"Control information such as a hopping flag, information on RB allocation, modulation coding scheme (MCS), redundancy version (RV), new data indicator (NDI), information on transmit power control (TPC), cyclic shift demodulation reference signal (DMRS), UL index, channel quality information (CQI) request, DL assignment index, HARQ process number, transmitted precoding matrix indicator (TPMI), precoding matrix indicator (PMI), etc.\",\n \"is selected and combined based on DCI format and transmitted to a UE as DCI.\",\n \"In general, a DCI format for a UE depends on transmission mode (TM) set for the UE.\",\n \"In other words, only a DCI format corresponding to a specific TM can be used for a UE configured in the specific TM.\",\n \"A PDCCH is transmitted on an aggregation of one or several consecutive control channel elements (CCEs).\",\n \"The CCE is a logical allocation unit used to provide the PDCCH with a coding rate based on a state of a radio channel.\",\n \"The CCE corresponds to a plurality of resource element groups (REGs).\",\n \"For example, a CCE corresponds to 9 REGs and an REG corresponds to 4 REs.\",\n \"3GPP LTE defines a CCE set in which a PDCCH can be located for each UE.\",\n \"A CCE set from which a UE can detect a PDCCH thereof is called a PDCCH search space, simply, search space.\",\n \"An individual resource through which the PDCCH can be transmitted within the search space is called a PDCCH candidate.\",\n \"A set of PDCCH candidates to be monitored by the UE is defined as the search space.\",\n \"In 3GPP LTE/LTE-A, search spaces for DCI formats may have different sizes and include a dedicated search space and a common search space.\",\n \"The dedicated search space is a UE-specific search space and is configured for each UE.\",\n \"The common search space is configured for a plurality of UEs.\",\n \"The aggregation levels defining the search space are indicated as follows: TABLE 3 Search Space Number of PDCCH Type Aggregation Level L Size [in CCEs] candidates M(L) UE- 1 6 6 specific 2 12 6 4 8 2 8 16 2 Common 4 16 4 8 16 2 A PDCCH candidate corresponds to 1, 2, 4 or 8 CCEs according to CCE aggregation level.\",\n \"An eNB transmits a PDCCH (DCI) on an arbitrary PDCCH candidate with in a search space and a UE monitors the search space to detect the PDCCH (DCI).\",\n \"Here, monitoring refers to attempting to decode each PDCCH in the corresponding search space according to all monitored DCI formats.\",\n \"The UE can detect the PDCCH thereof by monitoring plural PDCCHs.\",\n \"Since the UE does not know the position in which the PDCCH thereof is transmitted, the UE attempts to decode all PDCCHs of the corresponding DCI format for each subframe until a PDCCH having the ID thereof is detected.\",\n \"This process is called blind detection (or blind decoding (BD)).\",\n \"The eNB can transmit data for a UE or a UE group through the data region.\",\n \"Data transmitted through the data region may be called user data.\",\n \"For transmission of the user data, a physical downlink shared channel (PDSCH) may be allocated to the data region.\",\n \"A paging channel (PCH) and downlink-shared channel (DL-SCH) are transmitted through the PDSCH.\",\n \"The UE can read data transmitted through the PDSCH by decoding control information transmitted through a PDCCH.\",\n \"Information representing a UE or a UE group to which data on the PDSCH is transmitted, how the UE or UE group receives and decodes the PDSCH data, etc.\",\n \"is included in the PDCCH and transmitted.\",\n \"For example, if a specific PDCCH is CRC (cyclic redundancy check)-masked having radio network temporary identify (RNTI) of “A” and information about data transmitted using a radio resource (e.g.\",\n \"frequency position) of “B” and transmission format information (e.g.\",\n \"transport block size, modulation scheme, coding information, etc.)\",\n \"of “C” is transmitted through a specific DL subframe, the UE monitors PDCCHs using RNTI information and a UE having the RNTI of “A” detects a PDCCH and receives a PDSCH indicated by “B” and “C” using information about the PDCCH.\",\n \"A reference signal (RS) to be compared with a data signal is necessary for the UE to demodulate a signal received from the eNB.\",\n \"A reference signal refers to a predetermined signal having a specific waveform, which is transmitted from the eNB to the UE or from the UE to the eNB and known to both the eNB and UE.\",\n \"The reference signal is also called a pilot.\",\n \"Reference signals are categorized into a cell-specific RS shared by all UEs in a cell and a modulation RS (DM RS) dedicated for a specific UE.\",\n \"A DM RS transmitted by the eNB for demodulation of downlink data for a specific UE is called a UE-specific RS.\",\n \"Both or one of DM RS and CRS may be transmitted on downlink.\",\n \"When only the DM RS is transmitted without CRS, an RS for channel measurement needs to be additionally provided because the DM RS transmitted using the same precoder as used for data can be used for demodulation only.\",\n \"For example, in 3GPP LTE(-A), CSI-RS corresponding to an additional RS for measurement is transmitted to the UE such that the UE can measure channel state information.\",\n \"CSI-RS is transmitted in each transmission period corresponding to a plurality of subframes based on the fact that channel state variation with time is not large, unlike CRS transmitted per subframe.\",\n \"FIG.\",\n \"4 illustrates an exemplary uplink subframe structure used in 3GPP LTE/LTE-A.\",\n \"Referring to FIG.\",\n \"4, a UL subframe can be divided into a control region and a data region in the frequency domain.\",\n \"One or more PUCCHs (physical uplink control channels) can be allocated to the control region to carry uplink control information (UCI).\",\n \"One or more PUSCHs (Physical uplink shared channels) may be allocated to the data region of the UL subframe to carry user data.\",\n \"In the UL subframe, subcarriers spaced apart from a DC subcarrier are used as the control region.\",\n \"In other words, subcarriers corresponding to both ends of a UL transmission bandwidth are assigned to UCI transmission.\",\n \"The DC subcarrier is a component remaining unused for signal transmission and is mapped to the carrier frequency f0 during frequency up-conversion.\",\n \"A PUCCH for a UE is allocated to an RB pair belonging to resources operating at a carrier frequency and RBs belonging to the RB pair occupy different subcarriers in two slots.\",\n \"Assignment of the PUCCH in this manner is represented as frequency hopping of an RB pair allocated to the PUCCH at a slot boundary.\",\n \"When frequency hopping is not applied, the RB pair occupies the same subcarrier.\",\n \"The PUCCH can be used to transmit the following control information.\",\n \"Scheduling Request (SR): This is information used to request a UL-SCH resource and is transmitted using On-Off Keying (OOK) scheme.\",\n \"HARQ ACK/NACK: This is a response signal to a downlink data packet on a PDSCH and indicates whether the downlink data packet has been successfully received.\",\n \"A 1-bit ACK/NACK signal is transmitted as a response to a single downlink codeword and a 2-bit ACK/NACK signal is transmitted as a response to two downlink codewords.\",\n \"HARQ-ACK responses include positive ACK (ACK), negative ACK (NACK), discontinuous transmission (DTX) and NACK/DTX.\",\n \"Here, the term HARQ-ACK is used interchangeably with the term HARQ ACK/NACK and ACK/NACK.\",\n \"Channel State Indicator (CSI): This is feedback information about a downlink channel.\",\n \"Feedback information regarding MIMO includes a rank indicator (RI) and a precoding matrix indicator (PMI).\",\n \"The quantity of control information (UCI) that a UE can transmit through a subframe depends on the number of SC-FDMA symbols available for control information transmission.\",\n \"The SC-FDMA symbols available for control information transmission correspond to SC-FDMA symbols other than SC-FDMA symbols of the subframe, which are used for reference signal transmission.\",\n \"In the case of a subframe in which a sounding reference signal (SRS) is configured, the last SC-FDMA symbol of the subframe is excluded from the SC-FDMA symbols available for control information transmission.\",\n \"A reference signal is used to detect coherence of the PUCCH.\",\n \"The PUCCH supports various formats according to information transmitted thereon.\",\n \"Table 4 shows the mapping relationship between PUCCH formats and UCI in LTE/LTE-A.\",\n \"TABLE 4 Number of bits per PUCCH Modulation subframe, format scheme Mbit Usage Etc.\",\n \"1 N/A N/A SR (Scheduling Request) 1a BPSK 1 ACK/NACK or One SR + ACK/NACK codeword 1b QPSK 2 ACK/NACK or Two SR + ACK/NACK codeword 2 QPSK 20 CQI/PMI/RI Joint coding ACK/NACK (extended CP) 2a QPSK + BPSK 21 CQI/PMI/RI + Normal CP ACK/NACK only 2b QPSK + QPSK 22 CQI/PMI/RI + Normal CP ACK/NACK only 3 QPSK 48 ACK/NACK or SR + ACK/NACK or CQI/PMI/RI + ACK/NACK Referring to Table 4, PUCCH formats 1/1a/1b are used to transmit ACK/NACK information, PUCCH format 2/2a/2b are used to carry CSI such as CQI/PMI/RI and PUCCH format 3 is used to transmit ACK/NACK information.\",\n \"Reference Signal (RS) When a packet is transmitted in a wireless communication system, signal distortion may occur during transmission since the packet is transmitted through a radio channel.\",\n \"To correctly receive a distorted signal at a receiver, the distorted signal needs to be corrected using channel information.\",\n \"To detect channel information, a signal known to both a transmitter and the receiver is transmitted and channel information is detected with a degree of distortion of the signal when the signal is received through a channel.\",\n \"This signal is called a pilot signal or a reference signal.\",\n \"When data is transmitted/received using multiple antennas, the receiver can receive a correct signal only when the receiver is aware of a channel state between each transmit antenna and each receive antenna.\",\n \"Accordingly, a reference signal needs to be provided per transmit antenna, more specifically, per antenna port.\",\n \"Reference signals can be classified into an uplink reference signal and a downlink reference signal.\",\n \"In LTE, the uplink reference signal includes: i) a demodulation reference signal (DMRS) for channel estimation for coherent demodulation of information transmitted through a PUSCH and a PUCCH; and ii) a sounding reference signal (SRS) used for an eNB to measure uplink channel quality at a frequency of a different network.\",\n \"The downlink reference signal includes: i) a cell-specific reference signal (CRS) shared by all UEs in a cell; ii) a UE-specific reference signal for a specific UE only; iii) a DMRS transmitted for coherent demodulation when a PDSCH is transmitted; iv) a channel state information reference signal (CSI-RS) for delivering channel state information (CSI) when a downlink DMRS is transmitted; v) a multimedia broadcast single frequency network (MBSFN) reference signal transmitted for coherent demodulation of a signal transmitted in MBSFN mode; and vi) a positioning reference signal used to estimate geographic position information of a UE.\",\n \"Reference signals can be classified into a reference signal for channel information acquisition and a reference signal for data demodulation.\",\n \"The former needs to be transmitted in a wide band as it is used for a UE to acquire channel information on downlink transmission and received by a UE even if the UE does not receive downlink data in a specific subframe.\",\n \"This reference signal is used even in a handover situation.\",\n \"The latter is transmitted along with a corresponding resource by an eNB when the eNB transmits a downlink signal and is used for a UE to demodulate data through channel measurement.\",\n \"This reference signal needs to be transmitted in a region in which data is transmitted.\",\n \"General EPDCCH (Enhanced PDCCH) Owing to introduction of a multi-node system, although various communication schemes becomes available in a manner that channel quality improvement is achieved, introduction of a new control channel is being requested to apply the above-mentioned MIMO scheme and inter-cell coordinated communication scheme to the multi-node environment.\",\n \"Due to the above necessity, introduction of a new control channel is an Enhanced PDCCH (EPDCCH) is being intensively discussed, and the new control channel can be allocated to a data region (hereinafter referred to as a PDSCH region) instead of the legacy control region (hereinafter referred to as a PDCCH region).\",\n \"As a result, node control information can be transmitted per UE through EPDCCH, such that the problem of insufficiency of the legacy PDCCH region can also be solved.\",\n \"For reference, EPDCCH is not applied to the legacy UE, and can be received by the LTE-A UE only.\",\n \"FIG.\",\n \"5 is a conceptual diagram illustrating a carrier aggregation (CA) scheme.\",\n \"Referring to FIG.\",\n \"5, EPDCCH may define and use some parts of the PDSCH region configured to transmit data, and the UE has to perform blind decoding for detecting the presence or absence of EPDCCH.\",\n \"EPDCCH performs the same scheduling operation (i.e., PDSCH, PUSCH control) as in the legacy PDCCH.\",\n \"If the number of UEs connected to the same node as in RRH increases, many more EPDCCHs are allocated to the PDSCH region, such that the number of blind decoding times to be executed by the UE increases, resulting in increased complexity.\",\n \"Meanwhile, a method for multiplexing EPDCCH for a plurality of UEs needs to be considered.\",\n \"In more detail, according to the multiplexing scheme proposed by the present invention, on the condition that a common resource region (i.e., a common PRB set) is configured, EPDCCHs of multiple UEs can be cross-interleaved to the frequency domain or the time domain.\",\n \"FIG.\",\n \"6 is a conceptual diagram illustrating a method for multiplexing EPDCCH for a plurality of UEs.\",\n \"Specifically, FIG.\",\n \"6(a) shows an example in which a common PRB set is configured on the basis of a PRB pair and cross increasing is performed on the basis of the common PRB set.\",\n \"In contrast, FIG.\",\n \"6(b) shows another example in which a common PRB set is configured on a basis of a PRB and cross interleaving is performed on the basis of the common PRB set.\",\n \"The schemes of FIGS.\",\n \"6(a) and 6(b) have advantages in which a diversity gain of the time/frequency domains extending a plurality of RBs can be obtained.\",\n \"Carrier Aggregation (CA) Carrier aggregation will hereinafter be described in detail.\",\n \"FIG.\",\n \"7 is a conceptual diagram illustrating carrier aggregation (CA).\",\n \"Carrier aggregation refers to a method for allowing a UE to use a plurality of frequency blocks or (logical) cells, each of which is composed of uplink resources (or CCs) and/or downlink resources (or CCs), as one large logical band so as to provide a wireless communication system with a wider frequency bandwidth.\",\n \"For convenience of description and better understanding of the present invention, carrier aggregation will hereinafter be referred to as a component carrier (CC).\",\n \"Referring to FIG.\",\n \"7, the entire system bandwidth (System BW) includes a bandwidth of 100 MHz as a logical bandwidth.\",\n \"The entire system bandwidth (system BW) includes five component carriers (CCs) and each CC has a maximum bandwidth of 20 MHz.\",\n \"The CC includes one or more physically contiguous subcarriers.\",\n \"Although all CCs have the same bandwidth in FIG.\",\n \"7, this is only exemplary and the CCs may have different bandwidths.\",\n \"Although the CCs are shown as being contiguous in the frequency domain in FIG.\",\n \"8, FIG.\",\n \"8 merely shows the logical concept and thus the CCs may be physically contiguous or separated.\",\n \"Different center frequencies may be used for the CCs or one common center frequency may be used for physically contiguous CCs.\",\n \"For example, in FIG.\",\n \"7, if it is assumed that all CCs are physically contiguous, a center frequency A may be used.\",\n \"If it is assumed that CCs are not physically contiguous, a center frequency A, a center frequency B and the like may be used for the respective CCs.\",\n \"In the present specification, the CC may correspond to a system band of a legacy system.\",\n \"By defining the CC based on the legacy system, it is possible to facilitate backward compatibility and system design in a radio communication environment in which an evolved UE and a legacy UE coexist.\",\n \"For example, if the LTE-A system supports carrier aggregation, each CC may correspond to the system band of the LTE system.\",\n \"In this case, the CC may have any one bandwidth such as 1.25, 2.5, 5, 10 or 20 MHz.\",\n \"In the case in which the entire system band is extended by carrier aggregation, a frequency band used for communication with each UE is defined in CC units.\",\n \"A UE A may use 100 MHz which is the bandwidth of the entire system band and perform communication using all five CCs.\",\n \"Each of UEs B1 to B5 may only use a bandwidth of 20 MHz and perform communication using one CC.\",\n \"Each of UEs C1 and C2 may use a bandwidth of 40 MHz and perform communication using two CCs.\",\n \"The two CCs may be contiguous or non-contiguous.\",\n \"The UE C1 uses two non-contiguous CCs and the UE C2 uses two contiguous CCs.\",\n \"One downlink CC and one uplink CC may be used in the LTE system and several CCs may be used in the LTE-A system.\",\n \"At this time, a method of scheduling a data channel by a control channel may be divided into a linked carrier scheduling method and a cross carrier scheduling method.\",\n \"More specifically, in the linked carrier scheduling method, similarly to the LTE system using a single CC, a control channel transmitted via a specific CC schedules only a data channel via the specific CC.\",\n \"In contrast, in the cross carrier scheduling method, a control channel transmitted via a primary CC using a carrier indicator field (CIF) schedules a data channel transmitted via the primary CC or another CC.\",\n \"FIG.\",\n \"8 is a conceptual diagram of a cross carrier scheduling scheme.\",\n \"Specifically, as can be seen from FIG.\",\n \"8, the number of cells (or CCs) allocated to a relay node (RN) is set to 3, cross carrier scheduling is carried out using a CIF as described above.\",\n \"In this case, it is assumed that a downlink cell (or CC) #A is set to a primary downlink CC (i.e., a primary cell PCell), and the remaining CCs #B and #C are used as secondary cells (SCells).\",\n \"CoMP (Coordinated Multiple Point Transmission and Reception) In accordance with the improved system throughput requirements of the 3GPP LTE-A system, CoMP transmission/reception technology (also referred to as Co-MIMO, collaborative MIMO or network MIMO) has recently been proposed.\",\n \"The CoMP technology can increase throughput of a UE located at a cell edge and also increase average sector throughput.\",\n \"In general, in a multi-cell environment in which a frequency reuse factor is 1, the performance of the UE located on the cell edge and average sector throughput may be reduced due to Inter-Cell Interference (ICI).\",\n \"In order to reduce the ICI, in the legacy LTE system, a method of enabling the UE located at the cell edge to have appropriate throughput and performance using a simple passive method such as Fractional Frequency Reuse (FFR) through the UE-specific power control in the environment restricted by interference is applied.\",\n \"However, rather than decreasing the use of frequency resources per cell, it is preferable that the ICI is reduced or the UE reuses the ICI as a desired signal.\",\n \"In order to accomplish the above object, a CoMP transmission scheme may be applied.\",\n \"The CoMP scheme applicable to the downlink may be largely classified into a Joint Processing (JP) scheme and a Coordinated Scheduling/Beamforming (CS/CB) scheme.\",\n \"In the JP scheme, each point (eNB) of a CoMP unit may use data.\",\n \"The CoMP unit refers to a set of eNBs used in the CoMP scheme.\",\n \"The JP scheme may be classified into a joint transmission scheme and a dynamic cell selection scheme.\",\n \"The joint transmission scheme refers to a scheme for transmitting a PDSCH from a plurality of points (a part or the whole of the CoMP unit).\",\n \"That is, data transmitted to a single UE may be simultaneously transmitted from a plurality of transmission points.\",\n \"According to the joint transmission scheme, it is possible to coherently or non-coherently improve the quality of the received signals and to actively eliminate interference with another UE.\",\n \"The dynamic cell selection scheme refers to a scheme for transmitting a PDSCH from one point (of the CoMP unit).\",\n \"That is, data transmitted to a single UE at a specific time is transmitted from one point and the other points in the cooperative unit at that time do not transmit data to the UE.\",\n \"The point for transmitting the data to the UE may be dynamically selected.\",\n \"According to the CS/CB scheme, the CoMP units may cooperatively perform beamforming of data transmission to a single UE.\",\n \"Although only a serving cell transmits the data, user scheduling/beamforming may be determined by coordination of the cells of the CoMP unit.\",\n \"In uplink, coordinated multi-point reception refers to reception of a signal transmitted by coordination of a plurality of geographically separated points.\",\n \"The CoMP scheme applicable to the uplink may be classified into Joint Reception (JR) and Coordinated Scheduling/Beamforming (CS/CB).\",\n \"The JR scheme indicates that a plurality of reception points receives a signal transmitted through a PUSCH, the CS/CB scheme indicates that only one point receives a PUSCH, and user scheduling/beamforming is determined by the coordination of the cells of the CoMP unit.\",\n \"In addition, one case in which there are multiple UL points (i.e., multiple Rx points) is referred to as UL CoMP, and the other case in which there are multiple DL points (i.e., multiple Tx points) is referred to as DL CoMP.\",\n \"Quasi Co-Located (QCL) FIG.\",\n \"9 is a conceptual diagram illustrating a wireless communication system for enabling a UE to receive a Joint Transmission (JT) service from a CoMP set.\",\n \"That is, FIG.\",\n \"9 shows an example in which the UE is set to a Tx mode of 10.In FIG.\",\n \"9, the UE receives data from all transmission points (TPs) belonging to the CoMP set, for example, TP1 and TP2 and may transmit channel state information about all TPs belonging to the CoMP set.\",\n \"In this case, RSs may be transmitted to the UE from a plurality of TPs in the CoMP set.\",\n \"If characteristics for channel estimation with respect to different RS ports of different TPs can be shared, then reception processing load and complexity of the UE may be reduced.\",\n \"In addition, if characteristics for channel estimation with respect to different RS ports of the same TP can be shared by the RS ports, then reception processing load and complexity of the UE may be decreased.\",\n \"Accordingly, an LTE-A system has proposed a method for sharing characteristics for channel estimation between RS ports.\",\n \"For channel estimation between RS ports, the LTE-A system has introduced the concept of “quasi co-located (QCL)”.\",\n \"With regard to two antenna ports, for example, if a large-scale property of a radio channel on which a symbol is transmitted through one of the antenna ports can be inferred from a radio channel on which a symbol is transmitted through the other antenna port, then the two antenna ports can be considered quasi-co-located.\",\n \"The large-scale property includes at least one of delay spread, Doppler spread, Doppler shift, average gain and average delay.\",\n \"The term “quasi co-located” will now be referred to as QCL.\",\n \"That is, when two antenna ports are QCL, this means that the large-scale property of a radio channel from one antenna port corresponds to the large-scale property of a radio channel from the other antenna port.\",\n \"Considering a plurality of antenna ports through which RSs are transmitted, when antenna ports through which RSs of two different types are transmitted are QCL, the large-scale property of a radio channel from one antenna port may be replaced by the large-scale property of a radio channel from the other antenna port.\",\n \"According to the concept of quasi-co-location (QCL), the UE cannot assume the same large-scale property for radio channels from non-QCL antenna ports.\",\n \"In this case, the UE needs to perform independent processing per non-QCL antenna port for timing acquisition and tracking, frequency offset estimation and compensation, delay estimation and Doppler estimation, etc.\",\n \"For antenna ports for which QCL can be assumed, the UE can perform the following operations.\",\n \"With regard to delay spread and Doppler spread, the UE may equally apply a power-delay-profile, delay spread and Doppler spectrum and Doppler spread estimation result with respect to a radio channel from one antenna port to a Wiener filter used for channel estimation with respect to a radio channel from the other antenna port.\",\n \"With regard to frequency shift and received timing, the UE may perform time and frequency synchronization for one antenna port and then apply the same synchronization to demodulation with respect to the other antenna port.\",\n \"For average reception power, the UE may average RSRP (reference signal received power) measurement for two or more antenna ports.\",\n \"Upon reception of a specific DMRS-based DL-related DCI format through a control channel (PDCCH or ePDCCH), the UE performs channel estimation with respect to a corresponding PDSCH through a DMRS sequence and then performs data demodulation.\",\n \"For example, if the UE can assume QCL between a configuration of antenna ports (referred to as “DMRS ports” hereinafter) for transmission of a DMRS, received through a DL scheduling grant, and a configuration of antenna ports (referred to as “CRS ports” hereinafter) for transmission of a CRS of the DL serving cell of the UE or another cell, then the UE may apply an estimate of the large-scale property of a radio channel, which has been estimated from the CRS ports, to channel estimation through the DMRS ports, thereby improving performance of a processor of a DMRS-based receiver.\",\n \"Since the CRS is a reference signal that is broadcast with high density per subframe and over the entire band, as described above, the estimate of the large-scale property can be acquired from the CRS more stably.\",\n \"On the contrary, the DMRS is UE-specifically transmitted for a specific scheduled RB and a precoding matrix used by an eNB for transmission may be changed per PRG, and thus a valid channel received by the UE may be changed per PRG.\",\n \"Accordingly, performance deterioration may occur when the DMRS is used to estimate the large-scale property of a radio channel over a wide band even if a plurality of PRGs is scheduled for the UE.\",\n \"The CSI-RS has a transmission period of several to ten ms and is transmitted with as low density as 1 RE (2 REs when CDM is applied) per antenna port per RB.\",\n \"Thus, performance deterioration may occur when the CSI-RS is used to estimate the large-scale property of the radio channel.\",\n \"That is, QCL assumption between antenna ports may be used for reception of downlink reference signals, channel estimation, channel state reporting, etc.\",\n \"Semi-Persistent Scheduling (SPS) SPS (Semi-persistent scheduling) is a scheduling method for reducing overhead of control signaling and efficiently employing resources of a limited control channel.\",\n \"SPS is used when the UE uses time-frequency resources within a predetermined time having a relatively long period.\",\n \"According to SPS, signaling for repeatedly allocating resources within the predetermined time generates signaling overhead, so that time-frequency resources (or region) allocated to the UE can be simultaneously scheduled.\",\n \"Therefore, if time-frequency resources for SPS are allocated to the UE within one subframe, the UE may use the corresponding time-frequency resources without using a separate control channel in the next periodically-repeated SPS-subframe.\",\n \"SPS may be efficiently used for communication such as VoIP (Voice over Internet Protocol) in which timing or necessary resources can be estimated.\",\n \"RRC and PDCCH may be used as the SPS configuration method.\",\n \"An interval of radio resources being periodically allocated is indicated through RRC, and detailed resource allocation information (transmission attributes such as frequency domain RA or MCS) may be transmitted through PDCCH.\",\n \"SPS may use a special ID such as SPS C-RNTI so that SPS can be distinguished from general dynamic scheduling).\",\n \"The present invention relates to a method for deciding PDSCH-related parameters including a start symbol of SPS-scheduled PDSCH.\",\n \"In accordance with one embodiment of the present invention, the problems encountered when two or more EPDCCHs are configured in one subframe will hereinafter be described.\",\n \"As can be seen from the above description, EPDCCH may indicate a PDCCH applied to a legacy PDSCH region so as to increase capacity of a control signal, and it may be possible to obtain a beamforming gain using a UE-specific reference signal (RS).\",\n \"In the case of using EPDCCH, it may be assumed that a start symbol position of PDSCH is identical to the start symbol position of EPDCCH, and the start symbol position of EPDCCH may be transmitted through higher layer signaling such as RRC.\",\n \"However, the start symbol position of PDSCH may be independent of EPDCCH, may be determined according to PCFICH information (e.g., control formation indicator: CFI), or may be set to a predetermined value as necessary.\",\n \"The eNB may configure EPDCCH or may reconfigure the start symbol position of EPDCCH, and the EPDCCH configuration parameter including the start symbol position of EPDCCH may be transmitted to the UE through higher layer signaling such as RRC.\",\n \"After completion of SPS configuration through PDCCH, the UE may receive the EPDCCH configuration parameter.\",\n \"Alternatively, after reception of the EPDCCH configuration parameter, the UE may perform SPS configuration through PDCCH.\",\n \"As described above, SPS configuration and EPDCCH configuration parameter reception may be achieved simultaneously.\",\n \"In this case, if the SPS-configured subframe corresponds to a subframe needed for EPDCCH monitoring, there is a need to decide the periodic resource region (i.e., the start symbol position of SPS-scheduled PDSCH) scheduled through SPS configuration in the corresponding subframe.\",\n \"The start symbol position of the SPS-scheduled PDSCH may be determined from a PCFICH-indicated value (or a value derived from this indication value), because the PCFICH-indicated value may be different from the start symbol position (or from the position derived from this position) of EPDCCH contained in the EPDCCH configuration parameter received through RRC signaling.\",\n \"Therefore, if the UE receives the EPDCCH configuration parameter upon completion of SPS configuration, or if the UE performs SPS configuration after reception of the EPDCCH configuration parameter, it may be assumed that the start symbol position (or the position derived from this start symbol position) of EPDCCH contained in the above EPDCCH configuration parameter, prior to the PDSCH start symbol position decided by PCFICH, is the start symbol position of the SPS-scheduled PDSCH.\",\n \"In this case, it is assumed that the start symbol position of the SPS-scheduled PDSCH is identical to the start symbol position of EPDCCH, or is derived from the start symbol position of EPDCCH.\",\n \"Unless the above-mentioned assumption is applied, the eNB may separately perform RRC signaling of the start symbol position of the SPS-scheduled PDSCH, and the UE having received the corresponding information may have priority over PCFICH information.\",\n \"However, under the condition that the UE may receive the EPDCCH configuration parameter including the PDSCH start symbol position after completion of SPS configuration, or under the condition that SPS configuration is achieved after reception of the EPDCCH configuration parameter including the PDSCH start symbol position, if the SPS-scheduled subframe does not correspond to a subframe needed for EPDCCH monitoring, the start symbol position of the SPS-scheduled PDSCH may be based on PCFICH.\",\n \"The reason why the above-mentioned assumption is achieved is that EPDCCH monitoring can be configured only in some subframes.\",\n \"FIG.\",\n \"10 is a conceptual diagram illustrating a method for deciding the start symbol position of the SPS-scheduled PDSCH (hereinafter referred to as SPS-PDSCH) according to the above-mentioned embodiment.\",\n \"In FIG.\",\n \"10, the SPS-configured UE may receive the EPDCCH configuration parameter including the EPDCCH start symbol position through RRC signaling, and the corresponding position (symbol n1) is different from the PCFICH-indicated value (symbol n0).\",\n \"The start symbol position of SPS-PDSCH is based on RRC signaled information, simultaneously while having priority over the PCFICH-indicated information, so that “symbol n1” may be decided.\",\n \"A method for deciding the start symbol position of SPS-PDSCH is a common promise between the eNB and the UE.\",\n \"In a specific situation having a controversial issue, i.e., in a subframe in which SPS is configured and the UE has to monitor EPDCCH, the eNB must schedule or transmit the SPS-PDSCH from the beginning of the start symbol of EPDCCH, and the UE must decode the SPS-PDSCH from the beginning of the start symbol position of EPDCCH.\",\n \"In the meantime, the eNB can transmit two or more EPDCCH configuration parameters to the UE.\",\n \"In this case, each EPDCCH configuration parameter may include the start symbol position of each EPDCCH, and may be transmitted to the UE through higher layer signaling such as RRC signaling.\",\n \"If the start symbol positions of EPDCCH contained in at least two EPDCCH configuration parameters are identical to each other, the UE may determine the start symbol position of the RRC-signaled EPDCCCH to be the start symbol position of SPS-PDSCH.\",\n \"However, the start symbol positions of individual EPDCCHs contained in at least two EPDCCH configuration parameters may be different from each other.\",\n \"In this case, there occurs an unexpected problem in which the start symbol position of SPS-PDSCH needs to be determined.\",\n \"Therefore, the UE may assume that a higher one from among the respective EPDCCH start symbol positions (i.e., a higher OFDM symbol index from among the individual EPDCH start symbol positions) is the start symbol position of SPS-PDSCH.\",\n \"Specifically, if individual EPDCCHs are transmitted from different TPS as in dynamic point scheduling (DPS), and if each TP will be configured not to use several initial OFDM symbols in consideration of an interference environment, the start symbol position of SPS-PDSCH can be conservatively configured, so that the influence of inter-cell interference can be minimized.\",\n \"FIG.\",\n \"11 is a conceptual diagram illustrating a method for deciding the start symbol position of SPS-PDSCH when the SPS-configured UE receives at least two EPDCCH-related parameters.\",\n \"If the start symbol position of EPDCCH #1 is Symbol n1 and the start symbol position of EPDCCH #2 is Symbol n2, max(n1, n2) may indicate the start symbol position of SPS-PDSCH.\",\n \"In FIG.\",\n \"2, the situation of n1≥n2 is assumed so that the start symbol position of SPS-PDSCH may be set to n1.When at least two different EPDCCH configuration parameters (i.e., at least two EPDCCH start symbol positions) are signaled to the UE, a smaller one from among the individual EPDCCH start symbol positions may be set to the start symbol position of SPS-PDSCH according to another method for deciding the start symbol position of SPS-PDSCH.\",\n \"In still another method, in a specific situation having a controversial issue, a predetermined position may be set to the SPS-PDSCH start symbol position, or the SPS-PDSCH start symbol position may be separately signaled to the UE through separate RRC signaling or the like.\",\n \"In another method, a representative EPDCCH from among two or more EPDCCHs may be configured, and the start symbol position of the representative EPDCCH may be set to the SPS-PDSCH start symbol position.\",\n \"In accordance with the method for deciding the representative EPDCCH, a first signaling one from among EPDCCHs may be set to a representative one.\",\n \"In accordance with another scheme, a method for deciding the start symbol position of SPS-PDSCH in a subframe for detecting EPDCCH (i.e., in a subframe in which the UE has to monitor an EPDCCH) may be determined according to categories of a control channel needed for SPS-PDSCH scheduling.\",\n \"For example, assuming that the corresponding SPS is scheduled using EPDCCH, the EPDCCH set including the corresponding scheduling EPDCCH may be determined to be a representative EPDCCH set.\",\n \"In this case, whereas the EPDCCH start symbol position is determined to be the SPS-PDSCH start symbol position in the EPDCCH detection subframe, and if the corresponding SPS is scheduled by PDCCH, a higher one from among the start symbol positions of two EPDCCH sets may be selected, or a first one from among the EPDCCH set may be set to a representative one, so that the SPS-PDSCH start symbol position in the EPDCCH detection subframe may be determined.\",\n \"In the meantime, the method for deciding the start symbol position may be restrictively applied only when there is no explicit indicator for the SPS-PDSCH start symbol position.\",\n \"A more general embodiment of the above-mentioned embodiment will hereinafter be described.\",\n \"If two or more EPDCCHs are configured in UE, the start symbol positions of individual EPDCCHs may be different from each other as previously stated above.\",\n \"Meanwhile, individual EPDCCHs may be transmitted from different TPs.\",\n \"In this case, individual EPDCCHs (or PDSCHs scheduled by the corresponding EPDCCH) may have different PDSCH start symbol positions, different rate matching patterns (or PDSCH RE mapping patterns) related to a specific RS (e.g., CRS or CSI-RS), different antenna port configurations (e.g., DM-RS antenna port configurations used in EPDCCH/PDSCH decoding), different seeds of the pseudo random sequence used to generate the RS (e.g., DM-RS) sequence, and/or different scrambling IDs.\",\n \"Therefore, in case of the SPS-configured UE, the start symbol position of SPS-PDSCH and the above-mentioned parameters applied to SPS-PDSCH should be determined.\",\n \"The UE may receive information regarding two or more applicable parameter sets (i.e., several candidate parameter sets) through higher layer signaling such as RRC signaling.\",\n \"A) UE may assume that the CRS pattern of the serving cell is always applied to SPS-PDSCH, and DM-RS used for SPS-PDSCH (or EPDCCH) decoding is QCL-processed with the CRS of the serving cell.\",\n \"B) A set of actually applied parameters from among parameter sets applicable to SPS-PDSCH may be signaled to the UE through higher layer signaling such as RRC signaling.\",\n \"The UE having received the above set may assume that the RRC-signaled parameter sets are applied to SPS-PDSCH.\",\n \"Specifically, the corresponding signaling may be transmitted while simultaneously performing SPS scheduling (SPS configuration).\",\n \"C) Parameters applied to SPS-PDSCH may always be based on the serving cell as described in the above section (A), and may also be based on a control channel scheduling the corresponding SPS.\",\n \"In other words, assuming that SPS is scheduled through a specific control channel at a specific time, parameters to be applied to SPS-PDSCH may be based on parameters having been applied to transmission of the above specific control channel, prior to execution of SPS configuration due to transmission of still another control channel.\",\n \"For example, assuming SPS scheduling is achieved through PDCCH, the scheduling result may be based on parameters of PDCCH (i.e., parameters of the serving cell).\",\n \"When SPS scheduling is achieved through EPDCCH, the scheduling result may be based on parameters used for transmission of the corresponding EPDCCH.\",\n \"D) Parameters applied to SPS-PDSCH may be designated through a control channel having scheduled the corresponding SPS.\",\n \"In other words, assuming that SPS is scheduled through a specific control channel at a specific time, parameters to be applied to SPS-PDSCH may be based on parameters indicated through the above specific control channel, before SPS-PDSCH is scheduled after transmission of another control channel.\",\n \"Differently from the above method (C), parameters used for the above specific control channel may be different from parameters indicated by an indicator transmitted over the above specific control channel.\",\n \"For example, assuming that execution of rate matching is indicated according to the CRS pattern of an adjacent cell through a PDCCH transmitted using the CRS parameter of the serving cell, the next SPS-PDSCH needs to be rate-matched according to the CRS pattern of the indicated adjacent cell, as can be seen from the above method (D).\",\n \"E) If two or more EPDCCHs are configured, it may be assumed that parameters applied to SPS-PDSCH are based on a specific EPDCCH from among the corresponding EPDCCHs.\",\n \"For example, if the UE receives two or more EPDCCH configuration parameters through RRC signaling, parameters applied to SPS-PDSCH may always be based on configuration parameters of a first EPDCCH.\",\n \"F) Parameters applied to SPS-PDSCH may be predetermined as necessary.\",\n \"In this case, the corresponding parameters may be different from those of EPDCCH.\",\n \"Specifically, this scheme can be used, irrespective of whether a channel having scheduled the corresponding SPS-PDSCH is a PDCCH or an EPDCCH.\",\n \"G) Parameters applied to SPS-PDSCH may be based on parameters of a dynamic PDSCH.\",\n \"The dynamic PDSCH may be a PDSCH capable of being transmitted using at least two different parameter sets, and information as to which parameter set has been applied to a specific PDSCH may be contained in a DCI detected from PDCCH or EPDCCH, so that this information may be transmitted to the UE through DCI.\",\n \"Therefore, the UE may recognize parameters applied to the dynamic PDSCH by interpreting DCI, and a specific rule may be assumed between the UE and the eNB.\",\n \"This specific rule indicates that parameters applied to SPS-PDSCH are identical to those of the dynamic PDSCH.\",\n \"Information related to the above operation may be implicitly recognized according to a predetermined rule, or the eNB may inform the UE of this information through predefined signaling (e.g., higher layer signaling or physical layer signaling).\",\n \"In addition, different schemes may be applied according to the scheduling message categories (e.g., DCI format) for SPS scheduling.\",\n \"Specifically, according to the presence or absence of information as to whether the indicator indicating parameters applied to PDSCH is present in the scheduling message, different operation schemes may be used.\",\n \"For example, if SPS scheduling is performed using the scheduling message having the above indicator, the above method (D) may be used.\",\n \"On the contrary, if the scheduling message having no indicator is used, the above methods A), B) and C) may be used.\",\n \"In addition, some of various parameters applied to PDSCH may be determined according to different schemes.\",\n \"For example, the SPS-PDSCH start symbol may use a control channel for scheduling the SPS according to the above method (C), CRS to be assumed in the rate matching may use the CRS of the serving cell according to the above method (A), and CSI-RS to be assumed in the rate matching may use a series of parameters pre-signaled by RRC according to the above method (B).\",\n \"Specifically, the above-mentioned operations may be efficiently used when the explicit indicator is not present in the parameters related to the SPS scheduling message.\",\n \"In more detail, the method for deciding parameters applied to SPS-PDSCH based on the method (D) is used in a subframe corresponding to DCI format 2D.\",\n \"In a subframe corresponding to DCI format 0 or 1A, a method for deciding parameters applied to SPS-PDSCH based on the method (B) is used.\",\n \"In the meantime, when deciding the start symbol position of SPS-PDSCH, the SPS-PDSCH start symbol position must be limited to Symbol #2 in a subframe in which the PDSCH start symbol index is set to a maximum of 2 in the same manner as in the MBSFN subframe.\",\n \"For example, assuming that a higher one of the start symbol positions of EPDCCH configured through RRC signaling is set to the start symbol position of SPS-PDSCH, if the higher one is higher than 2, the corresponding value is used.\",\n \"If the higher one is not higher than 2 (i.e., if the higher one is less than 2), it is assumed that the symbol is Symbol #2.The above-mentioned assumption can be applied not only to the case in which a higher one from among the start symbol positions of EPDCCH is set to the SPS-PDSCH start symbol position, but also to the above-mentioned methods, i.e., a PCFICH-based method, a method based on a smaller one from among the EPDCCH start symbol positions, or a method based on the start symbol position of a representative EPDCCH.\",\n \"Some of the above-mentioned methods will be shown in the following table, and as such a detailed description thereof will be given below.\",\n \"Before or after SPS configuration is completed, if the UE does not receive the EPDCCH configuration parameter including the EPDCCH start symbol position information (i.e., if CCH configuration is not present), it is assumed that a value indicated by PCFICH is set to the SPS-PDSCH start symbol position (index), as can be seen from ‘1’ in the following Table.\",\n \"If SPS configuration is achieved before or after reception of the EPDCCH start symbol position information, it is assumed that the EPDCCH start symbol position is set to the start symbol position (as denoted by “2” in the following table).\",\n \"If at least two EPDCCH start symbol positions are different from each other, a higher one from among the at least two EPDCCH start symbol positions may be set to the SPS-PDSCH start symbol position (as denoted by “3” in the following table).\",\n \"In the case of the MBSFN subframe, if at least two EPDCCH start symbol positions are received, a higher one from among the at least two EPDCCH start symbols is used.\",\n \"If the corresponding value is less than 2, it is assumed that the SPS-PDSCH start symbol position is set to Symbol #2 (4).\",\n \"TABLE 5 1 2 3 4 PDSCH Starting symbol N0 N0 N0 N0 position indicated by PCFICH Starting symbol position of — N1 N1 N1 EPDCCH #1 Starting symbol position of — — N2 N2 EPDCCH #2 Starting symbol position of N0 N1 If N1 >= N2, N1 If N1 >= N2 SPS-scheduled PDSCH If N1 < N2, N2 & N1 > 2, N1 If N1 < N2 & N2 > 2, N2 Otherwise, 2 The above-mentioned operations may be selectively applied according to subframe configuration.\",\n \"For example, in the case of the MBSFN subframe, since SPS-PDSCH is transmitted on the basis of DM-RS, the SPS-PDSCH start symbol position or information (CRS, CSI-RS, etc.)\",\n \"to be assumed in the rate matching can be obtained using one of the methods based on the DMRS-based EPDCCH configuration parameter.\",\n \"On the contrary, in the case of the non-MBSFN subframe, SPS-PDSCH may be transmitted on the basis of CRS.\",\n \"In this case, the SPS-PDSCH start symbol position may be derived from PCFICH of the serving cell, or the rate matching is not assumed for CRS of a neighbor cell.\",\n \"Even in the case of the non-MBSFN subframe, if SPS-PDSCH is transmitted on the basis of DM-RS, one of the above-mentioned methods may also be used on the basis of the DMRS-based EPDCCH configuration parameters.\",\n \"The above-mentioned embodiments may also assume that the EPDCCH start symbol does not overlap with the PDCCH transmission region.\",\n \"If the above assumption is not present, the start symbol positions of EPDCCHs and the PDSCH start symbol position derived by the indicator transmitted by PCFICH may be simultaneously considered in the process for deciding the start symbol position of SPS-PDSCH.\",\n \"For example, according to case “3” shown in Table 5, if the PDSCH start symbol index derived by PCFICH is higher than the start symbol index of EPDCCHs, the value derived by PCFICH may be set to the SPS-PDSCH start symbol position.\",\n \"In the meantime, if CA (Carrier Aggregation) is configured, the UE may simultaneously monitor a PDCCH and an EPDCCH at a specific subframe.\",\n \"For example, in the case of the UE in which cross carrier scheduling (CCS) is configured, PDSCH of PCell of the corresponding UE is scheduled by EPDCCH transmitted to PCell.\",\n \"PDSCH of SCell may be CCS-processed by PDCCH transmitted to PCell.\",\n \"In this case, the following method may be used to determine the PDSCH start symbol position of PCell.\",\n \"a) Method for assuming the start symbol position of EPDCCH In accordance with a method for assuming the corresponding subframe to be a subframe which has to monitor the EPDCCH, since PDSCH of PCell is scheduled by EPDCCH, this means that the scheduling result may follow the start symbol position of a scheduling channel.\",\n \"b) Method for assuming the start symbol position derived by PCFICH In accordance with the method (b), the corresponding subframe is considered to be a subframe which monitors UE-specific Search Space (USS) at PDCCH.\",\n \"Specifically, if the EPDCCH start symbol position is RRC-signaled and configured and does not overlap with the PDCCH region, the start symbol position derived by PCFICH may be identical to or less than the start symbol index of EPDCCH, resources can be more efficiently used, resulting in higher efficiency in terms of resource utilization.\",\n \"In the case in which there is no explicit indicator regarding the PDSCH start symbol position of PCell in PDSCH scheduling of PCell, the above-mentioned situation may be efficiently used.\",\n \"Besides the above-mentioned methods, if the above indicator is present, the start symbol position indicated by the above indicator may be determined to be the PDSCH start symbol position of PCell.\",\n \"Specifically, even in the case of PDSCH of SCell, PDSCH scheduling of the corresponding SCell includes the explicit indicator, a value indicated by the above indicator may be determined to be the PDSCH start symbol position of SCell, while simultaneously having priority over a predetermined start symbol position being semi-persistently decided by RRC signaling.\",\n \"In this case, it is assumed that EPDCCH configuration parameters having the EPDCCH start symbol position may be configured through higher layer signaling, or may be set to predetermined values.\",\n \"If higher layer signaling is not present, the EPDCCH start symbol position may be derived from PCFICH.\",\n \"In the meantime, the CCS-configured UE may be SPS activated through EPDCCH of PCell, so that it may receive the SPS-PDSCH scheduling result of PCell.\",\n \"In a case in which the above-mentioned CC is not configured, the method for deciding the SPS-PDSCH start symbol position and various SPS-PDSCH parameters may be applied without change.\",\n \"However, in the case of the SPS-PDSCH start symbol position of PCell, the UE may monitor a PDCCH even in the subframe needed for EPDCCH monitoring, due to the presence of CCS regarding the SCell.\",\n \"As a result, another scheme for satisfying the start symbol position derived from PCFICH instead of the EPDCCH start symbol position may also be used.\",\n \"In the meantime, if PDSCH of SCell is CCS-processed by PDCCH or EPDCCH applied to PCell, the PDSCH start symbol of SCell may be determined as follows.\",\n \"a′) The above-mentioned PDSCH start symbol of SCell may satisfy a PDSCH start symbol position of SCell signaled by RRC.\",\n \"b′) If the explicit indicator for the PDSCH start symbol position of SCell is contained in the PDSCH scheduling message of SCell transmitted in PDCCH/EPDCCH, the UE may be based on the start symbol position indicated by the above indicator.\",\n \"This method (b′) is irrelevant to information as to whether the above scheduling message is transmitted over PDCCH or EPDCCH.\",\n \"c′) If the explicit indicator regarding the PDSCH start symbol of SCell is not contained in the PDSCH scheduling of SCell transmitted in PDCCH/EPDCCH, the PDSCH start symbol position of SCell and/or a parameter to be applied to PDSCH of SCell may be determined using any one of the above-mentioned methods (A) to (G).\",\n \"However, since the PDSCH start symbol position of the RRC-configured SCell is present, the start symbol position indicated by the corresponding RRC may be used as necessary.\",\n \"FIG.\",\n \"12 is a block diagram of a transmitting device 10 and a receiving device 20 configured to implement exemplary embodiments of the present invention.\",\n \"Referring to FIG.\",\n \"12, the transmitting device 10 and the receiving device 20 respectively include radio frequency (RF) units 13 and 23 for transmitting and receiving radio signals carrying information, data, signals, and/or messages, memories 12 and 22 for storing information related to communication in a wireless communication system, and processors 11 and 21 connected operationally to the RF units 13 and 23 and the memories 12 and 22 and configured to control the memories 12 and 22 and/or the RF units 13 and 23 so as to perform at least one of the above-described embodiments of the present invention.\",\n \"The memories 12 and 22 may store programs for processing and control of the processors 11 and 21 and may temporarily storing input/output information.\",\n \"The memories 12 and 22 may be used as buffers.\",\n \"The processors 11 and 21 control the overall operation of various modules in the transmitting device 10 or the receiving device 20.The processors 11 and 21 may perform various control functions to implement the present invention.\",\n \"The processors 11 and 21 may be controllers, microcontrollers, microprocessors, or microcomputers.\",\n \"The processors 11 and 21 may be implemented by hardware, firmware, software, or a combination thereof.\",\n \"In a hardware configuration, Application Specific Integrated Circuits (ASICs), Digital Signal Processors (DSPs), Digital Signal Processing Devices (DSPDs), Programmable Logic Devices (PLDs), or Field Programmable Gate Arrays (FPGAs) may be included in the processors 11 and 21.If the present invention is implemented using firmware or software, firmware or software may be configured to include modules, procedures, functions, etc.\",\n \"performing the functions or operations of the present invention.\",\n \"Firmware or software configured to perform the present invention may be included in the processors 11 and 21 or stored in the memories 12 and 22 so as to be driven by the processors 11 and 21.The processor 11 of the transmitting device 10 is scheduled from the processor 11 or a scheduler connected to the processor 11 and codes and modulates signals and/or data to be transmitted to the outside.\",\n \"The coded and modulated signals and/or data are transmitted to the RF unit 13.For example, the processor 11 converts a data stream to be transmitted into K layers through demultiplexing, channel coding, scrambling and modulation.\",\n \"The coded data stream is also referred to as a codeword and is equivalent to a transport block which is a data block provided by a MAC layer.\",\n \"One transport block (TB) is coded into one codeword and each codeword is transmitted to the receiving device in the form of one or more layers.\",\n \"For frequency up-conversion, the RF unit 13 may include an oscillator.\",\n \"The RF unit 13 may include Nt (where Nt is a positive integer) transmit antennas.\",\n \"A signal processing process of the receiving device 20 is the reverse of the signal processing process of the transmitting device 10.Under the control of the processor 21, the RF unit 23 of the receiving device 10 receives RF signals transmitted by the transmitting device 10.The RF unit 23 may include Nr receive antennas and frequency down-converts each signal received through receive antennas into a baseband signal.\",\n \"The RF unit 23 may include an oscillator for frequency down-conversion.\",\n \"The processor 21 decodes and demodulates the radio signals received through the receive antennas and restores data that the transmitting device 10 wishes to transmit.\",\n \"The RF units 13 and 23 include one or more antennas.\",\n \"An antenna performs a function of transmitting signals processed by the RF units 13 and 23 to the exterior or receiving radio signals from the exterior to transfer the radio signals to the RF units 13 and 23.The antenna may also be called an antenna port.\",\n \"Each antenna may correspond to one physical antenna or may be configured by a combination of more than one physical antenna element.\",\n \"A signal transmitted through each antenna cannot be decomposed by the receiving device 20.A reference signal (RS) transmitted through an antenna defines the corresponding antenna viewed from the receiving device 20 and enables the receiving device 20 to perform channel estimation for the antenna, irrespective of whether a channel is a single RF channel from one physical antenna or a composite channel from a plurality of physical antenna elements including the antenna.\",\n \"That is, an antenna is defined such that a channel transmitting a symbol on the antenna may be derived from the channel transmitting another symbol on the same antenna.\",\n \"An RF unit supporting a MIMO function of transmitting and receiving data using a plurality of antennas may be connected to two or more antennas.\",\n \"In embodiments of the present invention, a UE serves as the transmission device 10 on uplink and as the receiving device 20 on downlink.\",\n \"In embodiments of the present invention, an eNB serves as the receiving device 20 on uplink and as the transmission device 10 on downlink.\",\n \"The transmitting device and/or the receiving device may be configured as a combination of one or more embodiments of the present invention.\",\n \"The detailed description of the exemplary embodiments of the present invention has been given to enable those skilled in the art to implement and practice the invention.\",\n \"Although the invention has been described with reference to the exemplary embodiments, those skilled in the art will appreciate that various modifications and variations can be made in the present invention without departing from scope of the invention described in the appended claims.\",\n \"Accordingly, the invention should not be limited to the specific embodiments described herein, but should be accorded the broadest scope consistent with the principles and novel features disclosed herein.\",\n \"INDUSTRIAL APPLICABILITY The present invention may be used for a wireless communication apparatus such as a terminal, a relay and a base station (BS).\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874736"}}},{"rowIdx":4494678,"cells":{"text":{"kind":"list like","value":[["DATA ENCODING AND DECODING","A video coding or decoding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, comprises: storing one or more images preceding a current image; interpolating a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; detecting inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and generating a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolating step comprises: applying a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and subsampling the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples."],["1.","(canceled) 2.A video decoding method for decoding a video signal, the method being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the method comprising: generating prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit using only alternate fractional-position results as interpolated samples in the horizontal and vertical directions.","3.The video decoding method according to claim 2, in which the generating step comprises: accessing samples of the interpolated prediction unit pointed to by a motion vector to generate a motion compensated prediction of a prediction unit of the current image with respect to an area represented by the samples of the interpolated prediction unit.","4.The video decoding method according to claim 3, in which the motion vector is a sub-pixel accuracy motion vector.","5.The video decoding method according to claim 4, in which the step of applying the 4-tap ×8 chrominance filter comprises applying one of a set of 4-tap filters horizontally and one of the set of 4-tap filters vertically to a chrominance prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.","6.The video decoding method according to claim 5, in which: the 4-tap filters are indexed in order of fractional interpolation position; and for 4:4:4 format video, the deriving comprises applying a filter selected from a subset of alternate filters in the indexing order.","7.The video decoding method according to claim 5, in which the set of 4-tap filters comprises seven 4-tap filters.","8.The video decoding method according to claim 2, in which the alternate fractional-position results are even fractional-position results.","9.A video encoding method for encoding a video signal, the method being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the method comprising: generating motion vectors for prediction of prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically using only alternate fractional-position results as interpolated samples in the horizontal and vertical directions.","10.A non-transitory computer readable medium including computer program instructions, which when executed by a computer causes the computer to perform the method of claim 2.11.A non-transitory computer readable medium including computer program instructions, which when executed by a computer causes the computer to perform the method of claim 9.12.A video decoding apparatus for decoding a video signal, the apparatus being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the apparatus comprising: processing circuitry configured to generate prediction units of a current image from one or more stored images preceding the current image by: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically using only alternate fractional-position results as interpolated samples in the vertical direction.","13.A video encoding apparatus for encoding a video signal, the apparatus being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the apparatus comprising: processing circuitry configured to generate motion vectors for prediction of prediction units of a current image from one or more stored images preceding the current image by: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically using only alternate fractional-position results as interpolated samples in the horizontal and vertical directions.","14.A non-transitory computer readable medium including computer program instructions, which when executed by a computer causes the computer to perform the method of claim 3.15.The video decoding apparatus according to claim 12, wherein the processing circuitry generates the prediction units by accessing samples of the interpolated prediction unit pointed to by a motion vector to generate a motion compensated prediction of a prediction unit of the current image with respect to an area represented by the samples of the interpolated prediction unit.","16.The video decoding apparatus according to claim 15, wherein the motion vector is a sub-pixel accuracy motion vector.","17.The video decoding apparatus according to claim 16, wherein the processing circuitry applies the 4-tap ×8 chrominance filter comprises by applying one of a set of 4-tap filters horizontally and one of the set of 4-tap filters vertically to a chrominance prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.","18.The video decoding apparatus according to claim 16, wherein the 4-tap filters are indexed in order of fractional interpolation position, and for 4:4:4 format video, the processing circuitry devices the samples by applying a filter selected from a subset of alternate filters in the indexing order.","19.The video decoding apparatus according to claim 12, wherein the alternate fractional-position results are even fractional-position results.","20.An image capture device comprising an image sensor and the video encoding apparatus according to claim 13.21.An audio/video data receiver comprising the video decoding apparatus according to claim 12.22.The audio/video data receiver according to claim 21, further comprising a display."],["<SOH> BACKGROUND <EOH>"],["<SOH> SUMMARY <EOH>The present disclosure addresses or mitigates problems arising from this processing.","Respective aspects and features of the present disclosure are defined in the appended claims.","It is to be understood that both the foregoing general description and the following detailed description are exemplary, but are not restrictive, of the present technology."],["CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation application of U.S. application Ser.","No.","15/614,226, filed Jun.","5, 2017, which is a continuation application of U.S. application Ser.","No.","14/523,675, filed Oct. 24, 2014, which is a bypass continuation application of PCT application PCT/GB2013/051076 designating the United States of America filed 26 Apr.","2013 which claims the benefit of the earlier filing date of GB1211072.2, GB 1211073.0 and GB 1207459.7 filed in the United Kingdom Intellectual Property Office on 22 Jun.","2012, 22 Jun.","2012 and 26 Apr.","2012 respectively, the entire contents of which applications are incorporated herein by reference.","BACKGROUND Field This disclosure relates to data encoding and decoding.","Description of Related Art The “background” description provided herein is for the purpose of generally presenting the context of the disclosure.","Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, is neither expressly or impliedly admitted as prior art against the present disclosure.","There are several video data encoding and decoding systems which involve transforming video data into a frequency domain representation, quantising the frequency domain coefficients and then applying some form of entropy encoding to the quantised coefficients.","This can achieve compression of the video data.","A corresponding decoding or decompression technique is applied to recover a reconstructed version of the original video data.","Current video codecs (coder-decoders) such as those used in H.264/MPEG-4 Advanced Video Coding (AVC) achieve data compression primarily by only encoding the differences between successive video frames.","These codecs use a regular array of so-called macroblocks, each of which is used as a region of comparison with a corresponding macroblock in a previous video frame, and the image region within the macroblock is then encoded according to the degree of motion found between the corresponding current and previous macroblocks in the video sequence, or between neighbouring macroblocks within a single frame of the video sequence.","High Efficiency Video Coding (HEVC), also known as H.265 or MPEG-H Part 2, is a proposed successor to H.264/MPEG-4 AVC.","It is intended for HEVC to improve video quality and double the data compression ratio compared to H.264, and for it to be scalable from 128×96 to 7680×4320 pixels resolution, roughly equivalent to bit rates ranging from 128 kbit/s to 800 Mbit/s.","In HEVC a so-called 4:2:0 block structure is proposed for consumer equipment, in which the amount of data used in each chroma channel is one quarter that in the luma channel.","This is because subjectively people are more sensitive to brightness variations than to colour variations, and so it is possible to use greater compression and/or less information in the colour channels without a subjective loss of quality.","HEVC replaces the macroblocks found in existing H.264 and MPEG standards with a more flexible scheme based upon coding units (CUs), which are variable size structures.","Consequently, when encoding the image data in video frames, the CU sizes can be selected responsive to the apparent image complexity or detected motion levels, instead of using uniformly distributed macroblocks.","Consequently far greater compression can be achieved in regions with little motion between frames and with little variation within a frame, whilst better image quality can be preserved in areas of high inter-frame motion or image complexity.","Each CU contains one or more variable-block-sized prediction units (PUs) of either intra-picture or inter-picture prediction type, and one or more transform units (TUs) which contain coefficients for spatial block transform and quantisation.","Moreover, PU and TU blocks are provided for each of three channels; luma (Y), being a luminance or brightness channel, and which may be thought of as a greyscale channel, and two colour difference or chrominance (chroma) channels; Cb and Cr.","These channels provide the colour for the greyscale image of the luma channel.","The terms Y, luminance and luma are used interchangeably in this description, and similarly the terms Cb and Cr, chrominance and chroma, are used interchangeably as appropriate, noting that chrominance or chroma can be used generically for “one or both of Cr and Cb”, whereas when a specific chrominance channel is being discussed it will be identified by the term Cb or Cr.","Generally PUs are considered to be channel independent, except that a PU has a luma part and a chroma part.","Generally, this means that the samples forming part of the PU for each channel represent the same region of the image, so that there is a fixed relationship between the PUs between the three channels.","For example, for 4:2:0 video, an 8×8 PU for Luma always has a corresponding 4×4 PU for chroma, with the chroma parts of the PU representing the same area as the luma part, but containing a smaller number of pixels because of the subsampled nature of the 4:2:0 chroma data compared to the luma data in 4:2:0 video.","(In 4:4:4 the sampling rates are the same and so the same PU structures can be used for luma and chroma samples).","The two chroma channels share intra-prediction information; and the three channels share inter-prediction information.","Similarly, the TU structure also has a fixed relationship between the three channels.","However, for professional broadcast and digital cinema equipment, it is desirable to have less compression (or more information) in the chroma channels, and this may affect how current and proposed HEVC processing operates.","SUMMARY The present disclosure addresses or mitigates problems arising from this processing.","Respective aspects and features of the present disclosure are defined in the appended claims.","It is to be understood that both the foregoing general description and the following detailed description are exemplary, but are not restrictive, of the present technology.","BRIEF DESCRIPTION OF THE DRAWINGS A more complete appreciation of the disclosure and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein: FIG.","1 schematically illustrates an audio/video (A/V) data transmission and reception system using video data compression and decompression; FIG.","2 schematically illustrates a video display system using video data decompression; FIG.","3 schematically illustrates an audio/video storage system using video data compression and decompression; FIG.","4 schematically illustrates a video camera using video data compression; FIG.","5 provides a schematic overview of a video data compression and decompression apparatus; FIG.","6 schematically illustrates the generation of predicted images; FIG.","7 schematically illustrates a largest coding unit (LCU); FIG.","8 schematically illustrates a set of four coding units (CU); FIGS.","9 and 10 schematically illustrate the coding units of FIG.","8 sub-divided into smaller coding units; FIG.","11 schematically illustrates an array of prediction units (PU); FIG.","12 schematically illustrates an array of transform units (TU); FIG.","13 schematically illustrates a partially-encoded image; FIG.","14 schematically illustrates a set of possible intra-prediction directions; FIG.","15 schematically illustrates a set of prediction modes; FIG.","16 schematically illustrates an up-right diagonal scan; FIG.","17 schematically illustrates a video compression apparatus; FIGS.","18A and 18B schematically illustrate possible block sizes; FIG.","19 schematically illustrates the use of co-located information from chroma and luma blocks; FIG.","20 schematically illustrates a situation in which co-located information from one chroma channel is used in respect of another chroma channel; FIG.","21 schematically illustrates pixels used for an LM-CHROMA mode; FIG.","22 schematically illustrates a set of luma prediction directions; FIG.","23 schematically illustrates the directions of FIG.","22, as applied to a horizontally sparse chroma channel; FIG.","24 schematically illustrates the directions of FIG.","22 mapped to a rectangular chroma pixel array; FIGS.","25-28 schematically illustrate luma and chroma pixel interpolation; FIGS.","29A and 29B schematically illustrates quantisation parameter tables for 4:2:0 and 4:2:2 respectively; and FIGS.","30 and 31 schematically illustrate quantisation variation tables.","DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring now to the drawings, FIGS.","1-4 are provided to give schematic illustrations of apparatus or systems making use of the compression and/or decompression apparatus to be described below in connection with embodiments of the present technology.","All of the data compression and/or decompression apparatus to be described below may be implemented in hardware, in software running on a general-purpose data processing apparatus such as a general-purpose computer, as programmable hardware such as an application specific integrated circuit (ASIC) or field programmable gate array (FPGA) or as combinations of these.","In cases where the embodiments are implemented by software and/or firmware, it will be appreciated that such software and/or firmware, and non-transitory data storage media by which such software and/or firmware are stored or otherwise provided, are considered as embodiments of the present technology.","FIG.","1 schematically illustrates an audio/video data transmission and reception system using video data compression and decompression.","An input audio/video signal 10 is supplied to a video data compression apparatus 20 which compresses at least the video component of the audio/video signal 10 for transmission along a transmission route 30 such as a cable, an optical fibre, a wireless link or the like.","The compressed signal is processed by a decompression apparatus 40 to provide an output audio/video signal 50.For the return path, a compression apparatus 60 compresses an audio/video signal for transmission along the transmission route 30 to a decompression apparatus 70.The compression apparatus 20 and decompression apparatus 70 can therefore form one node of a transmission link.","The decompression apparatus 40 and decompression apparatus 60 can form another node of the transmission link.","Of course, in instances where the transmission link is uni-directional, only one of the nodes would require a compression apparatus and the other node would only require a decompression apparatus.","FIG.","2 schematically illustrates a video display system using video data decompression.","In particular, a compressed audio/video signal 100 is processed by a decompression apparatus 110 to provide a decompressed signal which can be displayed on a display 120.The decompression apparatus 110 could be implemented as an integral part of the display 120, for example being provided within the same casing as the display device.","Alternatively, the decompression apparatus 110 maybe provided as (for example) a so-called set top box (STB), noting that the expression “set-top” does not imply a requirement for the box to be sited in any particular orientation or position with respect to the display 120; it is simply a term used in the art to indicate a device which is connectable to a display as a peripheral device.","FIG.","3 schematically illustrates an audio/video storage system using video data compression and decompression.","An input audio/video signal 130 is supplied to a compression apparatus 140 which generates a compressed signal for storing by a store device 150 such as a magnetic disk device, an optical disk device, a magnetic tape device, a solid state storage device such as a semiconductor memory or other storage device.","For replay, compressed data is read from the store device 150 and passed to a decompression apparatus 160 for decompression to provide an output audio/video signal 170.It will be appreciated that the compressed or encoded signal, and a storage medium storing that signal, are considered as embodiments of the present technology.","FIG.","4 schematically illustrates a video camera using video data compression.","In FIG.","4, an image capture device 180, such as a charge coupled device (CCD) image sensor and associated control and read-out electronics, generates a video signal which is passed to a compression apparatus 190.A microphone (or plural microphones) 200 generates an audio signal to be passed to the compression apparatus 190.The compression apparatus 190 generates a compressed audio/video signal 210 to be stored and/or transmitted (shown generically as a schematic stage 220).","The techniques to be described below relate primarily to video data compression and decompression.","It will be appreciated that many existing techniques may be used for audio data compression in conjunction with the video data compression techniques which will be described, to generate a compressed audio/video signal.","Accordingly, a separate discussion of audio data compression will not be provided.","It will also be appreciated that the data rate associated with video data, in particular broadcast quality video data, is generally very much higher than the data rate associated with audio data (whether compressed or uncompressed).","It will therefore be appreciated that uncompressed audio data could accompany compressed video data to form a compressed audio/video signal.","It will further be appreciated that although the present examples (shown in FIGS.","1-4) relate to audio/video data, the techniques to be described below can find use in a system which simply deals with (that is to say, compresses, decompresses, stores, displays and/or transmits) video data.","That is to say, the embodiments can apply to video data compression without necessarily having any associated audio data handling at all.","FIG.","5 provides a schematic overview of a video data compression and decompression apparatus.","A controller 343 controls the overall operation of the apparatus and, in particular when referring to a compression mode, controls the trial encoding processes (to be described below) by acting as a selector to select various modes of operation such as CU, PU and TU block sizes and whether the video data is to be encoded losslessly or otherwise.","Successive images of an input video signal 300 are supplied to an adder 310 and to an image predictor 320.The image predictor 320 will be described below in more detail with reference to FIG.","6.The adder 310 in fact performs a subtraction (negative addition) operation, in that it receives the input video signal 300 on a “+” input and the output of the image predictor 320 on a “−” input, so that the predicted image is subtracted from the input image.","The result is to generate a so-called residual image signal 330 representing the difference between the actual and projected images.","One reason why a residual image signal is generated is as follows.","The data coding techniques to be described, that is to say the techniques which will be applied to the residual image signal, tend to work more efficiently when there is less “energy” in the image to be encoded.","Here, the term “efficiently” refers to the generation of a small amount of encoded data; for a particular image quality level, it is desirable (and considered “efficient”) to generate as little data as is practicably possible.","The reference to “energy” in the residual image relates to the amount of information contained in the residual image.","If the predicted image were to be identical to the real image, the difference between the two (that is to say, the residual image) would contain zero information (zero energy) and would be very easy to encode into a small amount of encoded data.","In general, if the prediction process can be made to work reasonably well, the expectation is that the residual image data will contain less information (less energy) than the input image and so will be easier to encode into a small amount of encoded data.","The remainder of the apparatus acting as an encoder (to encode the residual or difference image) will now be described.","The residual image data 330 is supplied to a transform unit 340 which generates a discrete cosine transform (DCT) representation of the residual image data.","The DCT technique itself is well known and will not be described in detail here.","There are however aspects of the techniques used in the present apparatus which will be described in more detail below, in particular relating to the selection of different blocks of data to which the DCT operation is applied.","These will be discussed with reference to FIGS.","7-12 below.","The output of the transform unit 340, which is to say, a set of DCT coefficients for each transformed block of image data, is supplied to a quantiser 350.Various quantisation techniques are known in the field of video data compression, ranging from a simple multiplication by a quantisation scaling factor through to the application of complicated lookup tables under the control of a quantisation parameter.","The general aim is twofold.","Firstly, the quantisation process reduces the number of possible values of the transformed data.","Secondly, the quantisation process can increase the likelihood that values of the transformed data are zero.","Both of these can make the entropy encoding process, to be described below, work more efficiently in generating small amounts of compressed video data.","A data scanning process is applied by a scan unit 360.The purpose of the scanning process is to reorder the quantised transformed data so as to gather as many as possible of the non-zero quantised transformed coefficients together, and of course therefore to gather as many as possible of the zero-valued coefficients together.","These features can allow so-called run-length coding or similar techniques to be applied efficiently.","So, the scanning process involves selecting coefficients from the quantised transformed data, and in particular from a block of coefficients corresponding to a block of image data which has been transformed and quantised, according to a “scanning order” so that (a) all of the coefficients are selected once as part of the scan, and (b) the scan tends to provide the desired reordering.","One example scanning order which can tend to give useful results is a so-called up-right diagonal scanning order.","The scanned coefficients are then passed to an entropy encoder (EE) 370.Again, various types of entropy encoding may be used.","Two examples are variants of the so-called CABAC (Context Adaptive Binary Arithmetic Coding) system and variants of the so-called CAVLC (Context Adaptive Variable-Length Coding) system.","In general terms, CABAC is considered to provide a better efficiency, and in some studies has been shown to provide a 10-20% reduction in the quantity of encoded output data for a comparable image quality compared to CAVLC.","However, CAVLC is considered to represent a much lower level of complexity (in terms of its implementation) than CABAC.","Note that the scanning process and the entropy encoding process are shown as separate processes, but in fact can be combined or treated together.","That is to say, the reading of data into the entropy encoder can take place in the scan order.","Corresponding considerations apply to the respective inverse processes to be described below.","Note that the current HEVC documents under consideration at the time of filing no longer include the possibility of a CAVLC coefficient encoder.","The output of the entropy encoder 370, along with additional data (mentioned above and/or discussed below), for example defining the manner in which the predictor 320 generated the predicted image, provides a compressed output video signal 380.However, a return path is also provided because the operation of the predictor 320 itself depends upon a decompressed version of the compressed output data.","The reason for this feature is as follows.","At the appropriate stage in the decompression process (to be described below) a decompressed version of the residual data is generated.","This decompressed residual data has to be added to a predicted image to generate an output image (because the original residual data was the difference between the input image and a predicted image).","In order that this process is comparable, as between the compression side and the decompression side, the predicted images generated by the predictor 320 should be the same during the compression process and during the decompression process.","Of course, at decompression, the apparatus does not have access to the original input images, but only to the decompressed images.","Therefore, at compression, the predictor 320 bases its prediction (at least, for inter-image encoding) on decompressed versions of the compressed images.","The entropy encoding process carried out by the entropy encoder 370 is considered to be “lossless”, which is to say that it can be reversed to arrive at exactly the same data which was first supplied to the entropy encoder 370.So, the return path can be implemented before the entropy encoding stage.","Indeed, the scanning process carried out by the scan unit 360 is also considered lossless, but in the present embodiment the return path 390 is from the output of the quantiser 350 to the input of a complimentary inverse quantiser 420.In general terms, an entropy decoder 410, the reverse scan unit 400, an inverse quantiser 420 and an inverse transform unit 430 provide the respective inverse functions of the entropy encoder 370, the scan unit 360, the quantiser 350 and the transform unit 340.For now, the discussion will continue through the compression process; the process to decompress an input compressed video signal will be discussed separately below.","In the compression process, the scanned coefficients are passed by the return path 390 from the quantiser 350 to the inverse quantiser 420 which carries out the inverse operation of the scan unit 360.An inverse quantisation and inverse transformation process are carried out by the units 420, 430 to generate a compressed-decompressed residual image signal 440.The image signal 440 is added, at an adder 450, to the output of the predictor 320 to generate a reconstructed output image 460.This forms one input to the image predictor 320, as will be described below.","Turning now to the process applied to decompress a received compressed video signal 470, the signal is supplied to the entropy decoder 410 and from there to the chain of the reverse scan unit 400, the inverse quantiser 420 and the inverse transform unit 430 before being added to the output of the image predictor 320 by the adder 450.So, at the decoder side, the decoder reconstructs a version of the residual image and then applies this (by the adder 450) to the predicted version of the image (on a block by block basis) so as to decode each block.","In straightforward terms, the output 460 of the adder 450 forms the output decompressed video signal 480.In practice, further filtering may be applied before the signal is output.","So, the apparatus of FIGS.","5 and 6 can act as a compression apparatus or a decompression apparatus.","The functions of the two types of apparatus overlap very heavily.","The scan unit 360 and entropy encoder 370 are not used in a decompression mode, and the operation of the predictor 320 (which will be described in detail below) and other units follow mode and parameter information contained in the received compressed bitstream rather than generating such information themselves.","FIG.","6 schematically illustrates the generation of predicted images, and in particular the operation of the image predictor 320.There are two basic modes of prediction carried out by the image predictor 320: so-called intra-image prediction and so-called inter-image, or motion-compensated (MC), prediction.","At the encoder side, each involves detecting a prediction direction in respect of a current block to be predicted, and generating a predicted block of samples according to other samples (in the same (intra) or another (inter) image).","By virtue of the units 310 or 450, the difference between the predicted block and the actual block is encoded or applied so as to encode or decode the block respectively.","Intra-image prediction bases a prediction of the content of a block of the image on data from within the same image.","This corresponds to so-called I-frame encoding in other video compression techniques.","In contrast to I-frame encoding, where the whole image is intra-encoded, in the present embodiments the choice between intra- and inter-encoding can be made on a block-by-block basis, though in other embodiments the choice is still made on an image-by-image basis.","Motion-compensated prediction is an example of inter-image prediction and makes use of motion information which attempts to define the source, in another adjacent or nearby image, of image detail to be encoded in the current image.","Accordingly, in an ideal example, the contents of a block of image data in the predicted image can be encoded very simply as a reference (a motion vector) pointing to a corresponding block at the same or a slightly different position in an adjacent image.","Returning to FIG.","6, two image prediction arrangements (corresponding to intra- and inter-image prediction) are shown, the results of which are selected by a multiplexer 500 under the control of a mode signal 510 so as to provide blocks of the predicted image for supply to the adders 310 and 450.The choice is made in dependence upon which selection gives the lowest “energy” (which, as discussed above, may be considered as information content requiring encoding), and the choice is signalled to the encoder within the encoded output datastream.","Image energy, in this context, can be detected, for example, by carrying out a trial subtraction of an area of the two versions of the predicted image from the input image, squaring each pixel value of the difference image, summing the squared values, and identifying which of the two versions gives rise to the lower mean squared value of the difference image relating to that image area.","The actual prediction, in the intra-encoding system, is made on the basis of image blocks received as part of the signal 460, which is to say, the prediction is based upon encoded-decoded image blocks in order that exactly the same prediction can be made at a decompression apparatus.","However, data can be derived from the input video signal 300 by an intra-mode selector 520 to control the operation of the intra-image predictor 530.For inter-image prediction, a motion compensated (MC) predictor 540 uses motion information such as motion vectors derived by a motion estimator 550 from the input video signal 300.Those motion vectors are applied to a processed version of the reconstructed image 460 by the motion compensated predictor 540 to generate blocks of the inter-image prediction.","Accordingly, the units 530 and 540 (operating with the estimator 550) each act as detectors to detect a prediction direction in respect of a current block to be predicted, and as a generator to generate a predicted block of samples (forming part of the prediction passed to the units 310 and 450) according to other samples defined by the prediction direction.","The processing applied to the signal 460 will now be described.","Firstly, the signal is filtered by a filter unit 560, which will be describe in greater detail below.","This involves applying a “deblocking” filter to remove or at least tend to reduce the effects of the block-based processing carried out by the transform unit 340 and subsequent operations.","A sample adaptive offsetting (SAO) filter (described further below) may also be used.","Also, an adaptive loop filter is applied using coefficients derived by processing the reconstructed signal 460 and the input video signal 300.The adaptive loop filter is a type of filter which, using known techniques, applies adaptive filter coefficients to the data to be filtered.","That is to say, the filter coefficients can vary in dependence upon various factors.","Data defining which filter coefficients to use is included as part of the encoded output datastream.","Adaptive filtering represents in-loop filtering for image restoration.","An LCU can be filtered by up to 16 filters, with a choice of filter and an ALF on/off status (adaptive loop filter—see below) being derived in respect of each CU within the LCU.","Currently the control is at the LCU level, not the CU level.","The filtered output from the filter unit 560 in fact forms the output video signal 480 when the apparatus is operating as a compression apparatus.","It is also buffered in one or more image or frame stores 570; the storage of successive images is a requirement of motion compensated prediction processing, and in particular the generation of motion vectors.","To save on storage requirements, the stored images in the image stores 570 may be held in a compressed form and then decompressed for use in generating motion vectors.","For this particular purpose, any known compression/decompression system may be used.","The stored images are passed to an interpolation filter 580 which generates a higher resolution version of the stored images; in this example, intermediate samples (sub-samples) are generated such that the resolution of the interpolated image is output by the interpolation filter 580 is 4 times (in each dimension) that of the images stored in the image stores 570 for the luminance channel of 4:2:0 and 8 times (in each dimension) that of the images stored in the image stores 570 for the chrominance channels of 4:2:0.The interpolated images are passed as an input to the motion estimator 550 and also to the motion compensated predictor 540.In embodiments, a further optional stage is provided, which is to multiply the data values of the input video signal by a factor of four using a multiplier 600 (effectively just shifting the data values left by two bits), and to apply a corresponding divide operation (shift right by two bits) at the output of the apparatus using a divider or right-shifter 610.So, the shifting left and shifting right changes the data purely for the internal operation of the apparatus.","This measure can provide for higher calculation accuracy within the apparatus, as the effect of any data rounding errors is reduced.","The way in which an image is partitioned for compression processing will now be described.","At a basic level, an image to be compressed is considered as an array of blocks of samples.","For the purposes of the present discussion, the largest such block under consideration is a so-called largest coding unit (LCU) 700 (FIG.","7), which represents a square array of typically 64×64 samples (the LCU size is configurable by the encoder, up to a maximum size such as defined by the HEVC documents).","Here, the discussion relates to luminance samples.","Depending on the chrominance mode, such as 4:4:4, 4:2:2, 4:2:0 or 4:4:4:4 (GBR plus key data), there will be differing numbers of corresponding chrominance samples corresponding to the luminance block.","Three basic types of blocks will be described: coding units, prediction units and transform units.","In general terms, the recursive subdividing of the LCUs allows an input picture to be partitioned in such a way that both the block sizes and the block coding parameters (such as prediction or residual coding modes) can be set according to the specific characteristics of the image to be encoded.","The LCU may be subdivided into so-called coding units (CU).","Coding units are always square and have a size between 8×8 samples and the full size of the LCU 700.The coding units can be arranged as a kind of tree structure, so that a first subdivision may take place as shown in FIG.","8, giving coding units 710 of 32×32 samples; subsequent subdivisions may then take place on a selective basis so as to give some coding units 720 of 16×16 samples (FIG.","9) and potentially some coding units 730 of 8×8 samples (FIG.","10).","Overall, this process can provide a content-adapting coding tree structure of CU blocks, each of which may be as large as the LCU or as small as 8×8 samples.","Encoding of the output video data takes place on the basis of the coding unit structure, which is to say that one LCU is encoded, and then the process moves to the next LCU, and so on.","FIG.","11 schematically illustrates an array of prediction units (PU).","A prediction unit is a basic unit for carrying information relating to the image prediction processes, or in other words the additional data added to the entropy encoded residual image data to form the output video signal from the apparatus of FIG.","5.In general, prediction units are not restricted to being square in shape.","They can take other shapes, in particular rectangular shapes forming half of one of the square coding units (for example, 8×8 CUs can have 8×4 or 4×8 PUs).","Employing PUs which align to image features is not a compulsory part of the HEVC system, but the general aim would be to allow a good encoder to align the boundary of adjacent prediction units to match (as closely as possible) the boundary of real objects in the picture, so that different prediction parameters can be applied to different real objects.","Each coding unit may contain one or more prediction units.","FIG.","12 schematically illustrates an array of transform units (TU).","A transform unit is a basic unit of the transform and quantisation process.","Transform units may or may not be square and can take a size from 4×4 up to 32×32 samples.","Each coding unit can contain one or more transform units.","The acronym SDIP-P in FIG.","12 signifies a so-called short distance intra-prediction partition.","In this arrangement only one dimensional transforms are used, so a 4×N block is passed through N transforms with input data to the transforms being based upon the previously decoded neighbouring blocks and the previously decoded neighbouring lines within the current SDIP-P. SDIP-P is currently not included in HEVC at the time of filing the present application.","As mentioned above, coding takes place as one LCU, then a next LCU, and so on.","Within an LCU, coding is carried out CU by CU.","Within a CU, coding is carried out for one TU, then a next TU and so on.","The intra-prediction process will now be discussed.","In general terms, intra-prediction involves generating a prediction of a current block (a prediction unit) of samples from previously-encoded and decoded samples in the same image.","FIG.","13 schematically illustrates a partially encoded image 800.Here, the image is being encoded from top-left to bottom-right on an LCU basis.","An example LCU encoded partway through the handling of the whole image is shown as a block 810.A shaded region 820 above and to the left of the block 810 has already been encoded.","The intra-image prediction of the contents of the block 810 can make use of any of the shaded area 820 but cannot make use of the unshaded area below that.","Note however that for an individual TU within the current LCU, the hierarchical order of encoding (CU by CU then TU by TU) discussed above means that there may be previously encoded samples in the current LCU and available to the coding of that TU which are, for example, above-right or below-left of that TU.","The block 810 represents an LCU; as discussed above, for the purposes of intra-image prediction processing, this may be subdivided into a set of smaller prediction units and transform units.","An example of a current TU 830 is shown within the LCU 810.The intra-image prediction takes into account samples coded prior to the current TU being considered, such as those above and/or to the left of the current TU.","Source samples, from which the required samples are predicted, may be located at different positions or directions relative to the current TU.","To decide which direction is appropriate for a current prediction unit, the mode selector 520 of an example encoder may test all combinations of available TU structures for each candidate direction and select the PU direction and TU structure with the best compression-efficiency.","The picture may also be encoded on a “slice” basis.","In one example, a slice is a horizontally adjacent group of LCUs.","But in more general terms, the entire residual image could form a slice, or a slice could be a single LCU, or a slice could be a row of LCUs, and so on.","Slices can give some resilience to errors as they are encoded as independent units.","The encoder and decoder states are completely reset at a slice boundary.","For example, intra-prediction is not carried out across slice boundaries; slice boundaries are treated as image boundaries for this purpose.","FIG.","14 schematically illustrates a set of possible (candidate) prediction directions.","The full set of 34 candidate directions is available to a prediction unit of 8×8, 16×16 or 32×32 samples.","The special cases of prediction unit sizes of 4×4 and 64×64 samples have a reduced set of candidate directions available to them (17 candidate directions and 5 candidate directions respectively).","The directions are determined by horizontal and vertical displacement relative to a current block position, but are encoded as prediction “modes”, a set of which is shown in FIG.","15.Note that the so-called DC mode represents a simple arithmetic mean of the surrounding upper and left-hand samples.","In general terms, after detecting a prediction direction in respect of each prediction unit, the systems are operable to generate a predicted block of samples according to other samples defined by the prediction direction.","FIG.","16 schematically illustrates a so-called up-right diagonal scan, being an example scan pattern which may be applied by the scan unit 360.In FIG.","16, the pattern is shown for an example block of 8×8 DCT coefficients, with the DC coefficient being positioned at the top left position 840 of the block, and increasing horizontal and vertical spatial frequencies being represented by coefficients at increasing distances downwards and to the right of the top-left position 840.Other alternative scan orders may be used instead.","Variations of the block arrangements and of the CU, PU and TU structures will be discussed below.","These will be discussed in the context of the apparatus of FIG.","17, which is similar in many respects to that illustrated in FIGS.","5 and 6 discussed above.","Indeed, many of the same reference numerals have been used, and these parts will not be discussed further.","The main substantive differences with respect to FIGS.","5 and 6 relate to the filter 560 (FIG.","6), which in FIG.","17 is shown in more detail as comprising a deblocking filter 1000 and associated encoding decision block 1030, a sample adaptive offsetting (SAO) filter 1010 and associated coefficient generator 1040, and an adaptive loop filter (ALF) 1020 and associated coefficient generator 1050.The deblocking filter 1000 attempts to reduce distortion and to improve visual quality and prediction performance by smoothing the sharp edges which can form between CU, PU and TU boundaries when block coding techniques are used.","The SAO filter 1010 classifies reconstructed pixels into different categories and then attempts to reduce distortion by simply adding an offset for each category of pixels.","The pixel intensity and edge properties are used for pixel classification.","To further improve the coding efficiency, a picture can be divided into regions for localization of offset parameters.","The ALF 1020 attempts to restore the compressed picture such that the difference between the reconstructed and source frames is minimized.","The coefficients of ALF are calculated and transmitted on a frame basis.","The ALF can be applied to the entire frame or to local areas.","As noted above, the proposed HEVC documents use a particular chroma sampling scheme known as the 4:2:0 scheme.","The 4:2:0 scheme can be used for domestic/consumer equipment.","However, several other schemes are possible.","In particular, a so-called 4:4:4 scheme would be suitable for professional broadcasting, mastering and digital cinema, and in principle would have the highest quality and data rate.","Similarly, a so-called 4:2:2 scheme could be used in professional broadcasting, mastering and digital cinema with some loss of fidelity.","These schemes and their corresponding possible PU and TU block structures are described below.","In addition, other schemes include the 4:0:0 monochrome scheme.","In the 4:4:4 scheme, each of the three Y, Cb and Cr channels have the same sample rate.","In principle therefore, in this scheme there would be twice as much chroma data as luma data.","Hence in HEVC, in this scheme each of the three Y, Cb and Cr channels would have corresponding PU and TU blocks that are the same size; for example an 8×8 luma block would have corresponding 8×8 chroma blocks for each of the two chroma channels.","Consequently in this scheme there would generally be a direct 1:1 relationship between block sizes in each channel.","In the 4:2:2 scheme, the two chroma components are sampled at half the sample rate of luma (for example using vertical or horizontal subsampling, but for the purposes of the present description, horizontal subsampling is assumed).","In principle therefore, in this scheme there would be as much chroma data as luma data, though the chroma data would be split between the two chroma channels.","Hence in HEVC, in this scheme the Cb and Cr channels would have different size PU and TU blocks to the luma channel; for example an 8×8 luma block could have corresponding 4 wide×8 high chroma blocks for each chroma channel.","Notably therefore in this scheme the chroma blocks could be non-square, even though they correspond to square luma blocks.","In the currently proposed HEVC 4:2:0 scheme, the two chroma components are sampled at a quarter of the sample rate of luma (for example using vertical and horizontal subsampling).","In principle therefore, in this scheme there is half as much chroma data as luma data, the chroma data being split between the two chroma channels.","Hence in HEVC, in this scheme again the Cb and Cr channels have different size PU and TU blocks to the luma channel.","For example an 8×8 luma block would have corresponding 4×4 chroma blocks for each chroma channel.","The above schemes are colloquially known in the art as ‘channel ratios’, as in ‘a 4:2:0 channel ratio’; however it will be appreciated from the above description that in fact this does not always mean that the Y, Cb and Cr channels are compressed or otherwise provided in that ratio.","Hence whilst referred to as a channel ratio, this should not be assumed to be literal.","In fact, the correct ratios for the 4:2:0 scheme are 4:1:1 (the ratios for the 4:2:2 scheme and 4:4:4 scheme are in fact correct).","Before discussing particular arrangements with reference to FIGS.","18a and 18b, some general terminology will be summarised or revisited.","A Largest Coding Unit (LCU) is a root picture object.","Typically, it covers the area equivalent to 64×64 luma pixels.","It is recursively split to form a tree-hierarchy of Coding Units (CUs).","In general terms, the three channels (one luma channel and two chroma channels) have the same CU tree-hierarchy.","Having said this, however, depending upon the channel ratio, a particular luma CU may comprise a different number of pixels to the corresponding chroma CUs.","The CUs at the end of the tree-hierarchy, which is to say, the smallest CUs resulting from the recursive splitting process (which may be referred to as leaf CUs) are then split into Prediction Units (PUs).","The three channels (luma and two chroma channels) have the same PU structure, except when the corresponding PU for a chroma channel would have too few samples, in which case just one PU for that channel is available.","This is configurable, but commonly the minimum dimension of an intra PU is 4 samples; the minimum dimension of an inter PU is 4 luma samples (or 2 chroma samples for 4:2:0).","The restriction on the minimum CU size always is large enough for at least one PU for any channel.","The leaf CUs are also split into Transform Units (TUs).","The TUs can—and, when they are too big (for example, over 32×32 samples), must—be split into further TUs.","A limit is applied so that TUs can be split down to a maximum tree depth, currently configured as 2 levels.","i.e.","there can be no more than 16 TUs for each CU.","An illustrative smallest allowable TU size is 4×4 samples and the largest allowable TU size is 32×32 samples.","Again, the three channels have the same TU structure wherever possible, but if a TU cannot be split to a particular depth for a given channel due to the size restriction, it remains at the larger size.","The so-called non-square quad-tree transform arrangement (NSQT) is similar, but the method of splitting into four TUs need not be 2×2, but can be 4×1 or 1×4.Referring to FIGS.","18a and 18b, the different block sizes possible are summarised for CU, PU and TU blocks, with ‘Y’ referring to luma blocks and ‘C’ referring in a generic sense to a representative one of the chroma blocks, and the numbers referring to pixels.","‘Inter’ refers to inter-frame prediction PUs (as opposed to intra-frame prediction PUs).","In many cases, only the block sizes for the luma blocks are shown.","The corresponding sizes of the associated chroma blocks are related to the luma block sizes according to the channel ratios.","So, for 4:4:4, the chroma channels have the same block sizes as the luma blocks shown in FIGS.","18a and 18b.","Accordingly, the chroma PU structure mirrors (or is respectively identical to) the luma PU structure at all split levels (where a “split level” refers to the choice of CU size options and, within a CU size option, the choice of PU size and shape options).","While it would be possible to employ the same set of possible block sizes and shapes but to allow different ones (of that set) to be selected in respect of luma and chroma components of a CU, in some embodiments of the disclosure the same PU block size and shape is selected for the chroma and the luma components corresponding to a CU.","Therefore, whichever PU size(s) and shape(s) is (are) selected for a luma CU, the identical size and shape PU(s) is (are) selected for the chroma components of that CU.","Note that as discussed below, the selection of block sizes and shapes and PUs is an encoder based decision, under the control of the controller 343.In such arrangements, the luminance and chrominance samples are in a 4:4:4 format and are arranged as plural coding units each comprising a block of luminance and chrominance samples; and a prediction direction is detected in respect of a current prediction unit, being a block of luminance or chrominance samples representing at least a subset of a respective coding unit.","For a particular coding unit, a size and shape of one or more prediction units each comprising luminance and chrominance samples from that coding unit is made (for example by the controller 343) such that the selection of the prediction unit size and shape are the same for luminance samples and for chrominance samples.","For 4:2:2 and 4:2:0, the chroma blocks will each have fewer pixels than the corresponding luma block, according to the channel ratio.","The arrangements shown in FIGS.","18a and 18b concern four possible CU sizes: 64×64, 32×32, 16×16 and 8×8 luma pixels respectively.","Each of these CUs has a corresponding row of PU options (shown in a column 1140) and TU options (shown in a column 1150).","For the possible CU sizes defined above, the rows of options are referenced as 1100, 1110, 1120 and 1130 respectively.","Note that 64×64 is currently a maximum CU size but this restriction could change.","Within each row 1100 .",".",".","1130, different PU options are shown applicable to that CU size.","The TU options applicable to those PU configurations are shown horizontally aligned with the respective PU option(s).","Note that in several cases, multiple PU options are provided.","As discussed above, the aim of the apparatus in selecting a PU configuration is to match (as closely as possible) the boundary of real objects in the picture, so that different prediction parameters can be applied to different real objects.","The block sizes and shapes and PUs are an encoder based decision, under the control of the controller 343.The current method involves conducting trials of many TU tree structures for many directions, getting the best “cost” at each level.","Here, the cost may be expressed as a measure of the distortion, or noise, or errors, or bit rate resulting from each block structure.","So, the encoder may try two or more (or even all available) permutations of block sizes and shapes within those allowed under the tree structures and hierarchies discussed above, before selecting the one of the trials which gives the lowest bit rate for a certain required quality measure, or the lowest distortion (or errors, or noise, or combinations of these measures) for a required bit rate, or a combination of these measures.","Given the selection of a particular PU configuration, various levels of splitting may be applied to generate the corresponding TUs.","Referring to the row 1100, in the case of a 64×64 PU, this block size is too large for use as a TU and so a first level of splitting (from “level 0” (not split) to “level 1”) is compulsory, resulting in an array of four 32×32 luma TUs.","Each of these may be subjected to further splitting in a tree hierarchy (from “level 1” to “level 2”) as required, with the splitting being carried out before transforming or quantising that TU is performed.","The maximum number of levels in the TU tree is limited by (for example) the HEVC documents.","Other options are provided for PU sizes and shapes in the case of a 64×64 luma pixel CU.","These are restricted to use only with inter-coded pictures and, in some cases, with the so-called AMP option enabled.","AMP refers to Asymmetric Motion Partitioning and allows for PUs to be partitioned asymmetrically.","Similarly, in some cases options are provided for TU sizes and shapes.","If NQST (non-square quad-tree transform, basically allowing a non-square TU) is enabled, then splitting to level 1 and/or level 2 can be carried out as shown, whereas if NQST is not enabled, the TU sizes follow the splitting pattern of the respective largest TU for that CU size.","Similar options are provided for other CU sizes.","In addition to the graphical representation shown in FIGS.","18a and 18b, the numerical part of the same information is provided in the following table, though the presentation in FIGS.","18a and 18b is considered definitive.","“n/a” indicates a mode which is not allowed.","The horizontal pixel size is recited first.","If a third figure is given, it relates to the number of instances of that block size, as in (horizontal)×(vertical)×(number of instances) blocks.","N is an integer.","TU Options CU Size PU Options Level 0 Level 1 Level 2 64 × 64 64 × 64 n/a 32 × 32 × 4 16 × 16 × 4 64 × 32 × 2 (horizontal configuration) n/a 32 × 32 × 4 32 × 8 × 4 64 × 16 + 64 × 48 (2 horizontal configurations) 32 × 64 × 2 (vertical configuration) n/a 32 × 32 × 4 8 × 32 × 4 16 × 64 + 48 × 64 (2 vertical configurations) 32 × 32 32 × 32 32 × 32 16 × 16 × 4 8 × 8 × 4 32 × 16 × 2 (horizontal configuration) n/a 32 × 8 × 4 16 × 4 × 4 (luma) + 32 × 8 + 32 × 24 (2 horizontal 4 × 4 × 4 (chroma, configurations) 4:2:0 or 4:2:2) or 8 × 4 × 4 (chroma, 4:2:2) 16 × 32 × 2 (vertical configuration) n/a 8 × 32 × 4 4 × 16 × 4 (luma) + 8 × 32 + 24 × 32 (2 vertical 4 × 4 × 4 (chroma) configurations) 16 × 16 16 × 16 16 × 16 8 × 8 × 4 4 × 4 × 4 (luma) + 4 × 8 × 4 (chroma) 16 × 8 × 2 (horizontal configuration) n/a 16 × 4 × 4 (luma) + 4 × 4 × 4 (luma) + 16 × 4 + 16 × 12 (2 horizontal 4 × 8 × 4 (chroma) 4 × 8 × 1 (chroma) configurations) (4:2:0 or 4:2:2) (4:2:0 or 4:2:2) 16 × 4 × 4 (luma) + 4 × 4 × 4 (luma) + 8 × 8 × 4 × 4 (chroma) 4 × 1 (chroma) (4:2:2) (4:2:2) 8 × 16 × 2 (vertical configuration) n/a 4 × 16 + 12 × 16 (2 vertical configurations) 8 × 8 8 × 8 8 × 8 4 × 4 × 4 (luma) + n/a 4 × 4 × 4 4 × 8 × 1 (chroma) 8 × 4 × 2 (horizontal configuration) 4 × 8 × 2 (vertical configuration) 4 × 4 × 4 (luma) + 4 × N (chroma) n/a 4 × 4 × 4 (luma) + n/a 4 × 8 × 1 (chroma) 4:2:0, 4:2:2 and 4:4:4 Block Structure Variants It has been appreciated that both 4:2:0 and 4:4:4 schemes have square PU blocks for intra-prediction coding.","Moreover, currently the 4:2:0 scheme permits 4×4 pixel PU & TU blocks.","In embodiments, it is consequently proposed that for the 4:4:4 scheme the recursion for CU blocks is permitted down to 4×4 pixels rather than 8×8 pixels, since as noted above in the 4:4:4 mode the luma and chroma blocks will be the same size (i.e.","the chroma data is not subsampled) and so for a 4×4 CU no PU or TU will need to be less than the already allowed minimum of 4×4 pixels.","This is therefore an example of selecting, for a particular coding unit, a size and shape of one or more prediction units each comprising luminance or chrominance samples from at least a subset of that coding unit, the selection of the prediction unit size and shape being the same for luminance samples and for chrominance samples.","Similarly, in the 4:4:4 scheme, in an embodiment each of the Y, Cr, Cb channels, or the Y and the two Cr, Cb channels together, could have respective CU tree-hierarchies.","A flag may then be used to signal which hierarchy or arrangement of hierarchies is to be used.","This approach could also be used for a 4:4:4 RGB colour space scheme.","However, in an alternative, the tree hierarchies for chroma and luma may instead be independent.","In the example of an 8×8 CU in the 4:2:0 scheme, this results in four 4×4 luma PUs and one 4×4 chroma PU.","Hence in the 4:2:2 scheme, having twice as much chroma data, one option is in this case is to have two 4×4 chroma PUs, where (for example) the bottom chroma block would correspond in position to the bottom left luma block.","However, it is has been appreciated that using one non-square 4×8 chroma PU in this case would be more consistent with arrangements for the 4:2:0 chroma format.","In the 4:2:0 scheme there are in principle some non-square TU blocks permitted for certain classes of inter-prediction coding, but not for intra-prediction coding.","However in inter-prediction coding, when non-square quad-tree transforms (NSQT) are disabled (which is the current default for the 4:2:0 scheme), all TUs are square.","Hence in effect the 4:2:0 scheme currently enforces square TUs.","For example, a 16×16 4:2:0 luma TU would correspond with respective Cb & Cr 8×8 4:2:0 Chroma TUs.","However, as noted previously, the 4:2:2 scheme can have non-square PUs.","Consequently in an embodiment it is proposed to allow non-square TUs for the 4:2:2 scheme.","For example, whilst a 16×16 4:2:2 luma TU could correspond with two respective Cb & Cr 8×8 4:2:2 Chroma TUs, in this embodiment it could instead correspond with respective Cb & Cr 8×16 4:2:2 Chroma TUs.","Similarly, four 4×4 4:2:2 luma TUs could correspond with two respective 4×4 Cb+Cr 4:2:2 TUs, or in this embodiment could instead correspond with respective 4×8 Cb & Cr 4:2:2 TUs.","Having non-square chroma TUs, and hence fewer TUs, may be more efficient as they are likely to contain less information.","However this may affect the transformation and scanning processes of such TUs, as will be described later.","Finally, for the 4:4:4 scheme it may be preferable to have the TU structure channel-independent, and selectable at the sequence, picture, slice or finer level.","As noted above, NSQT is currently disabled in the 4:2:0 scheme of HEVC.","However, if for inter-picture prediction, NSQT is enabled and asymmetric motion partitioning (AMP) is permitted, this allows for PUs to be partitioned asymmetrically; thus for example a 16×16 CU may have a 4×16 PU and a 12×16 PU.","In these circumstances, further considerations of block structure are important for each of the 4:2:0 and 4:2:2 schemes.","For the 4:2:0 scheme, in NSQT the minimum width/height of a TU may be restricted to 4 luma/chroma samples: Hence in a non-limiting example a 16×4/16×12 luma PU structure has four 16×4 luma TUs and four 4×4 chroma TUs, where the luma TUs are in a 1×4 vertical block arrangement and the chroma TUs are in a 2×2 block arrangement.","In a similar arrangement where the partitioning was vertical rather than horizontal, a 4×16/12×16 luma PU structure has four 4×16 luma TUs and four 4×4 chroma TUs, where the luma TUs are in a 4×1 horizontal block arrangement and the chroma TUs are in a 2×2 block arrangement.","For the 4:2:2 scheme, in NSQT as a non-limiting example a 4×16/12×16 luma PU structure has four 4×16 luma TUs and four 4×8 chroma TUs, where the luma TUs are in a 4×1 horizontal block arrangement; the chroma TUs are in a 2×2 block arrangement.","However, it has been appreciated that a different structure can be considered for some cases.","Hence in an embodiment, in NSQT as a non-limiting example 16×4/16×12 luma PU structure has four 16×4 luma TUs and four 8×4 chroma TUs, but now the luma and chroma TUs are in a 1×4 vertical block arrangement, aligned with the PU layout (as opposed to the 4:2:0 style arrangement of four 4×8 chroma TUs in a 2×2 block arrangement).","Similarly 32×8 PU can have four 16×4 luma TUs and four 8×4 chroma TUs, but now the luma and chroma TUs are in a 2×2 block arrangement.","Hence more generally, for the 4:2:2 scheme, in NSQT the TU block sizes are selected to align with the asymmetric PU block layout.","Consequently the NSQT usefully allows TU boundaries to align with PU boundaries, which reduces high frequency artefacts that may otherwise occur.","In general terms, embodiments of the disclosure can relate to a video coding method, apparatus or program operable in respect of images of a 4:2:2 format video signal.","An image to be encoded is divided into coding units, prediction units and transform units for encoding, a coding unit being a square array of luminance samples and the corresponding chrominance samples, there being one or more prediction units in a coding unit, and there being one or more transform units in a coding unit; in which a prediction unit is an elementary unit of prediction so that all samples within a single prediction unit are predicted using a common prediction technique, and a transform unit is a basic unit of transformation and quantisation.","A Non-square transform mode (such as an NSQT mode) is enabled so as to allow non-square prediction units.","Optionally, asymmetric motion partitioning is enabled so as to allow asymmetry between two or more prediction units corresponding to a single coding unit.","The controller 343 controls the selection of transform unit block sizes to align with the prediction unit block layout, for example by detecting image features in the portion of the image corresponding to a PU and selecting TU block sizes in respect of that PU so as to align TU boundaries with edges of image features in the portion of the image.","The rules discussed above dictate which combinations of block sizes are available.","The encoder may just try different combinations.","As discussed above, a trial may include two or more, through to all available options.","The trial encode processes can be carried out according to a cost function metric and a result selected according to an assessment of the cost function.","Given that there are three levels of variation, according to the CU size and shape, the PU size and shape and the TU size and shape, this could lead to a large number of permutations to be trial-encoded.","To reduce this variation, the system could trial encode for a CU size by using an arbitrarily selected one of the PU/TU configurations allowable for each CU size; then, having selected a CU size, a PU size and shape could be selected by trial encoding the different PU options each with a single arbitrarily chosen TU configuration.","Then, having selected a CU and PU, the system could try all applicable TU configurations to select a final TU configuration.","Another possibility is that some encoders may use a fixed choice of block configuration, or may allow a limited subset of the combinations set out in the discussions above.","Intra-Prediction 4:2:0 Intra-Prediction Turning now to FIG.","22, for intra-prediction, HEVC allows for angular chroma prediction.","By way of introduction, FIG.","22 illustrates 35 prediction modes applicable to luma blocks, 33 of which specify directions to reference samples for a current predicted sample position 110.The remaining two modes are mode 0 (planar) and mode 1 (dc).","HEVC allows chroma to have DC, Vertical, Horizontal, Planar, DM_CHROMA and LM_CHROMA modes.","DM_CHROMA indicates that the prediction mode to be used is the same as that of the co-located luma PU (i.e.","one of the 35 shown in FIG.","22).","LM_CHROMA (linear mode chroma) indicates that co-located luma samples (downsampled as appropriate to the channel ratios) are used to derive the predicted chroma samples.","In this case, if the luma PU from which the DM_CHROMA prediction mode would be taken selected DC, Vertical, Horizontal or Planar, that entry in the chroma prediction list is replaced using mode 34.In the LM_CHROMA mode, the luma pixels from which the chroma pixels are predicted are scaled (and have an offset applied if appropriate) according to a linear relationship between luma and chroma.","This linear relationship is derived from surrounding pixels, and the derivation can be carried out on a block by block basis, with the decoder finishing decoding one block before moving on to the next.","It is notable that the prediction modes 2-34 sample an angular range from 45 degrees to 225 degrees; that is to say, one diagonal half of a square.","This is useful in the case of the 4:2:0 scheme, which as noted above only uses square chroma PUs for intra-picture prediction.","4:2:2 Intra-Prediction Variants However, also as noted above the 4:2:2 scheme could have rectangular (non-square) chroma PUs even when the luma PUs are square.","Or indeed, the opposite could be true: a rectangular luma PU could correspond to a square chroma PU.","The reason for the discrepancy is that in 4:2:2, the chroma is subsampled horizontally (relative to the luma) but not vertically.","So the aspect ratio of a luma block and a corresponding chroma block would be expected to be different.","Consequently, in an embodiment, for chroma Pus having a different aspect ratio to the corresponding luma block, a mapping table may be required for the direction.","Assuming (for example) a 1-to-2 aspect ratio for rectangular chroma PUs, then for example mode 18 (currently at an angle of 135 degrees) may be re-mapped to 123 degrees.","Alternatively selection of current mode 18 may be remapped to a selection of current mode 22, to much the same effect.","Hence more generally, for non-square PUs, a different mapping between the direction of the reference sample and the selected intra prediction mode may be provided compared with that for square PUs.","More generally still, any of the modes, including the non-directional modes, may also be re-mapped based upon empirical evidence.","It is possible that such mapping will result in a many-to-one relationship, making the specification of the full set of modes redundant for 4:2:2 chroma PUs.","In this case, for example it may be that only 17 modes (corresponding to half the angular resolution) are necessary.","Alternatively or in addition, these modes may be angularly distributed in a non-uniform manner.","Similarly, the smoothing filter used on the reference sample when predicting the pixel at the sample position may be used differently; in the 4:2:0 scheme it is only used to smooth luma pixels, but not chroma ones.","However, in the 4:2:2 and 4:4:4 schemes this filter may also be used for the chroma PUs.","In the 4:2:2 scheme, again the filter may be modified in response to the different aspect ratio of the PU, for example only being used for a subset of near horizontal modes.","An example subset of modes is preferably 2-18 and 34, or more preferably 7-14.In 4:2:2, smoothing of only the left column of reference samples may be carried out in embodiments.","These arrangements are discussed later in more detail.","4:4:4 Intra-Prediction Variants In the 4:4:4 scheme, the chroma and luma PUs are the same size, and so the intra-prediction mode for a chroma PU can be either the same as the co-located luma PU (so saving some overhead in the bit stream by not having to encode a separate mode), or alternatively, it can be independently selected.","In this latter case therefore, in an embodiment the system may have 1, 2 or 3 different prediction modes for each of the PUs in a CU; In a first example, the Y, Cb and Cr PUs may all use the same intra-prediction mode.","In a second example, the Y PU may use one intra-prediction mode, and the Cb and Cr PUs both use another independently selected intra-prediction mode.","In a third example, the Y, Cb and Cr PUs each use a respective independently selected intra-prediction mode.","It will be appreciated that having independent prediction modes for the chroma channels (or each chroma channel) will improve the colour prediction accuracy.","But this is at the expense of an additional data overhead to communicate the independent prediction modes as part of the encoded data.","To alleviate this, the selection of the number of modes could be indicated in the high-level syntax (e.g.","at sequence, picture, or slice level).","Alternatively, the number of independent modes could be derived from the video format; for example, GBR could have up to 3, whilst YCbCr could be restricted to up to 2.In addition to independently selecting the modes, the available modes may be allowed to differ from the 4:2:0 scheme in the 4:4:4 scheme.","For example as the luma and chroma PUs are the same size in 4:4:4, the chroma PU may benefit from access to all of the 35+LM_CHROMA+DM_CHROMA directions available.","Hence for the case of Y, Cb and Cr each having independent prediction modes, then the Cb channel could have access to DM_CHROMA & LM_CHROMA, whilst the Cr channel could have access to DM_CHROMA_Y, DM_CHROMA_Cb, LM_CHROMA_Y and LM_CHROMA_Cb, where these replace references to the Luma channel with references to the Y or Cb chroma channels.","Where the luma prediction modes are signalled by deriving a list of most probable modes and sending an index for that list, then if the chroma prediction mode(s) are independent, it may be necessary to derive independent lists of most probable modes for each channel.","Finally, in a similar manner to that noted for the 4:2:2 case above, in the 4:4:4 scheme the smoothing filter used on the reference sample when predicting the pixel at the sample position may be used for chroma PUs in a similar manner to luma PUs.","Currently, a [1,2,1] low-pass filter can be applied to the reference samples prior to intra-prediction.","This is only used for luma TUs when using certain prediction modes.","One of the intra-prediction modes available to chroma TUs is to base the predicted samples on co-located luma samples.","Such an arrangement is illustrated schematically in FIG.","19, which shows an array of TUs 1200 (from a region of a source image) represented by small squares in the Cb, Cr and Y channels, showing the special alignment between image features (schematically indicated by dark and light shaded boxes 1200) in the Cb and Y channels and in the Cr and Y channels.","In this example, it is of benefit to force the chroma TUs to base their predicted samples on co-located luma samples.","However, it is not always the case that image features correspond between the three channels.","In fact, certain features may appear only in one or two of the channels, and in general the image content of the three channels may differ.","In embodiments, for Cr TUs, LM_Chroma could optionally be based on co-located samples from the Cb channel (or, in other embodiments, the dependence could be the other way around).","Such an arrangement is shown in schematic form in FIG.","20.Here, spatially aligned TUs are illustrated between the Cr, Cb and Y channels.","A further set of TUs labelled “source” is a schematic representation of the colour picture as seen as a whole.","The image features (a top left triangle and a lower right triangle) seen in the source image do not in fact represent changes in the luminance, but only changes in chrominance between the two triangular regions.","In this case, basing LM_Chroma for Cr on the luminance samples would produce a poor prediction, but basing it on the Cb samples could give a better prediction.","The decision as to which LM_Chroma mode to be used can be made by the controller 343 and/or the mode controller 520, based on trial encoding of different options (including the option of basing LM_Chroma on the co-located luma or co-located chroma samples), with the decision as to which mode to select being made by assessing a cost function, similar to that described above, with respect to the different trial encodings.","Examples of the cost function are noise, distortion, error rate or bit rate.","A mode from amongst those subjected to trial encoding which gives the lowest of any one or more of these cost functions is selected.","FIG.","21 schematically illustrates a method used to obtain reference samples for intra-prediction in embodiments.","In viewing FIG.","21, it should be borne in mind that encoding is carried out according to a scanning pattern, so that in general terms encoded versions of the blocks above and to the left of a current block to be encoded are available to the encoding process.","Sometimes samples below-left or to the above-right are used, if they have been previously coded as part of other already-encoded TUs within the current LCU.","Reference is made to FIG.","13 as described above, for example.","A shaded area 1210 represents a current TU, that is to say, a TU which is currently being encoded.","In 4:2:0 and 4:2:2, the column of pixels immediately to the left of the current TU does not contain co-located luminance and chrominance samples because of horizontal subsampling.","In other words, this is because the 4:2:0 and 4:2:2 formats have half as many chrominance pixels as luminance pixels (in a horizontal direction), so not every luminance sample position has a co-sited chrominance sample.","Therefore, although luminance samples may be present in the column of pixels immediately to the left of the TU, chrominance samples are not present.","Therefore, in some embodiments, the column located two samples to the left of the current TU is used to provide reference samples for LM_Chroma.","Note that the situation is different in 4:4:4, in that the column immediately to the left of the current TU does indeed contain co-located luma and chroma samples.","This column could therefore be used to provide reference samples.","The reference samples are used as follows.","In the LM_Chroma mode, predicted chroma samples are derived from reconstructed luma samples according to a linear relationship.","So, in general terms, it can be said that the predicted chrominance values within the TU are given by: PC=a+bPL where PC is a chrominance sample value, PL is a reconstructed luminance sample value at that sample position, and a and b are constants.","The constants are derived for a particular block by detecting the relationship between reconstructed luma samples and chroma samples in the row just above that block and in the column just to the left of that block, these being sample positions which have already been encoded (see above).","In some embodiments, the constants a and b are derived as follows: a=R(PL′,PC′)/R(PL′,PL′) where R represents a linear (least squares) regression function, and PL′ and PC′ are luminance and chrominance samples respectively from the adjacent row and column as discussed above, and: b=mean(PC′)−a·mean(PL′) For 4:4:4, the PL′ and PC′ values are taken from the column immediately to the left of the current TU, and the row immediately above the current TU.","For 4:2:2, the PL′ and PC′ values are taken from the row immediately above the current TU and the column in the adjacent block which is two sample positions away from the left edge of the current TU.","For 4:2:0 (which is subsampled vertically and horizontally) the PL′ and PC′ values would ideally be taken from a row which is two rows above the current TU, but in fact are taken from a row in the adjacent block which is one sample positions above the current TU, and the column in the adjacent block which is two sample positions away from the left edge of the current TU.","The reason is to avoid having to maintain an additional whole row of data in memory.","So in this regard, 4:2:2 and 4:2:0 are treated in a similar way.","Accordingly, these techniques apply to video coding methods having a chrominance prediction mode in which a current block of chrominance samples representing a region of the image is encoded by deriving and encoding a relationship of the chrominance samples with respect to a co-sited block of luminance samples (such as reconstructed luminance samples) representing the same region of the image.","The relationship (such as the linear relationship) is derived by comparing co-sited (otherwise expressed as correspondingly-sited) luminance and chrominance samples from adjacent already-encoded blocks.","The chrominance samples are derived from luminance samples according to the relationship; and the difference between the predicted chrominance samples and the actual chrominance samples is encoded as residual data.","In respect of a first sampling resolution (such as 4:4:4) where the chrominance samples have the same sampling rate as the luminance samples, the co-sited samples are samples in sample positions adjacent to the current block.","In respect of a second sampling resolution (such as 4:2:2 or 4:2:0) where the chrominance samples have a lower sampling rate than that of the luminance samples, a nearest column or row of co-sited luminance and chrominance samples from the adjacent already-encoded block is used to provide the co-sited samples.","Or where, in the case of the second sampling resolution being a 4:2:0 sampling resolution, the correspondingly-sited samples are a row of samples adjacent to the current block and a nearest column or row of correspondingly-sited luminance and chrominance samples, from the adjacent already-encoded blocks.","FIG.","22 schematically illustrates the available prediction angles for luma samples.","The current pixel being predicted as shown at the centre of the diagram as a pixel 1220.The smaller dots 1230 represent adjacent pixels.","Those located on the top or left sides of the current pixel are available as reference samples to generate a prediction, because they have been previously encoded.","Other pixels are currently unknown (at the time of predicting the pixel 1220) and will in due course be predicted themselves.","Each numbered prediction direction points to the reference samples 1230 on the top or left edges of the current block that are used to generate the current predicted pixel.","In the case of smaller blocks, where the prediction directions point to locations between reference samples, a linear interpolation between adjacent reference samples is used.","Turning now to intra-angular prediction for chroma samples, for 4:2:0, fewer prediction directions are available because of the relative scarcity of the chroma samples.","However, if the DM_CHROMA mode is selected then the current chroma block will use the same prediction direction as the co-located luma block.","In turn, this means that the luma directions for intra-prediction are also available to chroma.","However, for chroma samples in 4:2:2, it can be considered counter-intuitive to use the same prediction algorithm and direction as luma when DM_CHROMA is selected, given that chroma blocks now have a different aspect ratio to that of the luma blocks.","For example, a 45° line for a square luma array of samples should still map to a 45° line for chroma samples, albeit with an array of rectangular sized samples.","Overlaying the rectangular grid onto to a square grid indicates that the 45° line would then in fact map to a 26.6° line.","FIG.","23 schematically illustrates luma intra-prediction directions as applied to chroma pixels in 4:2:2, in respect of a current pixel to be predicted 1220.Note that there are half as many pixels horizontally as there are vertically, because 4:2:2 has half the horizontal sample rate in the chroma channel as compared to the luma channel.","FIG.","24 schematically illustrates the transformation or mapping of the 4:2:2 chroma pixels to a square grid, and subsequently how this transformation changes the prediction directions.","The luma prediction directions are shown as broken lines 1240.The chroma pixels 1250 are remapped to a square grid giving a rectangular array half the width 1260 of the corresponding luma array (such as that shown in FIG.","22).","The prediction directions shown in FIG.","23 have been remapped to the rectangular array.","It can be seen that for some pairs of directions (a pair being a luma direction and a chroma direction) there is either an overlap or a close relationship.","For example, direction 2 in the luma array substantially overlies the direction 6 in the chroma array.","However, it will also be noted that some luma directions, approximately half of them, have no corresponding chroma direction.","An example is the luma direction numbered 3.Also, some chroma directions (2-5) have no equivalent in the luma array, and some luma directions (31-34) have no equivalent in the chroma array.","But in general, the superposition as shown in FIG.","24 demonstrates that it would be inappropriate to use the same angle for both the luma and chroma channels.","Accordingly, in order to derive the appropriate prediction angle for chroma when (a) DM_CHROMA is selected and (b) the DM_CHROMA mode currently in use indicates that the chroma prediction direction should be that of the co-located luma block, the following procedure is applied: (i) derive the intra-prediction angle step and its inverse according to the luma direction according to usual HEVC rules (ii) if the luma direction is predominantly vertical (that is, for example, a mode numbered from 18 to 34 inclusive) then the intra-prediction angle step is halved and its inverse is doubled.","(iii) otherwise, if the luma direction is predominantly horizontal (that is, for example, a mode numbered from 2 to 17 inclusive) then the intra-prediction angle step is doubled and its inverse halved.","Accordingly these embodiments relate to video coding or decoding methods, apparatus or programs in which luminance and chrominance samples are predicted from other respective reference samples according to a prediction direction associated with a sample to be predicted.","In modes such as 4:2:2 the chrominance samples have a lower horizontal and/or vertical sampling rate than the luminance samples so that the ratio of luminance horizontal resolution to chrominance horizontal resolution is different to the ratio of luminance vertical resolution to chrominance vertical resolution.","In short, this means that a block of luminance samples has a different aspect ratio to a corresponding block of chrominance samples.","The intra frame predictor 530, for example, is operable to detect a first prediction direction defined in relation to a grid of a first aspect ratio in respect of a set of current samples to be predicted; and to apply a direction mapping to the prediction direction so as to generate a second prediction direction defined in relation to a grid of samples of a different aspect ratio of the same set of current samples to be predicted.","In embodiments, the first prediction direction is defined in respect of one of luminance or chrominance samples, and the second prediction direction is defined in respect of the other of luminance or chrominance samples.","In the particular examples discussed in the present description, the luminance prediction direction may be modified to provide the chrominance prediction direction.","But the other way round could be used.","The technique is particularly applicable to intra-prediction, so that the reference samples are samples of the same respective image as the samples to be predicted.","In at least some arrangements the first prediction direction is defined with respect to a square block of luminance samples including the current luminance sample; and the second prediction direction is defined with respect to a rectangular block of chrominance samples including the current chrominance sample.","It is possible to provide independent prediction modes for the two chrominance components.","In such an arrangement the chrominance samples comprise samples of first and second chrominance components, and the technique comprises applying the direction mapping discussed above step in respect of the first chrominance component (such as Cb); and providing a different prediction mode in respect of the second chrominance component (such as Cr).","The video data can be in a 4:2:2 format or a 4:4:4 format, for example.","In general terms, embodiments of the disclosure can provide for independent prediction modes for the chrominance components (for example, for each of the luminance and chrominance components separately).","These embodiments relate to video coding methods in which luminance and chrominance samples of an image are predicted from other respective reference samples of the same image according to a prediction direction associated with a sample to be predicted, the chrominance samples having a lower horizontal and/or vertical sampling rate than the luminance samples so that the ratio of luminance horizontal resolution to chrominance horizontal resolution is different to the ratio of luminance vertical resolution to chrominance vertical resolution so that a block of luminance samples has a different aspect ratio to a corresponding block of chrominance samples, and the chrominance samples representing first and second chrominance components.","The intra frame mode selector 520 selects a prediction mode defining a selection of one or more reference samples for predicting a current chrominance sample of the first chrominance component (such as Cb).","It also selects a different prediction mode defining a different selection of one or more reference samples for predicting a current chrominance sample of the second chrominance component (such as Cr), co-sited with the current chrominance sample of the first chrominance component.","A reference sample filter can optionally be applied, for example, as part of the operation of the frame stores 570 and/or the predictors 530, 540 acting as a filter arrangement, to horizontal samples or vertical samples (or both).","The filter can be a 3-tap “1 2 1” filter, currently applied to all luma reference samples except the bottom left and top right (the samples of a N×N block are gathered together to form a single 1D array of size 2N+1, and then optionally filtered).","In embodiments of the technology it is applied only the first (left hand edge) or last (top edge) N+1 chroma samples for 4:2:2, but noting that the bottom left, top right and top left would then not be adjusted; or all chroma samples (as for luma), for 4:2:2 and 4:4:4.Embodiments can also provide video coding or decoding methods, apparatus or programs in which luminance and first and second chrominance component samples are predicted from other respective reference samples according to a prediction direction associated with a sample to be predicted, involving predicting samples of the second chrominance component from samples of the first chrominance component.","Embodiments can also provide video coding or decoding methods, apparatus or programs in which luminance and first and second chrominance component samples are predicted from other respective reference samples according to a prediction direction associated with a sample to be predicted, involving filtering the reference samples.","As discussed with reference to FIGS.","19 and 20, it is possible that the different prediction mode comprises a mode by which samples of the second chrominance component are predicted from samples of the first chrominance component.","Note that modes 0 and 1 are not angular prediction modes and so are not included in this procedure.","The effect of the procedure shown above is to map the chroma prediction directions onto the luma prediction directions in FIG.","24.For 4:2:0, when either a purely horizontal prediction mode (luma mode 10) or a purely vertical prediction mode (luma mode 26) is selected, the top or left edges of the predicted TU are subject to filtering for the luma channel only.","For the horizontal prediction mode, the top row is filtered in the vertical direction.","For the vertical prediction mode, the left column is filtered in the horizontal direction.","Filtering a column of samples in the horizontal direction can be understood as applying a horizontally oriented filter to each sample in turn of the column of samples.","So, for an individual sample, its value will be modified by the action of the filter, based on a filtered value generated from the current value of that sample and of one or more other samples at sample positions displaced from that sample in a horizontal direction (that is, one or more other samples to the left and/or right of the sample in question).","Filtering a row of samples in the vertical direction can be understood as applying a vertically oriented filter to each sample in turn of the row of samples.","So, for an individual sample, its value will be modified by the action of the filter, based on a filtered value generated from the current value of that sample and of one or more other samples at sample positions displaced from that sample in a vertical direction (that is, one or more other samples above and/or below the sample in question).","One purpose of the edge pixel filtering process described above is to aim to reduce block based edge effects in the prediction thereby aiming to reduce energy in the residual image data.","In embodiments, a corresponding filtering process is also provided for chroma TUs in 4:4:4 and 4:2:2.Taking into account the horizontal subsampling, one proposal is only to filter the top row of the chroma TU in 4:2:2, but to filter both the top row and left column (as appropriate, according to the selected mode) in 4:4:4.It is considered appropriate to filter only in these regions so as to avoid filtering out too much useful detail, which (if filtered out) would lead to an increased energy of the residual data.","For 4:2:0, when DC mode is selected, one or both of the top and/or left edges of the predicted TU are subject to filtering for the luma channel only.","Here, this is an example of a case where the luminance samples represent a luminance component and respective chrominance samples represent two chrominance components, the filtering step is applied to a subset of the three components, the subset being either one or two of the three components.","The subset may consist of the luminance component.","The filtering may involve filtering one or both of the left column of samples in the predicted block of samples and the top row of samples in the predicted block of samples.","The filtering may be such that in DC Mode, the filter does a (1×neighbouring outside sample+3*edge sample)/4 averaging operation for all samples on both edges.","However, for the top left the filter function is (2×current sample+1×above sample+1×left sample)/4.This is an example of an operation in which in a DC mode in which a predicted sample is generated as a simple arithmetic mean of surrounding samples, the filtering step comprising filtering the left column of samples in the predicted block of samples and filtering the top row of samples in the predicted block of samples.","The H/V filter is an average between neighbouring outside sample and edge sample.","In some embodiments, this filtering process is also provided for chroma TUs in 4:4:4 and 4:2:2.Again, taking into account the horizontal subsampling, in some embodiments, only the top row of the chroma samples is filtered for 4:2:2, but the top row and left column of the chroma TU are filtered for 4:4:4.Accordingly, this technique can apply in respect of a video coding or decoding method, apparatus or program in which luminance and chrominance samples in (for example) a 4:4:4 format or a 4:2:2 format are predicted from other respective samples according to a prediction direction associated with blocks of samples to be predicted.","In embodiments of the technique, a prediction direction is detected in respect of a current block to be predicted.","A predicted block of chrominance samples is generated according to other chrominance samples defined by the prediction direction.","If the detected prediction direction is substantially vertical (for example, being within +/−n angle modes of the exactly vertical mode where n is (for example) 2), the left column of samples is filtered (for example, in a horizontal direction using a horizontally oriented filter) in the predicted block of chrominance samples.","Or, if the detected prediction direction is substantially horizontal (for example, being within +/−n angle modes of the exactly horizontal mode, where n is (for example) 2), the top row of samples is filtered (for example, in a vertical direction using a vertically oriented filter) in the predicted block of chrominance samples.","In each case, the operation may apply only to the left column or the top row, respectively.","Then the difference between the filtered predicted chrominance block and the actual chrominance block is encoded, for example as residual data.","Alternatively, the test could be for an exactly vertical or horizontal mode rather than a substantially vertical or horizontal mode.","The tolerance of +/−n could be applied to one of the tests (vertical or horizontal) but not the other.","In embodiments of the disclosure, only the left column or the top row of the predicted block may be filtered, and the filtering may be carried out by a horizontally oriented filter or a vertically oriented filter respectively.","The filtering may be carried out by the respective predictor 520, 530, acting as a filter in this regard.","After the filtering process, embodiments of the technique either encode a difference between the filtered predicted chrominance block and the actual chrominance block (at an encoder) or apply a decoded difference to the filtered predicted chrominance block so as to encode the block (at a decoder).","Inter-Prediction it is noted that inter prediction in HEVC already allows rectangular PUs, so 4:2:2 and 4:4:4 modes are already compatible with PU inter-prediction processing.","Each frame of a video image is a discrete sampling of a real scene, and as a result each pixel is a step-wise approximation of a real-world gradient in colour and brightness.","In recognition of this, when predicting the Y, Cb or Cr value of a pixel in a new video frame from a value in a previous video frame, the pixels in that previous video frame are interpolated to create a better estimate of the original real-world gradients, to allow a more accurate selection of brightness or colour for the new pixel.","Consequently the motion vectors used to point between video frames are not limited to an integer pixel resolution.","Rather, they can be sub-pixel accuracy motion vectors pointing to a respective sub-pixel position (a fractional position) within the interpolated image.","The filters used to derive samples of an interpolated luminance or chrominance prediction unit are implemented as multiple-tap filters such as 4-tap filters or 8-tap filters.","In the case of an m-tap ×N filter (where m is, for example, 4 or 8, N is a multiple such as 4 or 8, and the “x” signifies “interpolate by a factor of”), the filter can in fact be implemented in embodiments of the present disclosure as a set of filters such that the output of each filter, when applied to a group of m samples, provides a respective fractional-position output.","Here, a fractional position represents an effective sample position having an alignment at a respective one of fractional positions from 0 to N-1 (that is, N such fractional positions in all).","One of those fractional positions, for example fractional position 0, overlies an original sample position.","The other fractional positions are disposed between original sample positions, separated by 1/N of the original sample spacing.","So, for example, in the context of an example ×8 filter, the fractional positions could be expressed as follows: filter index fractional position 0 0 (aligned with an original sample location) 1 +0.125 of original sample spacing 2 +0.25 of original sample spacing 3 +0.375 of original sample spacing 4 +0.5 of original sample spacing 5 +0.625 of original sample spacing 6 +0.75 of original sample spacing 7 +0.875 of original sample spacing This arrangement could be implemented as a set of eight filters, including a filter with a fractional position of 0 (that is, an output aligned with an original sample position).","In such a case, the filter applicable to the fractional position 0 could be (in the example of a 4-tap filter) formed of the coefficients (0, 0, Y, 0), where Y is an integer such as 64, so that the fractional-position-zero filter in fact returns just the sample at the original sample position.","In an alternative notation, the ×N filter could in fact be implemented as a set of N-1 filters, because the original sample itself could simply be re-used if the filter index is 0 (that is, without referring to a “filtering” operation to re-use that sample) and the required fractional position is 0.The skilled person will appreciate that these arrangements are equivalent in their technical effect but simply differ in notation.","The skilled person will also appreciate that the notation which places fractional position zero (of positions zero to N-1) so as to be coincident with the original sample position is simply a matter of notation.","A different notation could place fractional position 1 (of positions 1 to N) to be coincident with the original sample position.","So, in examples embodiments discussed below, a set of seven 4-tap filters is used to provide a ×8 4-tap filtering function.","If a required fractional position is coincident with an original sample position, the original sample value is simply re-used.","Otherwise, for a required fractional sample position, the appropriate one of the N-1 filters is used.","This leads to a discussion of which filter values are actually required to be generated.","The interpolated PU samples are those pointed to by a sub-pixel accuracy motion vector.","For any particular instance of the use of such a motion vector, the fractional position of the required interpolated sample(s) will be determined by the sub-pixel accuracy motion vector.","But in general, for a single instance of use of the motion vector, only those interpolated samples corresponding to the fractional position pointed to by the motion vector are required to be generated.","This means that in some embodiments, instead of generating an interpolated block from a stored PU, a vertical filter of the set of N-1 filters is selected for use in the vertical direction, and a horizontal filter of the set of N-1 filters is selected for use in the horizontal direction, so as to produce interpolated sample(s) at just the required fractional position.","Note that “N” can be different or the same as for the horizontal and vertical directions, and the filter set can be the same or different for the two directions.","One of these filtering operations can be carried out before the other, so that (for example) a filter could be selected for use in the vertical direction according to the required fractional position in the vertical direction (which in turn is determined by the particular motion vector in use), the filter applied so that samples at the appropriate vertical fractional position are generated, a horizontal filter selected according to the required horizontal fractional position (also determined by the motion vector) and that horizontal filter applied to the fractional position samples output by the vertical filter.","Of course, the order could be reversed so that the horizontal filter is applied before the vertical filter.","Such arrangements mean that only two filter calculations are required to apply a motion vector, avoiding the need to interpolate an interpolated version of an entire block.","Accordingly, the operation of deriving samples of an interpolated prediction unit can involve applying a filter (such as a 4-tap ×8 filter) horizontally and vertically to a stored prediction unit.","The step of applying the filter can comprise applying one of a set of m-tap filters horizontally and one of the set of m-tap filters vertically to a prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.","In some examples, to be discussed further below, it may be that only a ×(N/2) filter operation is needed in one or other direction, but for consistency of processing with other operations it can be technically more convenient to use a ×N filter.","In such instances, the ×(N/2) operation can be achieved in an elegantly convenient manner by using the set of filters (N or N-1 filters, as discussed above) applicable to ×N operation, but selecting only alternate fractional-position filters of the set (such as fractional positions 0 (if present), 2, 4, 6).","Accordingly, the present arrangements including those discussed below provide an embodiment of a video decoding method for decoding a video signal, the method being operable in respect of a 4:2:0 and 4:2:2 format video signal, the method comprising: generating prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect of a 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect of a 4:2:2 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit, but using only alternate fractional-position results as interpolated samples in the vertical direction.","As discussed above, the choice of filters, and so the choice of which interpolated samples to derive, can be according to a current motion vector, providing an example of accessing samples of the interpolated prediction unit pointed to by a motion vector to generate a motion compensated prediction of a prediction unit of the current image with respect to an area represented by the samples of the interpolated prediction unit.","Embodiments to be discussed further below are also operable in respect of 4:4:4 video data, the same 4-tap ×8 chrominance filter being applied horizontally and vertically to generate samples of an interpolated chrominance prediction unit but only alternate fractional-position results being used as interpolated samples in the horizontal and vertical directions.","As discussed, not every interpolated sample needs to be generated.","Accordingly, in embodiments, the step of applying the 4-tap ×8 chrominance filter can comprise applying one of a set of 4-tap filters horizontally and one of the set of 4-tap filters vertically to a chrominance prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.","In example embodiments, the 4-tap filters are indexed in order of fractional interpolation position (for example, as given by the table above); and for 4:2:2 format video, the deriving step comprises applying a filter selected from a subset of alternate filters in the indexing order (such as those filters relating to even fractional-position results).","Similar techniques can be used in the encoding process, so that the above arrangements provide examples of a video encoding method for encoding a video signal, the method being operable in respect of a 4:2:0 and 4:2:2 format video signal, the method comprising: generating motion vectors for prediction of prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect of a 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect of a 4:2:2 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically but using only alternate fractional-position results as interpolated samples in the vertical direction.","Embodiments also provide apparatus for carrying out the above techniques, such as the apparatus of FIG.","5, operating under the control of the controller 343.4:2:0 Inter-Prediction Referring now to FIGS.","25 and 26, in the 4:2:0 scheme as noted above typically an 8×8 luma PU 1300 will be associated with Cb and Cr 4×4 chroma PUs 1310.Consequently to interpolate the luma and chroma pixel data up to the same effective resolution, different interpolation filters are used.","For example for the 8×8 4:2:0 luma PU, interpolation is ¼ pixel, and so an 8-tap ×4 filter is applied horizontally first, and then the same 8-tap ×4 filter is applied vertically, so that the luma PU is effectively stretched 4 times in each direction, to form an interpolated array 1320 as shown in FIG.","25.Meanwhile the corresponding 4×4 4:2:0 chroma PU is ⅛ pixel interpolated to generate the same eventual resolution, and so a 4-tap ×8 filter is applied horizontally first, then the same 4-tap ×8 filter is applied vertically, so that the 4:2:0 chroma PUs are effectively stretched 8 times in each direction to form an array 1330, as shown in FIG.","26.4:2:2 Inter-Prediction A similar arrangement for 4:2:2 will now be described with reference to FIGS.","27 and 28, which illustrate a luma PU 1350 and a pair of corresponding chroma PUs 1360.Referring to FIG.","28, as noted previously, in the 4:2:2 scheme the chroma PU 1360 can be non-square, and for the case of an 8×8 4:2:2 luma PU, will typically be a 4 wide×8 high 4:2:2 Chroma PU for each of the Cb and Cr channels.","Note that the chroma PU is drawn, for the purposes of FIG.","28, as a square shaped array of non-square pixels, but in general terms it is noted that the PUs 1360 are 4 (horizontal)×8 (vertical) pixel arrays.","Whilst it may be possible therefore to use the existing 8-tap ×4 luma filter vertically on the chroma PU, in an embodiment of the present disclosure it has been appreciated that the existing 4-tap ×8 chroma filter would suffice for vertical interpolation as in practice one is only interested in the even fractional locations of the interpolated chroma PU.","Hence FIG.","27 shows the 8×8 4:2:2 luma PU 1350 interpolated as before with an 8-tap ×4 filter, and the 4×8 4:2:2 chroma PUs 1360 interpolated with the existing 4-tap ×8 chroma filter in the horizontal and vertical direction, but only with the even fractional results used for forming the interpolated image in the vertical direction.","These techniques are applicable to video coding or decoding methods, apparatus or programs using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, For example, For 4:2:2, M=2, N=1.For 4:2:0, M=2, N=2.The frame store 570 is operable to store one or more images preceding a current image.","The interpolation filter 580 is operable to interpolate a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1.In the current examples, P=Q=4 so that the interpolation filter 580 is operable to generate an interpolated image at % sample resolution.","The motion estimator 550 is operable to detect inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images.","The motion compensated predictor 540 is operable to generate a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector.","Returning to a discussion of the operation of the interpolation filter 580, embodiments of this filter are operable to apply a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and to subsample the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.","So, in the case of 4:2:2, the interpolation filter 580 applies a ×8 interpolation in the horizontal and vertical directions, but then vertically subsamples by a factor of 2, for example by using every 2nd sample in the interpolated output.","One way to achieve this is by doubling an index value into the array of samples.","So, consider an array direction (such as the vertical direction in this example) in the array of samples which is 8 samples across, indexed as 0 .",".",".","7.A required sample in the subsampled range is indexed in the range 0 .",".",".","3.So, doubling this index will give values of 0, 2, 4 and 6 which can then be used to access samples in the original array so that every alternate sample is used.","This is an example of selecting a subset of samples of the interpolated chrominance prediction unit.","This technique therefore allows the same (for example, ×8) filter to be used in respect of 4:2:0 and 4:2:2, but with a further step of subsampling where needed with 4:2:2.In embodiments, as discussed, the interpolated chrominance prediction unit has a height in samples twice that of a 4:2:0 format prediction unit interpolated using the same ×R and ×S interpolation filters.","The need to provide different filters can be avoided or alleviated using these techniques, and in particular by using the same ×R horizontal and ×S vertical interpolation filters, in respect of 4:2:0 input video data and 4:2:2 input video data.","As discussed, the step of subsampling the interpolated chrominance prediction unit comprises using every Vth sample of the interpolated chrominance prediction unit in the vertical direction, and/or using every Uth sample of the interpolated chrominance prediction unit in the vertical direction.","More generally, the subsampling can comprise selecting a subset of samples of the interpolated chrominance prediction unit.","Embodiments can involve deriving a luminance motion vector for a prediction unit; and independently deriving one or more chrominance motion vectors for that prediction unit.","In some embodiments, at least one of R and S is equal to 2 or more, and in some embodiments the ×R horizontal and ×S vertical interpolation filters are also applied to the luminance components of the stored image.","Note that the same interpolation techniques can be used in the encoder and in the decoder.","4:4:4 Inter-Prediction Variants By extension, the same principle of only using the even fractional results for the existing 4-tap ×8 chroma filter can be applied both vertically and horizontally for the 8×8 4:4:4 chroma PUs.","Further to these examples, the ×8 chroma filter may be used for all interpolation, including luma.","Further Inter-Prediction Variants In one implementation of motion vector (MV) derivation, one vector is produced for a PU in a P-slice (and two vectors for a PU in a B-slice (where a P-slice takes predictions from a preceding frame, and a B-slice takes predictions from a preceding and following frame, in a similar manner to MPEG P and B frames).","Notably, in this implementation in the 4:2:0 scheme the vectors are common to all channels, and moreover, the chroma data need not be used to calculate the motion vectors.","In other words, all the channels use a motion vector based on the luma data.","In an embodiment, in the 4:2:2 scheme the chroma vector could be derived so as to be independent from luma (i.e.","a single vector for the Cb and Cr channels could be derived separately), and in the 4:4:4 scheme chroma vectors could further be independent for each of the Cb and Cr channels.","Transforms In HEVC, most images are encoded as motion vectors from previously encoded/decoded frames, with the motion vectors telling the decoder where, in these other decoded frames, to copy good approximations of the current image from.","The result is an approximate version of the current image.","HEVC then encodes the so-called residual, which is the error between that approximate version and the correct image.","This residual requires much less information than specifying the actual image directly.","However, it is still generally preferable to compress this residual information to reduce the overall bitrate further.","In many encoding methods including HEVC, such data is transformed into the spatial frequency domain using an integer cosine transform (ICT), and typically some compression is then achieved by retaining low spatial frequency data and discarding higher spatial frequency data according to the level of compression desired.","4:2:0 Transforms The spatial frequency transforms used in HEVC are conventionally ones that generate coefficients in powers of 4 (for example 64 frequency coefficients) as this is particularly amenable to common quantisation/compression methods.","The square TUs in the 4:2:0 scheme are all powers of 4 and hence this is straightforward to achieve.","If the NSQT options are enabled, some non-square transforms are available for non-square TUs, such as 4×16, but again notably these result in 64 coefficients, i.e.","again a power of 4.4:2:2 and 4:4:4 Transform Variants The 4:2:2 scheme can result in non-square TUs that are not powers of 4; for example a 4×8 TU has 32 pixels, and 32 is not a power of 4.In an embodiment therefore, a non-square transform for a non-power of 4 number of coefficients may be used, acknowledging that modifications may be required to the subsequent quantisation process.","Alternatively, in an embodiment non-square TUs are split into square blocks having a power of 4 area for transformation, and then the resulting coefficients can be interleaved.","For example, for 4×8 blocks odd/even vertical samples can be split into two square blocks.","Alternatively, for 4×8 blocks the top 4×4 pixels and the bottom 4×4 pixels could form two square blocks.","Alternatively again, for 4×8 blocks a Haar wavelet decomposition can be used to form a lower and an upper frequency 4×4 block.","Any of these options may be made available, and the selection of a particular alternative may be signalled to or derived by the decoder.","Other Transform Modes In the 4:2:0 scheme there is a proposed flag (the so-called rqpprime_y_zero_transquant_bypass_flag′) allowing the residual data to be included in the bit stream losslessly (i.e.","without being transformed, quantised or further filtered).","In the 4:2:0 scheme the flag applies to all channels.","Accordingly, such embodiments represent a video coding or decoding method, apparatus or program in which luminance and chrominance samples are predicted and the difference between the samples and the respective predicted samples is encoded, making use of an indicator configured to indicate whether luminance difference data is to be included in an output bitstream losslessly; and to independently indicate whether chrominance difference data is to be included in the bitstream losslessly.","Such a flag or flags (or indicator or indicators respectively) may be inserted by the controller 343, for example.","In an embodiment, it is proposed that the flag for the luma channel is separate to the chroma channels.","Hence for the 4:2:2 scheme, such flags should be provided separately for the luma channel and for the chroma channels, and for the 4:4:4 scheme, such flags should be provided either separately for the luma and chroma channels, or one flag is provided for each of the three channels.","This recognises the increased chroma data rates associated with the 4:2:2 and 4:4:4 schemes, and enables, for example, lossless luma data together with compressed chroma data.","For intra-prediction coding, mode-dependent directional transform (MDDT) allows the horizontal or vertical ICT (or both ICTs) for a TU to be replaced with an Integer Sine Transform depending upon the intra-prediction direction.","In the 4:2:0 scheme this is not applied to chroma TUs.","However in an embodiment it is proposed to apply it to 4:2:2 and 4:4:4 chroma TUs, noting that the IST is only currently defined for a 4 sample transform dimensions (either horizontally or vertically), and therefore cannot currently be applied vertically to a 4×8 chroma TU.","In methods of video coding, the various embodiments can be arranged so as to indicate whether luminance difference data is to be included in an output bitstream losslessly; and independently to indicate whether chrominance difference data is to be included in the bitstream losslessly, and to encode or include the relevant data in the form defined by such indications.","Quantisation In the 4:2:0 scheme, the quantisation calculation is the same for chrominance as for luminance.","Only the quantisation parameters (QPs) differ.","QPs for chrominance are calculated from the luminance QPs as follows: Qp Cb = scalingTable [ Qp luminance + chroma_qp _index _offset ] Qp Cr = scalingTable [ Qp luminance + second_chroma _qp _index _offset ] where the scaling table is defined as seen in FIG.","29a or 29b (for 4:2:0 and 4:2:2 respectively), and “chroma_qp_index_offset” and “second_chroma_qp_index_offset” are defined in the picture parameter set and may be the same or different for Cr and Cb.","In other words, the value in square brackets defines in each case an “index” into the scaling table (FIGS.","29a and b) and the scaling table then gives a revised value of Qp (“value”).","Note that “chroma_qp_index_offset” and “second_chroma_qp_index_offset” may instead be referred to as cb_qp_offset and cr_qp_offset respectively.","Chrominance channels typically contain less information than luminance and hence have smaller-magnitude coefficients; this limitation on the chrominance QP may prevent all chrominance detail being lost at heavy quantisation levels.","The QP-divisor relationship in the 4:2:0 is a logarithmic one such that an increase of 6 in the QP is equivalent to a doubling of the divisor (the quantisation step size discussed elsewhere in this description, though noting that it may be further modified by Qmatrices before use).","Hence the largest difference in the scaling table of 51−39=12 represents a factor-of-4 change in the divisor.","However, in an embodiment, for the 4:2:2 scheme, which potentially contains twice as much chroma information as the 4:2:0 scheme, the maximum chrominance QP value in the scaling table may be raised to 45 (i.e.","halving the divisor).","Similarly for the 4:4:4 scheme, the maximum chrominance QP value in the scaling table may be raised to 51 (i.e.","the same divisor).","In this case the scaling table is in effect redundant, but may be retained simply for operational efficiency (i.e.","so that the system works by reference to a table in the same way for each scheme).","Hence more generally in an embodiment the chroma QP divisor is modified responsive to the amount of information in the coding scheme relative to the 4:2:0 scheme.","Accordingly, embodiments apply to a video coding or decoding method operable to quantise blocks of frequency-transformed luminance and chrominance component video data in a 4:4:4 or a 4:2:2 format according to a selected quantisation parameter which defines a quantisation step size.","A quantisation parameter association (such as, for example, the appropriate table in FIG.","29a or 29b) is defined between luminance and chrominance quantisation parameters, where the association is such that a maximum chrominance quantisation step size is less than a maximum luminance quantisation step size for the 4:2:2 format (for example, 45) but equal to the maximum luminance quantisation step size for the 4:4:4 format (for example, 51).","The quantisation process operates in that each component of the frequency-transformed data is divided by a respective value derived from the respective quantisation step size, and the result is rounded to an integer value, to generate a corresponding block of quantised spatial frequency data.","It will be appreciated that the dividing and rounding steps are indicative examples of a generic quantising stage, according to the respective quantisation step size (or data derived from it, for example by the application of Qmatrices).","Embodiments include the step of selecting a quantisation parameter or index (QP for luminance) for quantising the spatial frequency coefficients, the quantisation parameter acting as a reference to a respective one of a set of quantisation step sizes according to the QP tables applicable to luminance data.","The process of defining the quantisation parameter association can then comprise: for chrominance components, referencing a table of modified quantisation parameters (such as the table of FIG.","29a or 29b) according to the selected quantisation parameter, which in turn can involve (i) for the first chrominance component, adding a first offset (such as chroma_qp_index_offset) to the quantisation parameter and selecting the modified quantisation index corresponding to the entry, in the table, for the quantisation index plus the first offset; and (ii) for the second chrominance component, adding a second offset (such as second_chroma_qp_index_offset) to the quantisation parameter and selecting the modified quantisation index corresponding to the entry, in the table, for the quantisation index plus the second offset; and referencing a respective quantisation step size in the set according to the quantisation parameter for the luminance data and the first and second modified quantisation indices for the first and second chrominance components.","Viewed in a different way, this is an example of a process involving selecting a quantisation parameter for quantising the spatial frequency coefficients, the quantisation parameter acting as a reference to a respective one of a set of quantisation step sizes; and in which the defining step comprises: for chrominance components, referencing a table of modified quantisation parameters according to the selected quantisation parameter, the referencing step comprising: for each chrominance component, adding a respective offset to the quantisation parameter and selecting the modified quantisation parameter corresponding to the entry, in the table, for the quantisation parameter plus the respective offset; and referencing a respective quantisation step size in the set according to the quantisation parameter for the luminance data and the first and second modified quantisation parameters for the first and second chrominance components.","The techniques are particularly applicable to arrangements in which successive values of the quantisation step sizes in the set are related logarithmically, so that a change in quantisation parameter of m (where m is an integer) represents a change in quantisation step size by a factor of p (where p is an integer greater than 1).","In the present embodiments, m=6 and p=2.In embodiments, as discussed above, a maximum luminance quantisation parameter is 51; a maximum chrominance quantisation parameter is 45 for the 4:2:2 format; and a maximum chrominance quantisation parameter is 51 for the 4:4:4 format.","In embodiments, the first and second offsets can be communicated in association with the encoded video data.","In 4:2:0 the transform matrices A are initially created (by the transform unit 340) from those of a true normalised N×N DCT A′ using: Aij=int(64×√{square root over (N)}×A′ij) where i and j indicate a position within the matrix.","This scaling with respect to a normalised transform matrix provides an increase in precision, avoids the need for fractional calculations and increases the internal precision.","Ignoring differences due to rounding of Aij, since X is multiplied by both A and AT (the transposition of the matrix A) the resulting coefficients differ from those of a true normalised M×N (M=height; N=width) DCT by a common scaling factor of: (64×√{square root over (N)})(64×√{square root over (M)})=4096√{square root over (N)}√{square root over (M)} Note that the common scaling factor could be different to this example.","Note also that matrix multiplying by both A and AT can be carried out in various ways, such as the so-called Butterfly method.","The significant fact is whether the operation that is carried out is equivalent to a traditional matrix multiplication, not whether it is performed in a particular traditional order of operations.","This scaling factor is equivalent to a binary left-shift bitwise operation by a number of bits transformShift, since in HEVC this results in a power of 2: transformShift=(12+0.5 log2(N)+0.5 log2(M)) To reduce the requirement on internal bit-precision, the coefficients are right-shifted (using positive rounding) twice during the transform process: shift1=log2(N)+bitDepth−9 shift2=log2(M)+6 As a result, the coefficients as they leave the forward transform process and enter the quantiser are effectively left-shifted by: resultingShift = ( 12 + 0.5 log 2 ( NM ) ) - ( shift 1 + shift 2 ) = ( 12 + 0.5 log 2 ( N ) + 0.5 log 2 ( M ) ) - ( log 2 ( N ) + bitDepth - 9 + log 2 ( M ) + 6 ) = 15 - ( 0.5 log 2 ( N ) + 0.5 log 2 ( M ) + bitDepth ) In 4:2:0, the frequency separated (for example, DCT) coefficients generated by the frequency transform are a factor of (2resultingShift) larger than those that a normalised DCT would produce.","In some embodiments, the blocks are either square or rectangular with a 2:1 aspect ratio.","Therefore, for a block size of N×M, either: N=M, in which case, resultingShift is an integer and S=N=M=sqrt(NM); or 0.5N=2M or 2N=0.5M, in which case resultingShift is still an integer and S=sqrt(NM) resultingShift=15−(0.5 log2(N)+0.5 log2(M)+bitDepth)=15−(log2(S)+bitDepth) The coefficients are subsequently quantised, where the quantising divisor is derived according to the quantisation parameter QP.","Note that resultingShift is equivalent to an integer, so the common scaling factor is an integer power of 2, the overall left-shift ‘resultingShift’ of the transform process is also accounted for at this stage by applying an equal but opposite right-shift, ‘quantTransformRightShift’.","This bit-shift operation is possible because resultingShift is an integer.","Also note that the divisor-QP (quantisation parameter or index) relationship follows a base-2 power curve, as mentioned above, in that an increase in QP by 6 has the effect of doubling the divisor whereas an increase in QP by 3 has the effect of increasing the divisor by a factor of sqrt(2) (square root of 2).","Due to the chroma format in 4:2:2, there are more TU width:height (N:M) ratios: N=M (from before) where S=N=M=sqrt(NM) (resultingShift is an integer) 0.5N=2M and 2N=0.5M, (from before), where S=sqrt(NM) (resultingShift is an integer) N=2M where S=sqrt(NM) 2M=N where S=sqrt(NM) 4N=0.5M where S=sqrt(NM) resultingShift=15−(log2(S)+bitDepth) In these latter three situations, resultingShift is not an integer.","For example, this may apply where at least some of the blocks of video data samples comprise M×N samples, where the square root of N/M is not equal to an integer power of 2.Such block sizes can occur in respect of chroma samples in some of the present embodiments.","Accordingly, in such instances, the following techniques are relevant, that is to say, in video coding or decoding methods, apparatus or programs operable to generate blocks of quantised spatial frequency data by performing frequency-transformation on blocks of video data samples using a transform matrix comprising an array of integer values which are each scaled with respect to respective values of a normalized transform matrix by an amount dependent upon a dimension of the transform matrix, and to quantise the spatial frequency data according to a selected quantisation step size, having the step of frequency-transforming a block of video data samples by matrix-multiplying the block by the transform matrix and the transposition of the transform matrix to generate a block of scaled spatial frequency coefficients which are each larger, by a common scaling factor (for example, resultingShift), than the spatial frequency coefficients which would result from a normalized frequency-transformation of that block of video data samples.","Therefore at the quantisation stage, an appropriate bit-shift operation cannot be used to cancel out the operation in a simple manner.","A solution to this is proposed as follows: At the quantiser stage, apply a right shift: quantTransformRightShift=15−log 2(S′)−bitDepth Where the value S′ is derived such that resultingShift−quantTransformRightShift=+½quantTransformRightShift is an integer The difference between shifts of ½ is equivalent to multiplication by sqrt(2), i.e.","at this point the coefficients are sqrt(2) times larger than they should be, making the bit shift an integer bit shift.","For the quantisation process, apply a quantisation parameter of (OP+3), meaning that the quantising divisor is effectively increased by a factor of sqrt(2), thus cancelling out the sqrt(2) scale factor from the previous step.","Accordingly, these steps can be summarised (in the context of a video coding or decoding method (or corresponding apparatus or program) operable to generate blocks of quantised spatial frequency data by performing frequency-transformation on blocks of video data samples using a transform matrix comprising an array of integer values which are each scaled with respect to respective values of a normalized transform matrix, and to quantise the spatial frequency data according to a selected quantisation step size, involving frequency-transforming a block of video data samples by matrix-multiplying the block by the transform matrix and the transposition of the transform matrix to generate a block of scaled spatial frequency coefficients which are each larger, by a common scaling factor, than the spatial frequency coefficients which would result from a normalized frequency-transformation of that block of video data samples) as follows: selecting a quantisation step size for quantising the spatial frequency coefficients; applying an n-bit shift (for example, quantTransformRightShift) to divide each of the scaled spatial frequency coefficients by a factor of 2n, where n is an integer; and detecting a residual scaling factor (for example, resultingShift−quantTransformRightShift), being the common scaling factor divided by 2n.","For example, in the situation discussed above, the quantisation step size is then according to the residual scaling factor to generate a modified quantisation step size; and each of the scaled spatial frequency coefficients in the block is divided by a value dependent upon the modified quantisation step size and rounding the result to an integer value, to generate the block of quantised spatial frequency data.","As discussed, the modification of the quantisation step size can be carried out simply by adding an offset to QP so as to select a different quantisation step size when QP is mapped into the table of quantisation step sizes.","The coefficients are now of the correct magnitude for the original QP.","The transform matrix can comprise an array of integer values which are each scaled with respect to respective values of a normalized transform matrix by an amount dependent upon a dimension of the transform matrix.","It follows that the required value for S′ can always be derived as follows: S′=sqrt(2*M*N) As an alternative proposal, S′ could be derived such that: resultingShift−quantTransformRightShift=−½ In this case, S′=sqrt(½*M*N), and the applied quantisation parameter is (QP−3) In either of these cases, (adding 3 to QP or subtracting 3 from QP), the step of selecting the quantisation step size comprises selecting a quantisation index (for example, QP), the quantisation index defining a respective entry in a table of quantisation step sizes, and the modifying step comprises changing the quantisation index so as to select a different quantisation step size, such that the ratio of the different quantisation step size to the originally selected quantisation step size is substantially equal to the residual scaling factor.","This works particularly well where, as in the present embodiments, successive values of the quantisation step sizes in the table are related logarithmically, so that a change in quantisation index (for example, QP) of m (where m is an integer) represents a change in quantisation step size by a factor of p (where p is an integer greater than 1).","In the present embodiments, m=6 and p=2, so that an increase of 6 in QP represents a doubling of the applied quantisation step size, and a decrease in QP of 6 represents a halving of the resulting quantisation step size.","As discussed above, the modification can be carried out by selecting a quantisation index (for example, a base QP) in respect of luminance samples; generating a quantisation index offset, relative to the quantisation index selected for the luminance samples, for samples of each or both chrominance components; changing the quantisation index offset according to the residual scaling factor; and communicating the quantisation index offset in association with the coded video data.","In embodiments of HEVC, QP offsets for the two chroma channels are sent in the bit stream.","These steps correspond to a system in which the QP offset (to account for the residual scaling factor) of +/−3 could be incorporated into these offsets, or they could be incremented/decremented when they are used to derive the chroma QP.","Note that the QP offset does not have to be +/−3 if differently shaped blocks were used; it is just that +/−3 represents an offset applicable to the block shapes and aspect ratios discussed above in respect of 4:2:2 video, for example.","In some embodiments, n (the bit shift as applied) is selected so that 2n is greater than or equal to the common scaling factor.","In other embodiments, n is selected so that 2n is less than or equal to the common scaling factor.","In embodiments (using either of these arrangements), a bit shift n can be selected so as to be the next nearest (in either direction) to the common scaling factor, so that the residual scaling factor represents a factor having a magnitude of less than 2.In other embodiments, the modification of the quantisation step size can simply be performed by multiplying the quantisation step size by a factor dependent upon the residual scaling factor.","That is to say, the modification need not involve modifying the index QP.","Note also that the quantisation step size as discussed is not necessarily the actual quantisation step size by which a transformed sample is divided.","The quantisation step size derived in this way can be further modified.","For example, in some arrangements, the quantisation step size is further modified by respective entries in a matrix of values (Qmatrix) so that different final quantisation step sizes are used at different coefficient positions in a quantised block of coefficients.","It is also notable that in the 4:2:0 scheme, the largest chroma TU is 16×16, whereas for the 4:2:2 scheme 16×32 TUs are possible, and for the 4:4:4 scheme, 32×32 chroma TUs are possible.","Consequently in an embodiment quantisation matrices (Qmatrices) for 32×32 chroma TUs are proposed.","Similarly, Qmatrices should be defined for non-square TUs such as the 16×32 TU, with one embodiment being the subsampling of a larger square Q matrix Qmatrices could be defined by any one of the following: values in a grid (as for 4×4 and 8×8 Qmatrices); interpolated spatially from respective smaller or larger matrices; in HEVC larger Qmatrices can be derived from respective groups of coefficients of smaller reference ones, or smaller matrices can be sub-sampled from larger matrices.","Note that this interpolation or subsampling can be carried out within a channel ratio—for example, a larger matrix for a channel ratio can be interpolated from a smaller one for that channel ratio.","relative to other Qmatrices (i.e.","difference values, or deltas); hence only the deltas need to be sent.","Taking a small example just for illustrative purposes, a particular matrix for one channel ratio could be defined, such as a 4×4 matrix in respect of 4:2:0 (a b) (c d) where a, b, c and d are respective coefficients.","This acts as a reference matrix.","Embodiments of the disclosure could then define a set of difference values for a similar-sized matrix in respect of another channel ratio: (diff1diff2) (diif3 diff4) so that in order to generate the Qmatrix for the other channel ratio, the matrix of differences is matrix-added to the reference matrix.","Instead of differences, a matrix of multiplicative factors could be defined for the other channel ratio, such that either (i) the matrix of multiplicative factors is matrix-multiplied with the reference matrix to generate the Qmatrix for the other channel ratio, or (ii) each coefficient in the reference matrix is individually multiplied by a respective factor to generate the Qmatrix for the other channel ratio.","as a function of another Qmatrix; e.g.","a scaling ratio relative to another matrix (so that each of a, b, c and d in the above example is multiplied by the same factor, or has the same difference added to it).","This reduces the data requirements for transmitting the difference or factor data.","hence only the coefficients of the functions need to be sent (such as the scaling ratio), as an equation/function (e.g.","piece-wise linear curve, exponential, polynomial); hence only the coefficients of the equations need to be sent to derive the matrix, or any combination of the above.","For example, each of a, b, c and d could in fact be defined by a function which could include a dependence upon the coefficient position (i,j) within the matrix.","(l, j) could represent, for example, the coefficient position from left to right followed by the coefficient position from top to bottom of the matrix.","An example is: coefficienti,j=3i+2j Note that Qmatrices can be referred to as Scaling Lists within the HEVC environment.","In embodiments in which the quantisation is applied after the scanning process, the scanned data may be a linear stream of successive data samples.","In such instances, the concept of a Qmatrix still applies, but the matrix (or Scanning List) may be considered as a 1×N matrix, such that the order of the N data values within the 1×N matrix corresponds to the order of scanned samples to which the respective Qmatrix value is to be applied.","In other words, there is a 1:1 relationship between data order in the scanned data, spatial frequency according to the scan pattern, and data order in the 1×N Qmatrix.","Note that it is possible, in some implementations, to bypass or omit the DCT (frequency separation) stage, but to retain the quantisation stage.","Other useful information includes an optional indicator of to which other matrix the values are related, i.e.","the previous channel or the first (primary) channel; for example the matrix for Cr could be a scaled factor of a matrix for Y, or for Cb, as indicated.","Accordingly, embodiments of the disclosure can provide a video coding or decoding method (and a corresponding apparatus or computer program) operable to generate blocks of quantised spatial frequency data by (optionally) performing frequency-transformation on blocks of video data samples and quantising the video data (such as the spatial frequency data) according to a selected quantisation step size and a matrix of data modifying the quantisation step size for use at different respective block positions within an ordered block of samples (such as an ordered block of frequency-transformed samples), the method being operable with respect to at least two different chrominance subsampling formats.","For at least one of the chrominance subsampling formats, one or more quantisation matrices are defined as one or more predetermined modifications with respect to one or more reference quantisation matrices defined for a reference one of the chrominance subsampling formats.","In embodiments of the disclosure, the defining step comprises defining one or more quantisation matrices as a matrix of values each interpolated from a respective plurality of values of a reference quantisation matrix.","In other embodiments, the defining step comprises defining one or more quantisation matrices as a matrix of values each subsampled from values of a reference quantisation matrix.","In embodiments of the disclosure, the defining step comprises defining one or more quantisation matrices as a matrix of differences with respect to corresponding values of a reference quantisation matrix.","In embodiments of the disclosure, the defining step comprises defining one or more quantisation matrices as a predetermined function of values of a reference quantisation matrix.","In such instances, the predetermined function may be a polynomial function.","In embodiments of the disclosure, one or both of the following is provided, for example as part of or in association with the coded video data: (i) reference-indicator data to indicate, with respect to encoded video data, the reference quantisation matrix; and (ii) modification-indicator data to indicate, with respect to encoded data values, the one or more predetermined modifications.","These techniques are particularly applicable where two of the chrominance subsampling formats are 4:4:4 and 4:2:2 formats.","The number of Q Matrices in HEVC 4:2:0 is currently 6 for each transform size: 3 for the corresponding channels, and one set for intra and for inter.","In the case of a 4:4:4 GBR scheme, it will be appreciated that either one set of quantisation matrices could be used for all channels, or three respective sets of quantisation matrices could be used.","In embodiments of the disclosure, at least one of the matrices is a 1×N matrix.","This would be the case in (as described here) one or more of the matrices is in fact a Scaling List or the like, being a linear 1×N ordered array of coefficients.","The proposed solutions involve incrementing or decrementing the applied QP.","However this could be achieved in a number of ways: In HEVC, QP offsets for the two chroma channels are sent in the bit stream.","The +/−3 could be incorporated into these offsets, or they could be incremented/decremented when they are used to derive the chroma QP.","As discussed, above, in HEVC, (luma QP+chroma offset) is used as an index to a table in order to derive the chroma QP.","This table could be modified to incorporate the +/−3 (i.e.","by incrementing/decrementing the values of the original table by 3) After the chroma QP has been derived, as per the normal HEVC process, the results could then be incremented (or decremented) by 3.As an alternative to modifying the QP, a factor of sqrt(2) or 1/sqrt(2) can be used to modify the quantisation coefficients.","For forward/inverse quantisation, the division/multiplication processes are implemented by using (QP % 6) as an index to a table to obtain a quantisation coefficient or quantisation step size, inverseQStep/scaledQStep.","(Here, QP % 6 signifies QP modulo 6).","Note that, as discussed above, this may not represent the final quantisation step size which is applied to the transformed data; it may be further modified by the Qmatrices before use.","The default tables in HEVC are of length 6, covering an octave (a doubling) of values.","This is simply a means of reducing storage requirements; the tables are extended for actual use by selecting an entry in the table according to the modulus of QP (mod 6) and then multiplying or dividing by an appropriate power of 2, dependent upon the difference of (QP−QP modulus 6) from a predetermined base value.","This arrangement could be varied to allow for the offset of +/−3 in the QP value.","The offset can be applied in the table look-up process, or the modulus process discussed above could instead be carried out using the modified QP.","Assuming the offset is applied at the table look-up, however, additional entries in the table can be provided as follows: One alternative is to extend the tables by 3 entries, where the new entries are as follows (for the index values of 6-8).","The example table shown in FIG.","30 would be indexed by [(QP % 6)+3] (a “QP increment method”), where the notation QP % 6 signifies “QP modulus 6”.","The example table shown in FIG.","31 would be indexed by [(QP % 6)−3] (a “QP decrement method”), having extra entries for the index values of −1 to −3: Entropy Encoding Basic entropy encoding comprises assigning codewords to input data symbols, where the shortest available codewords are assigned to the most probable symbols in the input data.","On average the result is a lossless but much smaller representation of the input data.","This basic scheme can be improved upon further by recognising that symbol probability is often conditional on recent prior data, and consequently making the assignment process context adaptive.","In such a scheme, context variables (CVs) are used to determine the choice of respective probability models, and such CVs are provided for in the HEVC 4:2:0 scheme.","To extend entropy encoding to the 4:2:2 scheme, which for example will use 4×8 chroma TUs rather than 4×4 TUs for an 8×8 luma TU, optionally the context variables can be provided for by simply vertically repeating the equivalent CV selections.","However, in an embodiment of the present disclosure the CV selections are not repeated for the top-left coefficients (i.e.","the high-energy, DC and/or low spatial frequency coefficients), and instead new CVs are derived.","In this case, for example, a mapping may be derived from the luma map.","This approach may also be used for the 4:4:4 scheme.","During coding, in the 4:2:0 scheme, a so-called zig-scan scans through the coefficients in order from high to low frequencies.","However, again it is noted that the chroma TUs in the 4:2:2 scheme can be non-square, and so in an embodiment of the present disclosure a different chroma scan is proposed with the angle of the scan be tilted to make it more horizontal, or more generally, responsive to the aspect ratio of the TU.","Similarly, the neighbourhood for significance map CV selection and the c1/c2 system for greater-than-one and greater-than-two CV selection may be adapted accordingly.","Likewise, in an embodiment of the present disclosure the last significant coefficient position (which becomes the start point during decoding) could also be adjusted for the 4:4:4 scheme, with last-significant positions for chroma TUs being coded differentially from the last-significant position in the co-located luma TU.","The coefficient scanning can also be made prediction mode dependent for certain TU sizes.","Hence a different scan order can be used for some TU sizes dependent on the intra-prediction mode.","In the 4:2:0 scheme, mode dependent coefficient scanning (MDCS) is only applied for 4×4/8×8 luma TUs and 4×4 chroma TUs for intra prediction.","MDCS is used dependent on the intra-prediction mode, with angles +/−4 from the horizontal and vertical being considered.","In an embodiment of the present disclosure, it is proposed that in the 4:2:2 scheme MDCS is applied to 4×8 and 8×4 chroma TUs for intra prediction.","Similarly, it is proposed that in the 4:4:4 scheme MDCS is applied to 8×8 and 4×4 chroma TUs.","MDCS for 4:2:2 may only be done in the horizontal or vertical directions, and that the angle ranges may differ for 4:4:4 chroma vs. 4:4:4 luma vs. 4:2:2 chroma vs. 4:2:2 luma vs. 4:2:0 luma.","In-Loop Filters Deblocking Deblocking is applied to all CU, PU and TU boundaries, and the CU/PU/TU shape is not taken into account.","The filter strength and size is dependent on local statistics, and deblocking has a granularity of 8×8 Luma pixels.","Consequently it is anticipated that the current deblocking applied for the 4:2:0 scheme should also be applicable for the 4:2:2 and 4:4:4 schemes.","Sample Adaptive Offsetting In sample adaptive offsetting (SAO) each channel is completely independent.","SAO splits the image data for each channel using a quad-tree, and the resulting blocks are at least one LCU in size.","The leaf blocks are aligned to LCU boundaries and each leaf can run in one of three modes, as determined by the encoder (“Central band offset”, “Side band offset” or “Edge offset”).","Each leaf categorises its pixels, and the encoder derives an offset value for each of the 16 categories by comparing the SAO input data to the source data.","These offsets are sent to the decoder.","The offset for a decoded pixel's category is added to its value to minimise the deviation from the source.","In addition, SAO is enabled or disabled at picture level; if enabled for luma, it can also be enabled separately for each chroma channel.","SAO will therefore be applied to chroma only if it is applied to luma.","Consequently the process is largely transparent to the underlying block scheme and it is anticipated that the current SAO applied for the 4:2:0 scheme should also be applicable for the 4:2:2 and 4:4:4 schemes.","Adaptive Loop Filtering In the 4:2:0 scheme, adaptive loop filtering (ALF) is disabled by default.","However, in principle (i.e.","if allowed) then ALF would be applied to the entire picture for chroma.","In ALF, luma samples may be sorted into one of a number of categories, as determined by the HEVC documents; each category uses a different Wiener-based filter.","By contrast, in 4:2:0 chroma samples are not categorised—there is just one Wiener-based filter for Cb, and one for Cr.","Hence in an embodiment of the present disclosure, in light of the increased chroma information in the 4:2:2 and 4:4:4 schemes, it is proposed that the chroma samples are categorised; for example with K categories for 4:2:2 and J categories for 4:4:4.Whilst in the 4:2:0 scheme ALF can be disabled for luma on a per-CU basis using an ALF control flag (down to the CU-level specified by the ALF control depth), it can only be disabled for chroma on a per-picture basis.","Note that in HEVC, this depth is currently limited to the LCU level only.","Consequently in an embodiment of the present disclosure, the 4:2:2 and 4:4:4 schemes are provided with one or two channel specific ALF control flags for chroma.","Syntax In HEVC, syntax is already present to indicate 4:2:0, 4:2:2 or 4:4:4 schemes, and is indicated at the sequence level.","However, in an embodiment of the present disclosure it is proposed to also indicate 4:4:4 GBR coding at this level.","Data Signals It will be appreciated that data signals generated by the variants of coding apparatus discussed above, and storage or transmission media carrying such signals, are considered to represent embodiments of the present disclosure.","Respective features of embodiments are defined by the following numbered clauses: 1.A video coding method operable in respect of images of a 4:2:2 format video signal, comprising: partitioning an image to be encoded into coding units, prediction units and transform units for encoding, a coding unit being a square array of luminance samples and the corresponding chrominance samples, there being one or more prediction units in a coding unit, and there being one or more transform units in a coding unit; in which a prediction unit is an elementary unit of prediction so that all samples within a single prediction unit are predicted using a common prediction technique, and a transform unit is a basic unit of transformation and quantisation; enabling non-square transforms so as to allow non-square prediction units; and selecting transform unit block sizes to align with the prediction unit block layout.","2.A method according to clause 1, comprising: enabling asymmetric motion partitioning so as to allow asymmetry between two or more prediction units corresponding to a single coding unit.","3.A method according to clause 1 or clause 2, in which the step of selecting transform unit block sizes comprises: detecting image features in the portion of the image corresponding to a prediction unit; and selecting transform unit block sizes in respect of that prediction unit so as to align transform unit boundaries with edges of image features in the portion of the image.","4.A method according to clause 3, in which the step of selecting transform unit block sizes comprises: selecting transform unit block sizes for the one or more transform units derived from a coding unit, according to a tree hierarchy of divisions defined with respect to the size of the respective prediction unit.","5.A method according to any one of the preceding clauses, in which the step of selecting transform unit block sizes comprises selecting transform unit block sizes from the following table, according to the selected coding unit and prediction unit configuration: TU Options CU Size PU Options Level 0 Level 1 Level 2 64 × 64 64 × 64 n/a 32 × 32 × 4 16 × 16 × 4 64 × 32 × 2 or n/a 32 × 32 × 4 32 × 8 × 4 64 × 16 + 64 × 48 32 × 64 × 2 or n/a 32 × 32 × 4 8 × 32 × 4 16 × 64 + 48 × 64 32 × 32 32 × 32 32 × 32 16 × 16 × 4 8 × 8 × 4 32 × 16 × 2 or n/a 32 × 8 × 4 16 × 4 × 4 (luminance) + 32 × 8 + 32 × 24 4 × 4 × 4 (chrominance) or 16 × 4 × 4 luminance) + 8 × 4 × 4 (chrominance) 16 × 32 × 2 or n/a 8 × 32 × 4 4 × 16 × 4 (luminance) + 8 × 32 + 24 × 32 4 × 4 × 4 (chrominance) 16 × 16 16 × 16 16 × 16 8 × 8 × 4 4 × 4 × 4 (luminance) + 4 × 8 × 4 (chrominance) 16 × 8 × 2 or n/a 16 × 4 × 4 (luminance) + 4 × 4 × 4 (luminance) + 16 × 4 + 16 × 12 4 × 8 × 4 4 × 8 × 1 (chrominance) (chrominance) 8 × 16 × 2 or n/a 4 × 16 + 12 × 16 8 × 8 8 × 8 or 8 × 8 4 × 4 × 4 (luminance) + n/a 4 × 4 × 4 or 4 × 8 × 1 (chrominance) 8 × 4 × 2 or 4 × 8 × 2 4 × 4 × 4 (luminance) + 4 × N n/a 4 × 4 × 4 (luminance) + n/a (chrominance) 4 × 8 × 1 (chrominance) where level 0, level 1 and level 2 represent successive levels in the tree hierarchy of divisions, n/a indicates an unallowable mode, each block size is represented by the notation (horizontal dimension)×(vertical dimension)×(number of instances, if applicable), and N is an integer greater than 1.6.A method according to any one of clauses 1 to 4, in which the step of selecting transform unit block sizes comprises selecting transform unit block sizes from the following table, according to the selected coding unit and prediction unit configuration: TU Options CU Size PU Options Level 0 Level 1 Level 2 64 × 64 64 × 64 n/a 32 × 32 × 4 16 × 16 × 4 64 × 32 × 2 or n/a 32 × 32 × 4 32 × 8 × 4 64 × 16 + 64 × 48 32 × 64 × 2 or n/a 32 × 32 × 4 8 × 32 × 4 16 × 64 + 48 × 64 32 × 32 32 × 32 32 × 32 16 × 16 × 4 8 × 8 × 4 32 × 16 × 2 or n/a 32 × 8 × 4 16 × 4 × 4 (luminance) + 32 × 8 + 32 × 24 4 × 4 × 4 (chrominance) or 16 × 4 × 4 luminance) + 8 × 4 × 4 (chrominance) 16 × 32 × 2 or n/a 8 × 32 × 4 4 × 16 × 4 (luminance) + 8 × 32 + 24 × 32 4 × 4 × 4 (chrominance) 16 × 16 16 × 16 16 × 16 8 × 8 × 4 4 × 4 × 4 (luminance) + 4 × 8 × 4 (chrominance) 16 × 8 × 2 or n/a 16 × 4 × 4 (luminance) + 8 × 4 × 4 4 × 4 × 4 (luminance) + 16 × 4 + 16 × 12 (chrominance) 8 × 4 × 1 (chrominance) 8 × 16 × 2 or n/a 4 × 16 + 12 × 16 8 × 8 8 × 8 or 8 × 8 4 × 4 × 4 (luminance) + n/a 4 × 4 × 4 or 4 × 8 × 1 (chrominance) 8 × 4 × 2 or 4 × 8 × 2 4 × 4 × 4 (luminance) + 4 × N n/a 4 × 4 × 4 (luminance) + n/a (chrominance) 4 × 8 × 1 (chrominance) where level 0, level 1 and level 2 represent successive levels in the tree hierarchy of divisions, n/a indicates an unallowable mode, each block size is represented by the notation (horizontal dimension)×(vertical dimension)×(number of instances, if applicable), and N is an integer greater than 1.7.A method according to any one of the preceding clauses, comprising the step of splitting a non-square transform unit into a plurality of square transform units prior to transforming or quantising that transform unit.","8.Computer software which, when executed by a computer, causes the computer to carry out a method according to any one of the preceding clauses.","9.A machine-readable non-transitory storage medium which stores software according to clause 8.10.A data signal comprising coded data generated according to the method of any one of clauses 1 to 7.11.A video coding apparatus operable in respect of images of a 4:2:2 format video signal, comprising: a controller configured to partition an image to be encoded into coding units, prediction units and transform units for encoding, a coding unit being a square array of luminance samples and the corresponding chrominance samples, there being one or more prediction units in a coding unit, and there being one or more transform units in a coding unit; in which a prediction unit is an elementary unit of prediction so that all samples within a single prediction unit are predicted using a common prediction technique, and a transform unit is a basic unit of transformation and quantisation; to enable non-square transforms so as to allow non-square prediction units; and to select transform unit block sizes to align with the prediction unit block layout.","Further respective embodiments are defined by the following numbered clauses: 1.A video decoding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the method comprising: storing one or more images preceding a current image; interpolating a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; detecting inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and generating a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolating step comprises: applying a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and subsampling the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.","Note that the detecting step may not be required in a decoding arrangement, as the decoder can use the motion vectors provided to it (for example, as part of the video datastream) by the encoder.","2.A method according to clause 1, in which M=2 and N=1.3.A method according to clause 2, in which the input video data is in a 4:2:2 format.","4.A method according to clause 3, in which the interpolated chrominance prediction unit has a height in samples twice that of a 4:2:0 format prediction unit interpolated using the same ×R and ×S interpolation filters.","5.A method according to clause 2, the method being separately operable, using the same ×R horizontal and ×S vertical interpolation filters, in respect of 4:2:0 input video data and 4:2:2 input video data.","6.A method according to any one of the preceding clauses, in which P=4.7.A method according to any one of the preceding clauses, in which Q=4.8.A method according to any one of the preceding clauses, in which the step of subsampling the interpolated chrominance prediction unit comprises using every Vth sample of the interpolated chrominance prediction unit in the vertical direction.","9.A method according to any one of the preceding clauses, in which the step of subsampling the interpolated chrominance prediction unit comprises using every Uth sample of the interpolated chrominance prediction unit in the vertical direction.","10.A method according to any one of the preceding clauses, comprising: deriving a luminance motion vector for a prediction unit; and independently deriving one or more chrominance motion vectors for that prediction unit.","11.A method according to any one of the preceding clauses, in which at least one of R and S is equal to 2 or more.","12.A method according to any one of the preceding clauses, comprising applying the ×R horizontal and ×S vertical interpolation filter to the luminance components of the stored image.","13.A method according to any one of the preceding clauses, in which the subsampling comprising selecting a subset of samples of the interpolated chrominance prediction unit.","14.A video coding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the method comprising: storing one or more images preceding a current image; interpolating a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; detecting inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and generating a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolating step comprises: applying a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and subsampling the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.","15.Computer software which, when executed by a computer, causes the computer to carry out a method according to any one of the preceding clauses.","16.A machine-readable non-transitory storage medium which stores software according to clause 15.17.A data signal comprising coded data generated according to the method of any one of clauses 1 to 14.18.A video decoding apparatus using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the apparatus comprising: an image store configured to store one or more images preceding a current image; an interpolator configured to interpolate a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; a detector configured to detect inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and a generator configured to generate a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolator is configured: to apply a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and to subsample the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.","19.A video coding apparatus using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the apparatus comprising: an image store configured to store one or more images preceding a current image; an interpolator configured to interpolate a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; a detector configured to detect inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and a generator configured to generate a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolator is configured: to apply a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and to subsample the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.","20.Video capture, display, transmission, reception and/or storage apparatus comprising apparatus according to clause 18 or clause 19."]],"string":"[\n [\n \"DATA ENCODING AND DECODING\",\n \"A video coding or decoding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, comprises: storing one or more images preceding a current image; interpolating a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; detecting inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and generating a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolating step comprises: applying a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and subsampling the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.\"\n ],\n [\n \"1.\",\n \"(canceled) 2.A video decoding method for decoding a video signal, the method being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the method comprising: generating prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit using only alternate fractional-position results as interpolated samples in the horizontal and vertical directions.\",\n \"3.The video decoding method according to claim 2, in which the generating step comprises: accessing samples of the interpolated prediction unit pointed to by a motion vector to generate a motion compensated prediction of a prediction unit of the current image with respect to an area represented by the samples of the interpolated prediction unit.\",\n \"4.The video decoding method according to claim 3, in which the motion vector is a sub-pixel accuracy motion vector.\",\n \"5.The video decoding method according to claim 4, in which the step of applying the 4-tap ×8 chrominance filter comprises applying one of a set of 4-tap filters horizontally and one of the set of 4-tap filters vertically to a chrominance prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.\",\n \"6.The video decoding method according to claim 5, in which: the 4-tap filters are indexed in order of fractional interpolation position; and for 4:4:4 format video, the deriving comprises applying a filter selected from a subset of alternate filters in the indexing order.\",\n \"7.The video decoding method according to claim 5, in which the set of 4-tap filters comprises seven 4-tap filters.\",\n \"8.The video decoding method according to claim 2, in which the alternate fractional-position results are even fractional-position results.\",\n \"9.A video encoding method for encoding a video signal, the method being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the method comprising: generating motion vectors for prediction of prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically using only alternate fractional-position results as interpolated samples in the horizontal and vertical directions.\",\n \"10.A non-transitory computer readable medium including computer program instructions, which when executed by a computer causes the computer to perform the method of claim 2.11.A non-transitory computer readable medium including computer program instructions, which when executed by a computer causes the computer to perform the method of claim 9.12.A video decoding apparatus for decoding a video signal, the apparatus being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the apparatus comprising: processing circuitry configured to generate prediction units of a current image from one or more stored images preceding the current image by: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically using only alternate fractional-position results as interpolated samples in the vertical direction.\",\n \"13.A video encoding apparatus for encoding a video signal, the apparatus being operable in respect of a 4:2:0 format video signal and a 4:4:4 format video signal, the apparatus comprising: processing circuitry configured to generate motion vectors for prediction of prediction units of a current image from one or more stored images preceding the current image by: in respect to the 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect to the 4:4:4 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically using only alternate fractional-position results as interpolated samples in the horizontal and vertical directions.\",\n \"14.A non-transitory computer readable medium including computer program instructions, which when executed by a computer causes the computer to perform the method of claim 3.15.The video decoding apparatus according to claim 12, wherein the processing circuitry generates the prediction units by accessing samples of the interpolated prediction unit pointed to by a motion vector to generate a motion compensated prediction of a prediction unit of the current image with respect to an area represented by the samples of the interpolated prediction unit.\",\n \"16.The video decoding apparatus according to claim 15, wherein the motion vector is a sub-pixel accuracy motion vector.\",\n \"17.The video decoding apparatus according to claim 16, wherein the processing circuitry applies the 4-tap ×8 chrominance filter comprises by applying one of a set of 4-tap filters horizontally and one of the set of 4-tap filters vertically to a chrominance prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.\",\n \"18.The video decoding apparatus according to claim 16, wherein the 4-tap filters are indexed in order of fractional interpolation position, and for 4:4:4 format video, the processing circuitry devices the samples by applying a filter selected from a subset of alternate filters in the indexing order.\",\n \"19.The video decoding apparatus according to claim 12, wherein the alternate fractional-position results are even fractional-position results.\",\n \"20.An image capture device comprising an image sensor and the video encoding apparatus according to claim 13.21.An audio/video data receiver comprising the video decoding apparatus according to claim 12.22.The audio/video data receiver according to claim 21, further comprising a display.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>\"\n ],\n [\n \"<SOH> SUMMARY <EOH>The present disclosure addresses or mitigates problems arising from this processing.\",\n \"Respective aspects and features of the present disclosure are defined in the appended claims.\",\n \"It is to be understood that both the foregoing general description and the following detailed description are exemplary, but are not restrictive, of the present technology.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation application of U.S. application Ser.\",\n \"No.\",\n \"15/614,226, filed Jun.\",\n \"5, 2017, which is a continuation application of U.S. application Ser.\",\n \"No.\",\n \"14/523,675, filed Oct. 24, 2014, which is a bypass continuation application of PCT application PCT/GB2013/051076 designating the United States of America filed 26 Apr.\",\n \"2013 which claims the benefit of the earlier filing date of GB1211072.2, GB 1211073.0 and GB 1207459.7 filed in the United Kingdom Intellectual Property Office on 22 Jun.\",\n \"2012, 22 Jun.\",\n \"2012 and 26 Apr.\",\n \"2012 respectively, the entire contents of which applications are incorporated herein by reference.\",\n \"BACKGROUND Field This disclosure relates to data encoding and decoding.\",\n \"Description of Related Art The “background” description provided herein is for the purpose of generally presenting the context of the disclosure.\",\n \"Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, is neither expressly or impliedly admitted as prior art against the present disclosure.\",\n \"There are several video data encoding and decoding systems which involve transforming video data into a frequency domain representation, quantising the frequency domain coefficients and then applying some form of entropy encoding to the quantised coefficients.\",\n \"This can achieve compression of the video data.\",\n \"A corresponding decoding or decompression technique is applied to recover a reconstructed version of the original video data.\",\n \"Current video codecs (coder-decoders) such as those used in H.264/MPEG-4 Advanced Video Coding (AVC) achieve data compression primarily by only encoding the differences between successive video frames.\",\n \"These codecs use a regular array of so-called macroblocks, each of which is used as a region of comparison with a corresponding macroblock in a previous video frame, and the image region within the macroblock is then encoded according to the degree of motion found between the corresponding current and previous macroblocks in the video sequence, or between neighbouring macroblocks within a single frame of the video sequence.\",\n \"High Efficiency Video Coding (HEVC), also known as H.265 or MPEG-H Part 2, is a proposed successor to H.264/MPEG-4 AVC.\",\n \"It is intended for HEVC to improve video quality and double the data compression ratio compared to H.264, and for it to be scalable from 128×96 to 7680×4320 pixels resolution, roughly equivalent to bit rates ranging from 128 kbit/s to 800 Mbit/s.\",\n \"In HEVC a so-called 4:2:0 block structure is proposed for consumer equipment, in which the amount of data used in each chroma channel is one quarter that in the luma channel.\",\n \"This is because subjectively people are more sensitive to brightness variations than to colour variations, and so it is possible to use greater compression and/or less information in the colour channels without a subjective loss of quality.\",\n \"HEVC replaces the macroblocks found in existing H.264 and MPEG standards with a more flexible scheme based upon coding units (CUs), which are variable size structures.\",\n \"Consequently, when encoding the image data in video frames, the CU sizes can be selected responsive to the apparent image complexity or detected motion levels, instead of using uniformly distributed macroblocks.\",\n \"Consequently far greater compression can be achieved in regions with little motion between frames and with little variation within a frame, whilst better image quality can be preserved in areas of high inter-frame motion or image complexity.\",\n \"Each CU contains one or more variable-block-sized prediction units (PUs) of either intra-picture or inter-picture prediction type, and one or more transform units (TUs) which contain coefficients for spatial block transform and quantisation.\",\n \"Moreover, PU and TU blocks are provided for each of three channels; luma (Y), being a luminance or brightness channel, and which may be thought of as a greyscale channel, and two colour difference or chrominance (chroma) channels; Cb and Cr.\",\n \"These channels provide the colour for the greyscale image of the luma channel.\",\n \"The terms Y, luminance and luma are used interchangeably in this description, and similarly the terms Cb and Cr, chrominance and chroma, are used interchangeably as appropriate, noting that chrominance or chroma can be used generically for “one or both of Cr and Cb”, whereas when a specific chrominance channel is being discussed it will be identified by the term Cb or Cr.\",\n \"Generally PUs are considered to be channel independent, except that a PU has a luma part and a chroma part.\",\n \"Generally, this means that the samples forming part of the PU for each channel represent the same region of the image, so that there is a fixed relationship between the PUs between the three channels.\",\n \"For example, for 4:2:0 video, an 8×8 PU for Luma always has a corresponding 4×4 PU for chroma, with the chroma parts of the PU representing the same area as the luma part, but containing a smaller number of pixels because of the subsampled nature of the 4:2:0 chroma data compared to the luma data in 4:2:0 video.\",\n \"(In 4:4:4 the sampling rates are the same and so the same PU structures can be used for luma and chroma samples).\",\n \"The two chroma channels share intra-prediction information; and the three channels share inter-prediction information.\",\n \"Similarly, the TU structure also has a fixed relationship between the three channels.\",\n \"However, for professional broadcast and digital cinema equipment, it is desirable to have less compression (or more information) in the chroma channels, and this may affect how current and proposed HEVC processing operates.\",\n \"SUMMARY The present disclosure addresses or mitigates problems arising from this processing.\",\n \"Respective aspects and features of the present disclosure are defined in the appended claims.\",\n \"It is to be understood that both the foregoing general description and the following detailed description are exemplary, but are not restrictive, of the present technology.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS A more complete appreciation of the disclosure and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein: FIG.\",\n \"1 schematically illustrates an audio/video (A/V) data transmission and reception system using video data compression and decompression; FIG.\",\n \"2 schematically illustrates a video display system using video data decompression; FIG.\",\n \"3 schematically illustrates an audio/video storage system using video data compression and decompression; FIG.\",\n \"4 schematically illustrates a video camera using video data compression; FIG.\",\n \"5 provides a schematic overview of a video data compression and decompression apparatus; FIG.\",\n \"6 schematically illustrates the generation of predicted images; FIG.\",\n \"7 schematically illustrates a largest coding unit (LCU); FIG.\",\n \"8 schematically illustrates a set of four coding units (CU); FIGS.\",\n \"9 and 10 schematically illustrate the coding units of FIG.\",\n \"8 sub-divided into smaller coding units; FIG.\",\n \"11 schematically illustrates an array of prediction units (PU); FIG.\",\n \"12 schematically illustrates an array of transform units (TU); FIG.\",\n \"13 schematically illustrates a partially-encoded image; FIG.\",\n \"14 schematically illustrates a set of possible intra-prediction directions; FIG.\",\n \"15 schematically illustrates a set of prediction modes; FIG.\",\n \"16 schematically illustrates an up-right diagonal scan; FIG.\",\n \"17 schematically illustrates a video compression apparatus; FIGS.\",\n \"18A and 18B schematically illustrate possible block sizes; FIG.\",\n \"19 schematically illustrates the use of co-located information from chroma and luma blocks; FIG.\",\n \"20 schematically illustrates a situation in which co-located information from one chroma channel is used in respect of another chroma channel; FIG.\",\n \"21 schematically illustrates pixels used for an LM-CHROMA mode; FIG.\",\n \"22 schematically illustrates a set of luma prediction directions; FIG.\",\n \"23 schematically illustrates the directions of FIG.\",\n \"22, as applied to a horizontally sparse chroma channel; FIG.\",\n \"24 schematically illustrates the directions of FIG.\",\n \"22 mapped to a rectangular chroma pixel array; FIGS.\",\n \"25-28 schematically illustrate luma and chroma pixel interpolation; FIGS.\",\n \"29A and 29B schematically illustrates quantisation parameter tables for 4:2:0 and 4:2:2 respectively; and FIGS.\",\n \"30 and 31 schematically illustrate quantisation variation tables.\",\n \"DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring now to the drawings, FIGS.\",\n \"1-4 are provided to give schematic illustrations of apparatus or systems making use of the compression and/or decompression apparatus to be described below in connection with embodiments of the present technology.\",\n \"All of the data compression and/or decompression apparatus to be described below may be implemented in hardware, in software running on a general-purpose data processing apparatus such as a general-purpose computer, as programmable hardware such as an application specific integrated circuit (ASIC) or field programmable gate array (FPGA) or as combinations of these.\",\n \"In cases where the embodiments are implemented by software and/or firmware, it will be appreciated that such software and/or firmware, and non-transitory data storage media by which such software and/or firmware are stored or otherwise provided, are considered as embodiments of the present technology.\",\n \"FIG.\",\n \"1 schematically illustrates an audio/video data transmission and reception system using video data compression and decompression.\",\n \"An input audio/video signal 10 is supplied to a video data compression apparatus 20 which compresses at least the video component of the audio/video signal 10 for transmission along a transmission route 30 such as a cable, an optical fibre, a wireless link or the like.\",\n \"The compressed signal is processed by a decompression apparatus 40 to provide an output audio/video signal 50.For the return path, a compression apparatus 60 compresses an audio/video signal for transmission along the transmission route 30 to a decompression apparatus 70.The compression apparatus 20 and decompression apparatus 70 can therefore form one node of a transmission link.\",\n \"The decompression apparatus 40 and decompression apparatus 60 can form another node of the transmission link.\",\n \"Of course, in instances where the transmission link is uni-directional, only one of the nodes would require a compression apparatus and the other node would only require a decompression apparatus.\",\n \"FIG.\",\n \"2 schematically illustrates a video display system using video data decompression.\",\n \"In particular, a compressed audio/video signal 100 is processed by a decompression apparatus 110 to provide a decompressed signal which can be displayed on a display 120.The decompression apparatus 110 could be implemented as an integral part of the display 120, for example being provided within the same casing as the display device.\",\n \"Alternatively, the decompression apparatus 110 maybe provided as (for example) a so-called set top box (STB), noting that the expression “set-top” does not imply a requirement for the box to be sited in any particular orientation or position with respect to the display 120; it is simply a term used in the art to indicate a device which is connectable to a display as a peripheral device.\",\n \"FIG.\",\n \"3 schematically illustrates an audio/video storage system using video data compression and decompression.\",\n \"An input audio/video signal 130 is supplied to a compression apparatus 140 which generates a compressed signal for storing by a store device 150 such as a magnetic disk device, an optical disk device, a magnetic tape device, a solid state storage device such as a semiconductor memory or other storage device.\",\n \"For replay, compressed data is read from the store device 150 and passed to a decompression apparatus 160 for decompression to provide an output audio/video signal 170.It will be appreciated that the compressed or encoded signal, and a storage medium storing that signal, are considered as embodiments of the present technology.\",\n \"FIG.\",\n \"4 schematically illustrates a video camera using video data compression.\",\n \"In FIG.\",\n \"4, an image capture device 180, such as a charge coupled device (CCD) image sensor and associated control and read-out electronics, generates a video signal which is passed to a compression apparatus 190.A microphone (or plural microphones) 200 generates an audio signal to be passed to the compression apparatus 190.The compression apparatus 190 generates a compressed audio/video signal 210 to be stored and/or transmitted (shown generically as a schematic stage 220).\",\n \"The techniques to be described below relate primarily to video data compression and decompression.\",\n \"It will be appreciated that many existing techniques may be used for audio data compression in conjunction with the video data compression techniques which will be described, to generate a compressed audio/video signal.\",\n \"Accordingly, a separate discussion of audio data compression will not be provided.\",\n \"It will also be appreciated that the data rate associated with video data, in particular broadcast quality video data, is generally very much higher than the data rate associated with audio data (whether compressed or uncompressed).\",\n \"It will therefore be appreciated that uncompressed audio data could accompany compressed video data to form a compressed audio/video signal.\",\n \"It will further be appreciated that although the present examples (shown in FIGS.\",\n \"1-4) relate to audio/video data, the techniques to be described below can find use in a system which simply deals with (that is to say, compresses, decompresses, stores, displays and/or transmits) video data.\",\n \"That is to say, the embodiments can apply to video data compression without necessarily having any associated audio data handling at all.\",\n \"FIG.\",\n \"5 provides a schematic overview of a video data compression and decompression apparatus.\",\n \"A controller 343 controls the overall operation of the apparatus and, in particular when referring to a compression mode, controls the trial encoding processes (to be described below) by acting as a selector to select various modes of operation such as CU, PU and TU block sizes and whether the video data is to be encoded losslessly or otherwise.\",\n \"Successive images of an input video signal 300 are supplied to an adder 310 and to an image predictor 320.The image predictor 320 will be described below in more detail with reference to FIG.\",\n \"6.The adder 310 in fact performs a subtraction (negative addition) operation, in that it receives the input video signal 300 on a “+” input and the output of the image predictor 320 on a “−” input, so that the predicted image is subtracted from the input image.\",\n \"The result is to generate a so-called residual image signal 330 representing the difference between the actual and projected images.\",\n \"One reason why a residual image signal is generated is as follows.\",\n \"The data coding techniques to be described, that is to say the techniques which will be applied to the residual image signal, tend to work more efficiently when there is less “energy” in the image to be encoded.\",\n \"Here, the term “efficiently” refers to the generation of a small amount of encoded data; for a particular image quality level, it is desirable (and considered “efficient”) to generate as little data as is practicably possible.\",\n \"The reference to “energy” in the residual image relates to the amount of information contained in the residual image.\",\n \"If the predicted image were to be identical to the real image, the difference between the two (that is to say, the residual image) would contain zero information (zero energy) and would be very easy to encode into a small amount of encoded data.\",\n \"In general, if the prediction process can be made to work reasonably well, the expectation is that the residual image data will contain less information (less energy) than the input image and so will be easier to encode into a small amount of encoded data.\",\n \"The remainder of the apparatus acting as an encoder (to encode the residual or difference image) will now be described.\",\n \"The residual image data 330 is supplied to a transform unit 340 which generates a discrete cosine transform (DCT) representation of the residual image data.\",\n \"The DCT technique itself is well known and will not be described in detail here.\",\n \"There are however aspects of the techniques used in the present apparatus which will be described in more detail below, in particular relating to the selection of different blocks of data to which the DCT operation is applied.\",\n \"These will be discussed with reference to FIGS.\",\n \"7-12 below.\",\n \"The output of the transform unit 340, which is to say, a set of DCT coefficients for each transformed block of image data, is supplied to a quantiser 350.Various quantisation techniques are known in the field of video data compression, ranging from a simple multiplication by a quantisation scaling factor through to the application of complicated lookup tables under the control of a quantisation parameter.\",\n \"The general aim is twofold.\",\n \"Firstly, the quantisation process reduces the number of possible values of the transformed data.\",\n \"Secondly, the quantisation process can increase the likelihood that values of the transformed data are zero.\",\n \"Both of these can make the entropy encoding process, to be described below, work more efficiently in generating small amounts of compressed video data.\",\n \"A data scanning process is applied by a scan unit 360.The purpose of the scanning process is to reorder the quantised transformed data so as to gather as many as possible of the non-zero quantised transformed coefficients together, and of course therefore to gather as many as possible of the zero-valued coefficients together.\",\n \"These features can allow so-called run-length coding or similar techniques to be applied efficiently.\",\n \"So, the scanning process involves selecting coefficients from the quantised transformed data, and in particular from a block of coefficients corresponding to a block of image data which has been transformed and quantised, according to a “scanning order” so that (a) all of the coefficients are selected once as part of the scan, and (b) the scan tends to provide the desired reordering.\",\n \"One example scanning order which can tend to give useful results is a so-called up-right diagonal scanning order.\",\n \"The scanned coefficients are then passed to an entropy encoder (EE) 370.Again, various types of entropy encoding may be used.\",\n \"Two examples are variants of the so-called CABAC (Context Adaptive Binary Arithmetic Coding) system and variants of the so-called CAVLC (Context Adaptive Variable-Length Coding) system.\",\n \"In general terms, CABAC is considered to provide a better efficiency, and in some studies has been shown to provide a 10-20% reduction in the quantity of encoded output data for a comparable image quality compared to CAVLC.\",\n \"However, CAVLC is considered to represent a much lower level of complexity (in terms of its implementation) than CABAC.\",\n \"Note that the scanning process and the entropy encoding process are shown as separate processes, but in fact can be combined or treated together.\",\n \"That is to say, the reading of data into the entropy encoder can take place in the scan order.\",\n \"Corresponding considerations apply to the respective inverse processes to be described below.\",\n \"Note that the current HEVC documents under consideration at the time of filing no longer include the possibility of a CAVLC coefficient encoder.\",\n \"The output of the entropy encoder 370, along with additional data (mentioned above and/or discussed below), for example defining the manner in which the predictor 320 generated the predicted image, provides a compressed output video signal 380.However, a return path is also provided because the operation of the predictor 320 itself depends upon a decompressed version of the compressed output data.\",\n \"The reason for this feature is as follows.\",\n \"At the appropriate stage in the decompression process (to be described below) a decompressed version of the residual data is generated.\",\n \"This decompressed residual data has to be added to a predicted image to generate an output image (because the original residual data was the difference between the input image and a predicted image).\",\n \"In order that this process is comparable, as between the compression side and the decompression side, the predicted images generated by the predictor 320 should be the same during the compression process and during the decompression process.\",\n \"Of course, at decompression, the apparatus does not have access to the original input images, but only to the decompressed images.\",\n \"Therefore, at compression, the predictor 320 bases its prediction (at least, for inter-image encoding) on decompressed versions of the compressed images.\",\n \"The entropy encoding process carried out by the entropy encoder 370 is considered to be “lossless”, which is to say that it can be reversed to arrive at exactly the same data which was first supplied to the entropy encoder 370.So, the return path can be implemented before the entropy encoding stage.\",\n \"Indeed, the scanning process carried out by the scan unit 360 is also considered lossless, but in the present embodiment the return path 390 is from the output of the quantiser 350 to the input of a complimentary inverse quantiser 420.In general terms, an entropy decoder 410, the reverse scan unit 400, an inverse quantiser 420 and an inverse transform unit 430 provide the respective inverse functions of the entropy encoder 370, the scan unit 360, the quantiser 350 and the transform unit 340.For now, the discussion will continue through the compression process; the process to decompress an input compressed video signal will be discussed separately below.\",\n \"In the compression process, the scanned coefficients are passed by the return path 390 from the quantiser 350 to the inverse quantiser 420 which carries out the inverse operation of the scan unit 360.An inverse quantisation and inverse transformation process are carried out by the units 420, 430 to generate a compressed-decompressed residual image signal 440.The image signal 440 is added, at an adder 450, to the output of the predictor 320 to generate a reconstructed output image 460.This forms one input to the image predictor 320, as will be described below.\",\n \"Turning now to the process applied to decompress a received compressed video signal 470, the signal is supplied to the entropy decoder 410 and from there to the chain of the reverse scan unit 400, the inverse quantiser 420 and the inverse transform unit 430 before being added to the output of the image predictor 320 by the adder 450.So, at the decoder side, the decoder reconstructs a version of the residual image and then applies this (by the adder 450) to the predicted version of the image (on a block by block basis) so as to decode each block.\",\n \"In straightforward terms, the output 460 of the adder 450 forms the output decompressed video signal 480.In practice, further filtering may be applied before the signal is output.\",\n \"So, the apparatus of FIGS.\",\n \"5 and 6 can act as a compression apparatus or a decompression apparatus.\",\n \"The functions of the two types of apparatus overlap very heavily.\",\n \"The scan unit 360 and entropy encoder 370 are not used in a decompression mode, and the operation of the predictor 320 (which will be described in detail below) and other units follow mode and parameter information contained in the received compressed bitstream rather than generating such information themselves.\",\n \"FIG.\",\n \"6 schematically illustrates the generation of predicted images, and in particular the operation of the image predictor 320.There are two basic modes of prediction carried out by the image predictor 320: so-called intra-image prediction and so-called inter-image, or motion-compensated (MC), prediction.\",\n \"At the encoder side, each involves detecting a prediction direction in respect of a current block to be predicted, and generating a predicted block of samples according to other samples (in the same (intra) or another (inter) image).\",\n \"By virtue of the units 310 or 450, the difference between the predicted block and the actual block is encoded or applied so as to encode or decode the block respectively.\",\n \"Intra-image prediction bases a prediction of the content of a block of the image on data from within the same image.\",\n \"This corresponds to so-called I-frame encoding in other video compression techniques.\",\n \"In contrast to I-frame encoding, where the whole image is intra-encoded, in the present embodiments the choice between intra- and inter-encoding can be made on a block-by-block basis, though in other embodiments the choice is still made on an image-by-image basis.\",\n \"Motion-compensated prediction is an example of inter-image prediction and makes use of motion information which attempts to define the source, in another adjacent or nearby image, of image detail to be encoded in the current image.\",\n \"Accordingly, in an ideal example, the contents of a block of image data in the predicted image can be encoded very simply as a reference (a motion vector) pointing to a corresponding block at the same or a slightly different position in an adjacent image.\",\n \"Returning to FIG.\",\n \"6, two image prediction arrangements (corresponding to intra- and inter-image prediction) are shown, the results of which are selected by a multiplexer 500 under the control of a mode signal 510 so as to provide blocks of the predicted image for supply to the adders 310 and 450.The choice is made in dependence upon which selection gives the lowest “energy” (which, as discussed above, may be considered as information content requiring encoding), and the choice is signalled to the encoder within the encoded output datastream.\",\n \"Image energy, in this context, can be detected, for example, by carrying out a trial subtraction of an area of the two versions of the predicted image from the input image, squaring each pixel value of the difference image, summing the squared values, and identifying which of the two versions gives rise to the lower mean squared value of the difference image relating to that image area.\",\n \"The actual prediction, in the intra-encoding system, is made on the basis of image blocks received as part of the signal 460, which is to say, the prediction is based upon encoded-decoded image blocks in order that exactly the same prediction can be made at a decompression apparatus.\",\n \"However, data can be derived from the input video signal 300 by an intra-mode selector 520 to control the operation of the intra-image predictor 530.For inter-image prediction, a motion compensated (MC) predictor 540 uses motion information such as motion vectors derived by a motion estimator 550 from the input video signal 300.Those motion vectors are applied to a processed version of the reconstructed image 460 by the motion compensated predictor 540 to generate blocks of the inter-image prediction.\",\n \"Accordingly, the units 530 and 540 (operating with the estimator 550) each act as detectors to detect a prediction direction in respect of a current block to be predicted, and as a generator to generate a predicted block of samples (forming part of the prediction passed to the units 310 and 450) according to other samples defined by the prediction direction.\",\n \"The processing applied to the signal 460 will now be described.\",\n \"Firstly, the signal is filtered by a filter unit 560, which will be describe in greater detail below.\",\n \"This involves applying a “deblocking” filter to remove or at least tend to reduce the effects of the block-based processing carried out by the transform unit 340 and subsequent operations.\",\n \"A sample adaptive offsetting (SAO) filter (described further below) may also be used.\",\n \"Also, an adaptive loop filter is applied using coefficients derived by processing the reconstructed signal 460 and the input video signal 300.The adaptive loop filter is a type of filter which, using known techniques, applies adaptive filter coefficients to the data to be filtered.\",\n \"That is to say, the filter coefficients can vary in dependence upon various factors.\",\n \"Data defining which filter coefficients to use is included as part of the encoded output datastream.\",\n \"Adaptive filtering represents in-loop filtering for image restoration.\",\n \"An LCU can be filtered by up to 16 filters, with a choice of filter and an ALF on/off status (adaptive loop filter—see below) being derived in respect of each CU within the LCU.\",\n \"Currently the control is at the LCU level, not the CU level.\",\n \"The filtered output from the filter unit 560 in fact forms the output video signal 480 when the apparatus is operating as a compression apparatus.\",\n \"It is also buffered in one or more image or frame stores 570; the storage of successive images is a requirement of motion compensated prediction processing, and in particular the generation of motion vectors.\",\n \"To save on storage requirements, the stored images in the image stores 570 may be held in a compressed form and then decompressed for use in generating motion vectors.\",\n \"For this particular purpose, any known compression/decompression system may be used.\",\n \"The stored images are passed to an interpolation filter 580 which generates a higher resolution version of the stored images; in this example, intermediate samples (sub-samples) are generated such that the resolution of the interpolated image is output by the interpolation filter 580 is 4 times (in each dimension) that of the images stored in the image stores 570 for the luminance channel of 4:2:0 and 8 times (in each dimension) that of the images stored in the image stores 570 for the chrominance channels of 4:2:0.The interpolated images are passed as an input to the motion estimator 550 and also to the motion compensated predictor 540.In embodiments, a further optional stage is provided, which is to multiply the data values of the input video signal by a factor of four using a multiplier 600 (effectively just shifting the data values left by two bits), and to apply a corresponding divide operation (shift right by two bits) at the output of the apparatus using a divider or right-shifter 610.So, the shifting left and shifting right changes the data purely for the internal operation of the apparatus.\",\n \"This measure can provide for higher calculation accuracy within the apparatus, as the effect of any data rounding errors is reduced.\",\n \"The way in which an image is partitioned for compression processing will now be described.\",\n \"At a basic level, an image to be compressed is considered as an array of blocks of samples.\",\n \"For the purposes of the present discussion, the largest such block under consideration is a so-called largest coding unit (LCU) 700 (FIG.\",\n \"7), which represents a square array of typically 64×64 samples (the LCU size is configurable by the encoder, up to a maximum size such as defined by the HEVC documents).\",\n \"Here, the discussion relates to luminance samples.\",\n \"Depending on the chrominance mode, such as 4:4:4, 4:2:2, 4:2:0 or 4:4:4:4 (GBR plus key data), there will be differing numbers of corresponding chrominance samples corresponding to the luminance block.\",\n \"Three basic types of blocks will be described: coding units, prediction units and transform units.\",\n \"In general terms, the recursive subdividing of the LCUs allows an input picture to be partitioned in such a way that both the block sizes and the block coding parameters (such as prediction or residual coding modes) can be set according to the specific characteristics of the image to be encoded.\",\n \"The LCU may be subdivided into so-called coding units (CU).\",\n \"Coding units are always square and have a size between 8×8 samples and the full size of the LCU 700.The coding units can be arranged as a kind of tree structure, so that a first subdivision may take place as shown in FIG.\",\n \"8, giving coding units 710 of 32×32 samples; subsequent subdivisions may then take place on a selective basis so as to give some coding units 720 of 16×16 samples (FIG.\",\n \"9) and potentially some coding units 730 of 8×8 samples (FIG.\",\n \"10).\",\n \"Overall, this process can provide a content-adapting coding tree structure of CU blocks, each of which may be as large as the LCU or as small as 8×8 samples.\",\n \"Encoding of the output video data takes place on the basis of the coding unit structure, which is to say that one LCU is encoded, and then the process moves to the next LCU, and so on.\",\n \"FIG.\",\n \"11 schematically illustrates an array of prediction units (PU).\",\n \"A prediction unit is a basic unit for carrying information relating to the image prediction processes, or in other words the additional data added to the entropy encoded residual image data to form the output video signal from the apparatus of FIG.\",\n \"5.In general, prediction units are not restricted to being square in shape.\",\n \"They can take other shapes, in particular rectangular shapes forming half of one of the square coding units (for example, 8×8 CUs can have 8×4 or 4×8 PUs).\",\n \"Employing PUs which align to image features is not a compulsory part of the HEVC system, but the general aim would be to allow a good encoder to align the boundary of adjacent prediction units to match (as closely as possible) the boundary of real objects in the picture, so that different prediction parameters can be applied to different real objects.\",\n \"Each coding unit may contain one or more prediction units.\",\n \"FIG.\",\n \"12 schematically illustrates an array of transform units (TU).\",\n \"A transform unit is a basic unit of the transform and quantisation process.\",\n \"Transform units may or may not be square and can take a size from 4×4 up to 32×32 samples.\",\n \"Each coding unit can contain one or more transform units.\",\n \"The acronym SDIP-P in FIG.\",\n \"12 signifies a so-called short distance intra-prediction partition.\",\n \"In this arrangement only one dimensional transforms are used, so a 4×N block is passed through N transforms with input data to the transforms being based upon the previously decoded neighbouring blocks and the previously decoded neighbouring lines within the current SDIP-P. SDIP-P is currently not included in HEVC at the time of filing the present application.\",\n \"As mentioned above, coding takes place as one LCU, then a next LCU, and so on.\",\n \"Within an LCU, coding is carried out CU by CU.\",\n \"Within a CU, coding is carried out for one TU, then a next TU and so on.\",\n \"The intra-prediction process will now be discussed.\",\n \"In general terms, intra-prediction involves generating a prediction of a current block (a prediction unit) of samples from previously-encoded and decoded samples in the same image.\",\n \"FIG.\",\n \"13 schematically illustrates a partially encoded image 800.Here, the image is being encoded from top-left to bottom-right on an LCU basis.\",\n \"An example LCU encoded partway through the handling of the whole image is shown as a block 810.A shaded region 820 above and to the left of the block 810 has already been encoded.\",\n \"The intra-image prediction of the contents of the block 810 can make use of any of the shaded area 820 but cannot make use of the unshaded area below that.\",\n \"Note however that for an individual TU within the current LCU, the hierarchical order of encoding (CU by CU then TU by TU) discussed above means that there may be previously encoded samples in the current LCU and available to the coding of that TU which are, for example, above-right or below-left of that TU.\",\n \"The block 810 represents an LCU; as discussed above, for the purposes of intra-image prediction processing, this may be subdivided into a set of smaller prediction units and transform units.\",\n \"An example of a current TU 830 is shown within the LCU 810.The intra-image prediction takes into account samples coded prior to the current TU being considered, such as those above and/or to the left of the current TU.\",\n \"Source samples, from which the required samples are predicted, may be located at different positions or directions relative to the current TU.\",\n \"To decide which direction is appropriate for a current prediction unit, the mode selector 520 of an example encoder may test all combinations of available TU structures for each candidate direction and select the PU direction and TU structure with the best compression-efficiency.\",\n \"The picture may also be encoded on a “slice” basis.\",\n \"In one example, a slice is a horizontally adjacent group of LCUs.\",\n \"But in more general terms, the entire residual image could form a slice, or a slice could be a single LCU, or a slice could be a row of LCUs, and so on.\",\n \"Slices can give some resilience to errors as they are encoded as independent units.\",\n \"The encoder and decoder states are completely reset at a slice boundary.\",\n \"For example, intra-prediction is not carried out across slice boundaries; slice boundaries are treated as image boundaries for this purpose.\",\n \"FIG.\",\n \"14 schematically illustrates a set of possible (candidate) prediction directions.\",\n \"The full set of 34 candidate directions is available to a prediction unit of 8×8, 16×16 or 32×32 samples.\",\n \"The special cases of prediction unit sizes of 4×4 and 64×64 samples have a reduced set of candidate directions available to them (17 candidate directions and 5 candidate directions respectively).\",\n \"The directions are determined by horizontal and vertical displacement relative to a current block position, but are encoded as prediction “modes”, a set of which is shown in FIG.\",\n \"15.Note that the so-called DC mode represents a simple arithmetic mean of the surrounding upper and left-hand samples.\",\n \"In general terms, after detecting a prediction direction in respect of each prediction unit, the systems are operable to generate a predicted block of samples according to other samples defined by the prediction direction.\",\n \"FIG.\",\n \"16 schematically illustrates a so-called up-right diagonal scan, being an example scan pattern which may be applied by the scan unit 360.In FIG.\",\n \"16, the pattern is shown for an example block of 8×8 DCT coefficients, with the DC coefficient being positioned at the top left position 840 of the block, and increasing horizontal and vertical spatial frequencies being represented by coefficients at increasing distances downwards and to the right of the top-left position 840.Other alternative scan orders may be used instead.\",\n \"Variations of the block arrangements and of the CU, PU and TU structures will be discussed below.\",\n \"These will be discussed in the context of the apparatus of FIG.\",\n \"17, which is similar in many respects to that illustrated in FIGS.\",\n \"5 and 6 discussed above.\",\n \"Indeed, many of the same reference numerals have been used, and these parts will not be discussed further.\",\n \"The main substantive differences with respect to FIGS.\",\n \"5 and 6 relate to the filter 560 (FIG.\",\n \"6), which in FIG.\",\n \"17 is shown in more detail as comprising a deblocking filter 1000 and associated encoding decision block 1030, a sample adaptive offsetting (SAO) filter 1010 and associated coefficient generator 1040, and an adaptive loop filter (ALF) 1020 and associated coefficient generator 1050.The deblocking filter 1000 attempts to reduce distortion and to improve visual quality and prediction performance by smoothing the sharp edges which can form between CU, PU and TU boundaries when block coding techniques are used.\",\n \"The SAO filter 1010 classifies reconstructed pixels into different categories and then attempts to reduce distortion by simply adding an offset for each category of pixels.\",\n \"The pixel intensity and edge properties are used for pixel classification.\",\n \"To further improve the coding efficiency, a picture can be divided into regions for localization of offset parameters.\",\n \"The ALF 1020 attempts to restore the compressed picture such that the difference between the reconstructed and source frames is minimized.\",\n \"The coefficients of ALF are calculated and transmitted on a frame basis.\",\n \"The ALF can be applied to the entire frame or to local areas.\",\n \"As noted above, the proposed HEVC documents use a particular chroma sampling scheme known as the 4:2:0 scheme.\",\n \"The 4:2:0 scheme can be used for domestic/consumer equipment.\",\n \"However, several other schemes are possible.\",\n \"In particular, a so-called 4:4:4 scheme would be suitable for professional broadcasting, mastering and digital cinema, and in principle would have the highest quality and data rate.\",\n \"Similarly, a so-called 4:2:2 scheme could be used in professional broadcasting, mastering and digital cinema with some loss of fidelity.\",\n \"These schemes and their corresponding possible PU and TU block structures are described below.\",\n \"In addition, other schemes include the 4:0:0 monochrome scheme.\",\n \"In the 4:4:4 scheme, each of the three Y, Cb and Cr channels have the same sample rate.\",\n \"In principle therefore, in this scheme there would be twice as much chroma data as luma data.\",\n \"Hence in HEVC, in this scheme each of the three Y, Cb and Cr channels would have corresponding PU and TU blocks that are the same size; for example an 8×8 luma block would have corresponding 8×8 chroma blocks for each of the two chroma channels.\",\n \"Consequently in this scheme there would generally be a direct 1:1 relationship between block sizes in each channel.\",\n \"In the 4:2:2 scheme, the two chroma components are sampled at half the sample rate of luma (for example using vertical or horizontal subsampling, but for the purposes of the present description, horizontal subsampling is assumed).\",\n \"In principle therefore, in this scheme there would be as much chroma data as luma data, though the chroma data would be split between the two chroma channels.\",\n \"Hence in HEVC, in this scheme the Cb and Cr channels would have different size PU and TU blocks to the luma channel; for example an 8×8 luma block could have corresponding 4 wide×8 high chroma blocks for each chroma channel.\",\n \"Notably therefore in this scheme the chroma blocks could be non-square, even though they correspond to square luma blocks.\",\n \"In the currently proposed HEVC 4:2:0 scheme, the two chroma components are sampled at a quarter of the sample rate of luma (for example using vertical and horizontal subsampling).\",\n \"In principle therefore, in this scheme there is half as much chroma data as luma data, the chroma data being split between the two chroma channels.\",\n \"Hence in HEVC, in this scheme again the Cb and Cr channels have different size PU and TU blocks to the luma channel.\",\n \"For example an 8×8 luma block would have corresponding 4×4 chroma blocks for each chroma channel.\",\n \"The above schemes are colloquially known in the art as ‘channel ratios’, as in ‘a 4:2:0 channel ratio’; however it will be appreciated from the above description that in fact this does not always mean that the Y, Cb and Cr channels are compressed or otherwise provided in that ratio.\",\n \"Hence whilst referred to as a channel ratio, this should not be assumed to be literal.\",\n \"In fact, the correct ratios for the 4:2:0 scheme are 4:1:1 (the ratios for the 4:2:2 scheme and 4:4:4 scheme are in fact correct).\",\n \"Before discussing particular arrangements with reference to FIGS.\",\n \"18a and 18b, some general terminology will be summarised or revisited.\",\n \"A Largest Coding Unit (LCU) is a root picture object.\",\n \"Typically, it covers the area equivalent to 64×64 luma pixels.\",\n \"It is recursively split to form a tree-hierarchy of Coding Units (CUs).\",\n \"In general terms, the three channels (one luma channel and two chroma channels) have the same CU tree-hierarchy.\",\n \"Having said this, however, depending upon the channel ratio, a particular luma CU may comprise a different number of pixels to the corresponding chroma CUs.\",\n \"The CUs at the end of the tree-hierarchy, which is to say, the smallest CUs resulting from the recursive splitting process (which may be referred to as leaf CUs) are then split into Prediction Units (PUs).\",\n \"The three channels (luma and two chroma channels) have the same PU structure, except when the corresponding PU for a chroma channel would have too few samples, in which case just one PU for that channel is available.\",\n \"This is configurable, but commonly the minimum dimension of an intra PU is 4 samples; the minimum dimension of an inter PU is 4 luma samples (or 2 chroma samples for 4:2:0).\",\n \"The restriction on the minimum CU size always is large enough for at least one PU for any channel.\",\n \"The leaf CUs are also split into Transform Units (TUs).\",\n \"The TUs can—and, when they are too big (for example, over 32×32 samples), must—be split into further TUs.\",\n \"A limit is applied so that TUs can be split down to a maximum tree depth, currently configured as 2 levels.\",\n \"i.e.\",\n \"there can be no more than 16 TUs for each CU.\",\n \"An illustrative smallest allowable TU size is 4×4 samples and the largest allowable TU size is 32×32 samples.\",\n \"Again, the three channels have the same TU structure wherever possible, but if a TU cannot be split to a particular depth for a given channel due to the size restriction, it remains at the larger size.\",\n \"The so-called non-square quad-tree transform arrangement (NSQT) is similar, but the method of splitting into four TUs need not be 2×2, but can be 4×1 or 1×4.Referring to FIGS.\",\n \"18a and 18b, the different block sizes possible are summarised for CU, PU and TU blocks, with ‘Y’ referring to luma blocks and ‘C’ referring in a generic sense to a representative one of the chroma blocks, and the numbers referring to pixels.\",\n \"‘Inter’ refers to inter-frame prediction PUs (as opposed to intra-frame prediction PUs).\",\n \"In many cases, only the block sizes for the luma blocks are shown.\",\n \"The corresponding sizes of the associated chroma blocks are related to the luma block sizes according to the channel ratios.\",\n \"So, for 4:4:4, the chroma channels have the same block sizes as the luma blocks shown in FIGS.\",\n \"18a and 18b.\",\n \"Accordingly, the chroma PU structure mirrors (or is respectively identical to) the luma PU structure at all split levels (where a “split level” refers to the choice of CU size options and, within a CU size option, the choice of PU size and shape options).\",\n \"While it would be possible to employ the same set of possible block sizes and shapes but to allow different ones (of that set) to be selected in respect of luma and chroma components of a CU, in some embodiments of the disclosure the same PU block size and shape is selected for the chroma and the luma components corresponding to a CU.\",\n \"Therefore, whichever PU size(s) and shape(s) is (are) selected for a luma CU, the identical size and shape PU(s) is (are) selected for the chroma components of that CU.\",\n \"Note that as discussed below, the selection of block sizes and shapes and PUs is an encoder based decision, under the control of the controller 343.In such arrangements, the luminance and chrominance samples are in a 4:4:4 format and are arranged as plural coding units each comprising a block of luminance and chrominance samples; and a prediction direction is detected in respect of a current prediction unit, being a block of luminance or chrominance samples representing at least a subset of a respective coding unit.\",\n \"For a particular coding unit, a size and shape of one or more prediction units each comprising luminance and chrominance samples from that coding unit is made (for example by the controller 343) such that the selection of the prediction unit size and shape are the same for luminance samples and for chrominance samples.\",\n \"For 4:2:2 and 4:2:0, the chroma blocks will each have fewer pixels than the corresponding luma block, according to the channel ratio.\",\n \"The arrangements shown in FIGS.\",\n \"18a and 18b concern four possible CU sizes: 64×64, 32×32, 16×16 and 8×8 luma pixels respectively.\",\n \"Each of these CUs has a corresponding row of PU options (shown in a column 1140) and TU options (shown in a column 1150).\",\n \"For the possible CU sizes defined above, the rows of options are referenced as 1100, 1110, 1120 and 1130 respectively.\",\n \"Note that 64×64 is currently a maximum CU size but this restriction could change.\",\n \"Within each row 1100 .\",\n \".\",\n \".\",\n \"1130, different PU options are shown applicable to that CU size.\",\n \"The TU options applicable to those PU configurations are shown horizontally aligned with the respective PU option(s).\",\n \"Note that in several cases, multiple PU options are provided.\",\n \"As discussed above, the aim of the apparatus in selecting a PU configuration is to match (as closely as possible) the boundary of real objects in the picture, so that different prediction parameters can be applied to different real objects.\",\n \"The block sizes and shapes and PUs are an encoder based decision, under the control of the controller 343.The current method involves conducting trials of many TU tree structures for many directions, getting the best “cost” at each level.\",\n \"Here, the cost may be expressed as a measure of the distortion, or noise, or errors, or bit rate resulting from each block structure.\",\n \"So, the encoder may try two or more (or even all available) permutations of block sizes and shapes within those allowed under the tree structures and hierarchies discussed above, before selecting the one of the trials which gives the lowest bit rate for a certain required quality measure, or the lowest distortion (or errors, or noise, or combinations of these measures) for a required bit rate, or a combination of these measures.\",\n \"Given the selection of a particular PU configuration, various levels of splitting may be applied to generate the corresponding TUs.\",\n \"Referring to the row 1100, in the case of a 64×64 PU, this block size is too large for use as a TU and so a first level of splitting (from “level 0” (not split) to “level 1”) is compulsory, resulting in an array of four 32×32 luma TUs.\",\n \"Each of these may be subjected to further splitting in a tree hierarchy (from “level 1” to “level 2”) as required, with the splitting being carried out before transforming or quantising that TU is performed.\",\n \"The maximum number of levels in the TU tree is limited by (for example) the HEVC documents.\",\n \"Other options are provided for PU sizes and shapes in the case of a 64×64 luma pixel CU.\",\n \"These are restricted to use only with inter-coded pictures and, in some cases, with the so-called AMP option enabled.\",\n \"AMP refers to Asymmetric Motion Partitioning and allows for PUs to be partitioned asymmetrically.\",\n \"Similarly, in some cases options are provided for TU sizes and shapes.\",\n \"If NQST (non-square quad-tree transform, basically allowing a non-square TU) is enabled, then splitting to level 1 and/or level 2 can be carried out as shown, whereas if NQST is not enabled, the TU sizes follow the splitting pattern of the respective largest TU for that CU size.\",\n \"Similar options are provided for other CU sizes.\",\n \"In addition to the graphical representation shown in FIGS.\",\n \"18a and 18b, the numerical part of the same information is provided in the following table, though the presentation in FIGS.\",\n \"18a and 18b is considered definitive.\",\n \"“n/a” indicates a mode which is not allowed.\",\n \"The horizontal pixel size is recited first.\",\n \"If a third figure is given, it relates to the number of instances of that block size, as in (horizontal)×(vertical)×(number of instances) blocks.\",\n \"N is an integer.\",\n \"TU Options CU Size PU Options Level 0 Level 1 Level 2 64 × 64 64 × 64 n/a 32 × 32 × 4 16 × 16 × 4 64 × 32 × 2 (horizontal configuration) n/a 32 × 32 × 4 32 × 8 × 4 64 × 16 + 64 × 48 (2 horizontal configurations) 32 × 64 × 2 (vertical configuration) n/a 32 × 32 × 4 8 × 32 × 4 16 × 64 + 48 × 64 (2 vertical configurations) 32 × 32 32 × 32 32 × 32 16 × 16 × 4 8 × 8 × 4 32 × 16 × 2 (horizontal configuration) n/a 32 × 8 × 4 16 × 4 × 4 (luma) + 32 × 8 + 32 × 24 (2 horizontal 4 × 4 × 4 (chroma, configurations) 4:2:0 or 4:2:2) or 8 × 4 × 4 (chroma, 4:2:2) 16 × 32 × 2 (vertical configuration) n/a 8 × 32 × 4 4 × 16 × 4 (luma) + 8 × 32 + 24 × 32 (2 vertical 4 × 4 × 4 (chroma) configurations) 16 × 16 16 × 16 16 × 16 8 × 8 × 4 4 × 4 × 4 (luma) + 4 × 8 × 4 (chroma) 16 × 8 × 2 (horizontal configuration) n/a 16 × 4 × 4 (luma) + 4 × 4 × 4 (luma) + 16 × 4 + 16 × 12 (2 horizontal 4 × 8 × 4 (chroma) 4 × 8 × 1 (chroma) configurations) (4:2:0 or 4:2:2) (4:2:0 or 4:2:2) 16 × 4 × 4 (luma) + 4 × 4 × 4 (luma) + 8 × 8 × 4 × 4 (chroma) 4 × 1 (chroma) (4:2:2) (4:2:2) 8 × 16 × 2 (vertical configuration) n/a 4 × 16 + 12 × 16 (2 vertical configurations) 8 × 8 8 × 8 8 × 8 4 × 4 × 4 (luma) + n/a 4 × 4 × 4 4 × 8 × 1 (chroma) 8 × 4 × 2 (horizontal configuration) 4 × 8 × 2 (vertical configuration) 4 × 4 × 4 (luma) + 4 × N (chroma) n/a 4 × 4 × 4 (luma) + n/a 4 × 8 × 1 (chroma) 4:2:0, 4:2:2 and 4:4:4 Block Structure Variants It has been appreciated that both 4:2:0 and 4:4:4 schemes have square PU blocks for intra-prediction coding.\",\n \"Moreover, currently the 4:2:0 scheme permits 4×4 pixel PU & TU blocks.\",\n \"In embodiments, it is consequently proposed that for the 4:4:4 scheme the recursion for CU blocks is permitted down to 4×4 pixels rather than 8×8 pixels, since as noted above in the 4:4:4 mode the luma and chroma blocks will be the same size (i.e.\",\n \"the chroma data is not subsampled) and so for a 4×4 CU no PU or TU will need to be less than the already allowed minimum of 4×4 pixels.\",\n \"This is therefore an example of selecting, for a particular coding unit, a size and shape of one or more prediction units each comprising luminance or chrominance samples from at least a subset of that coding unit, the selection of the prediction unit size and shape being the same for luminance samples and for chrominance samples.\",\n \"Similarly, in the 4:4:4 scheme, in an embodiment each of the Y, Cr, Cb channels, or the Y and the two Cr, Cb channels together, could have respective CU tree-hierarchies.\",\n \"A flag may then be used to signal which hierarchy or arrangement of hierarchies is to be used.\",\n \"This approach could also be used for a 4:4:4 RGB colour space scheme.\",\n \"However, in an alternative, the tree hierarchies for chroma and luma may instead be independent.\",\n \"In the example of an 8×8 CU in the 4:2:0 scheme, this results in four 4×4 luma PUs and one 4×4 chroma PU.\",\n \"Hence in the 4:2:2 scheme, having twice as much chroma data, one option is in this case is to have two 4×4 chroma PUs, where (for example) the bottom chroma block would correspond in position to the bottom left luma block.\",\n \"However, it is has been appreciated that using one non-square 4×8 chroma PU in this case would be more consistent with arrangements for the 4:2:0 chroma format.\",\n \"In the 4:2:0 scheme there are in principle some non-square TU blocks permitted for certain classes of inter-prediction coding, but not for intra-prediction coding.\",\n \"However in inter-prediction coding, when non-square quad-tree transforms (NSQT) are disabled (which is the current default for the 4:2:0 scheme), all TUs are square.\",\n \"Hence in effect the 4:2:0 scheme currently enforces square TUs.\",\n \"For example, a 16×16 4:2:0 luma TU would correspond with respective Cb & Cr 8×8 4:2:0 Chroma TUs.\",\n \"However, as noted previously, the 4:2:2 scheme can have non-square PUs.\",\n \"Consequently in an embodiment it is proposed to allow non-square TUs for the 4:2:2 scheme.\",\n \"For example, whilst a 16×16 4:2:2 luma TU could correspond with two respective Cb & Cr 8×8 4:2:2 Chroma TUs, in this embodiment it could instead correspond with respective Cb & Cr 8×16 4:2:2 Chroma TUs.\",\n \"Similarly, four 4×4 4:2:2 luma TUs could correspond with two respective 4×4 Cb+Cr 4:2:2 TUs, or in this embodiment could instead correspond with respective 4×8 Cb & Cr 4:2:2 TUs.\",\n \"Having non-square chroma TUs, and hence fewer TUs, may be more efficient as they are likely to contain less information.\",\n \"However this may affect the transformation and scanning processes of such TUs, as will be described later.\",\n \"Finally, for the 4:4:4 scheme it may be preferable to have the TU structure channel-independent, and selectable at the sequence, picture, slice or finer level.\",\n \"As noted above, NSQT is currently disabled in the 4:2:0 scheme of HEVC.\",\n \"However, if for inter-picture prediction, NSQT is enabled and asymmetric motion partitioning (AMP) is permitted, this allows for PUs to be partitioned asymmetrically; thus for example a 16×16 CU may have a 4×16 PU and a 12×16 PU.\",\n \"In these circumstances, further considerations of block structure are important for each of the 4:2:0 and 4:2:2 schemes.\",\n \"For the 4:2:0 scheme, in NSQT the minimum width/height of a TU may be restricted to 4 luma/chroma samples: Hence in a non-limiting example a 16×4/16×12 luma PU structure has four 16×4 luma TUs and four 4×4 chroma TUs, where the luma TUs are in a 1×4 vertical block arrangement and the chroma TUs are in a 2×2 block arrangement.\",\n \"In a similar arrangement where the partitioning was vertical rather than horizontal, a 4×16/12×16 luma PU structure has four 4×16 luma TUs and four 4×4 chroma TUs, where the luma TUs are in a 4×1 horizontal block arrangement and the chroma TUs are in a 2×2 block arrangement.\",\n \"For the 4:2:2 scheme, in NSQT as a non-limiting example a 4×16/12×16 luma PU structure has four 4×16 luma TUs and four 4×8 chroma TUs, where the luma TUs are in a 4×1 horizontal block arrangement; the chroma TUs are in a 2×2 block arrangement.\",\n \"However, it has been appreciated that a different structure can be considered for some cases.\",\n \"Hence in an embodiment, in NSQT as a non-limiting example 16×4/16×12 luma PU structure has four 16×4 luma TUs and four 8×4 chroma TUs, but now the luma and chroma TUs are in a 1×4 vertical block arrangement, aligned with the PU layout (as opposed to the 4:2:0 style arrangement of four 4×8 chroma TUs in a 2×2 block arrangement).\",\n \"Similarly 32×8 PU can have four 16×4 luma TUs and four 8×4 chroma TUs, but now the luma and chroma TUs are in a 2×2 block arrangement.\",\n \"Hence more generally, for the 4:2:2 scheme, in NSQT the TU block sizes are selected to align with the asymmetric PU block layout.\",\n \"Consequently the NSQT usefully allows TU boundaries to align with PU boundaries, which reduces high frequency artefacts that may otherwise occur.\",\n \"In general terms, embodiments of the disclosure can relate to a video coding method, apparatus or program operable in respect of images of a 4:2:2 format video signal.\",\n \"An image to be encoded is divided into coding units, prediction units and transform units for encoding, a coding unit being a square array of luminance samples and the corresponding chrominance samples, there being one or more prediction units in a coding unit, and there being one or more transform units in a coding unit; in which a prediction unit is an elementary unit of prediction so that all samples within a single prediction unit are predicted using a common prediction technique, and a transform unit is a basic unit of transformation and quantisation.\",\n \"A Non-square transform mode (such as an NSQT mode) is enabled so as to allow non-square prediction units.\",\n \"Optionally, asymmetric motion partitioning is enabled so as to allow asymmetry between two or more prediction units corresponding to a single coding unit.\",\n \"The controller 343 controls the selection of transform unit block sizes to align with the prediction unit block layout, for example by detecting image features in the portion of the image corresponding to a PU and selecting TU block sizes in respect of that PU so as to align TU boundaries with edges of image features in the portion of the image.\",\n \"The rules discussed above dictate which combinations of block sizes are available.\",\n \"The encoder may just try different combinations.\",\n \"As discussed above, a trial may include two or more, through to all available options.\",\n \"The trial encode processes can be carried out according to a cost function metric and a result selected according to an assessment of the cost function.\",\n \"Given that there are three levels of variation, according to the CU size and shape, the PU size and shape and the TU size and shape, this could lead to a large number of permutations to be trial-encoded.\",\n \"To reduce this variation, the system could trial encode for a CU size by using an arbitrarily selected one of the PU/TU configurations allowable for each CU size; then, having selected a CU size, a PU size and shape could be selected by trial encoding the different PU options each with a single arbitrarily chosen TU configuration.\",\n \"Then, having selected a CU and PU, the system could try all applicable TU configurations to select a final TU configuration.\",\n \"Another possibility is that some encoders may use a fixed choice of block configuration, or may allow a limited subset of the combinations set out in the discussions above.\",\n \"Intra-Prediction 4:2:0 Intra-Prediction Turning now to FIG.\",\n \"22, for intra-prediction, HEVC allows for angular chroma prediction.\",\n \"By way of introduction, FIG.\",\n \"22 illustrates 35 prediction modes applicable to luma blocks, 33 of which specify directions to reference samples for a current predicted sample position 110.The remaining two modes are mode 0 (planar) and mode 1 (dc).\",\n \"HEVC allows chroma to have DC, Vertical, Horizontal, Planar, DM_CHROMA and LM_CHROMA modes.\",\n \"DM_CHROMA indicates that the prediction mode to be used is the same as that of the co-located luma PU (i.e.\",\n \"one of the 35 shown in FIG.\",\n \"22).\",\n \"LM_CHROMA (linear mode chroma) indicates that co-located luma samples (downsampled as appropriate to the channel ratios) are used to derive the predicted chroma samples.\",\n \"In this case, if the luma PU from which the DM_CHROMA prediction mode would be taken selected DC, Vertical, Horizontal or Planar, that entry in the chroma prediction list is replaced using mode 34.In the LM_CHROMA mode, the luma pixels from which the chroma pixels are predicted are scaled (and have an offset applied if appropriate) according to a linear relationship between luma and chroma.\",\n \"This linear relationship is derived from surrounding pixels, and the derivation can be carried out on a block by block basis, with the decoder finishing decoding one block before moving on to the next.\",\n \"It is notable that the prediction modes 2-34 sample an angular range from 45 degrees to 225 degrees; that is to say, one diagonal half of a square.\",\n \"This is useful in the case of the 4:2:0 scheme, which as noted above only uses square chroma PUs for intra-picture prediction.\",\n \"4:2:2 Intra-Prediction Variants However, also as noted above the 4:2:2 scheme could have rectangular (non-square) chroma PUs even when the luma PUs are square.\",\n \"Or indeed, the opposite could be true: a rectangular luma PU could correspond to a square chroma PU.\",\n \"The reason for the discrepancy is that in 4:2:2, the chroma is subsampled horizontally (relative to the luma) but not vertically.\",\n \"So the aspect ratio of a luma block and a corresponding chroma block would be expected to be different.\",\n \"Consequently, in an embodiment, for chroma Pus having a different aspect ratio to the corresponding luma block, a mapping table may be required for the direction.\",\n \"Assuming (for example) a 1-to-2 aspect ratio for rectangular chroma PUs, then for example mode 18 (currently at an angle of 135 degrees) may be re-mapped to 123 degrees.\",\n \"Alternatively selection of current mode 18 may be remapped to a selection of current mode 22, to much the same effect.\",\n \"Hence more generally, for non-square PUs, a different mapping between the direction of the reference sample and the selected intra prediction mode may be provided compared with that for square PUs.\",\n \"More generally still, any of the modes, including the non-directional modes, may also be re-mapped based upon empirical evidence.\",\n \"It is possible that such mapping will result in a many-to-one relationship, making the specification of the full set of modes redundant for 4:2:2 chroma PUs.\",\n \"In this case, for example it may be that only 17 modes (corresponding to half the angular resolution) are necessary.\",\n \"Alternatively or in addition, these modes may be angularly distributed in a non-uniform manner.\",\n \"Similarly, the smoothing filter used on the reference sample when predicting the pixel at the sample position may be used differently; in the 4:2:0 scheme it is only used to smooth luma pixels, but not chroma ones.\",\n \"However, in the 4:2:2 and 4:4:4 schemes this filter may also be used for the chroma PUs.\",\n \"In the 4:2:2 scheme, again the filter may be modified in response to the different aspect ratio of the PU, for example only being used for a subset of near horizontal modes.\",\n \"An example subset of modes is preferably 2-18 and 34, or more preferably 7-14.In 4:2:2, smoothing of only the left column of reference samples may be carried out in embodiments.\",\n \"These arrangements are discussed later in more detail.\",\n \"4:4:4 Intra-Prediction Variants In the 4:4:4 scheme, the chroma and luma PUs are the same size, and so the intra-prediction mode for a chroma PU can be either the same as the co-located luma PU (so saving some overhead in the bit stream by not having to encode a separate mode), or alternatively, it can be independently selected.\",\n \"In this latter case therefore, in an embodiment the system may have 1, 2 or 3 different prediction modes for each of the PUs in a CU; In a first example, the Y, Cb and Cr PUs may all use the same intra-prediction mode.\",\n \"In a second example, the Y PU may use one intra-prediction mode, and the Cb and Cr PUs both use another independently selected intra-prediction mode.\",\n \"In a third example, the Y, Cb and Cr PUs each use a respective independently selected intra-prediction mode.\",\n \"It will be appreciated that having independent prediction modes for the chroma channels (or each chroma channel) will improve the colour prediction accuracy.\",\n \"But this is at the expense of an additional data overhead to communicate the independent prediction modes as part of the encoded data.\",\n \"To alleviate this, the selection of the number of modes could be indicated in the high-level syntax (e.g.\",\n \"at sequence, picture, or slice level).\",\n \"Alternatively, the number of independent modes could be derived from the video format; for example, GBR could have up to 3, whilst YCbCr could be restricted to up to 2.In addition to independently selecting the modes, the available modes may be allowed to differ from the 4:2:0 scheme in the 4:4:4 scheme.\",\n \"For example as the luma and chroma PUs are the same size in 4:4:4, the chroma PU may benefit from access to all of the 35+LM_CHROMA+DM_CHROMA directions available.\",\n \"Hence for the case of Y, Cb and Cr each having independent prediction modes, then the Cb channel could have access to DM_CHROMA & LM_CHROMA, whilst the Cr channel could have access to DM_CHROMA_Y, DM_CHROMA_Cb, LM_CHROMA_Y and LM_CHROMA_Cb, where these replace references to the Luma channel with references to the Y or Cb chroma channels.\",\n \"Where the luma prediction modes are signalled by deriving a list of most probable modes and sending an index for that list, then if the chroma prediction mode(s) are independent, it may be necessary to derive independent lists of most probable modes for each channel.\",\n \"Finally, in a similar manner to that noted for the 4:2:2 case above, in the 4:4:4 scheme the smoothing filter used on the reference sample when predicting the pixel at the sample position may be used for chroma PUs in a similar manner to luma PUs.\",\n \"Currently, a [1,2,1] low-pass filter can be applied to the reference samples prior to intra-prediction.\",\n \"This is only used for luma TUs when using certain prediction modes.\",\n \"One of the intra-prediction modes available to chroma TUs is to base the predicted samples on co-located luma samples.\",\n \"Such an arrangement is illustrated schematically in FIG.\",\n \"19, which shows an array of TUs 1200 (from a region of a source image) represented by small squares in the Cb, Cr and Y channels, showing the special alignment between image features (schematically indicated by dark and light shaded boxes 1200) in the Cb and Y channels and in the Cr and Y channels.\",\n \"In this example, it is of benefit to force the chroma TUs to base their predicted samples on co-located luma samples.\",\n \"However, it is not always the case that image features correspond between the three channels.\",\n \"In fact, certain features may appear only in one or two of the channels, and in general the image content of the three channels may differ.\",\n \"In embodiments, for Cr TUs, LM_Chroma could optionally be based on co-located samples from the Cb channel (or, in other embodiments, the dependence could be the other way around).\",\n \"Such an arrangement is shown in schematic form in FIG.\",\n \"20.Here, spatially aligned TUs are illustrated between the Cr, Cb and Y channels.\",\n \"A further set of TUs labelled “source” is a schematic representation of the colour picture as seen as a whole.\",\n \"The image features (a top left triangle and a lower right triangle) seen in the source image do not in fact represent changes in the luminance, but only changes in chrominance between the two triangular regions.\",\n \"In this case, basing LM_Chroma for Cr on the luminance samples would produce a poor prediction, but basing it on the Cb samples could give a better prediction.\",\n \"The decision as to which LM_Chroma mode to be used can be made by the controller 343 and/or the mode controller 520, based on trial encoding of different options (including the option of basing LM_Chroma on the co-located luma or co-located chroma samples), with the decision as to which mode to select being made by assessing a cost function, similar to that described above, with respect to the different trial encodings.\",\n \"Examples of the cost function are noise, distortion, error rate or bit rate.\",\n \"A mode from amongst those subjected to trial encoding which gives the lowest of any one or more of these cost functions is selected.\",\n \"FIG.\",\n \"21 schematically illustrates a method used to obtain reference samples for intra-prediction in embodiments.\",\n \"In viewing FIG.\",\n \"21, it should be borne in mind that encoding is carried out according to a scanning pattern, so that in general terms encoded versions of the blocks above and to the left of a current block to be encoded are available to the encoding process.\",\n \"Sometimes samples below-left or to the above-right are used, if they have been previously coded as part of other already-encoded TUs within the current LCU.\",\n \"Reference is made to FIG.\",\n \"13 as described above, for example.\",\n \"A shaded area 1210 represents a current TU, that is to say, a TU which is currently being encoded.\",\n \"In 4:2:0 and 4:2:2, the column of pixels immediately to the left of the current TU does not contain co-located luminance and chrominance samples because of horizontal subsampling.\",\n \"In other words, this is because the 4:2:0 and 4:2:2 formats have half as many chrominance pixels as luminance pixels (in a horizontal direction), so not every luminance sample position has a co-sited chrominance sample.\",\n \"Therefore, although luminance samples may be present in the column of pixels immediately to the left of the TU, chrominance samples are not present.\",\n \"Therefore, in some embodiments, the column located two samples to the left of the current TU is used to provide reference samples for LM_Chroma.\",\n \"Note that the situation is different in 4:4:4, in that the column immediately to the left of the current TU does indeed contain co-located luma and chroma samples.\",\n \"This column could therefore be used to provide reference samples.\",\n \"The reference samples are used as follows.\",\n \"In the LM_Chroma mode, predicted chroma samples are derived from reconstructed luma samples according to a linear relationship.\",\n \"So, in general terms, it can be said that the predicted chrominance values within the TU are given by: PC=a+bPL where PC is a chrominance sample value, PL is a reconstructed luminance sample value at that sample position, and a and b are constants.\",\n \"The constants are derived for a particular block by detecting the relationship between reconstructed luma samples and chroma samples in the row just above that block and in the column just to the left of that block, these being sample positions which have already been encoded (see above).\",\n \"In some embodiments, the constants a and b are derived as follows: a=R(PL′,PC′)/R(PL′,PL′) where R represents a linear (least squares) regression function, and PL′ and PC′ are luminance and chrominance samples respectively from the adjacent row and column as discussed above, and: b=mean(PC′)−a·mean(PL′) For 4:4:4, the PL′ and PC′ values are taken from the column immediately to the left of the current TU, and the row immediately above the current TU.\",\n \"For 4:2:2, the PL′ and PC′ values are taken from the row immediately above the current TU and the column in the adjacent block which is two sample positions away from the left edge of the current TU.\",\n \"For 4:2:0 (which is subsampled vertically and horizontally) the PL′ and PC′ values would ideally be taken from a row which is two rows above the current TU, but in fact are taken from a row in the adjacent block which is one sample positions above the current TU, and the column in the adjacent block which is two sample positions away from the left edge of the current TU.\",\n \"The reason is to avoid having to maintain an additional whole row of data in memory.\",\n \"So in this regard, 4:2:2 and 4:2:0 are treated in a similar way.\",\n \"Accordingly, these techniques apply to video coding methods having a chrominance prediction mode in which a current block of chrominance samples representing a region of the image is encoded by deriving and encoding a relationship of the chrominance samples with respect to a co-sited block of luminance samples (such as reconstructed luminance samples) representing the same region of the image.\",\n \"The relationship (such as the linear relationship) is derived by comparing co-sited (otherwise expressed as correspondingly-sited) luminance and chrominance samples from adjacent already-encoded blocks.\",\n \"The chrominance samples are derived from luminance samples according to the relationship; and the difference between the predicted chrominance samples and the actual chrominance samples is encoded as residual data.\",\n \"In respect of a first sampling resolution (such as 4:4:4) where the chrominance samples have the same sampling rate as the luminance samples, the co-sited samples are samples in sample positions adjacent to the current block.\",\n \"In respect of a second sampling resolution (such as 4:2:2 or 4:2:0) where the chrominance samples have a lower sampling rate than that of the luminance samples, a nearest column or row of co-sited luminance and chrominance samples from the adjacent already-encoded block is used to provide the co-sited samples.\",\n \"Or where, in the case of the second sampling resolution being a 4:2:0 sampling resolution, the correspondingly-sited samples are a row of samples adjacent to the current block and a nearest column or row of correspondingly-sited luminance and chrominance samples, from the adjacent already-encoded blocks.\",\n \"FIG.\",\n \"22 schematically illustrates the available prediction angles for luma samples.\",\n \"The current pixel being predicted as shown at the centre of the diagram as a pixel 1220.The smaller dots 1230 represent adjacent pixels.\",\n \"Those located on the top or left sides of the current pixel are available as reference samples to generate a prediction, because they have been previously encoded.\",\n \"Other pixels are currently unknown (at the time of predicting the pixel 1220) and will in due course be predicted themselves.\",\n \"Each numbered prediction direction points to the reference samples 1230 on the top or left edges of the current block that are used to generate the current predicted pixel.\",\n \"In the case of smaller blocks, where the prediction directions point to locations between reference samples, a linear interpolation between adjacent reference samples is used.\",\n \"Turning now to intra-angular prediction for chroma samples, for 4:2:0, fewer prediction directions are available because of the relative scarcity of the chroma samples.\",\n \"However, if the DM_CHROMA mode is selected then the current chroma block will use the same prediction direction as the co-located luma block.\",\n \"In turn, this means that the luma directions for intra-prediction are also available to chroma.\",\n \"However, for chroma samples in 4:2:2, it can be considered counter-intuitive to use the same prediction algorithm and direction as luma when DM_CHROMA is selected, given that chroma blocks now have a different aspect ratio to that of the luma blocks.\",\n \"For example, a 45° line for a square luma array of samples should still map to a 45° line for chroma samples, albeit with an array of rectangular sized samples.\",\n \"Overlaying the rectangular grid onto to a square grid indicates that the 45° line would then in fact map to a 26.6° line.\",\n \"FIG.\",\n \"23 schematically illustrates luma intra-prediction directions as applied to chroma pixels in 4:2:2, in respect of a current pixel to be predicted 1220.Note that there are half as many pixels horizontally as there are vertically, because 4:2:2 has half the horizontal sample rate in the chroma channel as compared to the luma channel.\",\n \"FIG.\",\n \"24 schematically illustrates the transformation or mapping of the 4:2:2 chroma pixels to a square grid, and subsequently how this transformation changes the prediction directions.\",\n \"The luma prediction directions are shown as broken lines 1240.The chroma pixels 1250 are remapped to a square grid giving a rectangular array half the width 1260 of the corresponding luma array (such as that shown in FIG.\",\n \"22).\",\n \"The prediction directions shown in FIG.\",\n \"23 have been remapped to the rectangular array.\",\n \"It can be seen that for some pairs of directions (a pair being a luma direction and a chroma direction) there is either an overlap or a close relationship.\",\n \"For example, direction 2 in the luma array substantially overlies the direction 6 in the chroma array.\",\n \"However, it will also be noted that some luma directions, approximately half of them, have no corresponding chroma direction.\",\n \"An example is the luma direction numbered 3.Also, some chroma directions (2-5) have no equivalent in the luma array, and some luma directions (31-34) have no equivalent in the chroma array.\",\n \"But in general, the superposition as shown in FIG.\",\n \"24 demonstrates that it would be inappropriate to use the same angle for both the luma and chroma channels.\",\n \"Accordingly, in order to derive the appropriate prediction angle for chroma when (a) DM_CHROMA is selected and (b) the DM_CHROMA mode currently in use indicates that the chroma prediction direction should be that of the co-located luma block, the following procedure is applied: (i) derive the intra-prediction angle step and its inverse according to the luma direction according to usual HEVC rules (ii) if the luma direction is predominantly vertical (that is, for example, a mode numbered from 18 to 34 inclusive) then the intra-prediction angle step is halved and its inverse is doubled.\",\n \"(iii) otherwise, if the luma direction is predominantly horizontal (that is, for example, a mode numbered from 2 to 17 inclusive) then the intra-prediction angle step is doubled and its inverse halved.\",\n \"Accordingly these embodiments relate to video coding or decoding methods, apparatus or programs in which luminance and chrominance samples are predicted from other respective reference samples according to a prediction direction associated with a sample to be predicted.\",\n \"In modes such as 4:2:2 the chrominance samples have a lower horizontal and/or vertical sampling rate than the luminance samples so that the ratio of luminance horizontal resolution to chrominance horizontal resolution is different to the ratio of luminance vertical resolution to chrominance vertical resolution.\",\n \"In short, this means that a block of luminance samples has a different aspect ratio to a corresponding block of chrominance samples.\",\n \"The intra frame predictor 530, for example, is operable to detect a first prediction direction defined in relation to a grid of a first aspect ratio in respect of a set of current samples to be predicted; and to apply a direction mapping to the prediction direction so as to generate a second prediction direction defined in relation to a grid of samples of a different aspect ratio of the same set of current samples to be predicted.\",\n \"In embodiments, the first prediction direction is defined in respect of one of luminance or chrominance samples, and the second prediction direction is defined in respect of the other of luminance or chrominance samples.\",\n \"In the particular examples discussed in the present description, the luminance prediction direction may be modified to provide the chrominance prediction direction.\",\n \"But the other way round could be used.\",\n \"The technique is particularly applicable to intra-prediction, so that the reference samples are samples of the same respective image as the samples to be predicted.\",\n \"In at least some arrangements the first prediction direction is defined with respect to a square block of luminance samples including the current luminance sample; and the second prediction direction is defined with respect to a rectangular block of chrominance samples including the current chrominance sample.\",\n \"It is possible to provide independent prediction modes for the two chrominance components.\",\n \"In such an arrangement the chrominance samples comprise samples of first and second chrominance components, and the technique comprises applying the direction mapping discussed above step in respect of the first chrominance component (such as Cb); and providing a different prediction mode in respect of the second chrominance component (such as Cr).\",\n \"The video data can be in a 4:2:2 format or a 4:4:4 format, for example.\",\n \"In general terms, embodiments of the disclosure can provide for independent prediction modes for the chrominance components (for example, for each of the luminance and chrominance components separately).\",\n \"These embodiments relate to video coding methods in which luminance and chrominance samples of an image are predicted from other respective reference samples of the same image according to a prediction direction associated with a sample to be predicted, the chrominance samples having a lower horizontal and/or vertical sampling rate than the luminance samples so that the ratio of luminance horizontal resolution to chrominance horizontal resolution is different to the ratio of luminance vertical resolution to chrominance vertical resolution so that a block of luminance samples has a different aspect ratio to a corresponding block of chrominance samples, and the chrominance samples representing first and second chrominance components.\",\n \"The intra frame mode selector 520 selects a prediction mode defining a selection of one or more reference samples for predicting a current chrominance sample of the first chrominance component (such as Cb).\",\n \"It also selects a different prediction mode defining a different selection of one or more reference samples for predicting a current chrominance sample of the second chrominance component (such as Cr), co-sited with the current chrominance sample of the first chrominance component.\",\n \"A reference sample filter can optionally be applied, for example, as part of the operation of the frame stores 570 and/or the predictors 530, 540 acting as a filter arrangement, to horizontal samples or vertical samples (or both).\",\n \"The filter can be a 3-tap “1 2 1” filter, currently applied to all luma reference samples except the bottom left and top right (the samples of a N×N block are gathered together to form a single 1D array of size 2N+1, and then optionally filtered).\",\n \"In embodiments of the technology it is applied only the first (left hand edge) or last (top edge) N+1 chroma samples for 4:2:2, but noting that the bottom left, top right and top left would then not be adjusted; or all chroma samples (as for luma), for 4:2:2 and 4:4:4.Embodiments can also provide video coding or decoding methods, apparatus or programs in which luminance and first and second chrominance component samples are predicted from other respective reference samples according to a prediction direction associated with a sample to be predicted, involving predicting samples of the second chrominance component from samples of the first chrominance component.\",\n \"Embodiments can also provide video coding or decoding methods, apparatus or programs in which luminance and first and second chrominance component samples are predicted from other respective reference samples according to a prediction direction associated with a sample to be predicted, involving filtering the reference samples.\",\n \"As discussed with reference to FIGS.\",\n \"19 and 20, it is possible that the different prediction mode comprises a mode by which samples of the second chrominance component are predicted from samples of the first chrominance component.\",\n \"Note that modes 0 and 1 are not angular prediction modes and so are not included in this procedure.\",\n \"The effect of the procedure shown above is to map the chroma prediction directions onto the luma prediction directions in FIG.\",\n \"24.For 4:2:0, when either a purely horizontal prediction mode (luma mode 10) or a purely vertical prediction mode (luma mode 26) is selected, the top or left edges of the predicted TU are subject to filtering for the luma channel only.\",\n \"For the horizontal prediction mode, the top row is filtered in the vertical direction.\",\n \"For the vertical prediction mode, the left column is filtered in the horizontal direction.\",\n \"Filtering a column of samples in the horizontal direction can be understood as applying a horizontally oriented filter to each sample in turn of the column of samples.\",\n \"So, for an individual sample, its value will be modified by the action of the filter, based on a filtered value generated from the current value of that sample and of one or more other samples at sample positions displaced from that sample in a horizontal direction (that is, one or more other samples to the left and/or right of the sample in question).\",\n \"Filtering a row of samples in the vertical direction can be understood as applying a vertically oriented filter to each sample in turn of the row of samples.\",\n \"So, for an individual sample, its value will be modified by the action of the filter, based on a filtered value generated from the current value of that sample and of one or more other samples at sample positions displaced from that sample in a vertical direction (that is, one or more other samples above and/or below the sample in question).\",\n \"One purpose of the edge pixel filtering process described above is to aim to reduce block based edge effects in the prediction thereby aiming to reduce energy in the residual image data.\",\n \"In embodiments, a corresponding filtering process is also provided for chroma TUs in 4:4:4 and 4:2:2.Taking into account the horizontal subsampling, one proposal is only to filter the top row of the chroma TU in 4:2:2, but to filter both the top row and left column (as appropriate, according to the selected mode) in 4:4:4.It is considered appropriate to filter only in these regions so as to avoid filtering out too much useful detail, which (if filtered out) would lead to an increased energy of the residual data.\",\n \"For 4:2:0, when DC mode is selected, one or both of the top and/or left edges of the predicted TU are subject to filtering for the luma channel only.\",\n \"Here, this is an example of a case where the luminance samples represent a luminance component and respective chrominance samples represent two chrominance components, the filtering step is applied to a subset of the three components, the subset being either one or two of the three components.\",\n \"The subset may consist of the luminance component.\",\n \"The filtering may involve filtering one or both of the left column of samples in the predicted block of samples and the top row of samples in the predicted block of samples.\",\n \"The filtering may be such that in DC Mode, the filter does a (1×neighbouring outside sample+3*edge sample)/4 averaging operation for all samples on both edges.\",\n \"However, for the top left the filter function is (2×current sample+1×above sample+1×left sample)/4.This is an example of an operation in which in a DC mode in which a predicted sample is generated as a simple arithmetic mean of surrounding samples, the filtering step comprising filtering the left column of samples in the predicted block of samples and filtering the top row of samples in the predicted block of samples.\",\n \"The H/V filter is an average between neighbouring outside sample and edge sample.\",\n \"In some embodiments, this filtering process is also provided for chroma TUs in 4:4:4 and 4:2:2.Again, taking into account the horizontal subsampling, in some embodiments, only the top row of the chroma samples is filtered for 4:2:2, but the top row and left column of the chroma TU are filtered for 4:4:4.Accordingly, this technique can apply in respect of a video coding or decoding method, apparatus or program in which luminance and chrominance samples in (for example) a 4:4:4 format or a 4:2:2 format are predicted from other respective samples according to a prediction direction associated with blocks of samples to be predicted.\",\n \"In embodiments of the technique, a prediction direction is detected in respect of a current block to be predicted.\",\n \"A predicted block of chrominance samples is generated according to other chrominance samples defined by the prediction direction.\",\n \"If the detected prediction direction is substantially vertical (for example, being within +/−n angle modes of the exactly vertical mode where n is (for example) 2), the left column of samples is filtered (for example, in a horizontal direction using a horizontally oriented filter) in the predicted block of chrominance samples.\",\n \"Or, if the detected prediction direction is substantially horizontal (for example, being within +/−n angle modes of the exactly horizontal mode, where n is (for example) 2), the top row of samples is filtered (for example, in a vertical direction using a vertically oriented filter) in the predicted block of chrominance samples.\",\n \"In each case, the operation may apply only to the left column or the top row, respectively.\",\n \"Then the difference between the filtered predicted chrominance block and the actual chrominance block is encoded, for example as residual data.\",\n \"Alternatively, the test could be for an exactly vertical or horizontal mode rather than a substantially vertical or horizontal mode.\",\n \"The tolerance of +/−n could be applied to one of the tests (vertical or horizontal) but not the other.\",\n \"In embodiments of the disclosure, only the left column or the top row of the predicted block may be filtered, and the filtering may be carried out by a horizontally oriented filter or a vertically oriented filter respectively.\",\n \"The filtering may be carried out by the respective predictor 520, 530, acting as a filter in this regard.\",\n \"After the filtering process, embodiments of the technique either encode a difference between the filtered predicted chrominance block and the actual chrominance block (at an encoder) or apply a decoded difference to the filtered predicted chrominance block so as to encode the block (at a decoder).\",\n \"Inter-Prediction it is noted that inter prediction in HEVC already allows rectangular PUs, so 4:2:2 and 4:4:4 modes are already compatible with PU inter-prediction processing.\",\n \"Each frame of a video image is a discrete sampling of a real scene, and as a result each pixel is a step-wise approximation of a real-world gradient in colour and brightness.\",\n \"In recognition of this, when predicting the Y, Cb or Cr value of a pixel in a new video frame from a value in a previous video frame, the pixels in that previous video frame are interpolated to create a better estimate of the original real-world gradients, to allow a more accurate selection of brightness or colour for the new pixel.\",\n \"Consequently the motion vectors used to point between video frames are not limited to an integer pixel resolution.\",\n \"Rather, they can be sub-pixel accuracy motion vectors pointing to a respective sub-pixel position (a fractional position) within the interpolated image.\",\n \"The filters used to derive samples of an interpolated luminance or chrominance prediction unit are implemented as multiple-tap filters such as 4-tap filters or 8-tap filters.\",\n \"In the case of an m-tap ×N filter (where m is, for example, 4 or 8, N is a multiple such as 4 or 8, and the “x” signifies “interpolate by a factor of”), the filter can in fact be implemented in embodiments of the present disclosure as a set of filters such that the output of each filter, when applied to a group of m samples, provides a respective fractional-position output.\",\n \"Here, a fractional position represents an effective sample position having an alignment at a respective one of fractional positions from 0 to N-1 (that is, N such fractional positions in all).\",\n \"One of those fractional positions, for example fractional position 0, overlies an original sample position.\",\n \"The other fractional positions are disposed between original sample positions, separated by 1/N of the original sample spacing.\",\n \"So, for example, in the context of an example ×8 filter, the fractional positions could be expressed as follows: filter index fractional position 0 0 (aligned with an original sample location) 1 +0.125 of original sample spacing 2 +0.25 of original sample spacing 3 +0.375 of original sample spacing 4 +0.5 of original sample spacing 5 +0.625 of original sample spacing 6 +0.75 of original sample spacing 7 +0.875 of original sample spacing This arrangement could be implemented as a set of eight filters, including a filter with a fractional position of 0 (that is, an output aligned with an original sample position).\",\n \"In such a case, the filter applicable to the fractional position 0 could be (in the example of a 4-tap filter) formed of the coefficients (0, 0, Y, 0), where Y is an integer such as 64, so that the fractional-position-zero filter in fact returns just the sample at the original sample position.\",\n \"In an alternative notation, the ×N filter could in fact be implemented as a set of N-1 filters, because the original sample itself could simply be re-used if the filter index is 0 (that is, without referring to a “filtering” operation to re-use that sample) and the required fractional position is 0.The skilled person will appreciate that these arrangements are equivalent in their technical effect but simply differ in notation.\",\n \"The skilled person will also appreciate that the notation which places fractional position zero (of positions zero to N-1) so as to be coincident with the original sample position is simply a matter of notation.\",\n \"A different notation could place fractional position 1 (of positions 1 to N) to be coincident with the original sample position.\",\n \"So, in examples embodiments discussed below, a set of seven 4-tap filters is used to provide a ×8 4-tap filtering function.\",\n \"If a required fractional position is coincident with an original sample position, the original sample value is simply re-used.\",\n \"Otherwise, for a required fractional sample position, the appropriate one of the N-1 filters is used.\",\n \"This leads to a discussion of which filter values are actually required to be generated.\",\n \"The interpolated PU samples are those pointed to by a sub-pixel accuracy motion vector.\",\n \"For any particular instance of the use of such a motion vector, the fractional position of the required interpolated sample(s) will be determined by the sub-pixel accuracy motion vector.\",\n \"But in general, for a single instance of use of the motion vector, only those interpolated samples corresponding to the fractional position pointed to by the motion vector are required to be generated.\",\n \"This means that in some embodiments, instead of generating an interpolated block from a stored PU, a vertical filter of the set of N-1 filters is selected for use in the vertical direction, and a horizontal filter of the set of N-1 filters is selected for use in the horizontal direction, so as to produce interpolated sample(s) at just the required fractional position.\",\n \"Note that “N” can be different or the same as for the horizontal and vertical directions, and the filter set can be the same or different for the two directions.\",\n \"One of these filtering operations can be carried out before the other, so that (for example) a filter could be selected for use in the vertical direction according to the required fractional position in the vertical direction (which in turn is determined by the particular motion vector in use), the filter applied so that samples at the appropriate vertical fractional position are generated, a horizontal filter selected according to the required horizontal fractional position (also determined by the motion vector) and that horizontal filter applied to the fractional position samples output by the vertical filter.\",\n \"Of course, the order could be reversed so that the horizontal filter is applied before the vertical filter.\",\n \"Such arrangements mean that only two filter calculations are required to apply a motion vector, avoiding the need to interpolate an interpolated version of an entire block.\",\n \"Accordingly, the operation of deriving samples of an interpolated prediction unit can involve applying a filter (such as a 4-tap ×8 filter) horizontally and vertically to a stored prediction unit.\",\n \"The step of applying the filter can comprise applying one of a set of m-tap filters horizontally and one of the set of m-tap filters vertically to a prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.\",\n \"In some examples, to be discussed further below, it may be that only a ×(N/2) filter operation is needed in one or other direction, but for consistency of processing with other operations it can be technically more convenient to use a ×N filter.\",\n \"In such instances, the ×(N/2) operation can be achieved in an elegantly convenient manner by using the set of filters (N or N-1 filters, as discussed above) applicable to ×N operation, but selecting only alternate fractional-position filters of the set (such as fractional positions 0 (if present), 2, 4, 6).\",\n \"Accordingly, the present arrangements including those discussed below provide an embodiment of a video decoding method for decoding a video signal, the method being operable in respect of a 4:2:0 and 4:2:2 format video signal, the method comprising: generating prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect of a 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect of a 4:2:2 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit, but using only alternate fractional-position results as interpolated samples in the vertical direction.\",\n \"As discussed above, the choice of filters, and so the choice of which interpolated samples to derive, can be according to a current motion vector, providing an example of accessing samples of the interpolated prediction unit pointed to by a motion vector to generate a motion compensated prediction of a prediction unit of the current image with respect to an area represented by the samples of the interpolated prediction unit.\",\n \"Embodiments to be discussed further below are also operable in respect of 4:4:4 video data, the same 4-tap ×8 chrominance filter being applied horizontally and vertically to generate samples of an interpolated chrominance prediction unit but only alternate fractional-position results being used as interpolated samples in the horizontal and vertical directions.\",\n \"As discussed, not every interpolated sample needs to be generated.\",\n \"Accordingly, in embodiments, the step of applying the 4-tap ×8 chrominance filter can comprise applying one of a set of 4-tap filters horizontally and one of the set of 4-tap filters vertically to a chrominance prediction unit, the selection of the filters to be applied horizontally and vertically depending on the motion vector.\",\n \"In example embodiments, the 4-tap filters are indexed in order of fractional interpolation position (for example, as given by the table above); and for 4:2:2 format video, the deriving step comprises applying a filter selected from a subset of alternate filters in the indexing order (such as those filters relating to even fractional-position results).\",\n \"Similar techniques can be used in the encoding process, so that the above arrangements provide examples of a video encoding method for encoding a video signal, the method being operable in respect of a 4:2:0 and 4:2:2 format video signal, the method comprising: generating motion vectors for prediction of prediction units of a current image from one or more stored images preceding the current image, the generating step comprising: in respect of a 4:2:0 format video signal, deriving samples of an interpolated prediction unit by using an 8-tap ×4 luminance filter applied vertically and horizontally to a stored luminance prediction unit and by applying a 4-tap ×8 chrominance filter horizontally and vertically to a stored chrominance prediction unit; and in respect of a 4:2:2 format video signal, deriving samples of an interpolated chrominance prediction unit by applying the same 4-tap ×8 chrominance filter horizontally and vertically but using only alternate fractional-position results as interpolated samples in the vertical direction.\",\n \"Embodiments also provide apparatus for carrying out the above techniques, such as the apparatus of FIG.\",\n \"5, operating under the control of the controller 343.4:2:0 Inter-Prediction Referring now to FIGS.\",\n \"25 and 26, in the 4:2:0 scheme as noted above typically an 8×8 luma PU 1300 will be associated with Cb and Cr 4×4 chroma PUs 1310.Consequently to interpolate the luma and chroma pixel data up to the same effective resolution, different interpolation filters are used.\",\n \"For example for the 8×8 4:2:0 luma PU, interpolation is ¼ pixel, and so an 8-tap ×4 filter is applied horizontally first, and then the same 8-tap ×4 filter is applied vertically, so that the luma PU is effectively stretched 4 times in each direction, to form an interpolated array 1320 as shown in FIG.\",\n \"25.Meanwhile the corresponding 4×4 4:2:0 chroma PU is ⅛ pixel interpolated to generate the same eventual resolution, and so a 4-tap ×8 filter is applied horizontally first, then the same 4-tap ×8 filter is applied vertically, so that the 4:2:0 chroma PUs are effectively stretched 8 times in each direction to form an array 1330, as shown in FIG.\",\n \"26.4:2:2 Inter-Prediction A similar arrangement for 4:2:2 will now be described with reference to FIGS.\",\n \"27 and 28, which illustrate a luma PU 1350 and a pair of corresponding chroma PUs 1360.Referring to FIG.\",\n \"28, as noted previously, in the 4:2:2 scheme the chroma PU 1360 can be non-square, and for the case of an 8×8 4:2:2 luma PU, will typically be a 4 wide×8 high 4:2:2 Chroma PU for each of the Cb and Cr channels.\",\n \"Note that the chroma PU is drawn, for the purposes of FIG.\",\n \"28, as a square shaped array of non-square pixels, but in general terms it is noted that the PUs 1360 are 4 (horizontal)×8 (vertical) pixel arrays.\",\n \"Whilst it may be possible therefore to use the existing 8-tap ×4 luma filter vertically on the chroma PU, in an embodiment of the present disclosure it has been appreciated that the existing 4-tap ×8 chroma filter would suffice for vertical interpolation as in practice one is only interested in the even fractional locations of the interpolated chroma PU.\",\n \"Hence FIG.\",\n \"27 shows the 8×8 4:2:2 luma PU 1350 interpolated as before with an 8-tap ×4 filter, and the 4×8 4:2:2 chroma PUs 1360 interpolated with the existing 4-tap ×8 chroma filter in the horizontal and vertical direction, but only with the even fractional results used for forming the interpolated image in the vertical direction.\",\n \"These techniques are applicable to video coding or decoding methods, apparatus or programs using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, For example, For 4:2:2, M=2, N=1.For 4:2:0, M=2, N=2.The frame store 570 is operable to store one or more images preceding a current image.\",\n \"The interpolation filter 580 is operable to interpolate a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1.In the current examples, P=Q=4 so that the interpolation filter 580 is operable to generate an interpolated image at % sample resolution.\",\n \"The motion estimator 550 is operable to detect inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images.\",\n \"The motion compensated predictor 540 is operable to generate a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector.\",\n \"Returning to a discussion of the operation of the interpolation filter 580, embodiments of this filter are operable to apply a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and to subsample the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.\",\n \"So, in the case of 4:2:2, the interpolation filter 580 applies a ×8 interpolation in the horizontal and vertical directions, but then vertically subsamples by a factor of 2, for example by using every 2nd sample in the interpolated output.\",\n \"One way to achieve this is by doubling an index value into the array of samples.\",\n \"So, consider an array direction (such as the vertical direction in this example) in the array of samples which is 8 samples across, indexed as 0 .\",\n \".\",\n \".\",\n \"7.A required sample in the subsampled range is indexed in the range 0 .\",\n \".\",\n \".\",\n \"3.So, doubling this index will give values of 0, 2, 4 and 6 which can then be used to access samples in the original array so that every alternate sample is used.\",\n \"This is an example of selecting a subset of samples of the interpolated chrominance prediction unit.\",\n \"This technique therefore allows the same (for example, ×8) filter to be used in respect of 4:2:0 and 4:2:2, but with a further step of subsampling where needed with 4:2:2.In embodiments, as discussed, the interpolated chrominance prediction unit has a height in samples twice that of a 4:2:0 format prediction unit interpolated using the same ×R and ×S interpolation filters.\",\n \"The need to provide different filters can be avoided or alleviated using these techniques, and in particular by using the same ×R horizontal and ×S vertical interpolation filters, in respect of 4:2:0 input video data and 4:2:2 input video data.\",\n \"As discussed, the step of subsampling the interpolated chrominance prediction unit comprises using every Vth sample of the interpolated chrominance prediction unit in the vertical direction, and/or using every Uth sample of the interpolated chrominance prediction unit in the vertical direction.\",\n \"More generally, the subsampling can comprise selecting a subset of samples of the interpolated chrominance prediction unit.\",\n \"Embodiments can involve deriving a luminance motion vector for a prediction unit; and independently deriving one or more chrominance motion vectors for that prediction unit.\",\n \"In some embodiments, at least one of R and S is equal to 2 or more, and in some embodiments the ×R horizontal and ×S vertical interpolation filters are also applied to the luminance components of the stored image.\",\n \"Note that the same interpolation techniques can be used in the encoder and in the decoder.\",\n \"4:4:4 Inter-Prediction Variants By extension, the same principle of only using the even fractional results for the existing 4-tap ×8 chroma filter can be applied both vertically and horizontally for the 8×8 4:4:4 chroma PUs.\",\n \"Further to these examples, the ×8 chroma filter may be used for all interpolation, including luma.\",\n \"Further Inter-Prediction Variants In one implementation of motion vector (MV) derivation, one vector is produced for a PU in a P-slice (and two vectors for a PU in a B-slice (where a P-slice takes predictions from a preceding frame, and a B-slice takes predictions from a preceding and following frame, in a similar manner to MPEG P and B frames).\",\n \"Notably, in this implementation in the 4:2:0 scheme the vectors are common to all channels, and moreover, the chroma data need not be used to calculate the motion vectors.\",\n \"In other words, all the channels use a motion vector based on the luma data.\",\n \"In an embodiment, in the 4:2:2 scheme the chroma vector could be derived so as to be independent from luma (i.e.\",\n \"a single vector for the Cb and Cr channels could be derived separately), and in the 4:4:4 scheme chroma vectors could further be independent for each of the Cb and Cr channels.\",\n \"Transforms In HEVC, most images are encoded as motion vectors from previously encoded/decoded frames, with the motion vectors telling the decoder where, in these other decoded frames, to copy good approximations of the current image from.\",\n \"The result is an approximate version of the current image.\",\n \"HEVC then encodes the so-called residual, which is the error between that approximate version and the correct image.\",\n \"This residual requires much less information than specifying the actual image directly.\",\n \"However, it is still generally preferable to compress this residual information to reduce the overall bitrate further.\",\n \"In many encoding methods including HEVC, such data is transformed into the spatial frequency domain using an integer cosine transform (ICT), and typically some compression is then achieved by retaining low spatial frequency data and discarding higher spatial frequency data according to the level of compression desired.\",\n \"4:2:0 Transforms The spatial frequency transforms used in HEVC are conventionally ones that generate coefficients in powers of 4 (for example 64 frequency coefficients) as this is particularly amenable to common quantisation/compression methods.\",\n \"The square TUs in the 4:2:0 scheme are all powers of 4 and hence this is straightforward to achieve.\",\n \"If the NSQT options are enabled, some non-square transforms are available for non-square TUs, such as 4×16, but again notably these result in 64 coefficients, i.e.\",\n \"again a power of 4.4:2:2 and 4:4:4 Transform Variants The 4:2:2 scheme can result in non-square TUs that are not powers of 4; for example a 4×8 TU has 32 pixels, and 32 is not a power of 4.In an embodiment therefore, a non-square transform for a non-power of 4 number of coefficients may be used, acknowledging that modifications may be required to the subsequent quantisation process.\",\n \"Alternatively, in an embodiment non-square TUs are split into square blocks having a power of 4 area for transformation, and then the resulting coefficients can be interleaved.\",\n \"For example, for 4×8 blocks odd/even vertical samples can be split into two square blocks.\",\n \"Alternatively, for 4×8 blocks the top 4×4 pixels and the bottom 4×4 pixels could form two square blocks.\",\n \"Alternatively again, for 4×8 blocks a Haar wavelet decomposition can be used to form a lower and an upper frequency 4×4 block.\",\n \"Any of these options may be made available, and the selection of a particular alternative may be signalled to or derived by the decoder.\",\n \"Other Transform Modes In the 4:2:0 scheme there is a proposed flag (the so-called rqpprime_y_zero_transquant_bypass_flag′) allowing the residual data to be included in the bit stream losslessly (i.e.\",\n \"without being transformed, quantised or further filtered).\",\n \"In the 4:2:0 scheme the flag applies to all channels.\",\n \"Accordingly, such embodiments represent a video coding or decoding method, apparatus or program in which luminance and chrominance samples are predicted and the difference between the samples and the respective predicted samples is encoded, making use of an indicator configured to indicate whether luminance difference data is to be included in an output bitstream losslessly; and to independently indicate whether chrominance difference data is to be included in the bitstream losslessly.\",\n \"Such a flag or flags (or indicator or indicators respectively) may be inserted by the controller 343, for example.\",\n \"In an embodiment, it is proposed that the flag for the luma channel is separate to the chroma channels.\",\n \"Hence for the 4:2:2 scheme, such flags should be provided separately for the luma channel and for the chroma channels, and for the 4:4:4 scheme, such flags should be provided either separately for the luma and chroma channels, or one flag is provided for each of the three channels.\",\n \"This recognises the increased chroma data rates associated with the 4:2:2 and 4:4:4 schemes, and enables, for example, lossless luma data together with compressed chroma data.\",\n \"For intra-prediction coding, mode-dependent directional transform (MDDT) allows the horizontal or vertical ICT (or both ICTs) for a TU to be replaced with an Integer Sine Transform depending upon the intra-prediction direction.\",\n \"In the 4:2:0 scheme this is not applied to chroma TUs.\",\n \"However in an embodiment it is proposed to apply it to 4:2:2 and 4:4:4 chroma TUs, noting that the IST is only currently defined for a 4 sample transform dimensions (either horizontally or vertically), and therefore cannot currently be applied vertically to a 4×8 chroma TU.\",\n \"In methods of video coding, the various embodiments can be arranged so as to indicate whether luminance difference data is to be included in an output bitstream losslessly; and independently to indicate whether chrominance difference data is to be included in the bitstream losslessly, and to encode or include the relevant data in the form defined by such indications.\",\n \"Quantisation In the 4:2:0 scheme, the quantisation calculation is the same for chrominance as for luminance.\",\n \"Only the quantisation parameters (QPs) differ.\",\n \"QPs for chrominance are calculated from the luminance QPs as follows: Qp Cb = scalingTable [ Qp luminance + chroma_qp _index _offset ] Qp Cr = scalingTable [ Qp luminance + second_chroma _qp _index _offset ] where the scaling table is defined as seen in FIG.\",\n \"29a or 29b (for 4:2:0 and 4:2:2 respectively), and “chroma_qp_index_offset” and “second_chroma_qp_index_offset” are defined in the picture parameter set and may be the same or different for Cr and Cb.\",\n \"In other words, the value in square brackets defines in each case an “index” into the scaling table (FIGS.\",\n \"29a and b) and the scaling table then gives a revised value of Qp (“value”).\",\n \"Note that “chroma_qp_index_offset” and “second_chroma_qp_index_offset” may instead be referred to as cb_qp_offset and cr_qp_offset respectively.\",\n \"Chrominance channels typically contain less information than luminance and hence have smaller-magnitude coefficients; this limitation on the chrominance QP may prevent all chrominance detail being lost at heavy quantisation levels.\",\n \"The QP-divisor relationship in the 4:2:0 is a logarithmic one such that an increase of 6 in the QP is equivalent to a doubling of the divisor (the quantisation step size discussed elsewhere in this description, though noting that it may be further modified by Qmatrices before use).\",\n \"Hence the largest difference in the scaling table of 51−39=12 represents a factor-of-4 change in the divisor.\",\n \"However, in an embodiment, for the 4:2:2 scheme, which potentially contains twice as much chroma information as the 4:2:0 scheme, the maximum chrominance QP value in the scaling table may be raised to 45 (i.e.\",\n \"halving the divisor).\",\n \"Similarly for the 4:4:4 scheme, the maximum chrominance QP value in the scaling table may be raised to 51 (i.e.\",\n \"the same divisor).\",\n \"In this case the scaling table is in effect redundant, but may be retained simply for operational efficiency (i.e.\",\n \"so that the system works by reference to a table in the same way for each scheme).\",\n \"Hence more generally in an embodiment the chroma QP divisor is modified responsive to the amount of information in the coding scheme relative to the 4:2:0 scheme.\",\n \"Accordingly, embodiments apply to a video coding or decoding method operable to quantise blocks of frequency-transformed luminance and chrominance component video data in a 4:4:4 or a 4:2:2 format according to a selected quantisation parameter which defines a quantisation step size.\",\n \"A quantisation parameter association (such as, for example, the appropriate table in FIG.\",\n \"29a or 29b) is defined between luminance and chrominance quantisation parameters, where the association is such that a maximum chrominance quantisation step size is less than a maximum luminance quantisation step size for the 4:2:2 format (for example, 45) but equal to the maximum luminance quantisation step size for the 4:4:4 format (for example, 51).\",\n \"The quantisation process operates in that each component of the frequency-transformed data is divided by a respective value derived from the respective quantisation step size, and the result is rounded to an integer value, to generate a corresponding block of quantised spatial frequency data.\",\n \"It will be appreciated that the dividing and rounding steps are indicative examples of a generic quantising stage, according to the respective quantisation step size (or data derived from it, for example by the application of Qmatrices).\",\n \"Embodiments include the step of selecting a quantisation parameter or index (QP for luminance) for quantising the spatial frequency coefficients, the quantisation parameter acting as a reference to a respective one of a set of quantisation step sizes according to the QP tables applicable to luminance data.\",\n \"The process of defining the quantisation parameter association can then comprise: for chrominance components, referencing a table of modified quantisation parameters (such as the table of FIG.\",\n \"29a or 29b) according to the selected quantisation parameter, which in turn can involve (i) for the first chrominance component, adding a first offset (such as chroma_qp_index_offset) to the quantisation parameter and selecting the modified quantisation index corresponding to the entry, in the table, for the quantisation index plus the first offset; and (ii) for the second chrominance component, adding a second offset (such as second_chroma_qp_index_offset) to the quantisation parameter and selecting the modified quantisation index corresponding to the entry, in the table, for the quantisation index plus the second offset; and referencing a respective quantisation step size in the set according to the quantisation parameter for the luminance data and the first and second modified quantisation indices for the first and second chrominance components.\",\n \"Viewed in a different way, this is an example of a process involving selecting a quantisation parameter for quantising the spatial frequency coefficients, the quantisation parameter acting as a reference to a respective one of a set of quantisation step sizes; and in which the defining step comprises: for chrominance components, referencing a table of modified quantisation parameters according to the selected quantisation parameter, the referencing step comprising: for each chrominance component, adding a respective offset to the quantisation parameter and selecting the modified quantisation parameter corresponding to the entry, in the table, for the quantisation parameter plus the respective offset; and referencing a respective quantisation step size in the set according to the quantisation parameter for the luminance data and the first and second modified quantisation parameters for the first and second chrominance components.\",\n \"The techniques are particularly applicable to arrangements in which successive values of the quantisation step sizes in the set are related logarithmically, so that a change in quantisation parameter of m (where m is an integer) represents a change in quantisation step size by a factor of p (where p is an integer greater than 1).\",\n \"In the present embodiments, m=6 and p=2.In embodiments, as discussed above, a maximum luminance quantisation parameter is 51; a maximum chrominance quantisation parameter is 45 for the 4:2:2 format; and a maximum chrominance quantisation parameter is 51 for the 4:4:4 format.\",\n \"In embodiments, the first and second offsets can be communicated in association with the encoded video data.\",\n \"In 4:2:0 the transform matrices A are initially created (by the transform unit 340) from those of a true normalised N×N DCT A′ using: Aij=int(64×√{square root over (N)}×A′ij) where i and j indicate a position within the matrix.\",\n \"This scaling with respect to a normalised transform matrix provides an increase in precision, avoids the need for fractional calculations and increases the internal precision.\",\n \"Ignoring differences due to rounding of Aij, since X is multiplied by both A and AT (the transposition of the matrix A) the resulting coefficients differ from those of a true normalised M×N (M=height; N=width) DCT by a common scaling factor of: (64×√{square root over (N)})(64×√{square root over (M)})=4096√{square root over (N)}√{square root over (M)} Note that the common scaling factor could be different to this example.\",\n \"Note also that matrix multiplying by both A and AT can be carried out in various ways, such as the so-called Butterfly method.\",\n \"The significant fact is whether the operation that is carried out is equivalent to a traditional matrix multiplication, not whether it is performed in a particular traditional order of operations.\",\n \"This scaling factor is equivalent to a binary left-shift bitwise operation by a number of bits transformShift, since in HEVC this results in a power of 2: transformShift=(12+0.5 log2(N)+0.5 log2(M)) To reduce the requirement on internal bit-precision, the coefficients are right-shifted (using positive rounding) twice during the transform process: shift1=log2(N)+bitDepth−9 shift2=log2(M)+6 As a result, the coefficients as they leave the forward transform process and enter the quantiser are effectively left-shifted by: resultingShift = ( 12 + 0.5 log 2 ( NM ) ) - ( shift 1 + shift 2 ) = ( 12 + 0.5 log 2 ( N ) + 0.5 log 2 ( M ) ) - ( log 2 ( N ) + bitDepth - 9 + log 2 ( M ) + 6 ) = 15 - ( 0.5 log 2 ( N ) + 0.5 log 2 ( M ) + bitDepth ) In 4:2:0, the frequency separated (for example, DCT) coefficients generated by the frequency transform are a factor of (2resultingShift) larger than those that a normalised DCT would produce.\",\n \"In some embodiments, the blocks are either square or rectangular with a 2:1 aspect ratio.\",\n \"Therefore, for a block size of N×M, either: N=M, in which case, resultingShift is an integer and S=N=M=sqrt(NM); or 0.5N=2M or 2N=0.5M, in which case resultingShift is still an integer and S=sqrt(NM) resultingShift=15−(0.5 log2(N)+0.5 log2(M)+bitDepth)=15−(log2(S)+bitDepth) The coefficients are subsequently quantised, where the quantising divisor is derived according to the quantisation parameter QP.\",\n \"Note that resultingShift is equivalent to an integer, so the common scaling factor is an integer power of 2, the overall left-shift ‘resultingShift’ of the transform process is also accounted for at this stage by applying an equal but opposite right-shift, ‘quantTransformRightShift’.\",\n \"This bit-shift operation is possible because resultingShift is an integer.\",\n \"Also note that the divisor-QP (quantisation parameter or index) relationship follows a base-2 power curve, as mentioned above, in that an increase in QP by 6 has the effect of doubling the divisor whereas an increase in QP by 3 has the effect of increasing the divisor by a factor of sqrt(2) (square root of 2).\",\n \"Due to the chroma format in 4:2:2, there are more TU width:height (N:M) ratios: N=M (from before) where S=N=M=sqrt(NM) (resultingShift is an integer) 0.5N=2M and 2N=0.5M, (from before), where S=sqrt(NM) (resultingShift is an integer) N=2M where S=sqrt(NM) 2M=N where S=sqrt(NM) 4N=0.5M where S=sqrt(NM) resultingShift=15−(log2(S)+bitDepth) In these latter three situations, resultingShift is not an integer.\",\n \"For example, this may apply where at least some of the blocks of video data samples comprise M×N samples, where the square root of N/M is not equal to an integer power of 2.Such block sizes can occur in respect of chroma samples in some of the present embodiments.\",\n \"Accordingly, in such instances, the following techniques are relevant, that is to say, in video coding or decoding methods, apparatus or programs operable to generate blocks of quantised spatial frequency data by performing frequency-transformation on blocks of video data samples using a transform matrix comprising an array of integer values which are each scaled with respect to respective values of a normalized transform matrix by an amount dependent upon a dimension of the transform matrix, and to quantise the spatial frequency data according to a selected quantisation step size, having the step of frequency-transforming a block of video data samples by matrix-multiplying the block by the transform matrix and the transposition of the transform matrix to generate a block of scaled spatial frequency coefficients which are each larger, by a common scaling factor (for example, resultingShift), than the spatial frequency coefficients which would result from a normalized frequency-transformation of that block of video data samples.\",\n \"Therefore at the quantisation stage, an appropriate bit-shift operation cannot be used to cancel out the operation in a simple manner.\",\n \"A solution to this is proposed as follows: At the quantiser stage, apply a right shift: quantTransformRightShift=15−log 2(S′)−bitDepth Where the value S′ is derived such that resultingShift−quantTransformRightShift=+½quantTransformRightShift is an integer The difference between shifts of ½ is equivalent to multiplication by sqrt(2), i.e.\",\n \"at this point the coefficients are sqrt(2) times larger than they should be, making the bit shift an integer bit shift.\",\n \"For the quantisation process, apply a quantisation parameter of (OP+3), meaning that the quantising divisor is effectively increased by a factor of sqrt(2), thus cancelling out the sqrt(2) scale factor from the previous step.\",\n \"Accordingly, these steps can be summarised (in the context of a video coding or decoding method (or corresponding apparatus or program) operable to generate blocks of quantised spatial frequency data by performing frequency-transformation on blocks of video data samples using a transform matrix comprising an array of integer values which are each scaled with respect to respective values of a normalized transform matrix, and to quantise the spatial frequency data according to a selected quantisation step size, involving frequency-transforming a block of video data samples by matrix-multiplying the block by the transform matrix and the transposition of the transform matrix to generate a block of scaled spatial frequency coefficients which are each larger, by a common scaling factor, than the spatial frequency coefficients which would result from a normalized frequency-transformation of that block of video data samples) as follows: selecting a quantisation step size for quantising the spatial frequency coefficients; applying an n-bit shift (for example, quantTransformRightShift) to divide each of the scaled spatial frequency coefficients by a factor of 2n, where n is an integer; and detecting a residual scaling factor (for example, resultingShift−quantTransformRightShift), being the common scaling factor divided by 2n.\",\n \"For example, in the situation discussed above, the quantisation step size is then according to the residual scaling factor to generate a modified quantisation step size; and each of the scaled spatial frequency coefficients in the block is divided by a value dependent upon the modified quantisation step size and rounding the result to an integer value, to generate the block of quantised spatial frequency data.\",\n \"As discussed, the modification of the quantisation step size can be carried out simply by adding an offset to QP so as to select a different quantisation step size when QP is mapped into the table of quantisation step sizes.\",\n \"The coefficients are now of the correct magnitude for the original QP.\",\n \"The transform matrix can comprise an array of integer values which are each scaled with respect to respective values of a normalized transform matrix by an amount dependent upon a dimension of the transform matrix.\",\n \"It follows that the required value for S′ can always be derived as follows: S′=sqrt(2*M*N) As an alternative proposal, S′ could be derived such that: resultingShift−quantTransformRightShift=−½ In this case, S′=sqrt(½*M*N), and the applied quantisation parameter is (QP−3) In either of these cases, (adding 3 to QP or subtracting 3 from QP), the step of selecting the quantisation step size comprises selecting a quantisation index (for example, QP), the quantisation index defining a respective entry in a table of quantisation step sizes, and the modifying step comprises changing the quantisation index so as to select a different quantisation step size, such that the ratio of the different quantisation step size to the originally selected quantisation step size is substantially equal to the residual scaling factor.\",\n \"This works particularly well where, as in the present embodiments, successive values of the quantisation step sizes in the table are related logarithmically, so that a change in quantisation index (for example, QP) of m (where m is an integer) represents a change in quantisation step size by a factor of p (where p is an integer greater than 1).\",\n \"In the present embodiments, m=6 and p=2, so that an increase of 6 in QP represents a doubling of the applied quantisation step size, and a decrease in QP of 6 represents a halving of the resulting quantisation step size.\",\n \"As discussed above, the modification can be carried out by selecting a quantisation index (for example, a base QP) in respect of luminance samples; generating a quantisation index offset, relative to the quantisation index selected for the luminance samples, for samples of each or both chrominance components; changing the quantisation index offset according to the residual scaling factor; and communicating the quantisation index offset in association with the coded video data.\",\n \"In embodiments of HEVC, QP offsets for the two chroma channels are sent in the bit stream.\",\n \"These steps correspond to a system in which the QP offset (to account for the residual scaling factor) of +/−3 could be incorporated into these offsets, or they could be incremented/decremented when they are used to derive the chroma QP.\",\n \"Note that the QP offset does not have to be +/−3 if differently shaped blocks were used; it is just that +/−3 represents an offset applicable to the block shapes and aspect ratios discussed above in respect of 4:2:2 video, for example.\",\n \"In some embodiments, n (the bit shift as applied) is selected so that 2n is greater than or equal to the common scaling factor.\",\n \"In other embodiments, n is selected so that 2n is less than or equal to the common scaling factor.\",\n \"In embodiments (using either of these arrangements), a bit shift n can be selected so as to be the next nearest (in either direction) to the common scaling factor, so that the residual scaling factor represents a factor having a magnitude of less than 2.In other embodiments, the modification of the quantisation step size can simply be performed by multiplying the quantisation step size by a factor dependent upon the residual scaling factor.\",\n \"That is to say, the modification need not involve modifying the index QP.\",\n \"Note also that the quantisation step size as discussed is not necessarily the actual quantisation step size by which a transformed sample is divided.\",\n \"The quantisation step size derived in this way can be further modified.\",\n \"For example, in some arrangements, the quantisation step size is further modified by respective entries in a matrix of values (Qmatrix) so that different final quantisation step sizes are used at different coefficient positions in a quantised block of coefficients.\",\n \"It is also notable that in the 4:2:0 scheme, the largest chroma TU is 16×16, whereas for the 4:2:2 scheme 16×32 TUs are possible, and for the 4:4:4 scheme, 32×32 chroma TUs are possible.\",\n \"Consequently in an embodiment quantisation matrices (Qmatrices) for 32×32 chroma TUs are proposed.\",\n \"Similarly, Qmatrices should be defined for non-square TUs such as the 16×32 TU, with one embodiment being the subsampling of a larger square Q matrix Qmatrices could be defined by any one of the following: values in a grid (as for 4×4 and 8×8 Qmatrices); interpolated spatially from respective smaller or larger matrices; in HEVC larger Qmatrices can be derived from respective groups of coefficients of smaller reference ones, or smaller matrices can be sub-sampled from larger matrices.\",\n \"Note that this interpolation or subsampling can be carried out within a channel ratio—for example, a larger matrix for a channel ratio can be interpolated from a smaller one for that channel ratio.\",\n \"relative to other Qmatrices (i.e.\",\n \"difference values, or deltas); hence only the deltas need to be sent.\",\n \"Taking a small example just for illustrative purposes, a particular matrix for one channel ratio could be defined, such as a 4×4 matrix in respect of 4:2:0 (a b) (c d) where a, b, c and d are respective coefficients.\",\n \"This acts as a reference matrix.\",\n \"Embodiments of the disclosure could then define a set of difference values for a similar-sized matrix in respect of another channel ratio: (diff1diff2) (diif3 diff4) so that in order to generate the Qmatrix for the other channel ratio, the matrix of differences is matrix-added to the reference matrix.\",\n \"Instead of differences, a matrix of multiplicative factors could be defined for the other channel ratio, such that either (i) the matrix of multiplicative factors is matrix-multiplied with the reference matrix to generate the Qmatrix for the other channel ratio, or (ii) each coefficient in the reference matrix is individually multiplied by a respective factor to generate the Qmatrix for the other channel ratio.\",\n \"as a function of another Qmatrix; e.g.\",\n \"a scaling ratio relative to another matrix (so that each of a, b, c and d in the above example is multiplied by the same factor, or has the same difference added to it).\",\n \"This reduces the data requirements for transmitting the difference or factor data.\",\n \"hence only the coefficients of the functions need to be sent (such as the scaling ratio), as an equation/function (e.g.\",\n \"piece-wise linear curve, exponential, polynomial); hence only the coefficients of the equations need to be sent to derive the matrix, or any combination of the above.\",\n \"For example, each of a, b, c and d could in fact be defined by a function which could include a dependence upon the coefficient position (i,j) within the matrix.\",\n \"(l, j) could represent, for example, the coefficient position from left to right followed by the coefficient position from top to bottom of the matrix.\",\n \"An example is: coefficienti,j=3i+2j Note that Qmatrices can be referred to as Scaling Lists within the HEVC environment.\",\n \"In embodiments in which the quantisation is applied after the scanning process, the scanned data may be a linear stream of successive data samples.\",\n \"In such instances, the concept of a Qmatrix still applies, but the matrix (or Scanning List) may be considered as a 1×N matrix, such that the order of the N data values within the 1×N matrix corresponds to the order of scanned samples to which the respective Qmatrix value is to be applied.\",\n \"In other words, there is a 1:1 relationship between data order in the scanned data, spatial frequency according to the scan pattern, and data order in the 1×N Qmatrix.\",\n \"Note that it is possible, in some implementations, to bypass or omit the DCT (frequency separation) stage, but to retain the quantisation stage.\",\n \"Other useful information includes an optional indicator of to which other matrix the values are related, i.e.\",\n \"the previous channel or the first (primary) channel; for example the matrix for Cr could be a scaled factor of a matrix for Y, or for Cb, as indicated.\",\n \"Accordingly, embodiments of the disclosure can provide a video coding or decoding method (and a corresponding apparatus or computer program) operable to generate blocks of quantised spatial frequency data by (optionally) performing frequency-transformation on blocks of video data samples and quantising the video data (such as the spatial frequency data) according to a selected quantisation step size and a matrix of data modifying the quantisation step size for use at different respective block positions within an ordered block of samples (such as an ordered block of frequency-transformed samples), the method being operable with respect to at least two different chrominance subsampling formats.\",\n \"For at least one of the chrominance subsampling formats, one or more quantisation matrices are defined as one or more predetermined modifications with respect to one or more reference quantisation matrices defined for a reference one of the chrominance subsampling formats.\",\n \"In embodiments of the disclosure, the defining step comprises defining one or more quantisation matrices as a matrix of values each interpolated from a respective plurality of values of a reference quantisation matrix.\",\n \"In other embodiments, the defining step comprises defining one or more quantisation matrices as a matrix of values each subsampled from values of a reference quantisation matrix.\",\n \"In embodiments of the disclosure, the defining step comprises defining one or more quantisation matrices as a matrix of differences with respect to corresponding values of a reference quantisation matrix.\",\n \"In embodiments of the disclosure, the defining step comprises defining one or more quantisation matrices as a predetermined function of values of a reference quantisation matrix.\",\n \"In such instances, the predetermined function may be a polynomial function.\",\n \"In embodiments of the disclosure, one or both of the following is provided, for example as part of or in association with the coded video data: (i) reference-indicator data to indicate, with respect to encoded video data, the reference quantisation matrix; and (ii) modification-indicator data to indicate, with respect to encoded data values, the one or more predetermined modifications.\",\n \"These techniques are particularly applicable where two of the chrominance subsampling formats are 4:4:4 and 4:2:2 formats.\",\n \"The number of Q Matrices in HEVC 4:2:0 is currently 6 for each transform size: 3 for the corresponding channels, and one set for intra and for inter.\",\n \"In the case of a 4:4:4 GBR scheme, it will be appreciated that either one set of quantisation matrices could be used for all channels, or three respective sets of quantisation matrices could be used.\",\n \"In embodiments of the disclosure, at least one of the matrices is a 1×N matrix.\",\n \"This would be the case in (as described here) one or more of the matrices is in fact a Scaling List or the like, being a linear 1×N ordered array of coefficients.\",\n \"The proposed solutions involve incrementing or decrementing the applied QP.\",\n \"However this could be achieved in a number of ways: In HEVC, QP offsets for the two chroma channels are sent in the bit stream.\",\n \"The +/−3 could be incorporated into these offsets, or they could be incremented/decremented when they are used to derive the chroma QP.\",\n \"As discussed, above, in HEVC, (luma QP+chroma offset) is used as an index to a table in order to derive the chroma QP.\",\n \"This table could be modified to incorporate the +/−3 (i.e.\",\n \"by incrementing/decrementing the values of the original table by 3) After the chroma QP has been derived, as per the normal HEVC process, the results could then be incremented (or decremented) by 3.As an alternative to modifying the QP, a factor of sqrt(2) or 1/sqrt(2) can be used to modify the quantisation coefficients.\",\n \"For forward/inverse quantisation, the division/multiplication processes are implemented by using (QP % 6) as an index to a table to obtain a quantisation coefficient or quantisation step size, inverseQStep/scaledQStep.\",\n \"(Here, QP % 6 signifies QP modulo 6).\",\n \"Note that, as discussed above, this may not represent the final quantisation step size which is applied to the transformed data; it may be further modified by the Qmatrices before use.\",\n \"The default tables in HEVC are of length 6, covering an octave (a doubling) of values.\",\n \"This is simply a means of reducing storage requirements; the tables are extended for actual use by selecting an entry in the table according to the modulus of QP (mod 6) and then multiplying or dividing by an appropriate power of 2, dependent upon the difference of (QP−QP modulus 6) from a predetermined base value.\",\n \"This arrangement could be varied to allow for the offset of +/−3 in the QP value.\",\n \"The offset can be applied in the table look-up process, or the modulus process discussed above could instead be carried out using the modified QP.\",\n \"Assuming the offset is applied at the table look-up, however, additional entries in the table can be provided as follows: One alternative is to extend the tables by 3 entries, where the new entries are as follows (for the index values of 6-8).\",\n \"The example table shown in FIG.\",\n \"30 would be indexed by [(QP % 6)+3] (a “QP increment method”), where the notation QP % 6 signifies “QP modulus 6”.\",\n \"The example table shown in FIG.\",\n \"31 would be indexed by [(QP % 6)−3] (a “QP decrement method”), having extra entries for the index values of −1 to −3: Entropy Encoding Basic entropy encoding comprises assigning codewords to input data symbols, where the shortest available codewords are assigned to the most probable symbols in the input data.\",\n \"On average the result is a lossless but much smaller representation of the input data.\",\n \"This basic scheme can be improved upon further by recognising that symbol probability is often conditional on recent prior data, and consequently making the assignment process context adaptive.\",\n \"In such a scheme, context variables (CVs) are used to determine the choice of respective probability models, and such CVs are provided for in the HEVC 4:2:0 scheme.\",\n \"To extend entropy encoding to the 4:2:2 scheme, which for example will use 4×8 chroma TUs rather than 4×4 TUs for an 8×8 luma TU, optionally the context variables can be provided for by simply vertically repeating the equivalent CV selections.\",\n \"However, in an embodiment of the present disclosure the CV selections are not repeated for the top-left coefficients (i.e.\",\n \"the high-energy, DC and/or low spatial frequency coefficients), and instead new CVs are derived.\",\n \"In this case, for example, a mapping may be derived from the luma map.\",\n \"This approach may also be used for the 4:4:4 scheme.\",\n \"During coding, in the 4:2:0 scheme, a so-called zig-scan scans through the coefficients in order from high to low frequencies.\",\n \"However, again it is noted that the chroma TUs in the 4:2:2 scheme can be non-square, and so in an embodiment of the present disclosure a different chroma scan is proposed with the angle of the scan be tilted to make it more horizontal, or more generally, responsive to the aspect ratio of the TU.\",\n \"Similarly, the neighbourhood for significance map CV selection and the c1/c2 system for greater-than-one and greater-than-two CV selection may be adapted accordingly.\",\n \"Likewise, in an embodiment of the present disclosure the last significant coefficient position (which becomes the start point during decoding) could also be adjusted for the 4:4:4 scheme, with last-significant positions for chroma TUs being coded differentially from the last-significant position in the co-located luma TU.\",\n \"The coefficient scanning can also be made prediction mode dependent for certain TU sizes.\",\n \"Hence a different scan order can be used for some TU sizes dependent on the intra-prediction mode.\",\n \"In the 4:2:0 scheme, mode dependent coefficient scanning (MDCS) is only applied for 4×4/8×8 luma TUs and 4×4 chroma TUs for intra prediction.\",\n \"MDCS is used dependent on the intra-prediction mode, with angles +/−4 from the horizontal and vertical being considered.\",\n \"In an embodiment of the present disclosure, it is proposed that in the 4:2:2 scheme MDCS is applied to 4×8 and 8×4 chroma TUs for intra prediction.\",\n \"Similarly, it is proposed that in the 4:4:4 scheme MDCS is applied to 8×8 and 4×4 chroma TUs.\",\n \"MDCS for 4:2:2 may only be done in the horizontal or vertical directions, and that the angle ranges may differ for 4:4:4 chroma vs. 4:4:4 luma vs. 4:2:2 chroma vs. 4:2:2 luma vs. 4:2:0 luma.\",\n \"In-Loop Filters Deblocking Deblocking is applied to all CU, PU and TU boundaries, and the CU/PU/TU shape is not taken into account.\",\n \"The filter strength and size is dependent on local statistics, and deblocking has a granularity of 8×8 Luma pixels.\",\n \"Consequently it is anticipated that the current deblocking applied for the 4:2:0 scheme should also be applicable for the 4:2:2 and 4:4:4 schemes.\",\n \"Sample Adaptive Offsetting In sample adaptive offsetting (SAO) each channel is completely independent.\",\n \"SAO splits the image data for each channel using a quad-tree, and the resulting blocks are at least one LCU in size.\",\n \"The leaf blocks are aligned to LCU boundaries and each leaf can run in one of three modes, as determined by the encoder (“Central band offset”, “Side band offset” or “Edge offset”).\",\n \"Each leaf categorises its pixels, and the encoder derives an offset value for each of the 16 categories by comparing the SAO input data to the source data.\",\n \"These offsets are sent to the decoder.\",\n \"The offset for a decoded pixel's category is added to its value to minimise the deviation from the source.\",\n \"In addition, SAO is enabled or disabled at picture level; if enabled for luma, it can also be enabled separately for each chroma channel.\",\n \"SAO will therefore be applied to chroma only if it is applied to luma.\",\n \"Consequently the process is largely transparent to the underlying block scheme and it is anticipated that the current SAO applied for the 4:2:0 scheme should also be applicable for the 4:2:2 and 4:4:4 schemes.\",\n \"Adaptive Loop Filtering In the 4:2:0 scheme, adaptive loop filtering (ALF) is disabled by default.\",\n \"However, in principle (i.e.\",\n \"if allowed) then ALF would be applied to the entire picture for chroma.\",\n \"In ALF, luma samples may be sorted into one of a number of categories, as determined by the HEVC documents; each category uses a different Wiener-based filter.\",\n \"By contrast, in 4:2:0 chroma samples are not categorised—there is just one Wiener-based filter for Cb, and one for Cr.\",\n \"Hence in an embodiment of the present disclosure, in light of the increased chroma information in the 4:2:2 and 4:4:4 schemes, it is proposed that the chroma samples are categorised; for example with K categories for 4:2:2 and J categories for 4:4:4.Whilst in the 4:2:0 scheme ALF can be disabled for luma on a per-CU basis using an ALF control flag (down to the CU-level specified by the ALF control depth), it can only be disabled for chroma on a per-picture basis.\",\n \"Note that in HEVC, this depth is currently limited to the LCU level only.\",\n \"Consequently in an embodiment of the present disclosure, the 4:2:2 and 4:4:4 schemes are provided with one or two channel specific ALF control flags for chroma.\",\n \"Syntax In HEVC, syntax is already present to indicate 4:2:0, 4:2:2 or 4:4:4 schemes, and is indicated at the sequence level.\",\n \"However, in an embodiment of the present disclosure it is proposed to also indicate 4:4:4 GBR coding at this level.\",\n \"Data Signals It will be appreciated that data signals generated by the variants of coding apparatus discussed above, and storage or transmission media carrying such signals, are considered to represent embodiments of the present disclosure.\",\n \"Respective features of embodiments are defined by the following numbered clauses: 1.A video coding method operable in respect of images of a 4:2:2 format video signal, comprising: partitioning an image to be encoded into coding units, prediction units and transform units for encoding, a coding unit being a square array of luminance samples and the corresponding chrominance samples, there being one or more prediction units in a coding unit, and there being one or more transform units in a coding unit; in which a prediction unit is an elementary unit of prediction so that all samples within a single prediction unit are predicted using a common prediction technique, and a transform unit is a basic unit of transformation and quantisation; enabling non-square transforms so as to allow non-square prediction units; and selecting transform unit block sizes to align with the prediction unit block layout.\",\n \"2.A method according to clause 1, comprising: enabling asymmetric motion partitioning so as to allow asymmetry between two or more prediction units corresponding to a single coding unit.\",\n \"3.A method according to clause 1 or clause 2, in which the step of selecting transform unit block sizes comprises: detecting image features in the portion of the image corresponding to a prediction unit; and selecting transform unit block sizes in respect of that prediction unit so as to align transform unit boundaries with edges of image features in the portion of the image.\",\n \"4.A method according to clause 3, in which the step of selecting transform unit block sizes comprises: selecting transform unit block sizes for the one or more transform units derived from a coding unit, according to a tree hierarchy of divisions defined with respect to the size of the respective prediction unit.\",\n \"5.A method according to any one of the preceding clauses, in which the step of selecting transform unit block sizes comprises selecting transform unit block sizes from the following table, according to the selected coding unit and prediction unit configuration: TU Options CU Size PU Options Level 0 Level 1 Level 2 64 × 64 64 × 64 n/a 32 × 32 × 4 16 × 16 × 4 64 × 32 × 2 or n/a 32 × 32 × 4 32 × 8 × 4 64 × 16 + 64 × 48 32 × 64 × 2 or n/a 32 × 32 × 4 8 × 32 × 4 16 × 64 + 48 × 64 32 × 32 32 × 32 32 × 32 16 × 16 × 4 8 × 8 × 4 32 × 16 × 2 or n/a 32 × 8 × 4 16 × 4 × 4 (luminance) + 32 × 8 + 32 × 24 4 × 4 × 4 (chrominance) or 16 × 4 × 4 luminance) + 8 × 4 × 4 (chrominance) 16 × 32 × 2 or n/a 8 × 32 × 4 4 × 16 × 4 (luminance) + 8 × 32 + 24 × 32 4 × 4 × 4 (chrominance) 16 × 16 16 × 16 16 × 16 8 × 8 × 4 4 × 4 × 4 (luminance) + 4 × 8 × 4 (chrominance) 16 × 8 × 2 or n/a 16 × 4 × 4 (luminance) + 4 × 4 × 4 (luminance) + 16 × 4 + 16 × 12 4 × 8 × 4 4 × 8 × 1 (chrominance) (chrominance) 8 × 16 × 2 or n/a 4 × 16 + 12 × 16 8 × 8 8 × 8 or 8 × 8 4 × 4 × 4 (luminance) + n/a 4 × 4 × 4 or 4 × 8 × 1 (chrominance) 8 × 4 × 2 or 4 × 8 × 2 4 × 4 × 4 (luminance) + 4 × N n/a 4 × 4 × 4 (luminance) + n/a (chrominance) 4 × 8 × 1 (chrominance) where level 0, level 1 and level 2 represent successive levels in the tree hierarchy of divisions, n/a indicates an unallowable mode, each block size is represented by the notation (horizontal dimension)×(vertical dimension)×(number of instances, if applicable), and N is an integer greater than 1.6.A method according to any one of clauses 1 to 4, in which the step of selecting transform unit block sizes comprises selecting transform unit block sizes from the following table, according to the selected coding unit and prediction unit configuration: TU Options CU Size PU Options Level 0 Level 1 Level 2 64 × 64 64 × 64 n/a 32 × 32 × 4 16 × 16 × 4 64 × 32 × 2 or n/a 32 × 32 × 4 32 × 8 × 4 64 × 16 + 64 × 48 32 × 64 × 2 or n/a 32 × 32 × 4 8 × 32 × 4 16 × 64 + 48 × 64 32 × 32 32 × 32 32 × 32 16 × 16 × 4 8 × 8 × 4 32 × 16 × 2 or n/a 32 × 8 × 4 16 × 4 × 4 (luminance) + 32 × 8 + 32 × 24 4 × 4 × 4 (chrominance) or 16 × 4 × 4 luminance) + 8 × 4 × 4 (chrominance) 16 × 32 × 2 or n/a 8 × 32 × 4 4 × 16 × 4 (luminance) + 8 × 32 + 24 × 32 4 × 4 × 4 (chrominance) 16 × 16 16 × 16 16 × 16 8 × 8 × 4 4 × 4 × 4 (luminance) + 4 × 8 × 4 (chrominance) 16 × 8 × 2 or n/a 16 × 4 × 4 (luminance) + 8 × 4 × 4 4 × 4 × 4 (luminance) + 16 × 4 + 16 × 12 (chrominance) 8 × 4 × 1 (chrominance) 8 × 16 × 2 or n/a 4 × 16 + 12 × 16 8 × 8 8 × 8 or 8 × 8 4 × 4 × 4 (luminance) + n/a 4 × 4 × 4 or 4 × 8 × 1 (chrominance) 8 × 4 × 2 or 4 × 8 × 2 4 × 4 × 4 (luminance) + 4 × N n/a 4 × 4 × 4 (luminance) + n/a (chrominance) 4 × 8 × 1 (chrominance) where level 0, level 1 and level 2 represent successive levels in the tree hierarchy of divisions, n/a indicates an unallowable mode, each block size is represented by the notation (horizontal dimension)×(vertical dimension)×(number of instances, if applicable), and N is an integer greater than 1.7.A method according to any one of the preceding clauses, comprising the step of splitting a non-square transform unit into a plurality of square transform units prior to transforming or quantising that transform unit.\",\n \"8.Computer software which, when executed by a computer, causes the computer to carry out a method according to any one of the preceding clauses.\",\n \"9.A machine-readable non-transitory storage medium which stores software according to clause 8.10.A data signal comprising coded data generated according to the method of any one of clauses 1 to 7.11.A video coding apparatus operable in respect of images of a 4:2:2 format video signal, comprising: a controller configured to partition an image to be encoded into coding units, prediction units and transform units for encoding, a coding unit being a square array of luminance samples and the corresponding chrominance samples, there being one or more prediction units in a coding unit, and there being one or more transform units in a coding unit; in which a prediction unit is an elementary unit of prediction so that all samples within a single prediction unit are predicted using a common prediction technique, and a transform unit is a basic unit of transformation and quantisation; to enable non-square transforms so as to allow non-square prediction units; and to select transform unit block sizes to align with the prediction unit block layout.\",\n \"Further respective embodiments are defined by the following numbered clauses: 1.A video decoding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the method comprising: storing one or more images preceding a current image; interpolating a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; detecting inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and generating a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolating step comprises: applying a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and subsampling the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.\",\n \"Note that the detecting step may not be required in a decoding arrangement, as the decoder can use the motion vectors provided to it (for example, as part of the video datastream) by the encoder.\",\n \"2.A method according to clause 1, in which M=2 and N=1.3.A method according to clause 2, in which the input video data is in a 4:2:2 format.\",\n \"4.A method according to clause 3, in which the interpolated chrominance prediction unit has a height in samples twice that of a 4:2:0 format prediction unit interpolated using the same ×R and ×S interpolation filters.\",\n \"5.A method according to clause 2, the method being separately operable, using the same ×R horizontal and ×S vertical interpolation filters, in respect of 4:2:0 input video data and 4:2:2 input video data.\",\n \"6.A method according to any one of the preceding clauses, in which P=4.7.A method according to any one of the preceding clauses, in which Q=4.8.A method according to any one of the preceding clauses, in which the step of subsampling the interpolated chrominance prediction unit comprises using every Vth sample of the interpolated chrominance prediction unit in the vertical direction.\",\n \"9.A method according to any one of the preceding clauses, in which the step of subsampling the interpolated chrominance prediction unit comprises using every Uth sample of the interpolated chrominance prediction unit in the vertical direction.\",\n \"10.A method according to any one of the preceding clauses, comprising: deriving a luminance motion vector for a prediction unit; and independently deriving one or more chrominance motion vectors for that prediction unit.\",\n \"11.A method according to any one of the preceding clauses, in which at least one of R and S is equal to 2 or more.\",\n \"12.A method according to any one of the preceding clauses, comprising applying the ×R horizontal and ×S vertical interpolation filter to the luminance components of the stored image.\",\n \"13.A method according to any one of the preceding clauses, in which the subsampling comprising selecting a subset of samples of the interpolated chrominance prediction unit.\",\n \"14.A video coding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the method comprising: storing one or more images preceding a current image; interpolating a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; detecting inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and generating a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolating step comprises: applying a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and subsampling the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.\",\n \"15.Computer software which, when executed by a computer, causes the computer to carry out a method according to any one of the preceding clauses.\",\n \"16.A machine-readable non-transitory storage medium which stores software according to clause 15.17.A data signal comprising coded data generated according to the method of any one of clauses 1 to 14.18.A video decoding apparatus using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the apparatus comprising: an image store configured to store one or more images preceding a current image; an interpolator configured to interpolate a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; a detector configured to detect inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and a generator configured to generate a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolator is configured: to apply a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and to subsample the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.\",\n \"19.A video coding apparatus using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are integers equal to 1 or more, the apparatus comprising: an image store configured to store one or more images preceding a current image; an interpolator configured to interpolate a higher resolution version of prediction units of the stored images so that the luminance component of an interpolated prediction unit has a horizontal resolution P times that of the corresponding portion of the stored image and a vertical resolution Q times that of the corresponding portion of the stored image, where P and Q are integers greater than 1; a detector configured to detect inter-image motion between a current image and the one or more interpolated stored images so as to generate motion vectors between a prediction unit of the current image and areas of the one or more preceding images; and a generator configured to generate a motion compensated prediction of the prediction unit of the current image with respect to an area of an interpolated stored image pointed to by a respective motion vector; in which the interpolator is configured: to apply a ×R horizontal and ×S vertical interpolation filter to the chrominance components of a stored image to generate an interpolated chrominance prediction unit, where R is equal to (U×M×P) and S is equal to (V×N×Q), U and V being integers equal to 1 or more; and to subsample the interpolated chrominance prediction unit, such that its horizontal resolution is divided by a factor of U and its vertical resolution is divided by a factor of V, thereby resulting in a block of MP×NQ samples.\",\n \"20.Video capture, display, transmission, reception and/or storage apparatus comprising apparatus according to clause 18 or clause 19.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874737"}}},{"rowIdx":4494679,"cells":{"text":{"kind":"list like","value":[["CAMERA CONTROL INTERFACE SLAVE DEVICE TO SLAVE DEVICE COMMUNICATION","In a shared bus where communications are managed by a master device, direct slave device to slave device (S2S) communications is implemented.","A first slave device wanting to communicate with a second slave device may make a S2S communication request to the master device.","The request may include a requested number of words that the first slave device wishes to send over the shared bus.","The master device may have a current word limit which may vary based upon operating parameters.","The master device may deny the request if the requested number of words is greater than the current word limit or if it does not support S2S communications.","Denial of the request may also be for other reasons, like activity over the shared bus.","If the master device grants the request, the slave device may send the requested number of words to another slave device over the shared bus."],["1.A master device, comprising: a bus interface circuit to couple to a control data bus shared with a plurality of slave devices; and a processing circuit coupled to the bus interface circuit and configured to: control access to the control data bus by the plurality of slave devices; receive a request from a slave device for access to the control data bus for slave device to slave device communication; grant or deny the request received from the slave device; and after granting the request, permit the slave to use the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices, without transmitting the data transferred during the direct data transfer.","2.The master device of claim 1, wherein the slave device to slave device communication request includes a requested number of words to be transferred by the requesting slave device to another slave device.","3.The master device of claim 1, wherein the slave device to slave device communication request includes a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus; and the processing circuit is further configured to: send, to the requesting slave device, a response granting the request.","4.The master device of claim 3, wherein the response grants the request by including a word limit number in the response that is equal to or greater than the maximum number of words included in the request.","5.The master device of claim 3, wherein the processing circuit is configured to: monitor the control data bus to detect an end of slave device to slave device communications; and regain control of the control data bus after an end of slave device to slave device communications is detected.","6.The master device of claim 1, wherein the slave device to slave device communication request includes a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus; and the processing circuit is further configured to: send, to the requesting slave device, a response denying the request.","7.The master device of claim 6, wherein the slave device to slave device communication request is denied if the requested maximum number of words is greater than a current word limit of the master device.","8.The master device of claim 6, wherein the processing circuit is further configured to: send, to the requesting slave device, a response denying the request by sending an acceptable number of words when the requested maximum number of words provided by the requesting slave device is greater than a current word limit.","9.The master device of claim 6, wherein the master device sends the response denying the request if the master device does not support slave device to slave device communications.","10.A method operational by a master device, comprising: controlling access to a control data bus shared with a plurality of slave devices; receiving a request from a slave device for access to the control data bus for slave device to slave device communication; granting or denying the request from the slave device; and after granting the request, permitting the slave to use the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices, without transmitting the data transferred during the direct data transfer.","11.The method of claim 10, wherein the slave device to slave device communication request includes a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","12.The method of claim 11, further comprising: sending, to the requesting slave device, a response granting the request.","13.The method of claim 12, further comprising: monitoring the control data bus to detect an end of slave device to slave device communications; and regaining control of the control data bus after an end of slave device to slave device communications is detected.","14.The method of claim 11, further comprising: sending, to the requesting slave device, a response denying the request.","15.The method of claim 14, further comprising: receiving a request from the requesting slave device to have the master device transfer a certain amount of information between the requesting slave device and the another slave device; and transferring data between the requested information between the requesting slave device and the another slave device.","16.The method of claim 14, wherein the response denying the request includes an acceptable number of words that is less than the requested maximum number of words.","17.A slave device, comprising: a bus interface circuit to couple to a control data bus shared with a plurality of slave devices and a master device; and a processing circuit coupled to the bus interface circuit and configured to: send a slave device to slave device communication request over the control data bus to the master device; receive a response granting or denying the request from the master device; and after receiving a response granting the request, use the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices in which data is transferred between the slave device and another slave device without being transmitted by the master device.","18.The slave device of claim 17, wherein the communication request includes a requested maximum number of words to be transmitted by the slave device to another slave device over the control data bus.","19.The slave device of claim 18, wherein the processing circuit is further configured to: receive a response denying the request from the master device.","20.The slave device of claim 19, wherein the response includes an otherwise acceptable number of words from the master device.","21.The slave device of claim 20, wherein the processing circuit is further configured to: send a new slave device to slave device communication request to the master device, wherein the new slave device to slave device communication request includes a new requested maximum number of words that is less than or equal to the acceptable number of words.","22.The slave device of claim 19, wherein the processing circuit is further configured to: send a new request to have the master device transfer a certain amount of information between the requesting slave device and the another slave device.","23.The slave device of claim 19, wherein the processing circuit is further configured to either: resend the same slave device to slave device communication request, with the same maximum number of words, to the master device at a later time; or send a new slave device to slave device communication request with a second word limit that is less than the previous maximum word limit requested but greater than an acceptable number of words identified by the master device in its denial of the initial request.","24.The slave device of claim 19, wherein the processing circuit is further configured to: send a master request to the master device to transfer control of the control data bus to the requesting slave device; operate as new master of the control data bus if the master request is granted by the master device; and send a desired amount of data words to another slave device.","25.The slave device of claim 17, wherein the processing circuit is further configured to: receive the response granting the request; and send a slave device to slave device communication to the control data bus.","26.The slave device of claim 17, wherein the slave device to slave device communication is limited to an acceptable number of words approved by the master device.","27.A method operational on a slave device coupled to a control data bus shared with a plurality of slave devices and a master device, comprising: sending a slave device to slave device communication request over the control data bus to the master device; receiving a response granting or denying the request from the master device; and after receiving a response granting the request, using the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices in which data is transferred between the slave device and another slave device without being transmitted by the master device.","28.The method of claim 27, wherein the slave device to slave device communication request includes a requested number of words to be transferred by the slave device to another device over the control data bus.","29.The method of claim 27, further comprising: receiving the response granting the request; and sending a slave device to slave device communication to the control data bus.","30.The method of claim 29, wherein the slave device to slave device communication is limited to an acceptable number of words approved by the master device."],["<SOH> BACKGROUND <EOH>I2C (also referred to as I 2 C) is a multi-master serial single-ended control data bus used for attaching low-speed peripherals to a motherboard, embedded system, cellphone, or other electronic devices.","The I2C control data bus includes a clock (SCL) and data (SDA) lines with 7-bit addressing.","The control data bus has two roles for nodes: master and slave.","A master node is a node that generates the clock and initiates communication with slave nodes.","A slave node is a node that receives the clock and responds when addressed by the master.","The I2C control data bus is a multi-master control data bus which means any number of master nodes can be present.","Additionally, master and slave roles may be changed between messages.","I2C defines basic types of messages, each of which begins with a START and ends with a STOP.","In this context of a camera implementation, unidirectional transmissions may be used to capture an image from a sensor and transmit such image data to memory in a baseband processor, while control data may be exchanged between the baseband processor and the sensor as well as other peripheral devices.","In one example, a Camera Control Interface (CCI) protocol may be used for such control data between the baseband processor and the image sensor (and/or one or more slave nodes).","In one example, the CCI protocol may be implemented over an I2C serial control data bus between the image sensor and the baseband processor.","Master devices control access to the control data bus.","While some slave devices may have the capability of switching to a master mode of operation, other slave devices cannot operate in the master mode.","One major distinction between a slave-only slave device versus a master-capable slave device is the ability to receive (e.g., handle) interrupts on an interrupt request line (IRQ).","The slave-only slave devices can cause/send interrupts but cannot handle such interrupts.","Therefore, because interrupt handling is extremely important, heretofore slave devices cannot communicate directly with other slave devices.","Accordingly, it would be desirable to enable slave device to slave device communications over a shared data bus controlled by a master device."],["<SOH> SUMMARY <EOH>A master device is provided comprising a bus interface circuit and a processing circuit.","The bus interface circuit may serve to couple to a control data bus shared with a plurality of slave devices.","The processing circuit may be coupled to the bus interface and configured to: (a) control access to the control data bus by the plurality of slave devices; and/or (b) receive, a slave device to slave device communication request, from a slave device requesting access to the control data bus.","In one example, the slave device to slave device communication request may include a requested number of words to be transferred by the requesting slave device to another slave device.","In another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","The processing circuit may be further configured to send, to the requesting slave device, a response granting the request.","The response grants the request by including a word limit number in the response that is equal to or greater than a maximum number of words specified in the request.","The processing circuit may be further configured to: (a) monitor the control data bus to detect an end of slave device to slave device communications; and/or (b) regain control of the control data bus after an end of slave device to slave device communications is detected.","In yet another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","The processing circuit may be further configured to send, to the requesting slave device, a response denying the request.","The slave device to slave device communication request may be denied if the requested maximum number of words is greater than a current word limit of the master device.","The processing circuit may be further configured to send, to the requesting slave device, a response denying the request by sending an acceptable number of words when a requested maximum number of words provided by the requesting slave device is greater than a current word limit.","The master device may also send the response denying the request if the master device does not support slave device to slave device communications.","A method operational by a master device is provided, comprising: (a) controlling access to a control data bus shared with a plurality of slave devices; and/or (b) receiving a slave device to slave device communication request from a slave device requesting access to the control data bus.","The slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","The method may further comprise: (a) sending, to the requesting slave device, a response granting the request; (b) monitoring the control data bus to detect an end of slave device to slave device communications; and/or (c) regaining control of the control data bus after an end of slave device to slave device communications is detected.","The method may further comprise sending, to the requesting slave device, a response denying the request.","In one example, in response to the request denial, the method may further include: (a) receiving a request from the requesting slave device to have the master device transfer a certain amount of information between the requesting slave device and the another slave device; and/or (b) transferring data between the requested information between the requesting slave device and the another slave device.","In another example, the response denying the request may include an acceptable number of words that is less than the requested maximum number of words.","A slave device, comprising a bus interface circuit and a processing circuit.","The bus interface circuit may serve to couple the slave device to a control data bus shared with a plurality of slave devices and at least one master device.","The processing circuit may be coupled to the bus interface circuit and configured to send a slave device to slave device communication request from the slave device to the master device over the control data bus.","The communication request may include a requested maximum number of words to be transmitted by the slave device to another slave device over the control data bus.","In one example, the processing circuit may be further configured to receive a response denying the request from the master device.","The denial response may include an otherwise acceptable number of words from the master device.","In another approach to a denial response, the processing circuit may be further configured to send a new slave device to slave device communication request to the master device, wherein the new slave device to slave device communication request includes a new requested maximum number of words that is less than or equal to the received acceptable number of words.","In yet another alternative approach to a denial response, the processing circuit may be further configured to send a new request to have the master device transfer a certain amount of information between the requesting slave device and the another slave device.","In yet another alternative approach to a denial response, the processing circuit may be further configured to either: (a) resend the same slave device to slave device communication request, with the same maximum number of words, to the master device at a later time; or (b) send a new slave device to slave device communication request with a second word limit that is less than the previous maximum word limit requested but greater than an acceptable number of words identified by the master device in its denial of the initial request.","In yet another alternative approach to a denial response, the processing circuit may be further configured to: (a) send a master request to the master device to transfer control of the control data bus to the requesting slave device; (b) operate as new master of the control data bus if the master request is granted by the master device; and/or (c) send a desired amount of data words to another slave device.","In another example, the processing circuit may be further configured to: (a) receive a response granting the request; and/or (b) send a slave device to slave device communication to the control data bus.","The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.","According to another aspect, a method operational on a slave device is provided, comprising: (a) coupling the slave device to a control data bus shared with a plurality of slave devices and at least one master device; and/or (b) sending a slave device to slave device communication request from the slave device to the master device over the control data bus.","The slave device to slave device communication request may include a requested number of words to be transferred by the slave device to another device over the control data bus.","In one example, the method may further comprise: (a) receiving a response granting the request; and/or (b) sending a slave device to slave device communication to the control data bus.","The slave device to slave device communication may be limited to an acceptable number of words approved by the master device."],["CROSS-REFERENCE TO RELATED APPLICATIONS The present Application for patent is a divisional of U.S. patent application Ser.","No.","14/507,179, entitled “Camera Control Interface Slave Device to Slave Device Communication” filed Oct. 6, 2014, which claims priority to now-expired U.S.","Provisional Patent Application No.","61/887,895, entitled “Camera Control Interface Slave Device to Slave Device Communication” filed Oct. 7, 2013, which applications are assigned to the assignee hereof and are hereby expressly incorporated by reference herein.","FIELD The present disclosure pertains to enabling operations over a shared control data bus and, more particularly, to communication of data from one slave device to another slave device over a multi-wire data and/or clock control data bus.","BACKGROUND I2C (also referred to as I2C) is a multi-master serial single-ended control data bus used for attaching low-speed peripherals to a motherboard, embedded system, cellphone, or other electronic devices.","The I2C control data bus includes a clock (SCL) and data (SDA) lines with 7-bit addressing.","The control data bus has two roles for nodes: master and slave.","A master node is a node that generates the clock and initiates communication with slave nodes.","A slave node is a node that receives the clock and responds when addressed by the master.","The I2C control data bus is a multi-master control data bus which means any number of master nodes can be present.","Additionally, master and slave roles may be changed between messages.","I2C defines basic types of messages, each of which begins with a START and ends with a STOP.","In this context of a camera implementation, unidirectional transmissions may be used to capture an image from a sensor and transmit such image data to memory in a baseband processor, while control data may be exchanged between the baseband processor and the sensor as well as other peripheral devices.","In one example, a Camera Control Interface (CCI) protocol may be used for such control data between the baseband processor and the image sensor (and/or one or more slave nodes).","In one example, the CCI protocol may be implemented over an I2C serial control data bus between the image sensor and the baseband processor.","Master devices control access to the control data bus.","While some slave devices may have the capability of switching to a master mode of operation, other slave devices cannot operate in the master mode.","One major distinction between a slave-only slave device versus a master-capable slave device is the ability to receive (e.g., handle) interrupts on an interrupt request line (IRQ).","The slave-only slave devices can cause/send interrupts but cannot handle such interrupts.","Therefore, because interrupt handling is extremely important, heretofore slave devices cannot communicate directly with other slave devices.","Accordingly, it would be desirable to enable slave device to slave device communications over a shared data bus controlled by a master device.","SUMMARY A master device is provided comprising a bus interface circuit and a processing circuit.","The bus interface circuit may serve to couple to a control data bus shared with a plurality of slave devices.","The processing circuit may be coupled to the bus interface and configured to: (a) control access to the control data bus by the plurality of slave devices; and/or (b) receive, a slave device to slave device communication request, from a slave device requesting access to the control data bus.","In one example, the slave device to slave device communication request may include a requested number of words to be transferred by the requesting slave device to another slave device.","In another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","The processing circuit may be further configured to send, to the requesting slave device, a response granting the request.","The response grants the request by including a word limit number in the response that is equal to or greater than a maximum number of words specified in the request.","The processing circuit may be further configured to: (a) monitor the control data bus to detect an end of slave device to slave device communications; and/or (b) regain control of the control data bus after an end of slave device to slave device communications is detected.","In yet another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","The processing circuit may be further configured to send, to the requesting slave device, a response denying the request.","The slave device to slave device communication request may be denied if the requested maximum number of words is greater than a current word limit of the master device.","The processing circuit may be further configured to send, to the requesting slave device, a response denying the request by sending an acceptable number of words when a requested maximum number of words provided by the requesting slave device is greater than a current word limit.","The master device may also send the response denying the request if the master device does not support slave device to slave device communications.","A method operational by a master device is provided, comprising: (a) controlling access to a control data bus shared with a plurality of slave devices; and/or (b) receiving a slave device to slave device communication request from a slave device requesting access to the control data bus.","The slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.","The method may further comprise: (a) sending, to the requesting slave device, a response granting the request; (b) monitoring the control data bus to detect an end of slave device to slave device communications; and/or (c) regaining control of the control data bus after an end of slave device to slave device communications is detected.","The method may further comprise sending, to the requesting slave device, a response denying the request.","In one example, in response to the request denial, the method may further include: (a) receiving a request from the requesting slave device to have the master device transfer a certain amount of information between the requesting slave device and the another slave device; and/or (b) transferring data between the requested information between the requesting slave device and the another slave device.","In another example, the response denying the request may include an acceptable number of words that is less than the requested maximum number of words.","A slave device, comprising a bus interface circuit and a processing circuit.","The bus interface circuit may serve to couple the slave device to a control data bus shared with a plurality of slave devices and at least one master device.","The processing circuit may be coupled to the bus interface circuit and configured to send a slave device to slave device communication request from the slave device to the master device over the control data bus.","The communication request may include a requested maximum number of words to be transmitted by the slave device to another slave device over the control data bus.","In one example, the processing circuit may be further configured to receive a response denying the request from the master device.","The denial response may include an otherwise acceptable number of words from the master device.","In another approach to a denial response, the processing circuit may be further configured to send a new slave device to slave device communication request to the master device, wherein the new slave device to slave device communication request includes a new requested maximum number of words that is less than or equal to the received acceptable number of words.","In yet another alternative approach to a denial response, the processing circuit may be further configured to send a new request to have the master device transfer a certain amount of information between the requesting slave device and the another slave device.","In yet another alternative approach to a denial response, the processing circuit may be further configured to either: (a) resend the same slave device to slave device communication request, with the same maximum number of words, to the master device at a later time; or (b) send a new slave device to slave device communication request with a second word limit that is less than the previous maximum word limit requested but greater than an acceptable number of words identified by the master device in its denial of the initial request.","In yet another alternative approach to a denial response, the processing circuit may be further configured to: (a) send a master request to the master device to transfer control of the control data bus to the requesting slave device; (b) operate as new master of the control data bus if the master request is granted by the master device; and/or (c) send a desired amount of data words to another slave device.","In another example, the processing circuit may be further configured to: (a) receive a response granting the request; and/or (b) send a slave device to slave device communication to the control data bus.","The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.","According to another aspect, a method operational on a slave device is provided, comprising: (a) coupling the slave device to a control data bus shared with a plurality of slave devices and at least one master device; and/or (b) sending a slave device to slave device communication request from the slave device to the master device over the control data bus.","The slave device to slave device communication request may include a requested number of words to be transferred by the slave device to another device over the control data bus.","In one example, the method may further comprise: (a) receiving a response granting the request; and/or (b) sending a slave device to slave device communication to the control data bus.","The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.","SUMMARY OF FIGURES Various features, nature, and advantages may become apparent from the detailed description set forth below when taken in conjunction with the drawings in which like reference characters identify correspondingly throughout.","FIG.","1 is a block diagram illustrating an exemplary device having a baseband processor and an image sensor and implementing an image data bus and a multi-mode control data bus.","FIG.","2 illustrates an exemplary slave to slave communication process.","FIG.","3 conceptually illustrates an exemplary write data word.","FIG.","4 is a block diagram illustrating an exemplary method for transcoding of data bits into sequential symbols at a transmitter to embed a clock signal within the sequential symbols.","FIG.","5 illustrates an exemplary conversion between transition numbers and sequential symbols.","FIG.","6 illustrates an exemplary conversion from bits to transition numbers at a transmitter and then from transition numbers to bits at a receiver.","FIG.","7 illustrates a general example of converting a ternary number (base-3 number) to a binary number, where each T in {T11, T10, .",".",".","T2, T1, T0} is a symbol transition number.","FIG.","8 illustrates an exemplary method for converting a binary number (bits) to a 12 digit ternary number (base-3 number).","FIG.","9 illustrates an example of one possible implementation of the division and the modulo operations of FIG.","8, which may be synthesizable by any commercial synthesis tools.","FIG.","10 illustrates an example of a 20-bit region comprising a 19 bit data region (e.g., bits 0-18) and an additional 20th bit region (e.g., bit 19).","FIG.","11 illustrates that besides the bit 19 being set for numbers 2221_2201_20023 to 2222_2222_22223, that range of numbers can be subdivided into six sections.","FIG.","12 illustrates an exemplary mapping of a portion of the Bit 19 mapping of FIG.","11.FIG.","13 conceptually illustrates a sequence of transmissions over a control data bus that may be performed for a slave device to slave device communication.","FIG.","14 conceptually illustrates an exemplary slave to slave transfer request.","FIG.","15 conceptually illustrates a grant command for a slave device to slave device communication protocol.","FIG.","16 conceptually illustrates details of a grant command for a slave device to slave device transfer.","FIG.","17 is a block diagram illustrating an exemplary master device adapted for slave device to slave device communication.","FIG.","18 illustrates a method operational on a master device to facilitate slave device to slave device communication.","FIG.","19 is a block diagram illustrating an exemplary slave device adapted for slave device to slave device communication.","FIG.","20 illustrates a method operational on a slave device to perform slave device to slave device communication.","DETAILED DESCRIPTION In the following description, specific details are given to provide a thorough understanding of the embodiments.","However, it will be understood by one of ordinary skill in the art that the embodiments may be practiced without these specific details.","For example, circuits may be shown in block diagrams in order not to obscure the embodiments in unnecessary detail.","In other instances, well-known circuits, structures, and techniques may not be shown in detail in order not to obscure the embodiments.","Overview A first feature provides for direct slave device to slave device communications over a shared control data bus managed by a master device.","A first slave device wishing to communicate with a second slave device may make a slave device to slave device communication request to the master device.","The request may include a requested number of words that the first slave device wishes to send to the second slave device over the shared control data bus managed by the master device.","Such communication request may be for a direct transfer (e.g., read or write operations) between the first slave device and the second slave device while bypassing the master device (e.g., the data to be transferred is not managed or sent by the master device).","The master device may have a current word limit which may vary based upon operating parameters.","For example, the master device may allow different numbers of words to be communicated between the slave devices at different times.","For instance, during peak control bus use periods, the slave devices may be limited to communicating with each other using no more than eight word at a time.","There may be times when no slave device to slave device communications are allowed (i.e., the current word limit may be zero).","Moreover, during periods of low control bus use, the current word limit may be 1024 words, for example.","Consequently, the current word limit may be dynamically adjusted by the master device managing the bus and may change over time according to control data bus conditions or for any other desirable reason.","Because the word limit may change dynamically, and a slave device may not know what the current word limit is, a second feature provides for communicating to the salve device the current word limit.","For example, the first slave device desiring to communicate with the second slave device sends the slave device to slave device communication request which includes a desired number of words to be communicated to the second slave device.","When the desired number of words is greater than the current word limit, the master device sends the first slave device a denial message that includes the current word limit such that the slave can request to send a smaller message to the second slave device.","The master device receives this request for a smaller message and sends the first slave device a message granting the request.","The first slave device then sends the message to the second slave device.","The master device monitors the message(s) being sent from the first slave device to the second slave device.","Upon detecting an “end” control code being sent from the first slave device to the second slave device, the master device knows the communication has ended and regains control of the control data bus exactly as the master device had done prior to granting the communication request by the first slave device.","Additionally, the master device may continuously monitor the IRQ line while the first slave device is communicating with the second slave device.","Any interrupt requests occurring during the slave device to slave device communication is handled once the slave device to slave device communication has ended.","In one feature, the current word limit is not only variable based upon control data bus traffic but also on recent frequency of interrupt requests.","Consequently, during periods of relatively high interrupt requests, the current word limit may be lower than periods of relatively low interrupt requests.","Exemplary System for Slave Device to Slave Device Communications FIG.","1 is a block diagram illustrating a device 102 having a baseband processor 104 and an image sensor 106 and implementing an image data bus 116 and a multi-mode control data bus 108 in which slave device to slave device communications may be enabled as described herein.","While FIG.","1 illustrates the multi-mode control data bus 108 within a camera device, it should be clear that this control data bus 108 may be implemented in various different devices and/or systems.","Image data may be sent from the image sensor 106 to the baseband processor 104 over an image data bus 116 (e.g., a high speed differential DPHY link).","In one example, the control data bus 108 may be an I2C control data bus comprising two wires, a clock line (SCL) and a serial data line (SDA).","The clock line SCL may be used to synchronize all data transfers over the I2C bus (control data bus 108).","The data line SDA and clock line SCL are coupled to all devices 112, 114, and 118 on the I2C bus (control data bus 108).","In this example, control data may be exchanged between the baseband processor 104 and the image sensor 106 as well as other peripheral devices 118 via the control data bus 108.In some implementations, the operating modes over an I2C control data bus may be referred to as a camera control interface (CCI) mode when used for camera applications.","According to one aspect, an improved mode of operation may be implemented over the multi-mode control data bus 108 to support camera operation.","This improved mode of operation over an I2C control data bus may be referred to as a camera control interface extension (CCIe) mode when used for camera applications.","In this example, the baseband processor 104 includes a master device 112 and the image sensor 106 includes a slave device 114, both the master device 112 and slave device 114 may operate according to the camera control interface extension (CCIe) mode over the control data bus 108 without affecting the proper operation of other legacy I2C devices coupled to the control data bus 108.According to one aspect, this improved mode over the control data bus 108 may be implemented without any bridge device between CCIe devices and any legacy I2C slave devices.","An interrupt request (IRQ) line/bus 120 couples the slave devices 114 and 118 to the master device 112 allowing the slave devices to notify the master device 112 that the slave device 114 and 118 is in need of attention.","In other words, the slave device requesting attention pulls the normally high IRQ line low (grounds the IRQ line 120), and the master device responds by first identifying which slave device requested the interrupt, and second, polling the slave for an IRQ status.","For example, the status may be a request to perform a slave device to slave device communication.","FIG.","2 illustrates an exemplary slave device to slave device communication process.","Similar to FIG.","1, a device may include a shared control data bus 202 (e.g., CCIe bus) and a separate single-line interrupt bus 204 to which a plurality of devices may be coupled.","In this example, an active/current master device 206 may control/manage access to the control data bus 202 by one or more other devices (e.g., non-active master devices and/or slave devices).","At a first stage 210, a first slave device 208 may wish to initiate communications with a second slave device 216.To do this, the first slave device may issue/send an interrupt signal 218 over the interrupt bus 204.The interrupt bus 204 may allow any device coupled to the interrupt bus 204 to unilaterally issue an interrupt signal over the interrupt bus 204 so long as no other device is already asserting an interrupt signal already.","In response to sensing or receiving the interrupt request signal 218, the master device 206 may attempt to ascertain the requesting slave device (e.g., the device that issued the interrupt signal 218).","This may be accomplished by the master device 206 polling or requesting 220 that each slave device to provide its status.","In one example, this may be done by the master device 206 requesting 220 the status from each device coupled to control data bus 202 until the first slave device 208 that issued the interrupt signal 218 is identified.","At a second stage 212, in response to receiving the status request 220, the first slave device 208 may send its status 222 which would indicate that it issued the interrupt 218 and/or that it wishes to perform a slave device to slave device transfer/communication.","Such slave device to slave device communication request may be for a direct data transfer (e.g., read or write operations) between the first slave device 208 and the second slave device 216 while bypassing the master device 206 (e.g., the data to be transferred is not managed or sent by the master device).","In one example, the status 222 may be obtained by the master device 206 reading information within status registers for the first slave device 208.Upon identifying the first slave device 208 as the issuer of the interrupt signal and ascertaining the desired service (e.g., use of the control data bus 202 for slave to slave communications), the master device 206 may grant such request by sending a grant indicator 224 via the interrupt bus 204.At that point, the first slave device 208 has been granted a limited permission to use the control data bus 202 for its own communications with another slave device 216.Note that because the master device 206 controls or manages use of the control data bus 202 by all devices coupled to the control data bus 202, there is no chance of conflicting use of the control data bus 202 by another device.","In one example, the first slave device 208 is granted use of the control data bus 202 to send or receive a predetermined number of data words.","The use of a slave device to slave device communication request is distinct from transferring control of the control data bus 202 to the first slave At a third stage 214, the first slave device 208 recognizes that the master device 206 has granted its request and may perform a slave to slave transfer or communication 224.The slave to slave transfer or communication 224 may read data from or send data to a second slave device 216.After the predetermined number of data words have been sent over the control data bus 202, the master device may regain control and use of the control data bus 202.The first slave device 208 stops transmitting over the control data bus 202 after sending and/or receiving the predetermined number of data words.","Exemplary Communication Protocol Supporting Slave Device to Slave Device Communications FIG.","3 illustrates an exemplary write data word format.","This illustrates that each data word 300 includes a 16-bit data portion 302, a 2-bit control code 304, a 1-bit error detection constant 310, and a spare bit 306.The 16-bit data portion 302 may be segmented into a 14-bit least significant bit portion 312 (located from bits 5 to 18 of the data word 300) and a 2-bit most significant bit portion 308 (located from bits 1 to 2 of the data word 300).","The 1-bit error detection constant 310 may serve to detect an error on the data word 300 if the value is anything other than the expected constant (e.g., “0”).","In one example, the write data word 300 may be a CCIe write data word.","A control code table 314 illustrates various possible values for the control code 304.In one example, multiple write data words can be sent sequentially.","If the control code of the current write word is ‘00’ (symbol C0), then the data is to be written to the previous address.","If the control code of the current write word is ‘01’ (symbol C1), then the data is to be written to the previous address+1.If the control code of the current write word is ‘10’ (symbol E), this indicates an end of frame and the next word may be a slave device identifier (SID) or an Exit code.","The data word 300 may also have a spare bit 306 (e.g., bit 19, also referred to as 20th bit) that may be used to transmit commands and other information between a master device and one or more slave devices.","The spare bit 306 (e.g., bit 19) may be used to encode commands between devices coupled to the control data bus 108.A spare bit data region that may be defined by the use of this spare bit 306 (e.g., bit 19, also referred to as 20th bit) is further illustrated and discussed in FIGS.","10, 11, and 12.FIG.","4 is a block diagram illustrating an exemplary method for transcoding of data bits into sequential symbols at a transmitter to embed a clock signal within the sequential symbols.","At the transmitter 402, a sequence of data bits 404 are converted into a ternary (base 3) number (e.g., where individual digits of the ternary number are a “transition number”), and the ternary numbers are converted into sequential symbols which are transmitted over a control data bus that includes a clock line SCL 412 and a data line SDA 414.In one example, an original 20-bits 404 of binary data is input to a bit-to-transition number converter block 408 to be converted to a 12-digits ternary number 409.Each digit of a 12-digits ternary number may represent a “transition number”.","Two consecutive digits of a transition number may be the same digit value.","Each digit of a transition number is converted into a sequential symbol at a transition-to-symbol block 410 such that no two consecutive sequential symbols have the same value.","Because a transition (e.g., change) is guaranteed at every sequential symbol, such sequential symbol transition may serve to embed a clock signal.","Each sequential symbol 416 is then sent over a two wire physical link (e.g., I2C control data bus comprising a SCL line 412 and a SDA line 414).","At a receiver 420 the process is reversed to convert the sequential symbols back to bits and, in the process, a clock signal is extracted from the sequential symbol transition.","The receiver 420 receives the sequential symbols 422 over the two wire physical link (e.g., an I2C control data bus comprising a SCL line 424 and a SDA line 426).","The received sequential symbols 422 are input into a clock-data recovery (CDR) block 428 to recover a clock timing and sample the sequential symbols (S).","A symbol-to-transition number converter block 430 then converts each sequential symbol to a transition number, where each transition number represents a digit of a ternary number.","Then, a transition number-to-bits converter 432 converts twelve (12) transition numbers (i.e., a ternary number) to restore twenty (20) bits of original data from the 12 digit ternary number.","The technique illustrated herein may be used to increase the link rate of a control data bus 108 (FIG.","1) beyond what the I2C standard control data bus provides and is referred hereto as CCIe mode.","In one example, a master node/device and/or a slave node/device coupled to the control data bus 108 may implement transmitters and/or receivers that embed a clock signal within sequential symbol changes/transitions (as illustrated in FIG.","5) in order to achieve higher bit rates over the same control data bus than is possible using a standard I2C control data bus.","FIG.","5 illustrates an exemplary conversion between transition numbers 502 and sequential symbols 504.An individual digit of ternary number, base-3 number, also referred to as a transition number, can have one of the three (3) possible digits or states, 0, 1, or 2.While the same digit may appear in two consecutive digits of the ternary number, no two consecutive sequential symbols have the same value.","The conversion between a transition number and a sequential symbol guarantees that the sequential symbol always changes (from sequential symbol to sequential symbol) even if consecutive transition numbers are the same.","In one example, the conversion function adds the transition number (e.g., digit of a ternary number) plus 1 to the previous raw sequential symbol value.","If the addition results in a number larger than 3, it rolls over from 0, then the result becomes the state number or value for the current sequential symbol.","In a first cycle 506, a previous sequential symbol (Ps) is 1 when a first transition number (Ta) 1 is input, so the first transition number 1 plus 1 is added to the previous sequential symbol (Ps), and the resulting current sequential symbol (Cs) of 3 becomes the current sequential symbol that is sent to the physical link.","In a second (next) cycle 508, a second transition number (Tb) of 0 is input, and the second transition number 0 plus 1 is added to the previous sequential symbol (Ps) of 3.Since the result of the addition (0+1+3) equals 4, is larger than 3, the rolled over number 0 becomes the current sequential symbol (Cs).","In a third cycle 510, a third transition number (Ta) of 0 is input.","The conversion logic adds the third transition number 0 plus 1 to the previous sequential symbol (Ps) 0 to generate current sequential symbol (Cs) 1.In a fourth cycle 512, a fourth transition number (Td) of 2 is input.","The conversion logic adds the fourth transition number (Td) 2 plus 1 to the previous symbol (Ps) 1 to generate current sequential symbol (Cs) 0 (since the result of the addition, 4, is larger than 3, the rolled over number 0 becomes the current sequential symbol).","Consequently, even if two consecutive ternary digits Tb and Tc have the same number, this conversion guarantees that two consecutive sequential symbols have different state values.","Because of this conversion, the guaranteed sequential symbol change or transition in the sequence of symbols 504 may serve to embed a clock signal, thereby freeing the clock line SCL in an I2C control data bus for data transmissions.","Note that while this example of transition number to sequential number conversions adds a guaranteed number “1” to increment between consecutive sequential symbols, other values may be used in other implementations to guarantee a transition or change between sequential symbols.","Referring again to FIG.","4, at the receiver 420 the process illustrated in FIG.","5 is reversed to convert the sequential symbols back to bits and, in the process, a clock signal is extracted from the symbol transition.","The receiver 420 receives sequential symbols 422 over the two wire physical link (e.g., I2C bus comprising a SCL line 424 and a SDA line 426).","The received sequential symbols 422 are input into a clock-data recovery (CDR) block 428 to recover a clock timing and sample the transcoded symbols (S).","A symbol-to-transition number converter block 430 then converts each sequential symbol to a transition number, i.e., which makes up a digit within a ternary number.","Then, a transition number-to-bits converter 32 converts 12 transition numbers (i.e., a ternary number) to restore 20 bits of original data from the 12 digit ternary number.","FIG.","6 illustrates an exemplary conversion from bits to transition numbers at a transmitter 602 and then from transition numbers to bits at a receiver 604.This example illustrates the transmission for a 2-wire system using 12 transition symbols.","The transmitter 602 feeds binary information, Bits, into a “Bits to 12×T” converter 606 to generate 12 symbol transition numbers, T0 to T11.The receiver 604 receives 12 symbols transition numbers, T0 to T11, which are fed into a “12×T to Bits” converter 608 to retrieve the binary information (Bits).","If there are r possible symbol transition states per one T, T0 to T11, 12 transitions can send r12 different states.","For a 2-wire bus, r=22−1.Consequently, transitions T0 .",".",".","T11 contain data that can have (22−1)12 different states.","Consequently, r=4−1=3 and the number of states=(4−1)̂12=531441.In this example for a 2-wire system using 12 symbol transition numbers, it may be assumed that the possible symbol transitions per one T, r is 3 (=22−1).","If the number of symbols in a group is 12, a 12-digit ternary number (base-3 number): T11, T10, .",".",".",", T2, T1, T0, where each Ti: 0, 1, 2, may be used.","For example, for {T11, T10, .",".",".","T2, T1, T0}={2, 1, 0, 0, 1, 1, 0, 1, 0, 1, 2, 1}, the ternary number is: 2100 _ 1101 _ 0121 3 ( Ternary number ) = 2 × 3 11 + 1 × 3 10 + 0 × 3 9 + 0 × 3 8 + 1 × 3 7 + 1 × 3 6 + 0 × 3 5 + 1 × 3 4 + 0 × 3 3 + 1 × 3 2 + 2 × 3 1 + 1 × 3 0 = 416356 ( 0 x 65 A 64 ) .","In this manner, 12 transitions numbers may be converted into a number.","Note that the ternary number 2100_1101_01213 may be used as the transition number, for example, in FIG.","4, so that each transition number (e.g., digit of a ternary number) may be mapped to a sequential symbol and vice versa.","The example illustrated in FIG.","6 for a 2-wire system and 12 symbol transition numbers may be generalized to a n-wire system and m symbol transition numbers.","If there are r possible symbol transition states per one T, T0 to Tm−1, m transitions can send rm different states, i.e., r=2n−1.Consequently, transitions numbers T0 .",".",".","Tm−1 contain data that can have (2n−1)m different states (e.g., sequential numbers).","FIG.","7 illustrates a general example of converting a ternary number (base-3 number) to a binary number, where each T in {T11, T10, .",".",".","T2, T1, T0} is a transition number.","FIG.","8 illustrates an exemplary method for converting a binary number (bits) to a 12 digit ternary number (base-3 number).","Each digit of the ternary number can be calculated by dividing the remainder (result of a modulo operation) from a higher digit calculation with 3 to the power of the digit number, discarding decimal points numbers.","FIG.","9 illustrates an example of one possible implementation of the division and the modulo operations of FIG.","8, which may be synthesizable by any commercial synthesis tools.","FIG.","10 conceptually illustrates a bit 19 (the 20th bit or “spare bit” 306 in FIG.","3) is mostly unused in the CCIe protocol and may be used to enable slave device to slave device communications.","More specifically, FIG.","10 illustrates the bit 19 (i.e., the 20th bit when the bit count starts at the first bit being bit 0).","In other words, as is typical in the computer sciences, counting bit wise begins at zero, and bit 19 is the 20th bit.","Here, the bits 0-18 are represented within the ternary number range of 0000_0000_00003 to 2221_2201_20013.The ternary numbers in the range of 2221_2201_20023 to 2222_2222_22223 are unused.","Consequently, the ternary number range 2221_2201_20023 to 2222_2222_22223 may be used to represent bit 19 (i.e., 20th bit).","In other words, 2221_2201_20023 ternary is 10,000,000,000,000,000,000 binary (0x80000 hexadecimal) and 2222_2222_22223 ternary (0x81BF0) is the largest 12 digit ternary number possible.","In one implementation of slave device to slave device communication, the 20th bit (bit 19) is utilized as described herein.","FIG.","11 conceptually illustrates a CCIe Bit 19 mapping protocol for ternary numbers 0000_0000_00003 to 2222_2222_22223.Note that different types of commands may be encoded within the bit 19 region (e.g., 20th Bit).","FIG.","12 illustrates an exemplary mapping of a portion of the Bit 19 mapping of FIG.","11.FIG.","13 conceptually illustrates a sequence of transmissions over a control data bus that may be performed for a slave device to slave device communication.","In this example, the slave device to slave device communication protocol utilizes the range from 2222_2112_11223 to 2222_2202_21203.The slave device may send an interrupt signal to the master device over the separate interrupt bus/line.","In response to such interrupt signal 1301, the master device may initiate/send an IRQ inquiry 1303 over the control data bus which causes the requesting slave device (S1) to respond 1304.The master device may then read the status 1305 of the requesting slave device (S1) in which a slave-to-slave communication request 1306 is indicated.","This slave-to-slave communication request 1306 may include an upper limit (max limit) of words for the requested transmission to another slave device.","The number of words may not just be the data portion of the message but rather may include the entire number of words to be transmitted between slave devices, including all overhead and/or envelope information such as a slave identifier (SID), a cyclic redundancy check or checksum (CRC) and/or synchronization (SYNC) information.","The master device, after granting 1308 a slave device's request then monitors the slave device's transmissions 1310 and after an end code is sent from the transmitting slave device, the master device resumes control over the control data bus.","In other words, the master device monitors the control data bus to detect an end of the granted access, after notifying the slave device that sent the request, that the request is granted.","Note that during this slave to slave transmission frame 1310, the requesting slave device may send write commands 1312 and/or read commands 1314 to another slave device.","FIG.","14 conceptually illustrates an exemplary slave to slave transfer request.","This exemplary slave to slave transfer request 1403 may be embedded with a portion 1402 of the bit 19 mapping illustrated in FIGS.","11 and 12 (e.g., utilizes the range from 2222_2112_11223 to 2222_2202_21203).","One example of the slave to slave transfer request 1403 is defined by a first bit sequence 1404 in conjunction with two tables 1406 and 1408.This slave to slave transfer request 1403 may include the number of words 1408 to be transmitted over the control data bus during the slave to slave transfer.","FIG.","15 conceptually illustrates a grant command for a slave device to slave device communication protocol.","In this example, the slave device to slave device communication protocol 1502 utilizes the range from 2222_2112_11223 to 2222_2202_21203 in sending request grants and/or denials.","The master device grants the slave device to slave device communication request by returning to the requesting slave device a message including the same word limit number in the slave device to slave device communication request originally sent from the slave device to the master device.","Alternatively, the master device returns a word limit number smaller than the requested number which the slave device understands to be a denial of the original request and a furnishing of a new word limit.","When the new (i.e., current) word limit is zero, the slave device knows that slave device to slave device communication is currently disabled and waits a pre-programmed amount of time before making a second request.","Else, if the returned current word limit is non-zero, the slave device then breaks the original too long message into a plurality of messages no larger than the returned current word limit.","Additionally, in some embodiments, one or more slave devices may have a sleep mode to save energy, and when an intended recipient of a slave device to slave device communication is in the sleep mode, the master device may wake up the sleeping slave device prior to granting a requesting slave device's communication request.","Alternatively, the master device may first deny the requesting slave device's communication request by sending a current word limit of zero and then wakes up the sleeping slave.","After a pre-programmed period of time, the denied slave device initiates a second request that the master device may now grant.","One example of the slave to slave transfer grant 1503 is defined by a first bit sequence 1504 in conjunction with two tables 1506 and 1508.This slave to slave transfer grant 1503 may include the number of words 1508 allowed to be transmitted over the control data bus during the slave to slave transfer.","FIG.","16 conceptually illustrates details of a grant command for a slave device to slave device transfer.","In this example, the master device may send a frame 1602 that includes the requesting slave device's identifier (SID), and extra words 1606.As part of the “address” field, the master device may provide the slave device to slave device grant 1608.Exemplary Master Device and Method Operational Therein FIG.","17 is a block diagram illustrating an exemplary master device adapted for slave device to slave device communication.","The master device 1702 may include a first communication interface/circuit 1706, a second communication interface/circuit 1708, and/or a processing circuit 1704.The first communication interface/circuit 1706 may serve to couple to a single line interrupt request (IRQ) bus to which a plurality of other devices may be coupled.","The second communication interface/circuit 1708 may serve to couple to a control data bus to which the plurality of other devices may also be coupled.","The processing circuit 1704 may include various sub-circuits and/or modules to carry out one or more functions described herein.","For example, a communication management circuit/module 1710 may be adapted to manage communications over the data bus for all devices coupled to the control data bus based on interrupt signals asserted over the IRQ bus.","An IRQ bus monitoring circuit/module 1712 may be adapted to monitor the IRQ bus to ascertain when an IRQ signal has been asserted (e.g., by a slave device).","A slave-to-slave communication grant/deny circuit/module 1714 may be adapted to respond (e.g., grant or deny) to a request by a slave device to communicate directly with another slave device over the control data bus.","A data bus monitoring circuit/module 1716 may be adapted to allow the master device to monitor the control data bus to ascertain when the slave-to-slave communications have ended.","FIG.","18 illustrates a method 1800 operational on a master device to facilitate slave device to slave device communication.","The method 1800 includes having a master device control/manage access to a control data bus shared with a plurality of slave devices 1802.The master device may receive a slave device to slave device communication/transfer request from a slave device requesting access to the control data bus 1804.The slave device to slave device communication/transfer request may include a maximum number of words that the requesting slave device wishes to transmit over the control date bus.","In response to such request, the master device may send, to the requesting slave device, a response denying the request by sending an acceptable maximum number of words when a requested maximum number of words is greater than a current maximum word limit 1806.For instance, the acceptable number of words may be equal to the current maximum word limit (maintained by the master device) and/or it may be a number less than the requested maximum number of words.","Alternatively, the master device may send, to the requesting slave device, a response granting the request 1808.Moreover, the master device may monitor the control data bus to detect an end of the granted access to the requesting slave device 1810.Upon detection of an end of slave device to slave device communications over the shared control bus is detected, the master device may regain control of the control data bus.","In one example, the response from the master device grants the request by including a word limit number in the response that is equal to or greater than a maximum number of words specified in the request.","That is, if the response includes a word limit number that matches the requested maximum number of words specified by the requesting slave device or is greater than the requested maximum number of words, the requesting slave device may recognize this as a grant of the request.","According to another aspect, if the master device does not support slave device to slave device communications, the master device respond to the request with a word limit number of zero (0) in its response.","Hence, if a master device may be required (e.g., by a protocol standard) to reply to the slave device to slave device communication request, but it may deny the request by including a word limit number of zero (0).","For this reason, it may be advisable for master devices that support slave device to slave device communications to reply with a non-zero word limit number in its response.","According to one aspect, if the master device denies the slave device to slave device communication request, the slave device may wait some amount of time and then resends the same slave device to slave device communication request (e.g., same desired number of words to be transferred) to the master device over the control data bus.","Note that the original denial may have been due to a busy control data bus, so retrying at a later time may result in the request being granted.","Additionally, the slave device may retry sending the same request several times before giving up.","According to another aspect, if the master device denies the slave device to slave device communication request, the slave device may resend the request but with a lower maximum number of words to be transferred by the requesting slave device over the control data bus.","In some implementations, the slave device may breakup a data transfer that is larger than the maximum number of words permitted by the master device into multiple slave device to slave device communication requests.","In an alternative approach, if the master device denies the slave device to slave device communication request, but the slave device cannot breakup the data transfer into multiple portions, the slave device may request the master device to take over the data transfer between the requesting slave device and another slave device.","Exemplary Slave Device and Method Operational Therein FIG.","19 is a block diagram illustrating an exemplary slave device adapted to perform slave device to slave device communication.","The slave device 1902 may include a first communication interface/circuit 1906, a second communication interface/circuit 1908, and/or a processing circuit 1904.The first communication interface/circuit 1906 may serve to couple to a single line interrupt request (IRQ) bus to which a plurality of other devices may be coupled.","The second communication interface/circuit 1908 may serve to couple to a control data bus to which the plurality of other devices may also be coupled.","The processing circuit 1904 may include various sub-circuits and/or modules to carry out one or more functions described herein.","For example, an interrupt (IRQ) generator circuit/module 1910 may be adapted to generate an interrupt request over the interrupt bus.","A slave-to-slave communication requesting circuit/module 1912 may be adapted to request use of the control data bus from a master device in order to perform slave-to-slave communications directly with another slave device.","A slave-to-slave communication transmission circuit/module 1914 may be adapted to send slave-to-slave communications over the control data bus.","FIG.","20 illustrates a method 2000 operational on a slave device to facilitate slave device to slave device communication.","The method 2000 includes coupling the slave device to a control data bus shared with a plurality of slave device and managed by a master device 2002.The slave device may send a slave device to slave device communication request to the master device over the control data bus 2004.In response to the request, the slave device may receive a response denying the request that includes an otherwise acceptable maximum number of words from the master device 2006.If the request is initially denied, the slave device may simply wait an amount of time and resend the same initial request.","Alternatively, the slave device may send a new slave device to slave device communication request including a requested maximum number of words less than or equal to the received acceptable maximum number of words to the master device 2008.The slave device may receive a response granting the request from the master device 2010.Upon receiving the grant response from the master device, the slave device may transmit information to a second slave device over the control data bus in, at most, the request number of words 2012.According to one aspect, if the master device denies the slave device to slave device communication request, the slave device may wait some amount of time and then resends the same slave device to slave device communication request (e.g., same desired number of words to be transferred) to the master device over the control data bus.","Note that the original denial may have been due to a busy control data bus, so retrying at a later time may result in the request being granted.","Additionally, the slave device may retry sending the same request several times before giving up.","According to another aspect, if the master device denies the slave device to slave device communication request, the slave device may resend the request but with a lower maximum number of words to be transferred by the requesting slave device over the control data bus.","In some implementations, the slave device may breakup a data transfer that is larger than the maximum number of words permitted by the master device into multiple slave device to slave device communication requests.","In an alternative approach, if the master device denies the slave device to slave device communication request, but the slave device cannot break up the data transfer into multiple portions, the slave device may request the master device to take over the data transfer between the requesting slave device and another slave device.","In yet another approach, if the master device denies the slave device to slave device communication request and the requesting slave device is capable of operating in either master mode or slave mode, the requesting slave device may request to become the master of the shared control data bus in order to transfer the desired number of words.","One or more of the components, steps, features, and/or functions illustrated in the Figures may be rearranged and/or combined into a single component, step, feature, or function or embodied in several components, steps, or functions.","Additional elements, components, steps, and/or functions may also be added without departing from novel features disclosed herein.","The apparatus, devices, and/or components illustrated in the Figures may be configured to perform one or more of the methods, features, or steps described in the Figures.","The novel algorithms described herein may also be efficiently implemented in software and/or embedded in hardware.","In addition, it is noted that the embodiments may be described as a process that is depicted as a flowchart, a flow diagram, a structure diagram, or a block diagram.","Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently.","In addition, the order of the operations may be re-arranged.","A process is terminated when its operations are completed.","A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc.","When a process corresponds to a function, its termination corresponds to a return of the function to the calling function or the main function.","Moreover, a storage medium may represent one or more devices for storing data, including read-only memory (ROM), random access memory (RAM), magnetic disk storage mediums, optical storage mediums, flash memory devices, and/or other machine-readable mediums for storing information.","The term “machine readable medium” includes, but is not limited to portable or fixed storage devices, optical storage devices, wireless channels and various other mediums capable of storing, containing, or carrying instruction(s) and/or data.","Furthermore, embodiments may be implemented by hardware, software, firmware, middleware, microcode, or any combination thereof.","When implemented in software, firmware, middleware, or microcode, the program code or code segments to perform the necessary tasks may be stored in a machine-readable medium such as a storage medium or other storage(s).","A processor may perform the necessary tasks.","A code segment may represent a procedure, a function, a subprogram, a program, a routine, a subroutine, a module, a software package, a class, or any combination of instructions, data structures, or program statements.","A code segment may be coupled to another code segment or a hardware circuit by passing and/or receiving information, data, arguments, parameters, or memory contents.","Information, arguments, parameters, data, etc.","may be passed, forwarded, or transmitted via any suitable means including memory sharing, message passing, token passing, network transmission, etc.","The various illustrative logical blocks, modules, circuits, elements, and/or components described in connection with the examples disclosed herein may be implemented or performed with a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic component, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein.","A general purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine.","A processor may also be implemented as a combination of computing components, e.g., a combination of a DSP and a microprocessor, a number of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.","The methods or algorithms described in connection with the examples disclosed herein may be embodied directly in hardware, in a software module executable by a processor, or in a combination of both, in the form of processing unit, programming instructions, or other directions, and may be contained in a single device or distributed across multiple devices.","A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium known in the art.","A storage medium may be coupled to the processor such that the processor can read information from, and write information to, the storage medium.","In the alternative, the storage medium may be integral to the processor.","Those of skill in the art would further appreciate that the various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both.","To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality.","Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system.","The various features of the invention described herein can be implemented in different systems without departing from the invention.","It should be noted that the foregoing embodiments are merely examples and are not to be construed as limiting the invention.","The description of the embodiments is intended to be illustrative, and not to limit the scope of the claims.","As such, the present teachings can be readily applied to other types of apparatuses and many alternatives, modifications, and variations will be apparent to those skilled in the art."]],"string":"[\n [\n \"CAMERA CONTROL INTERFACE SLAVE DEVICE TO SLAVE DEVICE COMMUNICATION\",\n \"In a shared bus where communications are managed by a master device, direct slave device to slave device (S2S) communications is implemented.\",\n \"A first slave device wanting to communicate with a second slave device may make a S2S communication request to the master device.\",\n \"The request may include a requested number of words that the first slave device wishes to send over the shared bus.\",\n \"The master device may have a current word limit which may vary based upon operating parameters.\",\n \"The master device may deny the request if the requested number of words is greater than the current word limit or if it does not support S2S communications.\",\n \"Denial of the request may also be for other reasons, like activity over the shared bus.\",\n \"If the master device grants the request, the slave device may send the requested number of words to another slave device over the shared bus.\"\n ],\n [\n \"1.A master device, comprising: a bus interface circuit to couple to a control data bus shared with a plurality of slave devices; and a processing circuit coupled to the bus interface circuit and configured to: control access to the control data bus by the plurality of slave devices; receive a request from a slave device for access to the control data bus for slave device to slave device communication; grant or deny the request received from the slave device; and after granting the request, permit the slave to use the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices, without transmitting the data transferred during the direct data transfer.\",\n \"2.The master device of claim 1, wherein the slave device to slave device communication request includes a requested number of words to be transferred by the requesting slave device to another slave device.\",\n \"3.The master device of claim 1, wherein the slave device to slave device communication request includes a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus; and the processing circuit is further configured to: send, to the requesting slave device, a response granting the request.\",\n \"4.The master device of claim 3, wherein the response grants the request by including a word limit number in the response that is equal to or greater than the maximum number of words included in the request.\",\n \"5.The master device of claim 3, wherein the processing circuit is configured to: monitor the control data bus to detect an end of slave device to slave device communications; and regain control of the control data bus after an end of slave device to slave device communications is detected.\",\n \"6.The master device of claim 1, wherein the slave device to slave device communication request includes a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus; and the processing circuit is further configured to: send, to the requesting slave device, a response denying the request.\",\n \"7.The master device of claim 6, wherein the slave device to slave device communication request is denied if the requested maximum number of words is greater than a current word limit of the master device.\",\n \"8.The master device of claim 6, wherein the processing circuit is further configured to: send, to the requesting slave device, a response denying the request by sending an acceptable number of words when the requested maximum number of words provided by the requesting slave device is greater than a current word limit.\",\n \"9.The master device of claim 6, wherein the master device sends the response denying the request if the master device does not support slave device to slave device communications.\",\n \"10.A method operational by a master device, comprising: controlling access to a control data bus shared with a plurality of slave devices; receiving a request from a slave device for access to the control data bus for slave device to slave device communication; granting or denying the request from the slave device; and after granting the request, permitting the slave to use the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices, without transmitting the data transferred during the direct data transfer.\",\n \"11.The method of claim 10, wherein the slave device to slave device communication request includes a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"12.The method of claim 11, further comprising: sending, to the requesting slave device, a response granting the request.\",\n \"13.The method of claim 12, further comprising: monitoring the control data bus to detect an end of slave device to slave device communications; and regaining control of the control data bus after an end of slave device to slave device communications is detected.\",\n \"14.The method of claim 11, further comprising: sending, to the requesting slave device, a response denying the request.\",\n \"15.The method of claim 14, further comprising: receiving a request from the requesting slave device to have the master device transfer a certain amount of information between the requesting slave device and the another slave device; and transferring data between the requested information between the requesting slave device and the another slave device.\",\n \"16.The method of claim 14, wherein the response denying the request includes an acceptable number of words that is less than the requested maximum number of words.\",\n \"17.A slave device, comprising: a bus interface circuit to couple to a control data bus shared with a plurality of slave devices and a master device; and a processing circuit coupled to the bus interface circuit and configured to: send a slave device to slave device communication request over the control data bus to the master device; receive a response granting or denying the request from the master device; and after receiving a response granting the request, use the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices in which data is transferred between the slave device and another slave device without being transmitted by the master device.\",\n \"18.The slave device of claim 17, wherein the communication request includes a requested maximum number of words to be transmitted by the slave device to another slave device over the control data bus.\",\n \"19.The slave device of claim 18, wherein the processing circuit is further configured to: receive a response denying the request from the master device.\",\n \"20.The slave device of claim 19, wherein the response includes an otherwise acceptable number of words from the master device.\",\n \"21.The slave device of claim 20, wherein the processing circuit is further configured to: send a new slave device to slave device communication request to the master device, wherein the new slave device to slave device communication request includes a new requested maximum number of words that is less than or equal to the acceptable number of words.\",\n \"22.The slave device of claim 19, wherein the processing circuit is further configured to: send a new request to have the master device transfer a certain amount of information between the requesting slave device and the another slave device.\",\n \"23.The slave device of claim 19, wherein the processing circuit is further configured to either: resend the same slave device to slave device communication request, with the same maximum number of words, to the master device at a later time; or send a new slave device to slave device communication request with a second word limit that is less than the previous maximum word limit requested but greater than an acceptable number of words identified by the master device in its denial of the initial request.\",\n \"24.The slave device of claim 19, wherein the processing circuit is further configured to: send a master request to the master device to transfer control of the control data bus to the requesting slave device; operate as new master of the control data bus if the master request is granted by the master device; and send a desired amount of data words to another slave device.\",\n \"25.The slave device of claim 17, wherein the processing circuit is further configured to: receive the response granting the request; and send a slave device to slave device communication to the control data bus.\",\n \"26.The slave device of claim 17, wherein the slave device to slave device communication is limited to an acceptable number of words approved by the master device.\",\n \"27.A method operational on a slave device coupled to a control data bus shared with a plurality of slave devices and a master device, comprising: sending a slave device to slave device communication request over the control data bus to the master device; receiving a response granting or denying the request from the master device; and after receiving a response granting the request, using the control data bus for direct data transfer between the slave device and another slave device of the plurality of slave devices in which data is transferred between the slave device and another slave device without being transmitted by the master device.\",\n \"28.The method of claim 27, wherein the slave device to slave device communication request includes a requested number of words to be transferred by the slave device to another device over the control data bus.\",\n \"29.The method of claim 27, further comprising: receiving the response granting the request; and sending a slave device to slave device communication to the control data bus.\",\n \"30.The method of claim 29, wherein the slave device to slave device communication is limited to an acceptable number of words approved by the master device.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>I2C (also referred to as I 2 C) is a multi-master serial single-ended control data bus used for attaching low-speed peripherals to a motherboard, embedded system, cellphone, or other electronic devices.\",\n \"The I2C control data bus includes a clock (SCL) and data (SDA) lines with 7-bit addressing.\",\n \"The control data bus has two roles for nodes: master and slave.\",\n \"A master node is a node that generates the clock and initiates communication with slave nodes.\",\n \"A slave node is a node that receives the clock and responds when addressed by the master.\",\n \"The I2C control data bus is a multi-master control data bus which means any number of master nodes can be present.\",\n \"Additionally, master and slave roles may be changed between messages.\",\n \"I2C defines basic types of messages, each of which begins with a START and ends with a STOP.\",\n \"In this context of a camera implementation, unidirectional transmissions may be used to capture an image from a sensor and transmit such image data to memory in a baseband processor, while control data may be exchanged between the baseband processor and the sensor as well as other peripheral devices.\",\n \"In one example, a Camera Control Interface (CCI) protocol may be used for such control data between the baseband processor and the image sensor (and/or one or more slave nodes).\",\n \"In one example, the CCI protocol may be implemented over an I2C serial control data bus between the image sensor and the baseband processor.\",\n \"Master devices control access to the control data bus.\",\n \"While some slave devices may have the capability of switching to a master mode of operation, other slave devices cannot operate in the master mode.\",\n \"One major distinction between a slave-only slave device versus a master-capable slave device is the ability to receive (e.g., handle) interrupts on an interrupt request line (IRQ).\",\n \"The slave-only slave devices can cause/send interrupts but cannot handle such interrupts.\",\n \"Therefore, because interrupt handling is extremely important, heretofore slave devices cannot communicate directly with other slave devices.\",\n \"Accordingly, it would be desirable to enable slave device to slave device communications over a shared data bus controlled by a master device.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>A master device is provided comprising a bus interface circuit and a processing circuit.\",\n \"The bus interface circuit may serve to couple to a control data bus shared with a plurality of slave devices.\",\n \"The processing circuit may be coupled to the bus interface and configured to: (a) control access to the control data bus by the plurality of slave devices; and/or (b) receive, a slave device to slave device communication request, from a slave device requesting access to the control data bus.\",\n \"In one example, the slave device to slave device communication request may include a requested number of words to be transferred by the requesting slave device to another slave device.\",\n \"In another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"The processing circuit may be further configured to send, to the requesting slave device, a response granting the request.\",\n \"The response grants the request by including a word limit number in the response that is equal to or greater than a maximum number of words specified in the request.\",\n \"The processing circuit may be further configured to: (a) monitor the control data bus to detect an end of slave device to slave device communications; and/or (b) regain control of the control data bus after an end of slave device to slave device communications is detected.\",\n \"In yet another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"The processing circuit may be further configured to send, to the requesting slave device, a response denying the request.\",\n \"The slave device to slave device communication request may be denied if the requested maximum number of words is greater than a current word limit of the master device.\",\n \"The processing circuit may be further configured to send, to the requesting slave device, a response denying the request by sending an acceptable number of words when a requested maximum number of words provided by the requesting slave device is greater than a current word limit.\",\n \"The master device may also send the response denying the request if the master device does not support slave device to slave device communications.\",\n \"A method operational by a master device is provided, comprising: (a) controlling access to a control data bus shared with a plurality of slave devices; and/or (b) receiving a slave device to slave device communication request from a slave device requesting access to the control data bus.\",\n \"The slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"The method may further comprise: (a) sending, to the requesting slave device, a response granting the request; (b) monitoring the control data bus to detect an end of slave device to slave device communications; and/or (c) regaining control of the control data bus after an end of slave device to slave device communications is detected.\",\n \"The method may further comprise sending, to the requesting slave device, a response denying the request.\",\n \"In one example, in response to the request denial, the method may further include: (a) receiving a request from the requesting slave device to have the master device transfer a certain amount of information between the requesting slave device and the another slave device; and/or (b) transferring data between the requested information between the requesting slave device and the another slave device.\",\n \"In another example, the response denying the request may include an acceptable number of words that is less than the requested maximum number of words.\",\n \"A slave device, comprising a bus interface circuit and a processing circuit.\",\n \"The bus interface circuit may serve to couple the slave device to a control data bus shared with a plurality of slave devices and at least one master device.\",\n \"The processing circuit may be coupled to the bus interface circuit and configured to send a slave device to slave device communication request from the slave device to the master device over the control data bus.\",\n \"The communication request may include a requested maximum number of words to be transmitted by the slave device to another slave device over the control data bus.\",\n \"In one example, the processing circuit may be further configured to receive a response denying the request from the master device.\",\n \"The denial response may include an otherwise acceptable number of words from the master device.\",\n \"In another approach to a denial response, the processing circuit may be further configured to send a new slave device to slave device communication request to the master device, wherein the new slave device to slave device communication request includes a new requested maximum number of words that is less than or equal to the received acceptable number of words.\",\n \"In yet another alternative approach to a denial response, the processing circuit may be further configured to send a new request to have the master device transfer a certain amount of information between the requesting slave device and the another slave device.\",\n \"In yet another alternative approach to a denial response, the processing circuit may be further configured to either: (a) resend the same slave device to slave device communication request, with the same maximum number of words, to the master device at a later time; or (b) send a new slave device to slave device communication request with a second word limit that is less than the previous maximum word limit requested but greater than an acceptable number of words identified by the master device in its denial of the initial request.\",\n \"In yet another alternative approach to a denial response, the processing circuit may be further configured to: (a) send a master request to the master device to transfer control of the control data bus to the requesting slave device; (b) operate as new master of the control data bus if the master request is granted by the master device; and/or (c) send a desired amount of data words to another slave device.\",\n \"In another example, the processing circuit may be further configured to: (a) receive a response granting the request; and/or (b) send a slave device to slave device communication to the control data bus.\",\n \"The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.\",\n \"According to another aspect, a method operational on a slave device is provided, comprising: (a) coupling the slave device to a control data bus shared with a plurality of slave devices and at least one master device; and/or (b) sending a slave device to slave device communication request from the slave device to the master device over the control data bus.\",\n \"The slave device to slave device communication request may include a requested number of words to be transferred by the slave device to another device over the control data bus.\",\n \"In one example, the method may further comprise: (a) receiving a response granting the request; and/or (b) sending a slave device to slave device communication to the control data bus.\",\n \"The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS The present Application for patent is a divisional of U.S. patent application Ser.\",\n \"No.\",\n \"14/507,179, entitled “Camera Control Interface Slave Device to Slave Device Communication” filed Oct. 6, 2014, which claims priority to now-expired U.S.\",\n \"Provisional Patent Application No.\",\n \"61/887,895, entitled “Camera Control Interface Slave Device to Slave Device Communication” filed Oct. 7, 2013, which applications are assigned to the assignee hereof and are hereby expressly incorporated by reference herein.\",\n \"FIELD The present disclosure pertains to enabling operations over a shared control data bus and, more particularly, to communication of data from one slave device to another slave device over a multi-wire data and/or clock control data bus.\",\n \"BACKGROUND I2C (also referred to as I2C) is a multi-master serial single-ended control data bus used for attaching low-speed peripherals to a motherboard, embedded system, cellphone, or other electronic devices.\",\n \"The I2C control data bus includes a clock (SCL) and data (SDA) lines with 7-bit addressing.\",\n \"The control data bus has two roles for nodes: master and slave.\",\n \"A master node is a node that generates the clock and initiates communication with slave nodes.\",\n \"A slave node is a node that receives the clock and responds when addressed by the master.\",\n \"The I2C control data bus is a multi-master control data bus which means any number of master nodes can be present.\",\n \"Additionally, master and slave roles may be changed between messages.\",\n \"I2C defines basic types of messages, each of which begins with a START and ends with a STOP.\",\n \"In this context of a camera implementation, unidirectional transmissions may be used to capture an image from a sensor and transmit such image data to memory in a baseband processor, while control data may be exchanged between the baseband processor and the sensor as well as other peripheral devices.\",\n \"In one example, a Camera Control Interface (CCI) protocol may be used for such control data between the baseband processor and the image sensor (and/or one or more slave nodes).\",\n \"In one example, the CCI protocol may be implemented over an I2C serial control data bus between the image sensor and the baseband processor.\",\n \"Master devices control access to the control data bus.\",\n \"While some slave devices may have the capability of switching to a master mode of operation, other slave devices cannot operate in the master mode.\",\n \"One major distinction between a slave-only slave device versus a master-capable slave device is the ability to receive (e.g., handle) interrupts on an interrupt request line (IRQ).\",\n \"The slave-only slave devices can cause/send interrupts but cannot handle such interrupts.\",\n \"Therefore, because interrupt handling is extremely important, heretofore slave devices cannot communicate directly with other slave devices.\",\n \"Accordingly, it would be desirable to enable slave device to slave device communications over a shared data bus controlled by a master device.\",\n \"SUMMARY A master device is provided comprising a bus interface circuit and a processing circuit.\",\n \"The bus interface circuit may serve to couple to a control data bus shared with a plurality of slave devices.\",\n \"The processing circuit may be coupled to the bus interface and configured to: (a) control access to the control data bus by the plurality of slave devices; and/or (b) receive, a slave device to slave device communication request, from a slave device requesting access to the control data bus.\",\n \"In one example, the slave device to slave device communication request may include a requested number of words to be transferred by the requesting slave device to another slave device.\",\n \"In another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"The processing circuit may be further configured to send, to the requesting slave device, a response granting the request.\",\n \"The response grants the request by including a word limit number in the response that is equal to or greater than a maximum number of words specified in the request.\",\n \"The processing circuit may be further configured to: (a) monitor the control data bus to detect an end of slave device to slave device communications; and/or (b) regain control of the control data bus after an end of slave device to slave device communications is detected.\",\n \"In yet another example, the slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"The processing circuit may be further configured to send, to the requesting slave device, a response denying the request.\",\n \"The slave device to slave device communication request may be denied if the requested maximum number of words is greater than a current word limit of the master device.\",\n \"The processing circuit may be further configured to send, to the requesting slave device, a response denying the request by sending an acceptable number of words when a requested maximum number of words provided by the requesting slave device is greater than a current word limit.\",\n \"The master device may also send the response denying the request if the master device does not support slave device to slave device communications.\",\n \"A method operational by a master device is provided, comprising: (a) controlling access to a control data bus shared with a plurality of slave devices; and/or (b) receiving a slave device to slave device communication request from a slave device requesting access to the control data bus.\",\n \"The slave device to slave device communication request may include a requested maximum number of words to be transferred from the requesting slave device to another slave device over the control data bus.\",\n \"The method may further comprise: (a) sending, to the requesting slave device, a response granting the request; (b) monitoring the control data bus to detect an end of slave device to slave device communications; and/or (c) regaining control of the control data bus after an end of slave device to slave device communications is detected.\",\n \"The method may further comprise sending, to the requesting slave device, a response denying the request.\",\n \"In one example, in response to the request denial, the method may further include: (a) receiving a request from the requesting slave device to have the master device transfer a certain amount of information between the requesting slave device and the another slave device; and/or (b) transferring data between the requested information between the requesting slave device and the another slave device.\",\n \"In another example, the response denying the request may include an acceptable number of words that is less than the requested maximum number of words.\",\n \"A slave device, comprising a bus interface circuit and a processing circuit.\",\n \"The bus interface circuit may serve to couple the slave device to a control data bus shared with a plurality of slave devices and at least one master device.\",\n \"The processing circuit may be coupled to the bus interface circuit and configured to send a slave device to slave device communication request from the slave device to the master device over the control data bus.\",\n \"The communication request may include a requested maximum number of words to be transmitted by the slave device to another slave device over the control data bus.\",\n \"In one example, the processing circuit may be further configured to receive a response denying the request from the master device.\",\n \"The denial response may include an otherwise acceptable number of words from the master device.\",\n \"In another approach to a denial response, the processing circuit may be further configured to send a new slave device to slave device communication request to the master device, wherein the new slave device to slave device communication request includes a new requested maximum number of words that is less than or equal to the received acceptable number of words.\",\n \"In yet another alternative approach to a denial response, the processing circuit may be further configured to send a new request to have the master device transfer a certain amount of information between the requesting slave device and the another slave device.\",\n \"In yet another alternative approach to a denial response, the processing circuit may be further configured to either: (a) resend the same slave device to slave device communication request, with the same maximum number of words, to the master device at a later time; or (b) send a new slave device to slave device communication request with a second word limit that is less than the previous maximum word limit requested but greater than an acceptable number of words identified by the master device in its denial of the initial request.\",\n \"In yet another alternative approach to a denial response, the processing circuit may be further configured to: (a) send a master request to the master device to transfer control of the control data bus to the requesting slave device; (b) operate as new master of the control data bus if the master request is granted by the master device; and/or (c) send a desired amount of data words to another slave device.\",\n \"In another example, the processing circuit may be further configured to: (a) receive a response granting the request; and/or (b) send a slave device to slave device communication to the control data bus.\",\n \"The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.\",\n \"According to another aspect, a method operational on a slave device is provided, comprising: (a) coupling the slave device to a control data bus shared with a plurality of slave devices and at least one master device; and/or (b) sending a slave device to slave device communication request from the slave device to the master device over the control data bus.\",\n \"The slave device to slave device communication request may include a requested number of words to be transferred by the slave device to another device over the control data bus.\",\n \"In one example, the method may further comprise: (a) receiving a response granting the request; and/or (b) sending a slave device to slave device communication to the control data bus.\",\n \"The slave device to slave device communication may be limited to an acceptable number of words approved by the master device.\",\n \"SUMMARY OF FIGURES Various features, nature, and advantages may become apparent from the detailed description set forth below when taken in conjunction with the drawings in which like reference characters identify correspondingly throughout.\",\n \"FIG.\",\n \"1 is a block diagram illustrating an exemplary device having a baseband processor and an image sensor and implementing an image data bus and a multi-mode control data bus.\",\n \"FIG.\",\n \"2 illustrates an exemplary slave to slave communication process.\",\n \"FIG.\",\n \"3 conceptually illustrates an exemplary write data word.\",\n \"FIG.\",\n \"4 is a block diagram illustrating an exemplary method for transcoding of data bits into sequential symbols at a transmitter to embed a clock signal within the sequential symbols.\",\n \"FIG.\",\n \"5 illustrates an exemplary conversion between transition numbers and sequential symbols.\",\n \"FIG.\",\n \"6 illustrates an exemplary conversion from bits to transition numbers at a transmitter and then from transition numbers to bits at a receiver.\",\n \"FIG.\",\n \"7 illustrates a general example of converting a ternary number (base-3 number) to a binary number, where each T in {T11, T10, .\",\n \".\",\n \".\",\n \"T2, T1, T0} is a symbol transition number.\",\n \"FIG.\",\n \"8 illustrates an exemplary method for converting a binary number (bits) to a 12 digit ternary number (base-3 number).\",\n \"FIG.\",\n \"9 illustrates an example of one possible implementation of the division and the modulo operations of FIG.\",\n \"8, which may be synthesizable by any commercial synthesis tools.\",\n \"FIG.\",\n \"10 illustrates an example of a 20-bit region comprising a 19 bit data region (e.g., bits 0-18) and an additional 20th bit region (e.g., bit 19).\",\n \"FIG.\",\n \"11 illustrates that besides the bit 19 being set for numbers 2221_2201_20023 to 2222_2222_22223, that range of numbers can be subdivided into six sections.\",\n \"FIG.\",\n \"12 illustrates an exemplary mapping of a portion of the Bit 19 mapping of FIG.\",\n \"11.FIG.\",\n \"13 conceptually illustrates a sequence of transmissions over a control data bus that may be performed for a slave device to slave device communication.\",\n \"FIG.\",\n \"14 conceptually illustrates an exemplary slave to slave transfer request.\",\n \"FIG.\",\n \"15 conceptually illustrates a grant command for a slave device to slave device communication protocol.\",\n \"FIG.\",\n \"16 conceptually illustrates details of a grant command for a slave device to slave device transfer.\",\n \"FIG.\",\n \"17 is a block diagram illustrating an exemplary master device adapted for slave device to slave device communication.\",\n \"FIG.\",\n \"18 illustrates a method operational on a master device to facilitate slave device to slave device communication.\",\n \"FIG.\",\n \"19 is a block diagram illustrating an exemplary slave device adapted for slave device to slave device communication.\",\n \"FIG.\",\n \"20 illustrates a method operational on a slave device to perform slave device to slave device communication.\",\n \"DETAILED DESCRIPTION In the following description, specific details are given to provide a thorough understanding of the embodiments.\",\n \"However, it will be understood by one of ordinary skill in the art that the embodiments may be practiced without these specific details.\",\n \"For example, circuits may be shown in block diagrams in order not to obscure the embodiments in unnecessary detail.\",\n \"In other instances, well-known circuits, structures, and techniques may not be shown in detail in order not to obscure the embodiments.\",\n \"Overview A first feature provides for direct slave device to slave device communications over a shared control data bus managed by a master device.\",\n \"A first slave device wishing to communicate with a second slave device may make a slave device to slave device communication request to the master device.\",\n \"The request may include a requested number of words that the first slave device wishes to send to the second slave device over the shared control data bus managed by the master device.\",\n \"Such communication request may be for a direct transfer (e.g., read or write operations) between the first slave device and the second slave device while bypassing the master device (e.g., the data to be transferred is not managed or sent by the master device).\",\n \"The master device may have a current word limit which may vary based upon operating parameters.\",\n \"For example, the master device may allow different numbers of words to be communicated between the slave devices at different times.\",\n \"For instance, during peak control bus use periods, the slave devices may be limited to communicating with each other using no more than eight word at a time.\",\n \"There may be times when no slave device to slave device communications are allowed (i.e., the current word limit may be zero).\",\n \"Moreover, during periods of low control bus use, the current word limit may be 1024 words, for example.\",\n \"Consequently, the current word limit may be dynamically adjusted by the master device managing the bus and may change over time according to control data bus conditions or for any other desirable reason.\",\n \"Because the word limit may change dynamically, and a slave device may not know what the current word limit is, a second feature provides for communicating to the salve device the current word limit.\",\n \"For example, the first slave device desiring to communicate with the second slave device sends the slave device to slave device communication request which includes a desired number of words to be communicated to the second slave device.\",\n \"When the desired number of words is greater than the current word limit, the master device sends the first slave device a denial message that includes the current word limit such that the slave can request to send a smaller message to the second slave device.\",\n \"The master device receives this request for a smaller message and sends the first slave device a message granting the request.\",\n \"The first slave device then sends the message to the second slave device.\",\n \"The master device monitors the message(s) being sent from the first slave device to the second slave device.\",\n \"Upon detecting an “end” control code being sent from the first slave device to the second slave device, the master device knows the communication has ended and regains control of the control data bus exactly as the master device had done prior to granting the communication request by the first slave device.\",\n \"Additionally, the master device may continuously monitor the IRQ line while the first slave device is communicating with the second slave device.\",\n \"Any interrupt requests occurring during the slave device to slave device communication is handled once the slave device to slave device communication has ended.\",\n \"In one feature, the current word limit is not only variable based upon control data bus traffic but also on recent frequency of interrupt requests.\",\n \"Consequently, during periods of relatively high interrupt requests, the current word limit may be lower than periods of relatively low interrupt requests.\",\n \"Exemplary System for Slave Device to Slave Device Communications FIG.\",\n \"1 is a block diagram illustrating a device 102 having a baseband processor 104 and an image sensor 106 and implementing an image data bus 116 and a multi-mode control data bus 108 in which slave device to slave device communications may be enabled as described herein.\",\n \"While FIG.\",\n \"1 illustrates the multi-mode control data bus 108 within a camera device, it should be clear that this control data bus 108 may be implemented in various different devices and/or systems.\",\n \"Image data may be sent from the image sensor 106 to the baseband processor 104 over an image data bus 116 (e.g., a high speed differential DPHY link).\",\n \"In one example, the control data bus 108 may be an I2C control data bus comprising two wires, a clock line (SCL) and a serial data line (SDA).\",\n \"The clock line SCL may be used to synchronize all data transfers over the I2C bus (control data bus 108).\",\n \"The data line SDA and clock line SCL are coupled to all devices 112, 114, and 118 on the I2C bus (control data bus 108).\",\n \"In this example, control data may be exchanged between the baseband processor 104 and the image sensor 106 as well as other peripheral devices 118 via the control data bus 108.In some implementations, the operating modes over an I2C control data bus may be referred to as a camera control interface (CCI) mode when used for camera applications.\",\n \"According to one aspect, an improved mode of operation may be implemented over the multi-mode control data bus 108 to support camera operation.\",\n \"This improved mode of operation over an I2C control data bus may be referred to as a camera control interface extension (CCIe) mode when used for camera applications.\",\n \"In this example, the baseband processor 104 includes a master device 112 and the image sensor 106 includes a slave device 114, both the master device 112 and slave device 114 may operate according to the camera control interface extension (CCIe) mode over the control data bus 108 without affecting the proper operation of other legacy I2C devices coupled to the control data bus 108.According to one aspect, this improved mode over the control data bus 108 may be implemented without any bridge device between CCIe devices and any legacy I2C slave devices.\",\n \"An interrupt request (IRQ) line/bus 120 couples the slave devices 114 and 118 to the master device 112 allowing the slave devices to notify the master device 112 that the slave device 114 and 118 is in need of attention.\",\n \"In other words, the slave device requesting attention pulls the normally high IRQ line low (grounds the IRQ line 120), and the master device responds by first identifying which slave device requested the interrupt, and second, polling the slave for an IRQ status.\",\n \"For example, the status may be a request to perform a slave device to slave device communication.\",\n \"FIG.\",\n \"2 illustrates an exemplary slave device to slave device communication process.\",\n \"Similar to FIG.\",\n \"1, a device may include a shared control data bus 202 (e.g., CCIe bus) and a separate single-line interrupt bus 204 to which a plurality of devices may be coupled.\",\n \"In this example, an active/current master device 206 may control/manage access to the control data bus 202 by one or more other devices (e.g., non-active master devices and/or slave devices).\",\n \"At a first stage 210, a first slave device 208 may wish to initiate communications with a second slave device 216.To do this, the first slave device may issue/send an interrupt signal 218 over the interrupt bus 204.The interrupt bus 204 may allow any device coupled to the interrupt bus 204 to unilaterally issue an interrupt signal over the interrupt bus 204 so long as no other device is already asserting an interrupt signal already.\",\n \"In response to sensing or receiving the interrupt request signal 218, the master device 206 may attempt to ascertain the requesting slave device (e.g., the device that issued the interrupt signal 218).\",\n \"This may be accomplished by the master device 206 polling or requesting 220 that each slave device to provide its status.\",\n \"In one example, this may be done by the master device 206 requesting 220 the status from each device coupled to control data bus 202 until the first slave device 208 that issued the interrupt signal 218 is identified.\",\n \"At a second stage 212, in response to receiving the status request 220, the first slave device 208 may send its status 222 which would indicate that it issued the interrupt 218 and/or that it wishes to perform a slave device to slave device transfer/communication.\",\n \"Such slave device to slave device communication request may be for a direct data transfer (e.g., read or write operations) between the first slave device 208 and the second slave device 216 while bypassing the master device 206 (e.g., the data to be transferred is not managed or sent by the master device).\",\n \"In one example, the status 222 may be obtained by the master device 206 reading information within status registers for the first slave device 208.Upon identifying the first slave device 208 as the issuer of the interrupt signal and ascertaining the desired service (e.g., use of the control data bus 202 for slave to slave communications), the master device 206 may grant such request by sending a grant indicator 224 via the interrupt bus 204.At that point, the first slave device 208 has been granted a limited permission to use the control data bus 202 for its own communications with another slave device 216.Note that because the master device 206 controls or manages use of the control data bus 202 by all devices coupled to the control data bus 202, there is no chance of conflicting use of the control data bus 202 by another device.\",\n \"In one example, the first slave device 208 is granted use of the control data bus 202 to send or receive a predetermined number of data words.\",\n \"The use of a slave device to slave device communication request is distinct from transferring control of the control data bus 202 to the first slave At a third stage 214, the first slave device 208 recognizes that the master device 206 has granted its request and may perform a slave to slave transfer or communication 224.The slave to slave transfer or communication 224 may read data from or send data to a second slave device 216.After the predetermined number of data words have been sent over the control data bus 202, the master device may regain control and use of the control data bus 202.The first slave device 208 stops transmitting over the control data bus 202 after sending and/or receiving the predetermined number of data words.\",\n \"Exemplary Communication Protocol Supporting Slave Device to Slave Device Communications FIG.\",\n \"3 illustrates an exemplary write data word format.\",\n \"This illustrates that each data word 300 includes a 16-bit data portion 302, a 2-bit control code 304, a 1-bit error detection constant 310, and a spare bit 306.The 16-bit data portion 302 may be segmented into a 14-bit least significant bit portion 312 (located from bits 5 to 18 of the data word 300) and a 2-bit most significant bit portion 308 (located from bits 1 to 2 of the data word 300).\",\n \"The 1-bit error detection constant 310 may serve to detect an error on the data word 300 if the value is anything other than the expected constant (e.g., “0”).\",\n \"In one example, the write data word 300 may be a CCIe write data word.\",\n \"A control code table 314 illustrates various possible values for the control code 304.In one example, multiple write data words can be sent sequentially.\",\n \"If the control code of the current write word is ‘00’ (symbol C0), then the data is to be written to the previous address.\",\n \"If the control code of the current write word is ‘01’ (symbol C1), then the data is to be written to the previous address+1.If the control code of the current write word is ‘10’ (symbol E), this indicates an end of frame and the next word may be a slave device identifier (SID) or an Exit code.\",\n \"The data word 300 may also have a spare bit 306 (e.g., bit 19, also referred to as 20th bit) that may be used to transmit commands and other information between a master device and one or more slave devices.\",\n \"The spare bit 306 (e.g., bit 19) may be used to encode commands between devices coupled to the control data bus 108.A spare bit data region that may be defined by the use of this spare bit 306 (e.g., bit 19, also referred to as 20th bit) is further illustrated and discussed in FIGS.\",\n \"10, 11, and 12.FIG.\",\n \"4 is a block diagram illustrating an exemplary method for transcoding of data bits into sequential symbols at a transmitter to embed a clock signal within the sequential symbols.\",\n \"At the transmitter 402, a sequence of data bits 404 are converted into a ternary (base 3) number (e.g., where individual digits of the ternary number are a “transition number”), and the ternary numbers are converted into sequential symbols which are transmitted over a control data bus that includes a clock line SCL 412 and a data line SDA 414.In one example, an original 20-bits 404 of binary data is input to a bit-to-transition number converter block 408 to be converted to a 12-digits ternary number 409.Each digit of a 12-digits ternary number may represent a “transition number”.\",\n \"Two consecutive digits of a transition number may be the same digit value.\",\n \"Each digit of a transition number is converted into a sequential symbol at a transition-to-symbol block 410 such that no two consecutive sequential symbols have the same value.\",\n \"Because a transition (e.g., change) is guaranteed at every sequential symbol, such sequential symbol transition may serve to embed a clock signal.\",\n \"Each sequential symbol 416 is then sent over a two wire physical link (e.g., I2C control data bus comprising a SCL line 412 and a SDA line 414).\",\n \"At a receiver 420 the process is reversed to convert the sequential symbols back to bits and, in the process, a clock signal is extracted from the sequential symbol transition.\",\n \"The receiver 420 receives the sequential symbols 422 over the two wire physical link (e.g., an I2C control data bus comprising a SCL line 424 and a SDA line 426).\",\n \"The received sequential symbols 422 are input into a clock-data recovery (CDR) block 428 to recover a clock timing and sample the sequential symbols (S).\",\n \"A symbol-to-transition number converter block 430 then converts each sequential symbol to a transition number, where each transition number represents a digit of a ternary number.\",\n \"Then, a transition number-to-bits converter 432 converts twelve (12) transition numbers (i.e., a ternary number) to restore twenty (20) bits of original data from the 12 digit ternary number.\",\n \"The technique illustrated herein may be used to increase the link rate of a control data bus 108 (FIG.\",\n \"1) beyond what the I2C standard control data bus provides and is referred hereto as CCIe mode.\",\n \"In one example, a master node/device and/or a slave node/device coupled to the control data bus 108 may implement transmitters and/or receivers that embed a clock signal within sequential symbol changes/transitions (as illustrated in FIG.\",\n \"5) in order to achieve higher bit rates over the same control data bus than is possible using a standard I2C control data bus.\",\n \"FIG.\",\n \"5 illustrates an exemplary conversion between transition numbers 502 and sequential symbols 504.An individual digit of ternary number, base-3 number, also referred to as a transition number, can have one of the three (3) possible digits or states, 0, 1, or 2.While the same digit may appear in two consecutive digits of the ternary number, no two consecutive sequential symbols have the same value.\",\n \"The conversion between a transition number and a sequential symbol guarantees that the sequential symbol always changes (from sequential symbol to sequential symbol) even if consecutive transition numbers are the same.\",\n \"In one example, the conversion function adds the transition number (e.g., digit of a ternary number) plus 1 to the previous raw sequential symbol value.\",\n \"If the addition results in a number larger than 3, it rolls over from 0, then the result becomes the state number or value for the current sequential symbol.\",\n \"In a first cycle 506, a previous sequential symbol (Ps) is 1 when a first transition number (Ta) 1 is input, so the first transition number 1 plus 1 is added to the previous sequential symbol (Ps), and the resulting current sequential symbol (Cs) of 3 becomes the current sequential symbol that is sent to the physical link.\",\n \"In a second (next) cycle 508, a second transition number (Tb) of 0 is input, and the second transition number 0 plus 1 is added to the previous sequential symbol (Ps) of 3.Since the result of the addition (0+1+3) equals 4, is larger than 3, the rolled over number 0 becomes the current sequential symbol (Cs).\",\n \"In a third cycle 510, a third transition number (Ta) of 0 is input.\",\n \"The conversion logic adds the third transition number 0 plus 1 to the previous sequential symbol (Ps) 0 to generate current sequential symbol (Cs) 1.In a fourth cycle 512, a fourth transition number (Td) of 2 is input.\",\n \"The conversion logic adds the fourth transition number (Td) 2 plus 1 to the previous symbol (Ps) 1 to generate current sequential symbol (Cs) 0 (since the result of the addition, 4, is larger than 3, the rolled over number 0 becomes the current sequential symbol).\",\n \"Consequently, even if two consecutive ternary digits Tb and Tc have the same number, this conversion guarantees that two consecutive sequential symbols have different state values.\",\n \"Because of this conversion, the guaranteed sequential symbol change or transition in the sequence of symbols 504 may serve to embed a clock signal, thereby freeing the clock line SCL in an I2C control data bus for data transmissions.\",\n \"Note that while this example of transition number to sequential number conversions adds a guaranteed number “1” to increment between consecutive sequential symbols, other values may be used in other implementations to guarantee a transition or change between sequential symbols.\",\n \"Referring again to FIG.\",\n \"4, at the receiver 420 the process illustrated in FIG.\",\n \"5 is reversed to convert the sequential symbols back to bits and, in the process, a clock signal is extracted from the symbol transition.\",\n \"The receiver 420 receives sequential symbols 422 over the two wire physical link (e.g., I2C bus comprising a SCL line 424 and a SDA line 426).\",\n \"The received sequential symbols 422 are input into a clock-data recovery (CDR) block 428 to recover a clock timing and sample the transcoded symbols (S).\",\n \"A symbol-to-transition number converter block 430 then converts each sequential symbol to a transition number, i.e., which makes up a digit within a ternary number.\",\n \"Then, a transition number-to-bits converter 32 converts 12 transition numbers (i.e., a ternary number) to restore 20 bits of original data from the 12 digit ternary number.\",\n \"FIG.\",\n \"6 illustrates an exemplary conversion from bits to transition numbers at a transmitter 602 and then from transition numbers to bits at a receiver 604.This example illustrates the transmission for a 2-wire system using 12 transition symbols.\",\n \"The transmitter 602 feeds binary information, Bits, into a “Bits to 12×T” converter 606 to generate 12 symbol transition numbers, T0 to T11.The receiver 604 receives 12 symbols transition numbers, T0 to T11, which are fed into a “12×T to Bits” converter 608 to retrieve the binary information (Bits).\",\n \"If there are r possible symbol transition states per one T, T0 to T11, 12 transitions can send r12 different states.\",\n \"For a 2-wire bus, r=22−1.Consequently, transitions T0 .\",\n \".\",\n \".\",\n \"T11 contain data that can have (22−1)12 different states.\",\n \"Consequently, r=4−1=3 and the number of states=(4−1)̂12=531441.In this example for a 2-wire system using 12 symbol transition numbers, it may be assumed that the possible symbol transitions per one T, r is 3 (=22−1).\",\n \"If the number of symbols in a group is 12, a 12-digit ternary number (base-3 number): T11, T10, .\",\n \".\",\n \".\",\n \", T2, T1, T0, where each Ti: 0, 1, 2, may be used.\",\n \"For example, for {T11, T10, .\",\n \".\",\n \".\",\n \"T2, T1, T0}={2, 1, 0, 0, 1, 1, 0, 1, 0, 1, 2, 1}, the ternary number is: 2100 _ 1101 _ 0121 3 ( Ternary number ) = 2 × 3 11 + 1 × 3 10 + 0 × 3 9 + 0 × 3 8 + 1 × 3 7 + 1 × 3 6 + 0 × 3 5 + 1 × 3 4 + 0 × 3 3 + 1 × 3 2 + 2 × 3 1 + 1 × 3 0 = 416356 ( 0 x 65 A 64 ) .\",\n \"In this manner, 12 transitions numbers may be converted into a number.\",\n \"Note that the ternary number 2100_1101_01213 may be used as the transition number, for example, in FIG.\",\n \"4, so that each transition number (e.g., digit of a ternary number) may be mapped to a sequential symbol and vice versa.\",\n \"The example illustrated in FIG.\",\n \"6 for a 2-wire system and 12 symbol transition numbers may be generalized to a n-wire system and m symbol transition numbers.\",\n \"If there are r possible symbol transition states per one T, T0 to Tm−1, m transitions can send rm different states, i.e., r=2n−1.Consequently, transitions numbers T0 .\",\n \".\",\n \".\",\n \"Tm−1 contain data that can have (2n−1)m different states (e.g., sequential numbers).\",\n \"FIG.\",\n \"7 illustrates a general example of converting a ternary number (base-3 number) to a binary number, where each T in {T11, T10, .\",\n \".\",\n \".\",\n \"T2, T1, T0} is a transition number.\",\n \"FIG.\",\n \"8 illustrates an exemplary method for converting a binary number (bits) to a 12 digit ternary number (base-3 number).\",\n \"Each digit of the ternary number can be calculated by dividing the remainder (result of a modulo operation) from a higher digit calculation with 3 to the power of the digit number, discarding decimal points numbers.\",\n \"FIG.\",\n \"9 illustrates an example of one possible implementation of the division and the modulo operations of FIG.\",\n \"8, which may be synthesizable by any commercial synthesis tools.\",\n \"FIG.\",\n \"10 conceptually illustrates a bit 19 (the 20th bit or “spare bit” 306 in FIG.\",\n \"3) is mostly unused in the CCIe protocol and may be used to enable slave device to slave device communications.\",\n \"More specifically, FIG.\",\n \"10 illustrates the bit 19 (i.e., the 20th bit when the bit count starts at the first bit being bit 0).\",\n \"In other words, as is typical in the computer sciences, counting bit wise begins at zero, and bit 19 is the 20th bit.\",\n \"Here, the bits 0-18 are represented within the ternary number range of 0000_0000_00003 to 2221_2201_20013.The ternary numbers in the range of 2221_2201_20023 to 2222_2222_22223 are unused.\",\n \"Consequently, the ternary number range 2221_2201_20023 to 2222_2222_22223 may be used to represent bit 19 (i.e., 20th bit).\",\n \"In other words, 2221_2201_20023 ternary is 10,000,000,000,000,000,000 binary (0x80000 hexadecimal) and 2222_2222_22223 ternary (0x81BF0) is the largest 12 digit ternary number possible.\",\n \"In one implementation of slave device to slave device communication, the 20th bit (bit 19) is utilized as described herein.\",\n \"FIG.\",\n \"11 conceptually illustrates a CCIe Bit 19 mapping protocol for ternary numbers 0000_0000_00003 to 2222_2222_22223.Note that different types of commands may be encoded within the bit 19 region (e.g., 20th Bit).\",\n \"FIG.\",\n \"12 illustrates an exemplary mapping of a portion of the Bit 19 mapping of FIG.\",\n \"11.FIG.\",\n \"13 conceptually illustrates a sequence of transmissions over a control data bus that may be performed for a slave device to slave device communication.\",\n \"In this example, the slave device to slave device communication protocol utilizes the range from 2222_2112_11223 to 2222_2202_21203.The slave device may send an interrupt signal to the master device over the separate interrupt bus/line.\",\n \"In response to such interrupt signal 1301, the master device may initiate/send an IRQ inquiry 1303 over the control data bus which causes the requesting slave device (S1) to respond 1304.The master device may then read the status 1305 of the requesting slave device (S1) in which a slave-to-slave communication request 1306 is indicated.\",\n \"This slave-to-slave communication request 1306 may include an upper limit (max limit) of words for the requested transmission to another slave device.\",\n \"The number of words may not just be the data portion of the message but rather may include the entire number of words to be transmitted between slave devices, including all overhead and/or envelope information such as a slave identifier (SID), a cyclic redundancy check or checksum (CRC) and/or synchronization (SYNC) information.\",\n \"The master device, after granting 1308 a slave device's request then monitors the slave device's transmissions 1310 and after an end code is sent from the transmitting slave device, the master device resumes control over the control data bus.\",\n \"In other words, the master device monitors the control data bus to detect an end of the granted access, after notifying the slave device that sent the request, that the request is granted.\",\n \"Note that during this slave to slave transmission frame 1310, the requesting slave device may send write commands 1312 and/or read commands 1314 to another slave device.\",\n \"FIG.\",\n \"14 conceptually illustrates an exemplary slave to slave transfer request.\",\n \"This exemplary slave to slave transfer request 1403 may be embedded with a portion 1402 of the bit 19 mapping illustrated in FIGS.\",\n \"11 and 12 (e.g., utilizes the range from 2222_2112_11223 to 2222_2202_21203).\",\n \"One example of the slave to slave transfer request 1403 is defined by a first bit sequence 1404 in conjunction with two tables 1406 and 1408.This slave to slave transfer request 1403 may include the number of words 1408 to be transmitted over the control data bus during the slave to slave transfer.\",\n \"FIG.\",\n \"15 conceptually illustrates a grant command for a slave device to slave device communication protocol.\",\n \"In this example, the slave device to slave device communication protocol 1502 utilizes the range from 2222_2112_11223 to 2222_2202_21203 in sending request grants and/or denials.\",\n \"The master device grants the slave device to slave device communication request by returning to the requesting slave device a message including the same word limit number in the slave device to slave device communication request originally sent from the slave device to the master device.\",\n \"Alternatively, the master device returns a word limit number smaller than the requested number which the slave device understands to be a denial of the original request and a furnishing of a new word limit.\",\n \"When the new (i.e., current) word limit is zero, the slave device knows that slave device to slave device communication is currently disabled and waits a pre-programmed amount of time before making a second request.\",\n \"Else, if the returned current word limit is non-zero, the slave device then breaks the original too long message into a plurality of messages no larger than the returned current word limit.\",\n \"Additionally, in some embodiments, one or more slave devices may have a sleep mode to save energy, and when an intended recipient of a slave device to slave device communication is in the sleep mode, the master device may wake up the sleeping slave device prior to granting a requesting slave device's communication request.\",\n \"Alternatively, the master device may first deny the requesting slave device's communication request by sending a current word limit of zero and then wakes up the sleeping slave.\",\n \"After a pre-programmed period of time, the denied slave device initiates a second request that the master device may now grant.\",\n \"One example of the slave to slave transfer grant 1503 is defined by a first bit sequence 1504 in conjunction with two tables 1506 and 1508.This slave to slave transfer grant 1503 may include the number of words 1508 allowed to be transmitted over the control data bus during the slave to slave transfer.\",\n \"FIG.\",\n \"16 conceptually illustrates details of a grant command for a slave device to slave device transfer.\",\n \"In this example, the master device may send a frame 1602 that includes the requesting slave device's identifier (SID), and extra words 1606.As part of the “address” field, the master device may provide the slave device to slave device grant 1608.Exemplary Master Device and Method Operational Therein FIG.\",\n \"17 is a block diagram illustrating an exemplary master device adapted for slave device to slave device communication.\",\n \"The master device 1702 may include a first communication interface/circuit 1706, a second communication interface/circuit 1708, and/or a processing circuit 1704.The first communication interface/circuit 1706 may serve to couple to a single line interrupt request (IRQ) bus to which a plurality of other devices may be coupled.\",\n \"The second communication interface/circuit 1708 may serve to couple to a control data bus to which the plurality of other devices may also be coupled.\",\n \"The processing circuit 1704 may include various sub-circuits and/or modules to carry out one or more functions described herein.\",\n \"For example, a communication management circuit/module 1710 may be adapted to manage communications over the data bus for all devices coupled to the control data bus based on interrupt signals asserted over the IRQ bus.\",\n \"An IRQ bus monitoring circuit/module 1712 may be adapted to monitor the IRQ bus to ascertain when an IRQ signal has been asserted (e.g., by a slave device).\",\n \"A slave-to-slave communication grant/deny circuit/module 1714 may be adapted to respond (e.g., grant or deny) to a request by a slave device to communicate directly with another slave device over the control data bus.\",\n \"A data bus monitoring circuit/module 1716 may be adapted to allow the master device to monitor the control data bus to ascertain when the slave-to-slave communications have ended.\",\n \"FIG.\",\n \"18 illustrates a method 1800 operational on a master device to facilitate slave device to slave device communication.\",\n \"The method 1800 includes having a master device control/manage access to a control data bus shared with a plurality of slave devices 1802.The master device may receive a slave device to slave device communication/transfer request from a slave device requesting access to the control data bus 1804.The slave device to slave device communication/transfer request may include a maximum number of words that the requesting slave device wishes to transmit over the control date bus.\",\n \"In response to such request, the master device may send, to the requesting slave device, a response denying the request by sending an acceptable maximum number of words when a requested maximum number of words is greater than a current maximum word limit 1806.For instance, the acceptable number of words may be equal to the current maximum word limit (maintained by the master device) and/or it may be a number less than the requested maximum number of words.\",\n \"Alternatively, the master device may send, to the requesting slave device, a response granting the request 1808.Moreover, the master device may monitor the control data bus to detect an end of the granted access to the requesting slave device 1810.Upon detection of an end of slave device to slave device communications over the shared control bus is detected, the master device may regain control of the control data bus.\",\n \"In one example, the response from the master device grants the request by including a word limit number in the response that is equal to or greater than a maximum number of words specified in the request.\",\n \"That is, if the response includes a word limit number that matches the requested maximum number of words specified by the requesting slave device or is greater than the requested maximum number of words, the requesting slave device may recognize this as a grant of the request.\",\n \"According to another aspect, if the master device does not support slave device to slave device communications, the master device respond to the request with a word limit number of zero (0) in its response.\",\n \"Hence, if a master device may be required (e.g., by a protocol standard) to reply to the slave device to slave device communication request, but it may deny the request by including a word limit number of zero (0).\",\n \"For this reason, it may be advisable for master devices that support slave device to slave device communications to reply with a non-zero word limit number in its response.\",\n \"According to one aspect, if the master device denies the slave device to slave device communication request, the slave device may wait some amount of time and then resends the same slave device to slave device communication request (e.g., same desired number of words to be transferred) to the master device over the control data bus.\",\n \"Note that the original denial may have been due to a busy control data bus, so retrying at a later time may result in the request being granted.\",\n \"Additionally, the slave device may retry sending the same request several times before giving up.\",\n \"According to another aspect, if the master device denies the slave device to slave device communication request, the slave device may resend the request but with a lower maximum number of words to be transferred by the requesting slave device over the control data bus.\",\n \"In some implementations, the slave device may breakup a data transfer that is larger than the maximum number of words permitted by the master device into multiple slave device to slave device communication requests.\",\n \"In an alternative approach, if the master device denies the slave device to slave device communication request, but the slave device cannot breakup the data transfer into multiple portions, the slave device may request the master device to take over the data transfer between the requesting slave device and another slave device.\",\n \"Exemplary Slave Device and Method Operational Therein FIG.\",\n \"19 is a block diagram illustrating an exemplary slave device adapted to perform slave device to slave device communication.\",\n \"The slave device 1902 may include a first communication interface/circuit 1906, a second communication interface/circuit 1908, and/or a processing circuit 1904.The first communication interface/circuit 1906 may serve to couple to a single line interrupt request (IRQ) bus to which a plurality of other devices may be coupled.\",\n \"The second communication interface/circuit 1908 may serve to couple to a control data bus to which the plurality of other devices may also be coupled.\",\n \"The processing circuit 1904 may include various sub-circuits and/or modules to carry out one or more functions described herein.\",\n \"For example, an interrupt (IRQ) generator circuit/module 1910 may be adapted to generate an interrupt request over the interrupt bus.\",\n \"A slave-to-slave communication requesting circuit/module 1912 may be adapted to request use of the control data bus from a master device in order to perform slave-to-slave communications directly with another slave device.\",\n \"A slave-to-slave communication transmission circuit/module 1914 may be adapted to send slave-to-slave communications over the control data bus.\",\n \"FIG.\",\n \"20 illustrates a method 2000 operational on a slave device to facilitate slave device to slave device communication.\",\n \"The method 2000 includes coupling the slave device to a control data bus shared with a plurality of slave device and managed by a master device 2002.The slave device may send a slave device to slave device communication request to the master device over the control data bus 2004.In response to the request, the slave device may receive a response denying the request that includes an otherwise acceptable maximum number of words from the master device 2006.If the request is initially denied, the slave device may simply wait an amount of time and resend the same initial request.\",\n \"Alternatively, the slave device may send a new slave device to slave device communication request including a requested maximum number of words less than or equal to the received acceptable maximum number of words to the master device 2008.The slave device may receive a response granting the request from the master device 2010.Upon receiving the grant response from the master device, the slave device may transmit information to a second slave device over the control data bus in, at most, the request number of words 2012.According to one aspect, if the master device denies the slave device to slave device communication request, the slave device may wait some amount of time and then resends the same slave device to slave device communication request (e.g., same desired number of words to be transferred) to the master device over the control data bus.\",\n \"Note that the original denial may have been due to a busy control data bus, so retrying at a later time may result in the request being granted.\",\n \"Additionally, the slave device may retry sending the same request several times before giving up.\",\n \"According to another aspect, if the master device denies the slave device to slave device communication request, the slave device may resend the request but with a lower maximum number of words to be transferred by the requesting slave device over the control data bus.\",\n \"In some implementations, the slave device may breakup a data transfer that is larger than the maximum number of words permitted by the master device into multiple slave device to slave device communication requests.\",\n \"In an alternative approach, if the master device denies the slave device to slave device communication request, but the slave device cannot break up the data transfer into multiple portions, the slave device may request the master device to take over the data transfer between the requesting slave device and another slave device.\",\n \"In yet another approach, if the master device denies the slave device to slave device communication request and the requesting slave device is capable of operating in either master mode or slave mode, the requesting slave device may request to become the master of the shared control data bus in order to transfer the desired number of words.\",\n \"One or more of the components, steps, features, and/or functions illustrated in the Figures may be rearranged and/or combined into a single component, step, feature, or function or embodied in several components, steps, or functions.\",\n \"Additional elements, components, steps, and/or functions may also be added without departing from novel features disclosed herein.\",\n \"The apparatus, devices, and/or components illustrated in the Figures may be configured to perform one or more of the methods, features, or steps described in the Figures.\",\n \"The novel algorithms described herein may also be efficiently implemented in software and/or embedded in hardware.\",\n \"In addition, it is noted that the embodiments may be described as a process that is depicted as a flowchart, a flow diagram, a structure diagram, or a block diagram.\",\n \"Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently.\",\n \"In addition, the order of the operations may be re-arranged.\",\n \"A process is terminated when its operations are completed.\",\n \"A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc.\",\n \"When a process corresponds to a function, its termination corresponds to a return of the function to the calling function or the main function.\",\n \"Moreover, a storage medium may represent one or more devices for storing data, including read-only memory (ROM), random access memory (RAM), magnetic disk storage mediums, optical storage mediums, flash memory devices, and/or other machine-readable mediums for storing information.\",\n \"The term “machine readable medium” includes, but is not limited to portable or fixed storage devices, optical storage devices, wireless channels and various other mediums capable of storing, containing, or carrying instruction(s) and/or data.\",\n \"Furthermore, embodiments may be implemented by hardware, software, firmware, middleware, microcode, or any combination thereof.\",\n \"When implemented in software, firmware, middleware, or microcode, the program code or code segments to perform the necessary tasks may be stored in a machine-readable medium such as a storage medium or other storage(s).\",\n \"A processor may perform the necessary tasks.\",\n \"A code segment may represent a procedure, a function, a subprogram, a program, a routine, a subroutine, a module, a software package, a class, or any combination of instructions, data structures, or program statements.\",\n \"A code segment may be coupled to another code segment or a hardware circuit by passing and/or receiving information, data, arguments, parameters, or memory contents.\",\n \"Information, arguments, parameters, data, etc.\",\n \"may be passed, forwarded, or transmitted via any suitable means including memory sharing, message passing, token passing, network transmission, etc.\",\n \"The various illustrative logical blocks, modules, circuits, elements, and/or components described in connection with the examples disclosed herein may be implemented or performed with a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic component, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein.\",\n \"A general purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine.\",\n \"A processor may also be implemented as a combination of computing components, e.g., a combination of a DSP and a microprocessor, a number of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.\",\n \"The methods or algorithms described in connection with the examples disclosed herein may be embodied directly in hardware, in a software module executable by a processor, or in a combination of both, in the form of processing unit, programming instructions, or other directions, and may be contained in a single device or distributed across multiple devices.\",\n \"A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium known in the art.\",\n \"A storage medium may be coupled to the processor such that the processor can read information from, and write information to, the storage medium.\",\n \"In the alternative, the storage medium may be integral to the processor.\",\n \"Those of skill in the art would further appreciate that the various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both.\",\n \"To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality.\",\n \"Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system.\",\n \"The various features of the invention described herein can be implemented in different systems without departing from the invention.\",\n \"It should be noted that the foregoing embodiments are merely examples and are not to be construed as limiting the invention.\",\n \"The description of the embodiments is intended to be illustrative, and not to limit the scope of the claims.\",\n \"As such, the present teachings can be readily applied to other types of apparatuses and many alternatives, modifications, and variations will be apparent to those skilled in the art.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874739"}}},{"rowIdx":4494680,"cells":{"text":{"kind":"list like","value":[["PHASE SHIFT AND ATTENUATION CIRCUITS FOR USE WITH MULTIPLE-PATH AMPLIFIERS","Embodiments of circuits for use with an amplifier that includes multiple amplifier paths include a first circuit and a second circuit in parallel with the first circuit.","The first circuit includes a first input coupled to a first power divider output, a first output coupled to a first amplifier path of the multiple amplifier paths, and a first adjustable phase shifter and a first attenuator series coupled between the first input and the first output.","The second circuit includes a second input coupled to a second power divider output, a second output coupled to a second amplifier path of the multiple amplifier paths, and a second adjustable phase shifter coupled between the second input and the second output."],["1.An adjustable power splitter circuit comprising: a power divider with a power divider input, a first power divider output, and a second power divider output, wherein the power divider is configured to divide a first radio frequency (RF) input signal received at the power divider input into first and second divided RF signals provided at the first and second power divider outputs, and the power divider is further configured to apply one or more fixed phase shifts to the first divided RF signal, the second divided RF signal, or both the first and second divided RF signals so that the first and second divided RF signals have about a ninety degree phase shift, with respect to each other, at the first and second power divider outputs; a first circuit comprising a first input coupled to the first power divider output and configured to receive the first divided RF signal, a first output configured to provide a first RF output signal, and a first adjustable phase shifter circuit coupled between the first input and the first output, wherein the first adjustable phase shifter circuit is configured to apply a first phase shift to the first divided RF signal; a second circuit in parallel with the first circuit, the second circuit comprising a second input coupled to the second power divider output and configured to receive the second divided RF signal, a second output configured to provide a second RF output signal, and a first variable attenuator circuit coupled between the second input and the second output, wherein the first variable attenuator circuit is configured to apply a first attenuation to the second divided RF signal; and a controller configured to receive data indicating the first phase shift and the first attenuation, and to control, based on the data, application of the first phase shift by the first adjustable phase shifter circuit, and application of the first attenuation by the first variable attenuator circuit.","2.The circuit of claim 1, wherein the first circuit further comprises: a second attenuator circuit coupled in series with the first adjustable phase shifter between the first input and the first output, wherein the first adjustable phase shifter circuit and the second attenuator circuit are separate circuits, and the second attenuator circuit is configured to apply a second attenuation to the first divided RF signal.","3.The circuit of claim 2, wherein: the second attenuator circuit is a second variable attenuator circuit; and the controller is configured to receive data indicating the second attenuation, and to control, based on the data, application of the second attenuation by the second variable attenuator circuit.","4.The circuit of claim 1, wherein the second circuit further comprises: a second phase shifter circuit coupled in series with the first variable attenuator circuit between the second input and the second output, wherein the first variable attenuator circuit and the second phase shifter circuit are separate circuits, and the second phase shifter circuit is configured to apply a second phase shift to the second divided RF signal.","5.The circuit of claim 4, wherein: the second phase shifter circuit is a second adjustable phase shifter circuit; and the controller is configured to receive data indicating the second phase shift, and to control, based on the data, application of the second phase shift by the second adjustable phase shifter circuit.","6.The circuit of claim 1, wherein the first adjustable phase shifter circuit and the first variable attenuator circuit are separately controllable, and wherein each of the first adjustable phase shifter circuit and the first variable attenuator circuit is digitally controlled and has a plurality of states.","7.The circuit of claim 1, further comprising: a third circuit in parallel with the first and second circuits, the third circuit comprising a third input coupled to a third power divider output, a third output, and a second attenuator circuit coupled between the third input and the third output.","8.The circuit of claim 7, wherein the power divider further comprises: the third power divider output, wherein the power divider is configured to divide the RF signal received at the power divider input into three RF signals provided at the first, second, and third power divider outputs.","9.The circuit of claim 1, further comprising: a third circuit in parallel with the first and second circuits, the third circuit comprising a third input coupled to a third power divider output, a third output, and a second phase shifter circuit coupled between the third input and the third output.","10.The circuit of claim 9, wherein the power divider further comprises: the third power divider output, wherein the power divider is configured to divide the RF signal received at the power divider input into three RF signals provided at the first, second, and third power divider outputs.","11.The circuit of claim 1, further comprising: an interface, wherein the controller is configured to receive the data indicating the first phase shift and the first attenuation to be applied via the interface.","12.The circuit of claim 11, wherein the interface is selected from a serial interface and a serial peripheral interface.","13.The circuit of claim 11, wherein the data includes a multiple-bit value that uniquely specifies one of multiple phase shifted states for the first adjustable phase shifter circuit and one of multiple attenuation states for the second attenuator circuit.","14.A Doherty power amplifier comprising: a main amplifier path; a peaking amplifier path; a power divider with a power divider input, a first power divider output, and a second power divider output, wherein the power divider is configured to divide a first radio frequency (RF) input signal received at the power divider input into first and second divided RF signals provided at the first and second power divider outputs, and the power divider is further configured to apply one or more fixed phase shifts to the first divided RF signal, the second divided RF signal, or both the first and second divided RF signals so that the first and second divided RF signals have about a ninety degree phase shift, with respect to each other, at the first and second power divider outputs; a first circuit comprising a first input coupled to the first power divider output and configured to receive the first divided RF signal, a first output configured to provide a first RF output signal, and a first adjustable phase shifter circuit coupled between the first input and the first output, wherein the first adjustable phase shifter circuit is configured to apply a first phase shift to the first divided RF signal; and a second circuit in parallel with the first circuit, the second circuit comprising a second input coupled to the second power divider output and configured to receive the second divided RF signal, a second output configured to provide a second RF output signal, and a first variable attenuator circuit coupled between the second input and the second output, wherein the first variable attenuator circuit is configured to apply a first attenuation to the second divided RF signal.","15.The amplifier of claim 14, further comprising: a controller configured to receive data indicating the first phase shift and the first attenuation, and to control, based on the data, application of the first phase shift by the first adjustable phase shifter circuit, and application of the first attenuation by the first variable attenuator circuit.","16.The amplifier of claim 15, wherein the controller separately controls the first adjustable phase shifter circuit and the first variable attenuator circuit.","17.The amplifier of claim 15, further comprising: a digital data interface, wherein the controller is configured to receive the data indicating the first phase shift and the data indicating the first attenuation via the interface.","18.The amplifier of claim 15, wherein: the first circuit is coupled between the first power divider output and the main amplifier path; and the second circuit is coupled between the second power divider output and the peaking amplifier path.","19.The amplifier of claim 15, wherein: the first circuit is coupled between the first power divider output and the peaking amplifier path; and the second circuit is coupled between the second power divider output and the main amplifier path."],["<SOH> BACKGROUND OF THE INVENTION <EOH>Power splitters or signal splitters or dividers are known.","They are used, as the name suggests, to divide or split a signal into two or more identical signals.","Identical or nearly identical signals can be used in various systems where the same signal is processed in varying manners or the same manner with more than one resultant signal being used in some combination for some purpose.","For example, if signals are subject to the same interferences or distortions a practitioner can start with identical signals and use differential processing and subtract the resultant signals to basically eliminate the common interferences.","As another example, some amplifiers use or start with identical signals and process these signals in distinctly different manners and then combine the resultant signals in some fashion to provide the final amplified signal.","In many of these cases where identical signals are used to begin with, the relative phase of the resultant or resulting processed signals is critical for a successful combination.","Practitioners have used a phase adjustment in one of the signal paths to attempt to address this problem."],["<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The accompanying figures where like reference numerals refer to identical or functionally similar elements throughout the separate views and which together with the detailed description below are incorporated in and form part of the specification, serve to further illustrate various embodiments and to explain various principles and advantages all in accordance with the present invention.","FIG.","1 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more embodiments; FIG.","2 in a representative form, shows a diagram of a power divider and fixed phase shifter in accordance with one or more embodiments, which is suitable for use in the FIG.","1 adjustable power splitter; FIG.","3 depicts a representative diagram of an adjustable attenuator in accordance with one or more embodiments; FIG.","4 depicts a representative diagram of an adjustable phase shifter in accordance with one or more embodiments; FIG.","5-8 show various performance data of one or more embodiments; FIG.","9 shows a flow chart of a method of adjusting a power split signal that may be used in conjunction with the FIG.","1 system in accordance with one or more embodiments; and FIG.","10 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more alternate embodiments.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","15/344,304, filed on Nov. 4, 2016, and issued on Jan. 23, 2018 as U.S. Pat.","No.","9,876,475, which is a continuation of U.S. patent application Ser.","No.","15/184,910, filed on Jun.","16, 2016, and now issued as U.S. Pat.","No.","9,490,755, which is a continuation of U.S. patent application Ser.","No.","14/728,196, filed on Jun.","2, 2015, and now issued as U.S. Pat.","No.","9,374,051, which is a continuation of U.S. patent application Ser.","No.","14/287,139, filed on May 26, 2014, and now issued as U.S. Pat.","No.","9,219,453, which is a continuation of U.S. patent application Ser.","No.","13/959,254, filed on Aug. 5, 2013, and now issued as U.S. Pat.","No.","8,736,347, which is a continuation of U.S. patent application Ser.","No.","13/360,473, filed on Jan. 27, 2012, and now issued as U.S. Pat.","No.","8,514,007.FIELD OF THE INVENTION This invention relates to power or signal splitters in general and more specifically to techniques and apparatus for adjustable power or signal splitting or dividing.","BACKGROUND OF THE INVENTION Power splitters or signal splitters or dividers are known.","They are used, as the name suggests, to divide or split a signal into two or more identical signals.","Identical or nearly identical signals can be used in various systems where the same signal is processed in varying manners or the same manner with more than one resultant signal being used in some combination for some purpose.","For example, if signals are subject to the same interferences or distortions a practitioner can start with identical signals and use differential processing and subtract the resultant signals to basically eliminate the common interferences.","As another example, some amplifiers use or start with identical signals and process these signals in distinctly different manners and then combine the resultant signals in some fashion to provide the final amplified signal.","In many of these cases where identical signals are used to begin with, the relative phase of the resultant or resulting processed signals is critical for a successful combination.","Practitioners have used a phase adjustment in one of the signal paths to attempt to address this problem.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying figures where like reference numerals refer to identical or functionally similar elements throughout the separate views and which together with the detailed description below are incorporated in and form part of the specification, serve to further illustrate various embodiments and to explain various principles and advantages all in accordance with the present invention.","FIG.","1 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more embodiments; FIG.","2 in a representative form, shows a diagram of a power divider and fixed phase shifter in accordance with one or more embodiments, which is suitable for use in the FIG.","1 adjustable power splitter; FIG.","3 depicts a representative diagram of an adjustable attenuator in accordance with one or more embodiments; FIG.","4 depicts a representative diagram of an adjustable phase shifter in accordance with one or more embodiments; FIG.","5-8 show various performance data of one or more embodiments; FIG.","9 shows a flow chart of a method of adjusting a power split signal that may be used in conjunction with the FIG.","1 system in accordance with one or more embodiments; and FIG.","10 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more alternate embodiments.","DETAILED DESCRIPTION In overview, the present disclosure concerns adjustable power splitters and methods therein and uses thereof, e.g., adjustable radio frequency power splitters, and more specifically techniques and apparatus for independently adjusting the signals at each output of the adjustable power splitter so the adjustable power splitter is or can be arranged and constructed for use with a Doherty power amplifier.","More particularly various inventive concepts and principles embodied in methods and apparatus corresponding to adjustable power splitters suitable for use in amplifiers or Doherty amplifiers for improved efficiency, etc.","will be discussed and disclosed.","The instant disclosure is provided to further explain in an enabling fashion the best modes, at the time of the application, of making and using various embodiments in accordance with the present invention.","The disclosure is further offered to enhance an understanding and appreciation for the inventive principles and advantages thereof, rather than to limit in any manner the invention.","The invention is defined solely by the appended claims including any amendments made during the pendency of this application and all equivalents of those claims as issued.","It is further understood that the use of relational terms, if any, such as first and second, top and bottom, and the like are used solely to distinguish one from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions.","Much of the inventive functionality and many of the inventive principles are best implemented with or in integrated circuits (ICs) including possibly application specific ICs or ICs with integrated processing or control or other structures.","It is expected that one of ordinary skill, notwithstanding possibly significant effort and many design choices motivated by, for example, available time, current technology, and economic considerations, when guided by the concepts and principles disclosed herein will be readily capable of generating such ICs and structures with minimal experimentation.","Therefore, in the interest of brevity and minimization of any risk of obscuring the principles and concepts according to the present invention, further discussion of such structures and ICs, if any, will be limited to the essentials with respect to the principles and concepts of the various embodiments.","Referring to FIG.","1, a simplified and representative high level diagram of an adjustable power splitter utilized, e.g., in a Doherty power amplifier system in accordance with one or more embodiments will be briefly discussed and described.","In FIG.","1 as shown, an adjustable power splitter 101 or radio frequency power splitter is coupled to or being utilized with or driving an amplifier, specifically a Doherty amplifier or Doherty power amplifier 103.The adjustable power splitter 101 includes a power divider 105 with an input 107 and a first and second divider output 109, 111.The power divider 105 operates to divide or split a signal at the input 107 into two (or more, as shown in FIG.","10) signals, which are identical or very nearly identical signals with in some embodiments equal power.","This equal power form of power divider is often referred to as a 3 dB divider since the resultant signals are each 3 dB less than the signal at the input.","While the 3 dB divider is typical, other dividers with multiple outputs or outputs with unequal signals could be fashioned and used in some applications.","One or more embodiments of the power divider can be a lumped element circuit including an inductive and a capacitive reactance as will be further discussed below with reference to FIG.","2.Further included in the adjustable radio frequency power splitter 101, as shown in FIG.","1, is a first adjustable phase shifter 113 and in some embodiments a first adjustable attenuator 115, which are series coupled to the first divider output 109 and configured for providing a first power output 117.It will be appreciated that the adjustable phase shifter and adjustable attenuator can be series coupled to each other in any order, i.e., attenuator followed by phase shifter as shown or vice versa.","Further included in the adjustable radio frequency power splitter 101 is a second adjustable phase shifter 119 and in some embodiments a second adjustable attenuator 121, which are series coupled to the second divider output 111 and configured for providing a second power output 123.As noted above the order in which these are series coupled to each other can be changed.","In various embodiments of the adjustable power splitter 101, the first and typically the second adjustable phase shifter 113, 119 are each digitally controlled, e.g., by controller 125 and have a plurality of states.","In one or more embodiments, the first adjustable phase shifter 113 and often the second adjustable phase shifter 119, each have eight phase shifted states.","It will be appreciated that the first and second phase shifter may have different phase shifted states, cover different ranges, and have different steps sizes, although typically they will be essentially the same.","While digitally controlled, the adjustable phase shifters in many embodiments are analog phase shifters.","One or more embodiments of the adjustable phase shifters 113, 119 will be discussed below with reference to FIG.","4.In various embodiments of the adjustable power splitter 101, the first and typically the second adjustable attenuator 115, 121 are each digitally controlled, e.g., by controller 125 and have a plurality of states.","In one or more embodiments, the first adjustable attenuator 115 and often the second adjustable attenuator 121, each have eight attenuation states or attenuation levels.","It will be appreciated that the first and second attenuation may have different attenuation states, cover different attenuation ranges, and have different attenuation steps sizes, although typically they will be essentially the same.","While digitally controlled, the adjustable attenuators in many embodiments are analog attenuators.","One or more embodiments of the adjustable attenuators 115, 121 will be discussed below with reference to FIG.","3.Some embodiments of the adjustable power splitter 101 further include a fixed phase shifter 127 that is configured for adding a fixed phase shift between first and second signals at the, respective, first and second power outputs 117, 123.In some embodiments this can be a fixed and predetermined phase shift, e.g., 90 degrees, added to one signal path, i.e., path between output 109 and power output 117 or path between output 111 and power output 123.In certain applications, e.g., Doherty amplifier 103, a ninety degree phase shift is added to one path in the amplifier and the fixed phase shift can be used to offset this amplifier phase shift.","The fixed phase shift in some embodiments is a phase shift in a direction (negative or positive), e.g., a negative shift λ/8 129, such as a negative forty five degree shift, for the first signal at the first power output 117 and a phase shift in the opposite direction, e.g., a positive shift λ/8 131 such as a positive forty five degree phase shift for the second signal at the second power output 123.Using the forty five degree shifts gives a ninety degree phase shift between the signals at the power outputs 117, 123.The phase shifter 127 or negative shift 129 and positive shift 131 can be lumped element circuits having an inductive and a capacitive reactance as will be further discussed below with reference to FIG.","2.As suggested above, the adjustable power splitter 101 typically further comprises the controller 125 which is configured and arranged to control or for controlling the adjustable phase shifters and adjustable attenuators.","The controller 125 can be provided data via an interface 133, such as a serial interface and in some embodiments this a serial peripheral interface (SPI), which as is known typically includes a data in and out, clock signal, and chip select lines.","Various approaches and variants or combinations of those approaches can be utilized by the controller.","Generally as will be explained below, control of the attenuators or phase shifters amounts to controlling switches, typically solid state or integrated switches such as some form of field effect transistor switch.","Thus the controller can be provided state information for all switches in all attenuators and phase shifters and essentially act as one or more latching buffers with outputs arranged and coupled to ensure that all switches are in the appropriate ON or OFF state.","Alternatively, the controller can be provided in essence an address or two or more addresses, which address(es) uniquely specify a state for each attenuator and phase shifter.","For example if all phase shifters and attenuators are 8 state devices a 3 bit address for each would uniquely specify the proper state and 4 such addresses could be provided to the controller, which would convert each address to the appropriate control signals for each attenuator and phase shifter and latch in these values, etc.","In other embodiments the amount of phase shift and attenuation for each of the four devices could be sent to the controller and it could determine the proper state to realize the desired shifts and attenuations.","The practitioner is free to choose from among these or other approaches or combinations to make and retain the appropriate adjustments to the adjustable attenuators and adjustable phase shifters.","In addition to the adjustable power splitter 101, the radio frequency Doherty power amplifier 103 is shown where this amplifier includes a main amplifier 135 coupled via a matching network or circuit 137 to the first power output 117 and a peaking amplifier 139 coupled by its matching circuit 141 to the second power output 123.As will be appreciated by those of ordinary skill the main and peaking amplifiers are comprised of one or more stages of low level amplification and higher power level amplification.","The main and peaking amplifiers are coupled via, respective, output matching circuits 143, 145 to a Doherty combiner 147, which as is known is configured such that the main amplifier provides the amplification for lower level signals and both amplifiers combine to provide the amplification for high level signals.","This is usually accomplished by, e.g., biasing the main amplifier, such that is operates in a class AB mode and biasing the peaking amplifier such that it operates in a class C mode More complex embodiments are possible, such as is illustrated in FIG.","10, where an adjustable power splitter 1001 has three outputs 1017, 1023, 1025, and the Doherty amplifier 1003 has a main amplifier 1035 and two peaking amplifiers 1039, 1041 with each peaking amplifier biased in different class C operating points.","In one or more of these manners, overall efficiency/linearity of the amplifier can be improved over a wider range of signal levels.","Adjustments to the adjustable attenuators and adjustable phase shifters can be made in an experimental manner by monitoring power drawn by the peaking stage or main stage or both as a function of signal levels and the like.","At certain signal levels the peaking amplifier should begin to operate and amplitude and phase adjustments can be made with this in mind.","FIG.","1 illustrates additional features for the adjustable power splitter with a Doherty amplifier where these features have been discussed above or will be discussed below in further detail.","For example, the first and second adjustable phase shifters and the first and second adjustable attenuators are digitally controlled with each having multiple states, e.g., 8 or more or less states.","The power divider can be a lumped element circuit including one or more inductive reactance and capacitive reactance and other elements.","The lumped element circuit can further include a first lumped element phase shifter configured to provide a negative forty five degree phase shift for a first signal at the first power output and a second lumped element phase shifter configured to provide a positive forty five degree phase shift for a second signal at the second power output.","As noted earlier the adjustable power splitter with Doherty amplifier can also include or comprise a controller for controlling the adjustable phase shifters and adjustable attenuators.","Referring to FIG.","2, a representative diagram of a power divider and fixed phase shifter(s) in accordance with one or more embodiments, which embodiments are suitable for use in the FIG.","1 adjustable power splitter, will be briefly discussed and described.","In FIG.","2 and all ensuing FIGS.","like reference numbers will designate like features from other FIGS.","FIG.","2 illustrates an input or RF input 107 to a power divider 201 which has a first output or divider output 109 and a second output or divider output 111 (I/O numbered same as FIG.","1).","The power divider as illustrated is implemented with one or more lumped element inductive reactances 203, 209 and one or more capacitive reactances 205, 207 as well as a resistive loss or resistor 211.As shown a shunt inductance 203 or inductor is coupled from the input to a reference node (ground) 204.This inductance will operate to reduce power in any low frequency signals at the input.","Two series capacitances 205, 207 or capacitors 205, 207 are coupled from the input to, respectively, the first divider output 109 and the second divider output 111.These capacitances will typically be equal valued for a 3 dB splitter.","A series coupled inductance 209 and resistance 211 is coupled between the first and second divider outputs and operates to balance the signal at these outputs.","The actual values for the inductors and capacitors and resistor will vary in accordance with operating frequencies and operating impedances.","Generally the shunt inductor 203 in combination with capacitor 207 forms a high pass structure which exhibits an impedance transformation between 107 (100 ohms for example) to 111 (50 ohms for example).","Similarly, inductor 203 in combination with capacitor 205 forms a high pass structure which exhibits an impedance transformation between 107 (100 ohms for example) to 109 (50 ohms for example).","Resistor 211 in combination with inductor 209 creates a 50 ohm (nominal) odd-mode impedance at nodes 111 and 109.The combination of the elements is such that nodes 107, 109, and 111 each exhibit an impedance of 50 ohms (for example) and he combination of elements can be further chosen such that and equal or unequal power is split from 107 to 111 and 107 to 109, respectively.","One of ordinary skill can readily and experimentally determine the appropriate values for a given application.","An alternative embodiment for the power splitter could use transmission lines although it is noted that these embodiments may not be as useful (e.g., much larger in physical size) over as broad of a bandwidth as the lumped element embodiments.","FIG.","2 also illustrates an embodiment of the fixed phase shifter in accordance with fixed phase shifter 127 and more specifically two fixed, but opposite direction phase shifters.","One is a negative shift 229 such as a negative forty five degree shift that is coupled to divider output 109 and provides an output that goes to adjustable attenuator 115 (see FIG.","1).","This negative shift 229 corresponds to negative shift 129 of FIG.","1.The negative shift 229 is a lumped element circuit having or implemented with an inductive reactance 233 coupled from divider output 109 to adjustable attenuator 115 and further having an input capacitive reactance 235 coupled from divider output 109 to a reference node (ground) 204 and an output capacitive reactance 237 or capacitor coupled from adjustable attenuator 115 input to the reference node 204.The specific values for the inductors and capacitors will depend on operating impedances and signal frequencies but can be experimentally determined by practitioners without undue experimentation.","The other fixed shift is a positive shift 231, such as a positive forty five degree shift that is coupled to divider output 111 and provides an output that goes to adjustable attenuator 121 (see FIG.","1).","The positive shift 231 corresponds to the positive shift 131 of FIG.","1.The positive shift 231 is a lumped element circuit having an input capacitive reactance 239 coupled from divider output 111 to a common node 240 and an output capacitive reactance 241 or capacitor coupled from the common node 240 to adjustable attenuator 121 input.","Further included is an inductive reactance 233 coupled from the common node 240 to the reference node (ground) 204.The specific values for the inductors and capacitors will depend on operating impedances and signal frequencies but can be experimentally determined by practitioners without undue experimentation.","Referring to FIG.","3, a representative diagram of an adjustable attenuator in accordance with one or more embodiments will be discussed and described.","FIG.","3 shows a representative embodiment of an adjustable attenuator suitable for use in the FIG.","1 adjustable power splitter.","FIG.","3 illustrates an input 301 (analogous to input to adjustable attenuator 115 or 121 in FIG.","1) to a first variable attenuator 303, which provides either 0 db or 2 db of attenuation, where 2 dB is provided when b2 304 is high or equal to 1.The first variable attenuator is a resistive divider with a switch around the divider (not specifically shown).","The control line b2 opens this switch.","The first variable attenuator 303 is coupled to a second variable attenuator 305 which provides an attenuated signal at output 307 (analogous to input to 113, 119 in FIG.","1).","The second variable attenuator is shown in more detail and is arranged and configured to provide 0 dB to 1.5 dB of attenuation in 0.5 dB steps, i.e., 0 dB, 0.5 dB, 1.0 dB, or 1.5 dB of attenuation where these steps or attenuations can be referred to as negative gains (e.g., −0.5 dB gain).","Thus the serial combination of adjustable attenuator 303 and 307 can provide from 0 dB up to 3.5 dB of attenuation depending on control signal states, i.e., step through 0-1.5 dB with attenuator 305 and then bring in 2 dB with attenuator 303 and go through or repeat the steps, 0-3.5 dB, with attenuator 305.Further shown in FIG.","3 is a table 309 of input signals b0, b1, and switch control signals s1-s4 which result from the input signals b0, b1 together with expected attenuation as a function of a particular combination of s1-s4.By observation s1 is the logical OR inverted (NOR) of b0, b1, i.e., high only when both inputs are low and low otherwise.","Similarly s2 is the OR of b0, b1, i.e., high if either input is high.","Further s3 is equal to b0 and s4 is the logical AND of b0, b1, i.e., high only if both inputs are high.","In more detail, the first adjustable attenuator 303 is coupled to a capacitance 311 which will have a near zero impedance for signals of interest and this capacitance is coupled to a resistor 313 which is a relatively high value and is used for biasing purposes.","Supply noise is coupled to ground by capacitor 314.Capacitor 311 is further coupled to switch S1 315, switch S2 317, and resistor 319.When S1 is ON, (s1=1 or high) there will be near zero attenuation as the input signal at capacitor 311 will be coupled via S1 to the output capacitor 321 and thus output 307 since the output capacitor is near zero impedance for signals of interest (see also table, line 1).","When S1 is OFF and S2 is ON (s1=0, s2=1 or high), the input signal at capacitor 311 will be coupled to resistor 323 and from there to the output capacitor 321.The input signal will also be coupled through the series combination of resistor 319 and 324 to the output capacitor 321.Resistors 323 in parallel with the series combination of resistors 319, 324 are chosen to provide an attenuation of 0.5 dB given the operating frequencies and impedances (see table, line 2).","If, in addition to S2 being ON, switch S3 325 is ON (s3=1 or high), the signal at the node between resistors 319, 324 will be coupled via resistor 327 to capacitor 328 and thus ground.","This will increase the attenuation and resistor 327 is selected such that an additional 0.5 dB or a total of 1.0 dB of attenuation is provided with this combination of switches (see table, line 3).","If in addition to S2 and S3, switch S4 331 is ON (s4=1 or high) resistor 333 will be added in parallel with resistor 327 and the signal will be further attenuated.","Resistor 333 is chosen to add a further 0.5 dB for a total of 1.5 dB of attenuation to the signal at the output (see table, line 4).","Those of ordinary skill given a specific application with operating frequencies and impedances can determine the appropriate values of the resistors by calculation or experimentation.","Referring to FIG.","4, a representative diagram of an adjustable phase shifter in accordance with one or more embodiments will be discussed and described.","The adjustable phase shifter illustrated in FIG.","4 is one embodiment of the subject matter of co-pending U.S. patent application Ser.","No.","13/360,119, filed on Jan. 27, 2012, which application is hereby incorporated herein by reference.","FIG.","4 illustrates a high level diagram of a phase shifter or delay line phase shifter with selectable phase shift in accordance with one or more embodiments.","In FIG.","4, an adjustable phase shifter 400 with selectable or variable phase shift is shown in a representative manner.","The phase shifter 400 has an input coming from adjustable attenuator 115 or 121 in FIG.","1 or a signal input for input signals, e.g., radio frequency (RF) signals and an output coupled to divider or divider power outputs 117, 123 or a signal output for phase shifted versions of the input signal, e.g., phase shifted versions of the RF signals.","Between the input and output are one or more switchable phase shifting elements or circuits, including specifically phase shifting elements 401, 411, 421, and possibly additional phase shifting elements or circuits 431 serially coupled as shown.","Generally speaking in many embodiments and as will be further discussed and described below, the switches shown are provided with a pair of single throw switches a, b for each phase shifting element 401, 411, 421.Each of the phase shifting elements can be designed, arranged and configured to provide some predetermined amount of phase shift.","If a practitioner needs to cover a certain range of phase shift and needs a certain resolution for the phase shift it can be advantageous to design the first or one of the phase shifting elements to provide a choice between nominally zero or a minimal phase shift and the smallest phase shift step one needs (i.e., the resolution) with the next or another phase shifting element configured to provide minimal or 2× the smallest step needed.","Thus with two phase shifting elements you can provide a near zero, 1×, 2×, and 3× small step in phase shift by activating different combinations of the a, b switches.","Adding another phase shifting element with a 4× shift, allows 8 states with corresponding 0 to 7× the small step and so on.","The number of phase shifting elements will be determined by the required resolution (step size) and the phase range needed to be covered (number of steps).","For example if you want to cover 49 degrees with a resolution of 7 degrees then 8 states, including 0 will be required and this can be accomplished with 3 phase shifting elements etc.","etc.","In more detail, switchable phase shifting element or circuit 401 (and the other similar phase shifting elements) further comprises a first signal path coupled between the input through a switch 403 or alternatively with switch 405 closed through phase shifting circuit 407 to an output 410.The first signal path, when activated by closing or activating switch 403 or integrated circuit switch, will be providing a near zero phase shift for a signal coupled through the first signal path.","Further included is a second signal path coupled between the input and the output 410 via the phase shifting circuit 407 (switch 405 closed).","The second path is configured for providing a second phase shift for a signal coupled through the second signal path.","Basically switch 403 selects between the first path and the second path or between zero and some phase shift.","Insertion loss is equalized between the first path and the second path by switching in (opening switch 405) a loss circuit, resistor 409, when the first signal path is selected.","The switches 403, 405, 413, 415, 423, and 425, etc.","are controlled by a control circuit, e.g., controller 125 or another controller or latch, which can alternatively be viewed as a portion of the phase shifter with selectable phase shift.","In these embodiments or other embodiments, when the switch or integrated circuit switch 403 is activated (closed or ON) thus selecting the first signal path, the resistive loss circuit or resistor 409 is switched in (switch 405 open or OFF) and is configured or value chosen to equalize the first insertion loss for the first path and the second insertion loss expected when the second signal path is selected (i.e., switch 403 is open and 405 is closed).","Various embodiments of the phase shifting circuit 407 as illustrated in FIG.","4 can further comprise a first reactance or inductor series coupled at a common node to a second reactance or inductor and a shunt circuit coupled from the common node to a reference node, e.g., a ground potential.","The shunt circuit in varying embodiments further comprises a third reactance or capacitor in series with the resistive loss or resistor 409 where the switch or integrated circuit switch 405 is in parallel with the resistor 409.One embodiment uses lumped element inductors and a metal insulator metal capacitor as well as pseudo morphic high electron mobility transistors (pHEMT) for switches.","When the first switch or first integrated circuit switch 403 is closed, ON, or activated it selects the first signal path (provides a short circuit around the second signal path) and when the first switch 403 is open, OFF, or inactivated it deselects (opens) the first signal path and signal is routed via the second signal path and reactive phase shifting or changing circuit 407.When the first switch is closed 403 the second switch 405 will be open thereby adding the resistive loss circuit 409 to the reactive circuit 407.This additional loss when the first signal path is chosen can be selected, i.e., resistor value chosen, by experimental processes to equalize the insertion loss when the first signal path is selected with the insertion loss when the second signal path is selected, thereby removing any relationship between phase shift and insertion loss.","Typically the resistive loss circuit or resistor will be several orders of magnitude larger than the ON resistance of an integrated circuit switch.","The first switch 403 or integrated circuit switch in series with the first signal path and the second switch 405 or integrated circuit switch for switching in the resistive loss circuit 409 are alternatively activated (when 403 is ON or CLOSED, 405 is OFF or OPEN and vice-a-versa).","Similarly the phase shifting element or circuit 411 which can comprise a third switch S2a 413 or integrated circuit switch in series with the third signal path and a fourth switch S2b 415 or integrated circuit switch for the switching in a second resistive loss circuit 419, wherein the third and fourth switch or integrated circuit switch are alternatively activated (when one closed other open).","In some embodiments, the first (and second) resistive loss circuit is a resistor in parallel with the second (and fourth) integrated circuit switch and the first (and second) resistive loss circuit is switched in by opening the second (and fourth) integrated circuit switch, thereby equalizing the first and second (and third and forth) insertion loss.","The control circuit is arranged to control first, second, third and fourth switches.","As suggested above in some embodiments the control circuit is configured to select at least one state from available states of minimal phase shift, a first phase shift, a second phase shift, and a first plus second phase shift by activating one or more of the first, thus second, and third, thus fourth, integrated circuit switches.","To select the states in order (near zero phase shift through first plus second phase shift), switches 403, 413 are ON for near zero, switches 405, 413 are ON for a first shift, switches 403, 415 are ON for a second phase shift, and switches 413, 415 are ON for a first plus second phase shift.","In the above, it is understood that undesignated or unspecified switches are OFF.","As suggested above, each time another switchable phase shifting element or circuit is added, e.g., 421 with switches 423, 425) the number of possible states can double and the range of phase shift for a given step size can therefore double or alternatively for a given range the resolution can double, i.e., step size can be cut in half.","The controller 125 or control circuit in addition to possibly selecting timing for activating switches and decoding inputs can, for many embodiments, by viewed as a register or buffer for storing switch state (ON or OFF) information with one output coupled to each of the switches.","The control circuit can be programmed or loaded via inputs 133.These inputs may simply specify a state for the phase shifter which is then decoded by the control circuit into switch states or the inputs can be the state for each switch or specify how much phase shift is desired with the control circuit then determining an appropriate state.","The inputs can be sent to the control circuit via the serial peripheral interface (SPI).","This is a generally known serial interface as indicated above.","Referring to FIG.","5-8 various experimental data showing assorted performance of one or more embodiments will be discussed and described.","FIG.","5-6 show efficiency and linearity as a function of phase for various attenuator settings where the data was gathered at a power output of 47 dBm from one amplifier and one set of amplifier transistors using an adjustable power splitter.","FIG.","5 specifically shows phase adjustment from zero degrees to approximately 45 degrees on the horizontal axis 501 and plots efficiency percentage on the vertical axis 503 as a function of the phase variation for 8 different attenuator settings 505.These 8 settings are represented by 8 line graphs 507 which is one graph for each 0.5 dB increment in attenuator setting.","As one example, at approximately 40 degrees the second line from the top, i.e., with 3 dB of attenuation, shows approximately 55% efficiency.","FIG.","6 shows linearity as a function of phase adjustment or shift.","The phase shift is shown on the horizontal axis 601 with linearity (adjacent channel power ratio-upper side in dB relative to the carrier) on the vertical graph 603 for 8 different attenuator settings 605.These 8 settings are represented by 8 line graphs 607 which is one graph for each 0.5 dB increment in attenuator setting.","As one example, at approximately 40 degrees the second line from the top, i.e., with 3 dB of attenuation, shows approximately 55 dBc linearity.","Generally, the way to use this data is select the attenuation and phase shift that provides acceptable linearity (55 dBc) and the best efficiency-in this instance approximately 55% FIG.","7-8 show amplifier performance for 20 random combinations of transistors, where these transistors were selected from non average lots.","The random combinations are each inserted into an amplifier fixture and measurements are taken with output power at 47 dBm.","FIG.","7 specifically shows adjacent channel power ratio on the low and high side of the carrier 701 with the measured results shown on the vertical axis 703.Measurements are taken for fixed or nominal phase setting 704 and for an optimized phase setting 705.A typical production specification or limit 706 is shown.","All of the measurements for all of the combinations under each condition are shown in boxes with fixed phase conditions for lower and higher side shown in boxes 707 and optimized phase conditions for lower and higher side shown in boxes 709.By observation many of the combinations were failing the production limit 706 with a fixed or nominal phase setting while all combinations were better than the limits with optimized phase settings.","Furthermore, the median measurement 711 in the fixed phase case was well above the limit and toward one end of the box, whereas the median measurement 713 for the optimized phase case is well within the production limits and much closer to the center of the box.","FIG.","8 shows measured % efficiencies on the vertical axis 801 for the random combinations in a Doherty amplifier using digital pre distortion (DPD) for fixed or nominal phase setting 803 and optimized phase settings 805 with measured efficiencies shown in, respective, boxes 806, 807.By observation % efficiencies have improved by 1 to 3% with an average improvement of approximately 2%.","Referring to FIG.","9, a flow chart of exemplary processes included in a method of adjusting a power split signal or power splitter that can be used in conjunction with the FIG.","1 system in accordance with one or more embodiments will be discussed and described.","It will be appreciated that this method uses many of the inventive concepts and principles discussed in detail above and thus this description will be somewhat in the nature of a summary with various details generally available in the earlier descriptions.","This method can be implemented in one or more of the structures or apparatus described earlier or other similarly configured and arranged structures.","It will be appreciated that the method can be performed as many times as desired or continually performed as needed The method of adjusting a power split signal or power splitter illustrated in FIG.","9 includes splitting 901 an input signal into first and second signals at first and second divider outputs.","This can include using a lumped element circuit including an inductive reactance and a capacitive reactance.","This may also necessitate providing a power divider or splitter with an input and a first and second divider output where the power divider is configured to split an input signal into first and second signals at the first and second divider outputs.","The providing can include providing a lumped element circuit including an inductive reactance and a capacitive reactance.","Also included in the method of FIG.","9 is adjusting 903 a phase shift and attenuation of the first signal to provide a first resultant signal at a first power output; which can include, e.g., using a first adjustable phase shifter and first adjustable attenuator that are each digitally controlled with each having multiple states.","In some embodiments this may include disposing a first adjustable phase shifter and first adjustable attenuator series coupled to the first divider output and arranged and configured to phase shift and attenuate the first signal and provide a first resultant signal at a first power output.","These can each be digitally controlled with each having multiple states, e.g., 8 states.","Next shown is adjusting 905 a phase shift and attenuation of the second signal to provide a second resultant signal at a second power output; which can include, e.g., using a second adjustable phase shifter and second adjustable attenuator that are each digitally controlled with each having multiple states.","This can be accomplished in some instances by disposing a second adjustable phase shifter and second adjustable attenuator series coupled to the second divider output and arranged and configured to phase shift and attenuate the second signal and provide a second resultant signal at a second power output.","Again, these can each be digitally controlled with each having multiple states.","In some embodiments, the method includes providing 907 a fixed phase shift between the first and second resultant signals, which can further comprise, e.g., providing a negative forty five degree shift for the first resultant signal at the first power output and a positive forty five degree phase shift for the second resultant signal at the second power output.","Again disposing a fixed phase shifter arranged and configured to provide a fixed phase shift between signals at the first and second power output, e.g., to provide a negative forty five degree shift for the first resultant signal at the first power output and a positive forty five degree phase shift for the second resultant signal at the second power output.","In most embodiments, the method includes controlling 909 the adjustable phase shifters and adjustable attenuators.","It will be appreciated that the above described functions and adjustable signal or power splitters may be implemented with one or more integrated circuits or hybrid structures or combinations or the like.","The processes, apparatus, and systems, discussed above, and the inventive principles thereof are intended to and can alleviate yield and performance issues caused by prior art techniques.","Using these principles of independent adjustment of phase or signal level or signal attenuation within a power splitter can quickly resolve performance and production yield problems in, e.g., Doherty amplifiers with relatively minor costs and the like.","This disclosure is intended to explain how to fashion and use various embodiments in accordance with the invention rather than to limit the true, intended, and fair scope and spirit thereof.","The foregoing description is not intended to be exhaustive or to limit the invention to the precise form disclosed.","Modifications or variations are possible in light of the above teachings.","The embodiment(s) was chosen and described to provide the best illustration of the principles of the invention and its practical application, and to enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated.","All such modifications and variations are within the scope of the invention as determined by the appended claims, as may be amended during the pendency of this application for patent, and all equivalents thereof, when interpreted in accordance with the breadth to which they are fairly, legally, and equitably entitled."]],"string":"[\n [\n \"PHASE SHIFT AND ATTENUATION CIRCUITS FOR USE WITH MULTIPLE-PATH AMPLIFIERS\",\n \"Embodiments of circuits for use with an amplifier that includes multiple amplifier paths include a first circuit and a second circuit in parallel with the first circuit.\",\n \"The first circuit includes a first input coupled to a first power divider output, a first output coupled to a first amplifier path of the multiple amplifier paths, and a first adjustable phase shifter and a first attenuator series coupled between the first input and the first output.\",\n \"The second circuit includes a second input coupled to a second power divider output, a second output coupled to a second amplifier path of the multiple amplifier paths, and a second adjustable phase shifter coupled between the second input and the second output.\"\n ],\n [\n \"1.An adjustable power splitter circuit comprising: a power divider with a power divider input, a first power divider output, and a second power divider output, wherein the power divider is configured to divide a first radio frequency (RF) input signal received at the power divider input into first and second divided RF signals provided at the first and second power divider outputs, and the power divider is further configured to apply one or more fixed phase shifts to the first divided RF signal, the second divided RF signal, or both the first and second divided RF signals so that the first and second divided RF signals have about a ninety degree phase shift, with respect to each other, at the first and second power divider outputs; a first circuit comprising a first input coupled to the first power divider output and configured to receive the first divided RF signal, a first output configured to provide a first RF output signal, and a first adjustable phase shifter circuit coupled between the first input and the first output, wherein the first adjustable phase shifter circuit is configured to apply a first phase shift to the first divided RF signal; a second circuit in parallel with the first circuit, the second circuit comprising a second input coupled to the second power divider output and configured to receive the second divided RF signal, a second output configured to provide a second RF output signal, and a first variable attenuator circuit coupled between the second input and the second output, wherein the first variable attenuator circuit is configured to apply a first attenuation to the second divided RF signal; and a controller configured to receive data indicating the first phase shift and the first attenuation, and to control, based on the data, application of the first phase shift by the first adjustable phase shifter circuit, and application of the first attenuation by the first variable attenuator circuit.\",\n \"2.The circuit of claim 1, wherein the first circuit further comprises: a second attenuator circuit coupled in series with the first adjustable phase shifter between the first input and the first output, wherein the first adjustable phase shifter circuit and the second attenuator circuit are separate circuits, and the second attenuator circuit is configured to apply a second attenuation to the first divided RF signal.\",\n \"3.The circuit of claim 2, wherein: the second attenuator circuit is a second variable attenuator circuit; and the controller is configured to receive data indicating the second attenuation, and to control, based on the data, application of the second attenuation by the second variable attenuator circuit.\",\n \"4.The circuit of claim 1, wherein the second circuit further comprises: a second phase shifter circuit coupled in series with the first variable attenuator circuit between the second input and the second output, wherein the first variable attenuator circuit and the second phase shifter circuit are separate circuits, and the second phase shifter circuit is configured to apply a second phase shift to the second divided RF signal.\",\n \"5.The circuit of claim 4, wherein: the second phase shifter circuit is a second adjustable phase shifter circuit; and the controller is configured to receive data indicating the second phase shift, and to control, based on the data, application of the second phase shift by the second adjustable phase shifter circuit.\",\n \"6.The circuit of claim 1, wherein the first adjustable phase shifter circuit and the first variable attenuator circuit are separately controllable, and wherein each of the first adjustable phase shifter circuit and the first variable attenuator circuit is digitally controlled and has a plurality of states.\",\n \"7.The circuit of claim 1, further comprising: a third circuit in parallel with the first and second circuits, the third circuit comprising a third input coupled to a third power divider output, a third output, and a second attenuator circuit coupled between the third input and the third output.\",\n \"8.The circuit of claim 7, wherein the power divider further comprises: the third power divider output, wherein the power divider is configured to divide the RF signal received at the power divider input into three RF signals provided at the first, second, and third power divider outputs.\",\n \"9.The circuit of claim 1, further comprising: a third circuit in parallel with the first and second circuits, the third circuit comprising a third input coupled to a third power divider output, a third output, and a second phase shifter circuit coupled between the third input and the third output.\",\n \"10.The circuit of claim 9, wherein the power divider further comprises: the third power divider output, wherein the power divider is configured to divide the RF signal received at the power divider input into three RF signals provided at the first, second, and third power divider outputs.\",\n \"11.The circuit of claim 1, further comprising: an interface, wherein the controller is configured to receive the data indicating the first phase shift and the first attenuation to be applied via the interface.\",\n \"12.The circuit of claim 11, wherein the interface is selected from a serial interface and a serial peripheral interface.\",\n \"13.The circuit of claim 11, wherein the data includes a multiple-bit value that uniquely specifies one of multiple phase shifted states for the first adjustable phase shifter circuit and one of multiple attenuation states for the second attenuator circuit.\",\n \"14.A Doherty power amplifier comprising: a main amplifier path; a peaking amplifier path; a power divider with a power divider input, a first power divider output, and a second power divider output, wherein the power divider is configured to divide a first radio frequency (RF) input signal received at the power divider input into first and second divided RF signals provided at the first and second power divider outputs, and the power divider is further configured to apply one or more fixed phase shifts to the first divided RF signal, the second divided RF signal, or both the first and second divided RF signals so that the first and second divided RF signals have about a ninety degree phase shift, with respect to each other, at the first and second power divider outputs; a first circuit comprising a first input coupled to the first power divider output and configured to receive the first divided RF signal, a first output configured to provide a first RF output signal, and a first adjustable phase shifter circuit coupled between the first input and the first output, wherein the first adjustable phase shifter circuit is configured to apply a first phase shift to the first divided RF signal; and a second circuit in parallel with the first circuit, the second circuit comprising a second input coupled to the second power divider output and configured to receive the second divided RF signal, a second output configured to provide a second RF output signal, and a first variable attenuator circuit coupled between the second input and the second output, wherein the first variable attenuator circuit is configured to apply a first attenuation to the second divided RF signal.\",\n \"15.The amplifier of claim 14, further comprising: a controller configured to receive data indicating the first phase shift and the first attenuation, and to control, based on the data, application of the first phase shift by the first adjustable phase shifter circuit, and application of the first attenuation by the first variable attenuator circuit.\",\n \"16.The amplifier of claim 15, wherein the controller separately controls the first adjustable phase shifter circuit and the first variable attenuator circuit.\",\n \"17.The amplifier of claim 15, further comprising: a digital data interface, wherein the controller is configured to receive the data indicating the first phase shift and the data indicating the first attenuation via the interface.\",\n \"18.The amplifier of claim 15, wherein: the first circuit is coupled between the first power divider output and the main amplifier path; and the second circuit is coupled between the second power divider output and the peaking amplifier path.\",\n \"19.The amplifier of claim 15, wherein: the first circuit is coupled between the first power divider output and the peaking amplifier path; and the second circuit is coupled between the second power divider output and the main amplifier path.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>Power splitters or signal splitters or dividers are known.\",\n \"They are used, as the name suggests, to divide or split a signal into two or more identical signals.\",\n \"Identical or nearly identical signals can be used in various systems where the same signal is processed in varying manners or the same manner with more than one resultant signal being used in some combination for some purpose.\",\n \"For example, if signals are subject to the same interferences or distortions a practitioner can start with identical signals and use differential processing and subtract the resultant signals to basically eliminate the common interferences.\",\n \"As another example, some amplifiers use or start with identical signals and process these signals in distinctly different manners and then combine the resultant signals in some fashion to provide the final amplified signal.\",\n \"In many of these cases where identical signals are used to begin with, the relative phase of the resultant or resulting processed signals is critical for a successful combination.\",\n \"Practitioners have used a phase adjustment in one of the signal paths to attempt to address this problem.\"\n ],\n [\n \"<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The accompanying figures where like reference numerals refer to identical or functionally similar elements throughout the separate views and which together with the detailed description below are incorporated in and form part of the specification, serve to further illustrate various embodiments and to explain various principles and advantages all in accordance with the present invention.\",\n \"FIG.\",\n \"1 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more embodiments; FIG.\",\n \"2 in a representative form, shows a diagram of a power divider and fixed phase shifter in accordance with one or more embodiments, which is suitable for use in the FIG.\",\n \"1 adjustable power splitter; FIG.\",\n \"3 depicts a representative diagram of an adjustable attenuator in accordance with one or more embodiments; FIG.\",\n \"4 depicts a representative diagram of an adjustable phase shifter in accordance with one or more embodiments; FIG.\",\n \"5-8 show various performance data of one or more embodiments; FIG.\",\n \"9 shows a flow chart of a method of adjusting a power split signal that may be used in conjunction with the FIG.\",\n \"1 system in accordance with one or more embodiments; and FIG.\",\n \"10 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more alternate embodiments.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/344,304, filed on Nov. 4, 2016, and issued on Jan. 23, 2018 as U.S. Pat.\",\n \"No.\",\n \"9,876,475, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/184,910, filed on Jun.\",\n \"16, 2016, and now issued as U.S. Pat.\",\n \"No.\",\n \"9,490,755, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/728,196, filed on Jun.\",\n \"2, 2015, and now issued as U.S. Pat.\",\n \"No.\",\n \"9,374,051, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/287,139, filed on May 26, 2014, and now issued as U.S. Pat.\",\n \"No.\",\n \"9,219,453, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"13/959,254, filed on Aug. 5, 2013, and now issued as U.S. Pat.\",\n \"No.\",\n \"8,736,347, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"13/360,473, filed on Jan. 27, 2012, and now issued as U.S. Pat.\",\n \"No.\",\n \"8,514,007.FIELD OF THE INVENTION This invention relates to power or signal splitters in general and more specifically to techniques and apparatus for adjustable power or signal splitting or dividing.\",\n \"BACKGROUND OF THE INVENTION Power splitters or signal splitters or dividers are known.\",\n \"They are used, as the name suggests, to divide or split a signal into two or more identical signals.\",\n \"Identical or nearly identical signals can be used in various systems where the same signal is processed in varying manners or the same manner with more than one resultant signal being used in some combination for some purpose.\",\n \"For example, if signals are subject to the same interferences or distortions a practitioner can start with identical signals and use differential processing and subtract the resultant signals to basically eliminate the common interferences.\",\n \"As another example, some amplifiers use or start with identical signals and process these signals in distinctly different manners and then combine the resultant signals in some fashion to provide the final amplified signal.\",\n \"In many of these cases where identical signals are used to begin with, the relative phase of the resultant or resulting processed signals is critical for a successful combination.\",\n \"Practitioners have used a phase adjustment in one of the signal paths to attempt to address this problem.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying figures where like reference numerals refer to identical or functionally similar elements throughout the separate views and which together with the detailed description below are incorporated in and form part of the specification, serve to further illustrate various embodiments and to explain various principles and advantages all in accordance with the present invention.\",\n \"FIG.\",\n \"1 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more embodiments; FIG.\",\n \"2 in a representative form, shows a diagram of a power divider and fixed phase shifter in accordance with one or more embodiments, which is suitable for use in the FIG.\",\n \"1 adjustable power splitter; FIG.\",\n \"3 depicts a representative diagram of an adjustable attenuator in accordance with one or more embodiments; FIG.\",\n \"4 depicts a representative diagram of an adjustable phase shifter in accordance with one or more embodiments; FIG.\",\n \"5-8 show various performance data of one or more embodiments; FIG.\",\n \"9 shows a flow chart of a method of adjusting a power split signal that may be used in conjunction with the FIG.\",\n \"1 system in accordance with one or more embodiments; and FIG.\",\n \"10 depicts in a simplified and representative form an adjustable power splitter being used in a Doherty power amplifier system in accordance with one or more alternate embodiments.\",\n \"DETAILED DESCRIPTION In overview, the present disclosure concerns adjustable power splitters and methods therein and uses thereof, e.g., adjustable radio frequency power splitters, and more specifically techniques and apparatus for independently adjusting the signals at each output of the adjustable power splitter so the adjustable power splitter is or can be arranged and constructed for use with a Doherty power amplifier.\",\n \"More particularly various inventive concepts and principles embodied in methods and apparatus corresponding to adjustable power splitters suitable for use in amplifiers or Doherty amplifiers for improved efficiency, etc.\",\n \"will be discussed and disclosed.\",\n \"The instant disclosure is provided to further explain in an enabling fashion the best modes, at the time of the application, of making and using various embodiments in accordance with the present invention.\",\n \"The disclosure is further offered to enhance an understanding and appreciation for the inventive principles and advantages thereof, rather than to limit in any manner the invention.\",\n \"The invention is defined solely by the appended claims including any amendments made during the pendency of this application and all equivalents of those claims as issued.\",\n \"It is further understood that the use of relational terms, if any, such as first and second, top and bottom, and the like are used solely to distinguish one from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions.\",\n \"Much of the inventive functionality and many of the inventive principles are best implemented with or in integrated circuits (ICs) including possibly application specific ICs or ICs with integrated processing or control or other structures.\",\n \"It is expected that one of ordinary skill, notwithstanding possibly significant effort and many design choices motivated by, for example, available time, current technology, and economic considerations, when guided by the concepts and principles disclosed herein will be readily capable of generating such ICs and structures with minimal experimentation.\",\n \"Therefore, in the interest of brevity and minimization of any risk of obscuring the principles and concepts according to the present invention, further discussion of such structures and ICs, if any, will be limited to the essentials with respect to the principles and concepts of the various embodiments.\",\n \"Referring to FIG.\",\n \"1, a simplified and representative high level diagram of an adjustable power splitter utilized, e.g., in a Doherty power amplifier system in accordance with one or more embodiments will be briefly discussed and described.\",\n \"In FIG.\",\n \"1 as shown, an adjustable power splitter 101 or radio frequency power splitter is coupled to or being utilized with or driving an amplifier, specifically a Doherty amplifier or Doherty power amplifier 103.The adjustable power splitter 101 includes a power divider 105 with an input 107 and a first and second divider output 109, 111.The power divider 105 operates to divide or split a signal at the input 107 into two (or more, as shown in FIG.\",\n \"10) signals, which are identical or very nearly identical signals with in some embodiments equal power.\",\n \"This equal power form of power divider is often referred to as a 3 dB divider since the resultant signals are each 3 dB less than the signal at the input.\",\n \"While the 3 dB divider is typical, other dividers with multiple outputs or outputs with unequal signals could be fashioned and used in some applications.\",\n \"One or more embodiments of the power divider can be a lumped element circuit including an inductive and a capacitive reactance as will be further discussed below with reference to FIG.\",\n \"2.Further included in the adjustable radio frequency power splitter 101, as shown in FIG.\",\n \"1, is a first adjustable phase shifter 113 and in some embodiments a first adjustable attenuator 115, which are series coupled to the first divider output 109 and configured for providing a first power output 117.It will be appreciated that the adjustable phase shifter and adjustable attenuator can be series coupled to each other in any order, i.e., attenuator followed by phase shifter as shown or vice versa.\",\n \"Further included in the adjustable radio frequency power splitter 101 is a second adjustable phase shifter 119 and in some embodiments a second adjustable attenuator 121, which are series coupled to the second divider output 111 and configured for providing a second power output 123.As noted above the order in which these are series coupled to each other can be changed.\",\n \"In various embodiments of the adjustable power splitter 101, the first and typically the second adjustable phase shifter 113, 119 are each digitally controlled, e.g., by controller 125 and have a plurality of states.\",\n \"In one or more embodiments, the first adjustable phase shifter 113 and often the second adjustable phase shifter 119, each have eight phase shifted states.\",\n \"It will be appreciated that the first and second phase shifter may have different phase shifted states, cover different ranges, and have different steps sizes, although typically they will be essentially the same.\",\n \"While digitally controlled, the adjustable phase shifters in many embodiments are analog phase shifters.\",\n \"One or more embodiments of the adjustable phase shifters 113, 119 will be discussed below with reference to FIG.\",\n \"4.In various embodiments of the adjustable power splitter 101, the first and typically the second adjustable attenuator 115, 121 are each digitally controlled, e.g., by controller 125 and have a plurality of states.\",\n \"In one or more embodiments, the first adjustable attenuator 115 and often the second adjustable attenuator 121, each have eight attenuation states or attenuation levels.\",\n \"It will be appreciated that the first and second attenuation may have different attenuation states, cover different attenuation ranges, and have different attenuation steps sizes, although typically they will be essentially the same.\",\n \"While digitally controlled, the adjustable attenuators in many embodiments are analog attenuators.\",\n \"One or more embodiments of the adjustable attenuators 115, 121 will be discussed below with reference to FIG.\",\n \"3.Some embodiments of the adjustable power splitter 101 further include a fixed phase shifter 127 that is configured for adding a fixed phase shift between first and second signals at the, respective, first and second power outputs 117, 123.In some embodiments this can be a fixed and predetermined phase shift, e.g., 90 degrees, added to one signal path, i.e., path between output 109 and power output 117 or path between output 111 and power output 123.In certain applications, e.g., Doherty amplifier 103, a ninety degree phase shift is added to one path in the amplifier and the fixed phase shift can be used to offset this amplifier phase shift.\",\n \"The fixed phase shift in some embodiments is a phase shift in a direction (negative or positive), e.g., a negative shift λ/8 129, such as a negative forty five degree shift, for the first signal at the first power output 117 and a phase shift in the opposite direction, e.g., a positive shift λ/8 131 such as a positive forty five degree phase shift for the second signal at the second power output 123.Using the forty five degree shifts gives a ninety degree phase shift between the signals at the power outputs 117, 123.The phase shifter 127 or negative shift 129 and positive shift 131 can be lumped element circuits having an inductive and a capacitive reactance as will be further discussed below with reference to FIG.\",\n \"2.As suggested above, the adjustable power splitter 101 typically further comprises the controller 125 which is configured and arranged to control or for controlling the adjustable phase shifters and adjustable attenuators.\",\n \"The controller 125 can be provided data via an interface 133, such as a serial interface and in some embodiments this a serial peripheral interface (SPI), which as is known typically includes a data in and out, clock signal, and chip select lines.\",\n \"Various approaches and variants or combinations of those approaches can be utilized by the controller.\",\n \"Generally as will be explained below, control of the attenuators or phase shifters amounts to controlling switches, typically solid state or integrated switches such as some form of field effect transistor switch.\",\n \"Thus the controller can be provided state information for all switches in all attenuators and phase shifters and essentially act as one or more latching buffers with outputs arranged and coupled to ensure that all switches are in the appropriate ON or OFF state.\",\n \"Alternatively, the controller can be provided in essence an address or two or more addresses, which address(es) uniquely specify a state for each attenuator and phase shifter.\",\n \"For example if all phase shifters and attenuators are 8 state devices a 3 bit address for each would uniquely specify the proper state and 4 such addresses could be provided to the controller, which would convert each address to the appropriate control signals for each attenuator and phase shifter and latch in these values, etc.\",\n \"In other embodiments the amount of phase shift and attenuation for each of the four devices could be sent to the controller and it could determine the proper state to realize the desired shifts and attenuations.\",\n \"The practitioner is free to choose from among these or other approaches or combinations to make and retain the appropriate adjustments to the adjustable attenuators and adjustable phase shifters.\",\n \"In addition to the adjustable power splitter 101, the radio frequency Doherty power amplifier 103 is shown where this amplifier includes a main amplifier 135 coupled via a matching network or circuit 137 to the first power output 117 and a peaking amplifier 139 coupled by its matching circuit 141 to the second power output 123.As will be appreciated by those of ordinary skill the main and peaking amplifiers are comprised of one or more stages of low level amplification and higher power level amplification.\",\n \"The main and peaking amplifiers are coupled via, respective, output matching circuits 143, 145 to a Doherty combiner 147, which as is known is configured such that the main amplifier provides the amplification for lower level signals and both amplifiers combine to provide the amplification for high level signals.\",\n \"This is usually accomplished by, e.g., biasing the main amplifier, such that is operates in a class AB mode and biasing the peaking amplifier such that it operates in a class C mode More complex embodiments are possible, such as is illustrated in FIG.\",\n \"10, where an adjustable power splitter 1001 has three outputs 1017, 1023, 1025, and the Doherty amplifier 1003 has a main amplifier 1035 and two peaking amplifiers 1039, 1041 with each peaking amplifier biased in different class C operating points.\",\n \"In one or more of these manners, overall efficiency/linearity of the amplifier can be improved over a wider range of signal levels.\",\n \"Adjustments to the adjustable attenuators and adjustable phase shifters can be made in an experimental manner by monitoring power drawn by the peaking stage or main stage or both as a function of signal levels and the like.\",\n \"At certain signal levels the peaking amplifier should begin to operate and amplitude and phase adjustments can be made with this in mind.\",\n \"FIG.\",\n \"1 illustrates additional features for the adjustable power splitter with a Doherty amplifier where these features have been discussed above or will be discussed below in further detail.\",\n \"For example, the first and second adjustable phase shifters and the first and second adjustable attenuators are digitally controlled with each having multiple states, e.g., 8 or more or less states.\",\n \"The power divider can be a lumped element circuit including one or more inductive reactance and capacitive reactance and other elements.\",\n \"The lumped element circuit can further include a first lumped element phase shifter configured to provide a negative forty five degree phase shift for a first signal at the first power output and a second lumped element phase shifter configured to provide a positive forty five degree phase shift for a second signal at the second power output.\",\n \"As noted earlier the adjustable power splitter with Doherty amplifier can also include or comprise a controller for controlling the adjustable phase shifters and adjustable attenuators.\",\n \"Referring to FIG.\",\n \"2, a representative diagram of a power divider and fixed phase shifter(s) in accordance with one or more embodiments, which embodiments are suitable for use in the FIG.\",\n \"1 adjustable power splitter, will be briefly discussed and described.\",\n \"In FIG.\",\n \"2 and all ensuing FIGS.\",\n \"like reference numbers will designate like features from other FIGS.\",\n \"FIG.\",\n \"2 illustrates an input or RF input 107 to a power divider 201 which has a first output or divider output 109 and a second output or divider output 111 (I/O numbered same as FIG.\",\n \"1).\",\n \"The power divider as illustrated is implemented with one or more lumped element inductive reactances 203, 209 and one or more capacitive reactances 205, 207 as well as a resistive loss or resistor 211.As shown a shunt inductance 203 or inductor is coupled from the input to a reference node (ground) 204.This inductance will operate to reduce power in any low frequency signals at the input.\",\n \"Two series capacitances 205, 207 or capacitors 205, 207 are coupled from the input to, respectively, the first divider output 109 and the second divider output 111.These capacitances will typically be equal valued for a 3 dB splitter.\",\n \"A series coupled inductance 209 and resistance 211 is coupled between the first and second divider outputs and operates to balance the signal at these outputs.\",\n \"The actual values for the inductors and capacitors and resistor will vary in accordance with operating frequencies and operating impedances.\",\n \"Generally the shunt inductor 203 in combination with capacitor 207 forms a high pass structure which exhibits an impedance transformation between 107 (100 ohms for example) to 111 (50 ohms for example).\",\n \"Similarly, inductor 203 in combination with capacitor 205 forms a high pass structure which exhibits an impedance transformation between 107 (100 ohms for example) to 109 (50 ohms for example).\",\n \"Resistor 211 in combination with inductor 209 creates a 50 ohm (nominal) odd-mode impedance at nodes 111 and 109.The combination of the elements is such that nodes 107, 109, and 111 each exhibit an impedance of 50 ohms (for example) and he combination of elements can be further chosen such that and equal or unequal power is split from 107 to 111 and 107 to 109, respectively.\",\n \"One of ordinary skill can readily and experimentally determine the appropriate values for a given application.\",\n \"An alternative embodiment for the power splitter could use transmission lines although it is noted that these embodiments may not be as useful (e.g., much larger in physical size) over as broad of a bandwidth as the lumped element embodiments.\",\n \"FIG.\",\n \"2 also illustrates an embodiment of the fixed phase shifter in accordance with fixed phase shifter 127 and more specifically two fixed, but opposite direction phase shifters.\",\n \"One is a negative shift 229 such as a negative forty five degree shift that is coupled to divider output 109 and provides an output that goes to adjustable attenuator 115 (see FIG.\",\n \"1).\",\n \"This negative shift 229 corresponds to negative shift 129 of FIG.\",\n \"1.The negative shift 229 is a lumped element circuit having or implemented with an inductive reactance 233 coupled from divider output 109 to adjustable attenuator 115 and further having an input capacitive reactance 235 coupled from divider output 109 to a reference node (ground) 204 and an output capacitive reactance 237 or capacitor coupled from adjustable attenuator 115 input to the reference node 204.The specific values for the inductors and capacitors will depend on operating impedances and signal frequencies but can be experimentally determined by practitioners without undue experimentation.\",\n \"The other fixed shift is a positive shift 231, such as a positive forty five degree shift that is coupled to divider output 111 and provides an output that goes to adjustable attenuator 121 (see FIG.\",\n \"1).\",\n \"The positive shift 231 corresponds to the positive shift 131 of FIG.\",\n \"1.The positive shift 231 is a lumped element circuit having an input capacitive reactance 239 coupled from divider output 111 to a common node 240 and an output capacitive reactance 241 or capacitor coupled from the common node 240 to adjustable attenuator 121 input.\",\n \"Further included is an inductive reactance 233 coupled from the common node 240 to the reference node (ground) 204.The specific values for the inductors and capacitors will depend on operating impedances and signal frequencies but can be experimentally determined by practitioners without undue experimentation.\",\n \"Referring to FIG.\",\n \"3, a representative diagram of an adjustable attenuator in accordance with one or more embodiments will be discussed and described.\",\n \"FIG.\",\n \"3 shows a representative embodiment of an adjustable attenuator suitable for use in the FIG.\",\n \"1 adjustable power splitter.\",\n \"FIG.\",\n \"3 illustrates an input 301 (analogous to input to adjustable attenuator 115 or 121 in FIG.\",\n \"1) to a first variable attenuator 303, which provides either 0 db or 2 db of attenuation, where 2 dB is provided when b2 304 is high or equal to 1.The first variable attenuator is a resistive divider with a switch around the divider (not specifically shown).\",\n \"The control line b2 opens this switch.\",\n \"The first variable attenuator 303 is coupled to a second variable attenuator 305 which provides an attenuated signal at output 307 (analogous to input to 113, 119 in FIG.\",\n \"1).\",\n \"The second variable attenuator is shown in more detail and is arranged and configured to provide 0 dB to 1.5 dB of attenuation in 0.5 dB steps, i.e., 0 dB, 0.5 dB, 1.0 dB, or 1.5 dB of attenuation where these steps or attenuations can be referred to as negative gains (e.g., −0.5 dB gain).\",\n \"Thus the serial combination of adjustable attenuator 303 and 307 can provide from 0 dB up to 3.5 dB of attenuation depending on control signal states, i.e., step through 0-1.5 dB with attenuator 305 and then bring in 2 dB with attenuator 303 and go through or repeat the steps, 0-3.5 dB, with attenuator 305.Further shown in FIG.\",\n \"3 is a table 309 of input signals b0, b1, and switch control signals s1-s4 which result from the input signals b0, b1 together with expected attenuation as a function of a particular combination of s1-s4.By observation s1 is the logical OR inverted (NOR) of b0, b1, i.e., high only when both inputs are low and low otherwise.\",\n \"Similarly s2 is the OR of b0, b1, i.e., high if either input is high.\",\n \"Further s3 is equal to b0 and s4 is the logical AND of b0, b1, i.e., high only if both inputs are high.\",\n \"In more detail, the first adjustable attenuator 303 is coupled to a capacitance 311 which will have a near zero impedance for signals of interest and this capacitance is coupled to a resistor 313 which is a relatively high value and is used for biasing purposes.\",\n \"Supply noise is coupled to ground by capacitor 314.Capacitor 311 is further coupled to switch S1 315, switch S2 317, and resistor 319.When S1 is ON, (s1=1 or high) there will be near zero attenuation as the input signal at capacitor 311 will be coupled via S1 to the output capacitor 321 and thus output 307 since the output capacitor is near zero impedance for signals of interest (see also table, line 1).\",\n \"When S1 is OFF and S2 is ON (s1=0, s2=1 or high), the input signal at capacitor 311 will be coupled to resistor 323 and from there to the output capacitor 321.The input signal will also be coupled through the series combination of resistor 319 and 324 to the output capacitor 321.Resistors 323 in parallel with the series combination of resistors 319, 324 are chosen to provide an attenuation of 0.5 dB given the operating frequencies and impedances (see table, line 2).\",\n \"If, in addition to S2 being ON, switch S3 325 is ON (s3=1 or high), the signal at the node between resistors 319, 324 will be coupled via resistor 327 to capacitor 328 and thus ground.\",\n \"This will increase the attenuation and resistor 327 is selected such that an additional 0.5 dB or a total of 1.0 dB of attenuation is provided with this combination of switches (see table, line 3).\",\n \"If in addition to S2 and S3, switch S4 331 is ON (s4=1 or high) resistor 333 will be added in parallel with resistor 327 and the signal will be further attenuated.\",\n \"Resistor 333 is chosen to add a further 0.5 dB for a total of 1.5 dB of attenuation to the signal at the output (see table, line 4).\",\n \"Those of ordinary skill given a specific application with operating frequencies and impedances can determine the appropriate values of the resistors by calculation or experimentation.\",\n \"Referring to FIG.\",\n \"4, a representative diagram of an adjustable phase shifter in accordance with one or more embodiments will be discussed and described.\",\n \"The adjustable phase shifter illustrated in FIG.\",\n \"4 is one embodiment of the subject matter of co-pending U.S. patent application Ser.\",\n \"No.\",\n \"13/360,119, filed on Jan. 27, 2012, which application is hereby incorporated herein by reference.\",\n \"FIG.\",\n \"4 illustrates a high level diagram of a phase shifter or delay line phase shifter with selectable phase shift in accordance with one or more embodiments.\",\n \"In FIG.\",\n \"4, an adjustable phase shifter 400 with selectable or variable phase shift is shown in a representative manner.\",\n \"The phase shifter 400 has an input coming from adjustable attenuator 115 or 121 in FIG.\",\n \"1 or a signal input for input signals, e.g., radio frequency (RF) signals and an output coupled to divider or divider power outputs 117, 123 or a signal output for phase shifted versions of the input signal, e.g., phase shifted versions of the RF signals.\",\n \"Between the input and output are one or more switchable phase shifting elements or circuits, including specifically phase shifting elements 401, 411, 421, and possibly additional phase shifting elements or circuits 431 serially coupled as shown.\",\n \"Generally speaking in many embodiments and as will be further discussed and described below, the switches shown are provided with a pair of single throw switches a, b for each phase shifting element 401, 411, 421.Each of the phase shifting elements can be designed, arranged and configured to provide some predetermined amount of phase shift.\",\n \"If a practitioner needs to cover a certain range of phase shift and needs a certain resolution for the phase shift it can be advantageous to design the first or one of the phase shifting elements to provide a choice between nominally zero or a minimal phase shift and the smallest phase shift step one needs (i.e., the resolution) with the next or another phase shifting element configured to provide minimal or 2× the smallest step needed.\",\n \"Thus with two phase shifting elements you can provide a near zero, 1×, 2×, and 3× small step in phase shift by activating different combinations of the a, b switches.\",\n \"Adding another phase shifting element with a 4× shift, allows 8 states with corresponding 0 to 7× the small step and so on.\",\n \"The number of phase shifting elements will be determined by the required resolution (step size) and the phase range needed to be covered (number of steps).\",\n \"For example if you want to cover 49 degrees with a resolution of 7 degrees then 8 states, including 0 will be required and this can be accomplished with 3 phase shifting elements etc.\",\n \"etc.\",\n \"In more detail, switchable phase shifting element or circuit 401 (and the other similar phase shifting elements) further comprises a first signal path coupled between the input through a switch 403 or alternatively with switch 405 closed through phase shifting circuit 407 to an output 410.The first signal path, when activated by closing or activating switch 403 or integrated circuit switch, will be providing a near zero phase shift for a signal coupled through the first signal path.\",\n \"Further included is a second signal path coupled between the input and the output 410 via the phase shifting circuit 407 (switch 405 closed).\",\n \"The second path is configured for providing a second phase shift for a signal coupled through the second signal path.\",\n \"Basically switch 403 selects between the first path and the second path or between zero and some phase shift.\",\n \"Insertion loss is equalized between the first path and the second path by switching in (opening switch 405) a loss circuit, resistor 409, when the first signal path is selected.\",\n \"The switches 403, 405, 413, 415, 423, and 425, etc.\",\n \"are controlled by a control circuit, e.g., controller 125 or another controller or latch, which can alternatively be viewed as a portion of the phase shifter with selectable phase shift.\",\n \"In these embodiments or other embodiments, when the switch or integrated circuit switch 403 is activated (closed or ON) thus selecting the first signal path, the resistive loss circuit or resistor 409 is switched in (switch 405 open or OFF) and is configured or value chosen to equalize the first insertion loss for the first path and the second insertion loss expected when the second signal path is selected (i.e., switch 403 is open and 405 is closed).\",\n \"Various embodiments of the phase shifting circuit 407 as illustrated in FIG.\",\n \"4 can further comprise a first reactance or inductor series coupled at a common node to a second reactance or inductor and a shunt circuit coupled from the common node to a reference node, e.g., a ground potential.\",\n \"The shunt circuit in varying embodiments further comprises a third reactance or capacitor in series with the resistive loss or resistor 409 where the switch or integrated circuit switch 405 is in parallel with the resistor 409.One embodiment uses lumped element inductors and a metal insulator metal capacitor as well as pseudo morphic high electron mobility transistors (pHEMT) for switches.\",\n \"When the first switch or first integrated circuit switch 403 is closed, ON, or activated it selects the first signal path (provides a short circuit around the second signal path) and when the first switch 403 is open, OFF, or inactivated it deselects (opens) the first signal path and signal is routed via the second signal path and reactive phase shifting or changing circuit 407.When the first switch is closed 403 the second switch 405 will be open thereby adding the resistive loss circuit 409 to the reactive circuit 407.This additional loss when the first signal path is chosen can be selected, i.e., resistor value chosen, by experimental processes to equalize the insertion loss when the first signal path is selected with the insertion loss when the second signal path is selected, thereby removing any relationship between phase shift and insertion loss.\",\n \"Typically the resistive loss circuit or resistor will be several orders of magnitude larger than the ON resistance of an integrated circuit switch.\",\n \"The first switch 403 or integrated circuit switch in series with the first signal path and the second switch 405 or integrated circuit switch for switching in the resistive loss circuit 409 are alternatively activated (when 403 is ON or CLOSED, 405 is OFF or OPEN and vice-a-versa).\",\n \"Similarly the phase shifting element or circuit 411 which can comprise a third switch S2a 413 or integrated circuit switch in series with the third signal path and a fourth switch S2b 415 or integrated circuit switch for the switching in a second resistive loss circuit 419, wherein the third and fourth switch or integrated circuit switch are alternatively activated (when one closed other open).\",\n \"In some embodiments, the first (and second) resistive loss circuit is a resistor in parallel with the second (and fourth) integrated circuit switch and the first (and second) resistive loss circuit is switched in by opening the second (and fourth) integrated circuit switch, thereby equalizing the first and second (and third and forth) insertion loss.\",\n \"The control circuit is arranged to control first, second, third and fourth switches.\",\n \"As suggested above in some embodiments the control circuit is configured to select at least one state from available states of minimal phase shift, a first phase shift, a second phase shift, and a first plus second phase shift by activating one or more of the first, thus second, and third, thus fourth, integrated circuit switches.\",\n \"To select the states in order (near zero phase shift through first plus second phase shift), switches 403, 413 are ON for near zero, switches 405, 413 are ON for a first shift, switches 403, 415 are ON for a second phase shift, and switches 413, 415 are ON for a first plus second phase shift.\",\n \"In the above, it is understood that undesignated or unspecified switches are OFF.\",\n \"As suggested above, each time another switchable phase shifting element or circuit is added, e.g., 421 with switches 423, 425) the number of possible states can double and the range of phase shift for a given step size can therefore double or alternatively for a given range the resolution can double, i.e., step size can be cut in half.\",\n \"The controller 125 or control circuit in addition to possibly selecting timing for activating switches and decoding inputs can, for many embodiments, by viewed as a register or buffer for storing switch state (ON or OFF) information with one output coupled to each of the switches.\",\n \"The control circuit can be programmed or loaded via inputs 133.These inputs may simply specify a state for the phase shifter which is then decoded by the control circuit into switch states or the inputs can be the state for each switch or specify how much phase shift is desired with the control circuit then determining an appropriate state.\",\n \"The inputs can be sent to the control circuit via the serial peripheral interface (SPI).\",\n \"This is a generally known serial interface as indicated above.\",\n \"Referring to FIG.\",\n \"5-8 various experimental data showing assorted performance of one or more embodiments will be discussed and described.\",\n \"FIG.\",\n \"5-6 show efficiency and linearity as a function of phase for various attenuator settings where the data was gathered at a power output of 47 dBm from one amplifier and one set of amplifier transistors using an adjustable power splitter.\",\n \"FIG.\",\n \"5 specifically shows phase adjustment from zero degrees to approximately 45 degrees on the horizontal axis 501 and plots efficiency percentage on the vertical axis 503 as a function of the phase variation for 8 different attenuator settings 505.These 8 settings are represented by 8 line graphs 507 which is one graph for each 0.5 dB increment in attenuator setting.\",\n \"As one example, at approximately 40 degrees the second line from the top, i.e., with 3 dB of attenuation, shows approximately 55% efficiency.\",\n \"FIG.\",\n \"6 shows linearity as a function of phase adjustment or shift.\",\n \"The phase shift is shown on the horizontal axis 601 with linearity (adjacent channel power ratio-upper side in dB relative to the carrier) on the vertical graph 603 for 8 different attenuator settings 605.These 8 settings are represented by 8 line graphs 607 which is one graph for each 0.5 dB increment in attenuator setting.\",\n \"As one example, at approximately 40 degrees the second line from the top, i.e., with 3 dB of attenuation, shows approximately 55 dBc linearity.\",\n \"Generally, the way to use this data is select the attenuation and phase shift that provides acceptable linearity (55 dBc) and the best efficiency-in this instance approximately 55% FIG.\",\n \"7-8 show amplifier performance for 20 random combinations of transistors, where these transistors were selected from non average lots.\",\n \"The random combinations are each inserted into an amplifier fixture and measurements are taken with output power at 47 dBm.\",\n \"FIG.\",\n \"7 specifically shows adjacent channel power ratio on the low and high side of the carrier 701 with the measured results shown on the vertical axis 703.Measurements are taken for fixed or nominal phase setting 704 and for an optimized phase setting 705.A typical production specification or limit 706 is shown.\",\n \"All of the measurements for all of the combinations under each condition are shown in boxes with fixed phase conditions for lower and higher side shown in boxes 707 and optimized phase conditions for lower and higher side shown in boxes 709.By observation many of the combinations were failing the production limit 706 with a fixed or nominal phase setting while all combinations were better than the limits with optimized phase settings.\",\n \"Furthermore, the median measurement 711 in the fixed phase case was well above the limit and toward one end of the box, whereas the median measurement 713 for the optimized phase case is well within the production limits and much closer to the center of the box.\",\n \"FIG.\",\n \"8 shows measured % efficiencies on the vertical axis 801 for the random combinations in a Doherty amplifier using digital pre distortion (DPD) for fixed or nominal phase setting 803 and optimized phase settings 805 with measured efficiencies shown in, respective, boxes 806, 807.By observation % efficiencies have improved by 1 to 3% with an average improvement of approximately 2%.\",\n \"Referring to FIG.\",\n \"9, a flow chart of exemplary processes included in a method of adjusting a power split signal or power splitter that can be used in conjunction with the FIG.\",\n \"1 system in accordance with one or more embodiments will be discussed and described.\",\n \"It will be appreciated that this method uses many of the inventive concepts and principles discussed in detail above and thus this description will be somewhat in the nature of a summary with various details generally available in the earlier descriptions.\",\n \"This method can be implemented in one or more of the structures or apparatus described earlier or other similarly configured and arranged structures.\",\n \"It will be appreciated that the method can be performed as many times as desired or continually performed as needed The method of adjusting a power split signal or power splitter illustrated in FIG.\",\n \"9 includes splitting 901 an input signal into first and second signals at first and second divider outputs.\",\n \"This can include using a lumped element circuit including an inductive reactance and a capacitive reactance.\",\n \"This may also necessitate providing a power divider or splitter with an input and a first and second divider output where the power divider is configured to split an input signal into first and second signals at the first and second divider outputs.\",\n \"The providing can include providing a lumped element circuit including an inductive reactance and a capacitive reactance.\",\n \"Also included in the method of FIG.\",\n \"9 is adjusting 903 a phase shift and attenuation of the first signal to provide a first resultant signal at a first power output; which can include, e.g., using a first adjustable phase shifter and first adjustable attenuator that are each digitally controlled with each having multiple states.\",\n \"In some embodiments this may include disposing a first adjustable phase shifter and first adjustable attenuator series coupled to the first divider output and arranged and configured to phase shift and attenuate the first signal and provide a first resultant signal at a first power output.\",\n \"These can each be digitally controlled with each having multiple states, e.g., 8 states.\",\n \"Next shown is adjusting 905 a phase shift and attenuation of the second signal to provide a second resultant signal at a second power output; which can include, e.g., using a second adjustable phase shifter and second adjustable attenuator that are each digitally controlled with each having multiple states.\",\n \"This can be accomplished in some instances by disposing a second adjustable phase shifter and second adjustable attenuator series coupled to the second divider output and arranged and configured to phase shift and attenuate the second signal and provide a second resultant signal at a second power output.\",\n \"Again, these can each be digitally controlled with each having multiple states.\",\n \"In some embodiments, the method includes providing 907 a fixed phase shift between the first and second resultant signals, which can further comprise, e.g., providing a negative forty five degree shift for the first resultant signal at the first power output and a positive forty five degree phase shift for the second resultant signal at the second power output.\",\n \"Again disposing a fixed phase shifter arranged and configured to provide a fixed phase shift between signals at the first and second power output, e.g., to provide a negative forty five degree shift for the first resultant signal at the first power output and a positive forty five degree phase shift for the second resultant signal at the second power output.\",\n \"In most embodiments, the method includes controlling 909 the adjustable phase shifters and adjustable attenuators.\",\n \"It will be appreciated that the above described functions and adjustable signal or power splitters may be implemented with one or more integrated circuits or hybrid structures or combinations or the like.\",\n \"The processes, apparatus, and systems, discussed above, and the inventive principles thereof are intended to and can alleviate yield and performance issues caused by prior art techniques.\",\n \"Using these principles of independent adjustment of phase or signal level or signal attenuation within a power splitter can quickly resolve performance and production yield problems in, e.g., Doherty amplifiers with relatively minor costs and the like.\",\n \"This disclosure is intended to explain how to fashion and use various embodiments in accordance with the invention rather than to limit the true, intended, and fair scope and spirit thereof.\",\n \"The foregoing description is not intended to be exhaustive or to limit the invention to the precise form disclosed.\",\n \"Modifications or variations are possible in light of the above teachings.\",\n \"The embodiment(s) was chosen and described to provide the best illustration of the principles of the invention and its practical application, and to enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated.\",\n \"All such modifications and variations are within the scope of the invention as determined by the appended claims, as may be amended during the pendency of this application for patent, and all equivalents thereof, when interpreted in accordance with the breadth to which they are fairly, legally, and equitably entitled.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874740"}}},{"rowIdx":4494681,"cells":{"text":{"kind":"list like","value":[["REMANUFACTURING METHOD OF DEVELOPER ACCOMMODATING UNIT","Provided is a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container.","The remanufacturing method includes refilling the developer into the flexible container."],["1.A remanufacturing method of a cartridge detachably mountable to an image forming apparatus, the cartridge including a used flexible container being configured to accommodate developer and provided with a plurality of openings for discharging developer, the remanufacturing method comprising: filling the used flexible container with developer; and attaching a sealing member to an outside surface of the used flexible container such that the sealing member covers the plurality of openings.","2.The remanufacturing method according to claim 1, wherein the used flexible container comprises a developer accommodating portion for accommodating developer, and the used flexible container is deformable to change a capacity of the developer accommodating portion.","3.The remanufacturing method according to claim 1, wherein the remanufacturing method comprises removing at least part of a frame member for accommodating the used flexible container such that at least part of the used flexible container is exposed.","4.The remanufacturing method according to claim 1, wherein the used flexible container is a flexible container with developer consumed.","5.The remanufacturing method according to claim 1, wherein the remanufacturing method comprises attaching an image bearing member for bearing a latent image to the cartridge.","6.The remanufacturing method according to claim 1, wherein the remanufacturing method comprises attaching a developer bearing member for developing a latent image to the cartridge.","7.A cartridge detachably mountable to an image forming apparatus comprising: an used flexible container configured to accommodate developer and provided with a plurality of openings for discharging developer; developer filled in the used flexible container; and a sealing member bonded to an outside of the used flexible container such that the plurality of the openings are covered by the sealing member.","8.The cartridge according to claim 7, wherein the used flexible container comprises a fixed portion being provided with a plurality of the holes.","9.The cartridge according to claim 7, wherein the used flexible container comprises a developer accommodating portion for accommodating developer, and the used flexible container is deformable to change a capacity of the developer accommodating portion.","10.The cartridge according to claim 7, wherein the used flexible container is a flexible container with developer consumed.","11.The cartridge according to claim 7, wherein the cartridge includes an image bearing member for bearing a latent image.","12.The cartridge according to claim 7, wherein the cartridge includes a developer bearing member for developing a latent image.","13.A cartridge detachably mountable to an image forming apparatus comprising: developer filled in an used flexible container being configured to accommodate developer and provided with a plurality of openings for discharging developer, wherein the plurality of the openings are covered by a sealing member bonded to an outside of the used flexible container.","14.The cartridge according to claim 13, wherein the used flexible container comprises a fixed portion being provided with a plurality of holes.","15.The cartridge according to claim 13, wherein the used flexible container comprises a developer accommodating portion for accommodating developer, and the used flexible container is deformable to change a capacity of the developer accommodating portion.","16.The cartridge according to claim 13, wherein the used flexible container is a flexible container with developer consumed.","17.The cartridge according to claim 13, wherein the cartridge includes an image bearing member for bearing a latent image.","18.The cartridge according to claim 13, wherein the cartridge includes a developer bearing member for developing a latent image."],["<SOH> BACKGROUND OF THE INVENTION <EOH>"],["<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is directed to a remanufacturing method of a developer accommodating unit including a flexible container.","According to an aspect of the present invention, a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container, includes refilling the developer into the flexible container.","Further features of the present invention will become apparent from the following description of embodiments with reference to the attached drawings."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","15/359,382 filed Nov. 22, 2016, which is a continuation of U.S. patent application Ser.","No.","14/920,316 filed Oct. 22, 2015, now U.S. Pat.","No.","9,535,372 issued Jan. 3, 2017, which claims the benefit of Japanese Patent Application No.","2014-218519, filed Oct. 27, 2014, all of which are hereby incorporated by reference herein in their entirety.","BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a remanufacturing method of a developer accommodating unit for refilling a developer.","An image forming apparatus forms an image on a recording medium using an electrophotographic image forming process.","Examples of image forming apparatuses include electrophotographic copying machines, electrophotographic printers (for example, laser beam printers and light emitting diode (LED) printers), facsimile apparatuses, and word processors.","A developing device includes developer, and a developing roller as a developer bearing member for developing an electrostatic latent image formed on a photosensitive drum as an image bearing member.","The developing device is detachably attached to an image forming apparatus or a photosensitive drum unit including a photosensitive drum.","A cartridge (process cartridge) integrally includes a photosensitive drum and a developing roller, and is detachably attached to an image forming apparatus.","Description of the Related Art Japanese Patent No.","3320403 discloses a remanufacturing method of a cartridge having a developing device, more specifically, a remanufacturing method of a cartridge for refilling, using a funnel, toner into a storage container for storing toner, after removing a developing roller and a developing blade.","SUMMARY OF THE INVENTION The present invention is directed to a remanufacturing method of a developer accommodating unit including a flexible container.","According to an aspect of the present invention, a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container, includes refilling the developer into the flexible container.","Further features of the present invention will become apparent from the following description of embodiments with reference to the attached drawings.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a sectional view illustrating an image forming apparatus.","FIG.","2 is a sectional view illustrating a cartridge.","FIG.","3 is a perspective view illustrating the cartridge viewed from a drive side.","FIG.","4 is a perspective view illustrating the cartridge viewed from a non-drive side.","FIG.","5 is an exploded perspective view illustrating a developing unit.","FIG.","6 is a sectional view of the cartridge illustrating a process for processing a first communication hole.","FIG.","7 is a sectional view of the cartridge illustrating a process for processing a second communication hole.","FIGS.","8A, 8B, and 8C are perspective views of a flexible container illustrating shapes of the second communication hole.","FIG.","9 is a sectional view illustrating a process for refilling developer into the cartridge through the first and the second communication holes.","FIG.","10 is a sectional view of the cartridge illustrating a process for sealing the first communication hole.","FIG.","11 is a sectional view of the cartridge illustrating a process for resealing the second communication hole.","FIG.","12 is a sectional view of the cartridge illustrating a state before resealing by a sealing member.","FIG.","13 is a sectional view of the cartridge illustrating a state after resealing by the sealing member.","FIGS.","14A, 14B, and 14C are perspective views illustrating a process for detaching the sealing member from the flexible container.","FIG.","15A is a perspective view illustrating a state of the flexible container containing no developer, before the developer is refilled, and FIG.","15B is a perspective view illustrating a state of a new flexible container.","FIG.","16 is a sectional view illustrating a process for refilling the developer.","FIG.","17 is a perspective view illustrating a process for injecting compressed air into the flexible container to increase a capacity of the flexible container.","FIG.","18 is a perspective view illustrating a process for refilling the developer into a frame member through an opening of the flexible container, using a funnel.","FIG.","19 is a sectional view illustrating a process for refilling the developer.","FIG.","20 is a sectional view illustrating a process for refilling the developer through an opening of the flexible container, using a funnel.","FIG.","21 is a sectional view illustrating a developing unit.","FIG.","22 is a sectional view illustrating a process for refilling the developer into the flexible container inside the developing unit.","FIG.","23 is a sectional view of the developing unit illustrating a state where the developer is refilled.","FIG.","24 is a front view illustrating the frame member viewed from an opening side of the flexible container.","FIG.","25 is a sectional view illustrating the cartridge in which the developing unit includes an unsealing member and a pressing member.","FIG.","26 is a front view illustrating the frame member of the cartridge in which the developing unit includes the unsealing member and the pressing member, viewed from an opening side of the flexible container.","FIG.","27 is a front view illustrating the frame member of the cartridge in which the developing unit includes the unsealing member and the pressing member, viewed from an opening side of the flexible container.","FIG.","28 is a side view illustrating the sealing member and the unsealing member.","FIG.","29 is an exploded perspective view illustrating the developing unit.","FIGS.","30A and 30B are enlarged views illustrating a non-drive side portion of the frame member (a portion A illustrated in FIG.","29).","FIGS.","31A, 31B, 31C, and 31D are perspective views of the flexible container illustrating an enlargement process for enlarging an opening of the flexible container.","FIG.","32 is a sectional view of the frame member illustrating a process for refilling the developer through a refilling opening.","FIGS.","33A and 33B are perspective views of the flexible container illustrating the enlargement process for enlarging an opening of the flexible container according to an eleventh embodiment.","FIGS.","34A, 34B, and 34C are perspective views of the flexible container illustrating a process for processing a refilling opening on the flexible container fixed to the inside of the frame member.","DESCRIPTION OF THE EMBODIMENTS Embodiments of the present invention will be described in detail below with reference to the accompanying drawings.","However, sizes, materials, shapes, and relative positions of elements described in the embodiments are not limited thereto, and can be appropriately modified depending on the configuration of an apparatus according to the present invention and other various conditions.","Unless otherwise specifically described, the scope of the present invention is not limited to the embodiments described below.","Elements in subsequent embodiments that are identical to those in preceding embodiments are assigned the same reference numerals, and descriptions in the preceding embodiments will be incorporated by reference.","In the following descriptions, a developer accommodating unit includes at least a frame member and a flexible container.","A developing device includes at least a developer bearing member.","Further, a process cartridge includes at least an image bearing member.","In the embodiments, a developer accommodating unit is equal to a developing device.","In the embodiments, a developing unit may be independently configured as a developing device.","First Embodiment FIG.","1 is a sectional view illustrating an image forming apparatus 1.The image forming apparatus 1 performs full color image formation, and is provided with an apparatus body 2.Inside the apparatus body 2, four cartridges P are detachably attached.","In the following descriptions of the image forming apparatus 1, the front surface is on the right side, the rear surface is on the left side, the drive side is on the rear side, and the non-drive side is on the front side, as illustrated in FIG.","1.The cartridges P attached to the apparatus body 2 are the following four cartridges: a first cartridge PY, a second cartridge PM, a third cartridge PC, and a fourth cartridge PK.","These cartridges P are disposed in a horizontal direction.","These cartridges P have an approximately similar configuration expect for different toner colors.","The first cartridge PY accommodates yellow developer, the second cartridge PM accommodates magenta developer, the third cartridge PC accommodates cyan developer, and the fourth cartridge PK accommodates black developer.","The image forming apparatus 1 performs color image formation on a recording material S. The image forming apparatus 1 is a cartridge type image forming apparatus in which the cartridges P are detachably attached to the apparatus body 2 and a color image is formed on the recording material S. A mechanism inside the cartridge P is driven by a rotational driving force received from a drive output unit (not illustrated) of the apparatus body 2.Internal devices in the cartridge P is supplied with bias voltages (a charging bias voltage, a developing bias voltage, etc.)","from the apparatus body 2.An exposure device 200 is disposed above the plurality of cartridges P. The exposure device 200 is a laser scanner unit for irradiating a photosensitive drum 4 with laser light LS based on information transmitted from a controller 50 in the apparatus body 2.This laser light LS passes through an exposure window portion 10 (refer to FIG.","2) inside the cartridge P, and the surface of the photosensitive drum 4 is exposed to the laser light LS to be scanned.","An intermediate transfer belt unit 11 is disposed below the plurality of cartridges P. The intermediate transfer belt unit 11 includes a transfer belt 12, and a drive roller 13 and tension rollers 14 and 15 for stretching the transfer belt 12.The transfer belt 12 is made of a flexible material.","The bottom surface of the photosensitive drum 4 inside the cartridge P contacts the upper surface of the transfer belt 12.The relevant contact portion is a primary transfer portion.","Inside the transfer belt 12, primary transfer rollers 16 are disposed to surface respective photosensitive drums 4.A secondary transfer roller 17 is disposed at a position facing the tension roller 14 via the transfer belt 12.The contact portion between the secondary transfer roller 17 and the transfer belt 12 is a secondary transfer portion.","A feed unit 18 is disposed below the intermediate transfer belt unit 11.The feed unit 18 includes a tray 19 on which recording materials S are stacked, and a feed roller 20.A fixing unit 21 and a discharge unit 22 are disposed at the upper left position of the cartridge P. A discharge tray 23 is formed on the upper surface of the apparatus body 2.The recording material S is fixed by the fixing unit 21 and then discharged onto the discharge tray 23.FIG.","2 is a sectional view illustrating the cartridge P. The cartridge P includes a photosensitive unit 8 and a developing unit 9 as a “developer accommodating unit”.","The photosensitive unit 8 includes the photosensitive drum 4 as an “image bearing member”, a charging roller 5, and a cleaning member 7.The charging roller 5 uniformly charges the surface of the photosensitive drum 4.The cleaning member 7 is a blade for removing residual toner that has been developed on the surface of the photosensitive drum 4, but has not been transferred onto the primary transfer roller 16.The developing unit 9 includes a developing roller 6 as a “developer bearing member”, a supply roller 61, and an agitating member 74.The developing roller 6 develops an electrostatic image on the surface of the photosensitive drum 4 using toner.","The supply roller 61 supplies developer to the developing roller 6.The agitating member 74 agitates the developer inside the developing unit 9.Operations of the image forming apparatus 1 will be described below with reference to above-described FIGS.","1 and 2.The surface of the photosensitive drum 4 is uniformly charged by the charging roller 5 and then is exposed to light by the exposure device 200, so that an electrostatic image is formed on the surface of the photosensitive drum 4.When the electrostatic image is developed by the developing unit 9 using the developer, a developer image is formed.","The developer image on the surface of the photosensitive drum 4 is transferred onto the transfer belt 12 rotating in a forward direction (the direction indicated by an arrow C illustrated in FIG.","1) of the rotational direction of the photosensitive drum 4.Yellow, magenta, cyan, and black developer images are primarily transferred sequentially from the respective photosensitive drums 4 of the first to the fourth cartridges P onto the transfer belt 12 to be superimposed upon one another.","Meanwhile, the recording materials S stacked on the tray 19 are separated and fed one by one according to a predetermined control timing.","Each of the recording materials S is conveyed to the secondary transfer portion between the secondary transfer roller 17 and the transfer belt 12.At the secondary transfer portion, the developer image on the surface of the transfer belt 12 is secondarily transferred onto the recording material S. The developing unit 9 includes a flexible container 251 for accommodating (storing) the developer, and a frame member 29 for accommodating (storing) the flexible container 251.The flexible container 251 is provided with openings 251h for discharging the developer.","The developing unit 9 further includes a sealing member 253 for sealing the openings 251h, and exposing the openings 251h when being moved, and an unsealing member 254 attached to the sealing member 253 and for unsealing the openings 251h when being moved.","In other words, the developing unit 9 refers to a unit including at least the flexible container 251, the sealing member 253, and the unsealing member 254 inside the frame member 29.The flexible container 251 includes an accommodating portion 251b for accommodating (storing) the developer T, and the openings 251h for discharging the developer T. FIG.","3 is a perspective view illustrating the cartridge P viewed from the drive side.","FIG.","4 is a perspective view illustrating the cartridge P viewed from the non-drive side.","As illustrated in FIGS.","3 and 4, the photosensitive unit 8 and the developing unit 9 are integrally formed by covers 24 and 25.Therefore, the photosensitive unit 8 includes the photosensitive drum 4, the charging roller 5, the cleaning member 7, a cleaning container 26, and the covers 24 and 25.The photosensitive drum 4 is rotatably supported on the cleaning container 26 by the covers 24 and 25.One end side of the photosensitive drum 4 in the longitudinal direction is provided with a coupling member 4a for transmitting a driving force to the photosensitive drum 4.When the coupling member 4a is engaged with a drum drive output unit of the apparatus body 2, the driving force of the drive motor (not illustrated) of the apparatus body 2 is transmitted to the photosensitive drum 4.The charging roller 5 is supported by the cleaning container 26 so that the charging roller 5 can be rotatably driven with being in contact with the photosensitive drum 4.The cleaning member 7 is supported by the cleaning container 26 so that the cleaning member 7 contacts the circumferential surface of the photosensitive drum 4 at a predetermined pressure.","Residual developer removed from the circumferential surface of the photosensitive drum 4 by the cleaning member 7 is stored in the cleaning container 26.Holes 24a and 25a for rotatably supporting the developing unit 9 are formed on the covers 24 and 25, respectively.","FIG.","5 is an exploded perspective view illustrating the developing unit 9.The flexible container 251 is stored in the developing unit 9 illustrated in FIG.","5.As illustrated in FIG.","5, the developing unit 9 includes the developing roller 6, a developing blade 31, the frame member 29, bearings 45 and 46, and a cover 32.As illustrated in FIG.","2, the frame member 29 is provided with a projection 29d as a “fixing member” for fixing a fixed member 251Z of the flexible container 251.The projection 29d is a portion to be inserted into a hole 251a.","The flexible container 251 includes the fixed member 251Z on which the hole 251a to be fixed to the frame member 29 is formed, the accommodating portion 251b for accommodating (storing) the developer, and the openings 251h (251h1 to 251h6) for discharging the developer.","The hole 251a formed on the fixed member 251Z is a hole different from the openings 251h.","When the hole 251a is hooked on the projection 29d, the flexible container 251 is fixed to the frame member 29.When the hole 251a is unhooked from the projection 29d, the flexible container 251 becomes separable from the frame member 29.When the cartridge P is new, since the openings 251h (251h1 to 251h6) (refer to FIGS.","15A and 15B) are covered by the sealing member 253 detachably welded to the flexible container 251, the developer is sealed inside the flexible container 251.The sealing member 253 is coupled to the unsealing member 254.The unsealing member 254 is supported so as to be rotatable in the direction indicated by an arrow J by receiving a driving force from the apparatus body 2.When the new cartridge P is used, the cartridge P is attached to the apparatus body 2.Then, the unsealing member 254 receives a driving force from the apparatus body 2 to rotate.","At this timing, the sealing member 253 is detached from the flexible container 251 and is rolled up by the unsealing member 254.Thus, the openings 251h (251h1 to 251h6) of the flexible container 251 are exposed, enabling the developer in the flexible container 251 to be discharged into the frame member 29.The developing blade 31 for regulating the layer thickness of the developer on the circumferential surface of the developing roller 6 is fixed to the frame member 29 (refer to FIG.","5).","The bearings 45 and 46 are fixed at both ends of the frame member 29 in the longitudinal direction.","Gears 70, 69, and 68 are disposed on the drive side end.","The shaft of the supply roller 61 is fitted into the gear 70.The shaft of the developing roller 6 is fitted into the gear 69.The shaft of the agitating member 74 (FIG.","2) is fitted into the gear 68.The gear 69 is set to rotate when the gear 68 rotates.","The bearing 45 is provided with the gears 68, 69, and 70.The cover 32 is fixed to the outside of the gears 68, 69, and 70.End seals 62 are disposed at both ends of the shaft of the supply roller 61 to seal between the supply roller 61 and the frame member 29.As illustrated in FIG.","5, the cover 32 is provided with a cylindrical portion 32b.","A drive transmission portion 68a of the gear 68 is exposed through an opening 32d inside the cylindrical portion 32b.","When the cartridge P is attached to the apparatus body 2, the drive transmission portion 68a of the gear 68 is engaged with an apparatus body drive transmission member (not illustrated), so that a driving force from a drive motor (not illustrated) provided in the apparatus body 2 is transmitted.","The driving force input from the apparatus body 2 to the gear 68 is transmitted to the developing roller 6 via the gear 69.Photosensitive Unit and Developing Unit Assembling Process As illustrated in FIGS.","3 and 4, when assembling the developing unit 9 and the photosensitive unit 8, the outer diameter portion of the cylindrical portion 32b of the cover 32 is fitted into the hole 24a of the cover 24 on one end side.","Then, a protruding portion 46b protruding from the bearing 46 is fitted into the hole 25a of the cover 25 on the other end side.","Thus, the developing unit 9 is supported so as to be rotatable with respect to the photosensitive unit 8.The developing unit 9 is rotatable around an axis line connecting the hole 24a of the cover 24 and the hole 25a of the cover 25.The rotation center of the developing unit 9 is referred to as a rotation center X.","As illustrated in FIG.","2, the developing unit 9 is urged by a pressure spring 95 as an elastic member so that the developing roller 6 contacts the photosensitive drum 4 around the rotation center X.","More specifically, the developing unit 9 is pressed in the direction indicated by an arrow G illustrated in FIG.","2 by an urging force of the pressure spring 95 so that a moment in the direction indicated by an arrow H acts around the rotation center X.","Referring to FIG.","5, the gear 68 receives a rotational driving force in the direction indicated by the arrow H (refer to FIG.","2) from an apparatus body drive transmission member (not illustrated) provided on the apparatus body 2.The gear 69 engaged with the gear 68 thereby rotates in the direction indicated by an arrow E. Likewise, the developing roller 6 thereby rotates in the direction indicated by the arrow E. When a driving force required for rotating the developing roller 6 is input to the gear 68, a rotational moment in the direction indicated by the arrow H arises in the developing unit 9.A pressing force of the above-described pressure spring 95 and a rotational driving force from the apparatus body 2 cause the developing unit 9 to receive a moment in the direction indicated by the arrow H around the rotation center X.","Then, the developing roller 6 contacts the photosensitive drum 4 at a predetermined pressure.","Although, in the first embodiment, two forces, i.e., the pressing force by the pressure spring 95 and the rotational driving force from the apparatus body 2 are used to press the developing roller 6 against the photosensitive drum 4, only either one force may be used for the relevant purpose.","With the cartridge P being attached to the inside of the apparatus body 2, image formation is performed while consuming the developer inside the developing unit 9.The remanufacturing method of the cartridge P of refilling the developer into the developing unit 9 after consuming the developer inside the developing unit 9 will be sequentially described below.","Unit Separation Process The remanufacturing method of the developing unit 9 will be described below.","A unit separation process for separating the photosensitive unit 8 and the developing unit 9 of the cartridge P will be described below.","As illustrated in FIG.","3, when the covers 24 and 25 are removed from the cleaning container 26, the developing unit 9 and the photosensitive unit 8 can be separated.","As described above, since the covers 24 and 25 and the cleaning container 26 rotatably support the photosensitive drum 4, the above-described unit separation process enables the separation of the photosensitive drum 4 from the photosensitive unit 8.Developing Unit Disassembling Process A process for disassembling the developing unit 9 will be described below with reference to FIG.","5.First of all, the cover 32 provided at the drive side end of the developing unit 9 is separated from the frame member 29.When the cover 32 is fixed to the bearing 45 and the frame member 29 with a screw 93, the screw 93 is removed and then the cover 32 is separated from the developing unit 9.Then, on the drive side of the developing unit 9, the gears 68, 69, and 70 disposed inside the cover 32 in the longitudinal direction are separated from the developing unit 9.The gear 68 is slidably supported by the cover 32 and the bearing 45, and the gear 69 is fitted into an end of the shaft of the developing roller 6.The gear 70 is fitted into the shaft of the supply roller 61.Therefore, the gears 68, 69, and 70, the developing roller 6, and the supply roller 61 can be easily separated from the developing unit 9.Then, the bearings 45 and 46 and the developing roller 6 are separated from the developing unit 9.When the bearing 45 is fixed to the frame member 29 with a screw, the screw is removed and then the bearing 45 is separated from the frame member 29.In the present embodiment, the bearing 45 and the cover 32 are fixed together to the frame member 29 with the screw 93.Since the screw 93 has been removed when the cover 32 is separated from the frame member 29, the bearing 45 can be easily separated from the frame member 29.Likewise, when the bearing 46 is fixed to the frame member 29 with a screw, the bearing 46 can be separated from the frame member 29 after the screw is removed.","As described above, the developing roller 6 is slidably supported on the frame member 29 by the bearings 45 and 46.Therefore, in a state where the bearings 45 and 46 are separated from the frame member 29, the developing roller 6 can be easily separated from the frame member 29.Although, in the above descriptions, a process for separating both the bearings 45 and 46 from the frame member 29 is performed to separate the developing roller 6 from the frame member 29, the method is not limited thereto.","For example, after only the bearing 46 is separated from the frame member 29, the developing roller 6 may be pulled out toward the non-drive side to separate the developing roller 6 from the frame member 29.Then, the developing blade 31 is separated from the frame member 29.When the developing blade 31 is fixed to the frame member 29 with screw 91 and 92, the screws 91 and 92 are removed and then the developing blade 31 is separated from the frame member 29.FIGS.","14A, 14B, and 14C are perspective views illustrating a process for detaching the sealing member 253 from the flexible container 251.The flexible container 251 is accommodated (stored) inside the frame member 29.When the unsealing member 254 rotates, the sealing member 253 is separated from an attachment and detachment area around the openings 251h1 to 251h4 of the accommodating portion 251b of the flexible container 251.Although four openings 251h are illustrated in FIGS.","14A, 14B, and 14C, there are six openings 251h in the present embodiment.","The attachment and detachment area has two different portions on the downstream side in the detachment direction: parallel portions 80b parallel to the axis direction of the developing roller 6, and mountain-shaped portions 80c having a mountain shape toward the downstream side in the detachment direction.","The attachment and detachment area further includes a detachment start portion 80a parallel to the axis direction of the developing roller 6, at the upstream side in the detachment direction.","The sealing member 253 is pulled in the direction indicated by an arrow O1 and the direction indicated by the arrow O2 to be detached in states illustrated in FIGS.","14A, 14B, and 14C in this order.","First Communication Hole Processing Process FIG.","6 is a sectional view of the cartridge P illustrating a process for processing a first communication hole 101.First of all, a process for processing the first communication hole 101 on the frame member 29 of the developing unit 9 will be described below with reference to FIG.","6.A user holds the cartridge P so that the developing unit 9 is disposed on the vertically upper side.","Then, the user processes the first communication hole 101 as a “frame member communication hole” on the vertically upper surface of the frame member 29 (frame member processing process).","The flexible container 251 fixed to the inside of the frame member 29 is thereby exposed through the first communication hole 101.Second Communication Hole Processing Process FIG.","7 is a sectional view of the cartridge P illustrating a process for processing a second communication hole 102.A process for processing the second communication hole 102 on the flexible container 251 fixed to the inside of the frame member 29 will be described below with reference to FIG.","7.Since the first communication hole 101 is processed, the flexible container 251 is exposed.","The second communication hole 102 as a “container communication hole” is processed on the exposed flexible container 251 (container processing process).","The outside of the cartridge P and the inside of the flexible container 251 are thereby communicated with each other, making it possible to refill the developer into the flexible container 251 through the first communication hole 101 and the second communication hole 102.FIGS.","8A to 8C are perspective views of the flexible container 251 illustrating possible shapes of the second communication hole 102.As illustrated in FIGS.","8A to 8C, the second communication hole 102 may be a through hole such as a round hole (refer to FIG.","8A) and a square hole, or a cut portion such as a straight line cut portion, a cross-shaped cut portion (refer to FIG.","8B), and a U-shaped cut portion (refer to FIG.","8C).","Further, the second communication hole 102 may have any shape as long as it enables communication between the inside of the frame member 29 and the inside of the flexible container 251, and a funnel 201 (described below) can be inserted therein.","As the second communication hole 102, an opening larger than one of the openings 251h (251h1 to 251h6) of the flexible container 251 can be formed.","Developer Refilling Process FIG.","9 is a sectional view illustrating a process for refilling the developer into the cartridge P through the first communication hole 101 and the second communication hole 102.As illustrated in FIG.","9, the user refills the developer into the flexible container 251 inside the cartridge P in a state where the developing unit 9 is disposed on the vertically upper side.","In this case, the user inserts the funnel 201 for refilling the developer, in the direction indicated by an arrow K illustrated in FIG.","9.A tip portion 201a of the funnel 201 is inserted into the flexible container 251 inside the frame member 29 from the outside of the frame member 29 through the first communication hole 101 and the second communication hole 102, and the developer is refilled into the flexible container 251 (refilling process).","The user pours the developer into the funnel 201 from, for example, a toner bottle (not illustrated) to refill the developer into the flexible container 251 inside the frame member 29.As described above, an opening larger than the openings 251h of the flexible container 251 can be formed as the second communication hole 102.Thus, when the developer is refilled into the flexible container 251 through the second communication hole 102, the funnel 201 having a larger cross-sectional area of the tip portion 201a can be used as compared to the case of refilling the developer into the flexible container 251 through the openings 251h.","Therefore, the use of the second communication hole 102 enables more quick and efficient refilling of toner.","First Communication Hole Sealing Process FIG.","10 is a sectional view of the cartridge P illustrating a process for sealing the first communication hole 101.Then, the user attaches a first resealing member 103 for sealing the first communication hole 101, to the first communication hole 101 using a two-sided tape to prevent leakage of the developer from the frame member 29 (resealing process).","As illustrated in FIG.","10, the first resealing member 103 is attached in a state where the cartridge P is held so that the developing unit 9 is disposed on the upper side.","Then, the first resealing member 103 is attached to the frame member 29 so as to cover the first communication hole 101.The first resealing member 103 may have any shape as long as it covers the first communication hole 101 to prevent leakage of the developer from the frame member 29.Further, the first resealing member 103 may be attached by using an adhesive instead of a two-sided tape.","Further, the first resealing member 103 may not necessarily be a member to be attached using a two-sided tape or an adhesive, and may be a member to be fitted into the first communication hole 101, such as a cap.","The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P without disassembling the cartridge P. Second Communication Hole Sealing Process (Optional) FIG.","11 is a sectional view of the cartridge P illustrating a process for resealing the second communication hole 102.Similar to the first communication hole 101, the resealing process may be applied to the second communication hole 102.This process is performed for attaching a second resealing member 104 for sealing the second communication hole 102, to the second communication hole 102 using a two-sided tape to prevent leakage of the developer from the flexible container 251.The second resealing member 104 is attached in a state where the developing unit 9 is oriented vertically upward.","Then, the second resealing member 104 is attached to the flexible container 251 so as to cover the second communication hole 102.The second resealing member 104 may have any shape as long as it covers the second communication hole 102 to prevent leakage of the developer from the flexible container 251.Further, the second resealing member 104 may be attached by using an adhesive instead of a two-sided tape.","Then, after performing the second communication hole sealing process for sealing the second communication hole 102, the user performs the first communication hole sealing process for sealing the first communication hole 101 as described above.","It is only required to seal at least either one of the above-described first communication hole 101 and the second communication hole 102 to seal the developer refilled in the flexible container 251 (communication hole sealing process).","The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P, in which toner is refilled only into the flexible container 251 to reduce the possibility of leakage of toner from the cartridge P. Second Embodiment In the first embodiment, the developer is refilled through the frame member 29 and the flexible container 251 without sealing the openings 251h of the flexible container 251.Alternatively, prior to toner refilling, the user may disassemble the cartridge P until the openings 251h are exposed, seal the openings 251h of the flexible container 251, and then reassemble the cartridge P. After these processes, toner may be refilled only into the flexible container 251.FIG.","12 is a sectional view of the cartridge P illustrating a state before resealing by the sealing member 253.FIG.","13 is a sectional view of the cartridge P illustrating a state after resealing by the sealing member 253.Unit Separation Process and Developing Unit Disassembling Process In the above-described unit disassembling process, the user performs a separation process of the photosensitive unit 8 and the developing unit 9, and a disassembling process of the developing unit 9.Then, when the separation process of the developing unit 9 is completed, the openings 251h of the flexible container 251 inside the frame member 29 are exposed, allowing the user to refill the developer into the flexible container 251.However, the user does not refill the developer in this process.","Then, the user seals the openings 251h of the flexible container 251 without refilling of the developer through openings 251h.","This process will be described in detail below with reference to FIGS.","12 and 13.Opening Resealing Process As illustrated in FIG.","12, in the above-described separation process, the sealing member 253 is detached and the openings 251h are exposed.","In this state, the sealing member 253 is accessed from the direction indicated by an arrow V illustrated in FIG.","12, the sealing member 253 once used for sealing is welded to the flexible container 251 again, and the sealing member 253 is attached to the openings 251h of the flexible container 251 to reseal the openings 251h.","This results in the resealed state illustrated in FIG.","13.The leakage of toner from the flexible container 251 can be thereby prevented, and toner can be refilled only into the flexible container 251.The openings 251h are not necessarily sealed by welding, and may be sealed by adhesion by using a two-sided tape.","After performing the opening resealing processes, the cartridge P is reassembled.","Developing Unit Assembling Process and Unit Combining Process More specifically, the user performs an assembling process of the developing unit 9 and an assembling process of the photosensitive unit 8 and the developing unit 9.After completion of the assembling process of the cartridge P, the user performs the first communication hole processing process, the second communication hole processing process, and the toner refilling process which are similar to the processes according to the above-described embodiment.","The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Third Embodiment Developer Refilling Process FIG.","15A is a perspective view illustrating a state of the flexible container 251 containing no developer, before refilling of the developer.","FIG.","15B is a perspective view illustrating a state of the new flexible container 251.As illustrated in FIGS.","15A and 15B, the flexible container 251 before refilling of the developer has a different shape from that of the new flexible container 251, and has a smaller capacity than that of the new flexible container 251.The user holds the frame member 29 so that the openings 251h (251h1 to 251h6) of the flexible container 251 are oriented vertically upward, and refills the developer.","More specifically, when the size of the flexible container 251 before remanufacturing is represented by H0 in height, D0 in depth, and W0 in width, and the size of the new flexible container 251 is represented by H1 in height, D1 in depth, and W1 in width, a relationship “W1<W0, D1<D0, and H1<H0” may be satisfied.","To refill more developer into the flexible container 251, it is desirable to make the capacity of the flexible container 251 approximately equivalent to that of the new flexible container 251.Therefore, for example, before refilling the developer, the user may inject compressed air into the flexible container 251 to increase the capacity of the flexible container 251.FIG.","17 is a perspective view illustrating a process for injecting compressed air into the flexible container 251 to increase the capacity of the flexible container 251.The tip portion 201a of the funnel 201 is inserted into the flexible container 251 through the openings 251h (251h1 to 251h6) of the flexible container 251.When the flexible container 251 is provided with a plurality of openings 251h, the tip portion 201a of the funnel 201 may be inserted into any one of the openings 251h1 to 251h6.When compressed air is injected into the flexible container 251 from the funnel 201 in the direction indicated by an arrow A1 as illustrated in FIG.","17, compressed air is injected into the flexible container 251 from the tip portion 201a of the funnel 201 in the directions indicated by arrows A2 to A4 (air injection process).","Then, the flexible container 251 inflates in the directions indicated by arrows B1 to B3, and accordingly the size (the height H1, the depth D1, and the width W1) of the flexible container 251 recovers to almost the same size as the new flexible container 251.FIG.","18 is a perspective view illustrating a process for refilling the developer into the frame member 29 through the openings 251h of the flexible container 251, using the funnel 201.FIG.","20 is a sectional view illustrating a process for refilling the developer through the openings 251h (251h1 to 251h6) of the flexible container 251, using the funnel 201.The tip portion 201a of the funnel 201 is inserted through the openings 251h (251h1 to 251h6) of the flexible container 251.The user refills the developer into the flexible container 251 by dropping the developer into the funnel 201 from a developer bottle (not illustrated).","In addition, using a fixed-rate feeding device having an auger in the funnel-shaped main body enables efficient refilling of the developer.","When the flexible container 251 is provided with a plurality of openings 251h, the tip portion 201a of the funnel 201 may be inserted into any one of the openings 251h1 to 251h6.Developing Unit Assembling Process and Unit Combining Process When the refilling of the developer is completed, the user performs the assembling process of the developing unit 9 and the combining process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.","3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Fourth Embodiment FIG.","21 is a sectional view illustrating the developing unit 9.In the fourth embodiment, similar to the third embodiment, the user performs a developer refilling process without removing the developing roller 6 and the developing blade 31.Similar to the above descriptions, the user performs a unit separation process and a developing unit separation process to make the developing unit 9 a single unit.","As illustrated in FIG.","21, the user processes, on the frame member 29, a filling port 29r as a “frame member communication hole” as a hole for refilling the developer (frame member processing process).","The filling port 29r may have any shape as long as the tip portion 201a of the funnel 201 (described below) can be inserted therein.","FIG.","22 is a sectional view illustrating a process for refilling the developer into the flexible container 251 inside the developing unit 9.As illustrated in FIG.","22, the user inserts the tip portion 201a of the funnel 201 into the flexible container 251 inside the frame member 29 through the filling port 29r of the frame member 29 and the openings 251h of the flexible container 251, and then refills the developer.","FIG.","23 is a sectional view of the developing unit 9 illustrating a state where the developer is refilled.","As illustrated in FIG.","23, the filling port 29r of the frame member 29 is sealed by a hole sealing member 300.As the hole sealing member 300, an adhesive tape, a plastic plate with an adhesion layer, etc.","can be desirably used.","In the subsequent processes, the user combines the unit in reverse order of the unit separation process to complete the assembling process.","Fifth Embodiment Sealing Member Removing Process FIG.","24 is a front view illustrating the frame member 29 viewed from the side of the openings 251h of the flexible container 251.The sealing member 253 is fixed at fixing portions 254b (254b1 to 254b6) of the unsealing member 254 through ultrasonic welding.","On the drive side of the unsealing member 254, a gear 254a is fitted into the unsealing member 254.The non-drive side of the unsealing member 254 is held by the frame member 29.After the flexible container 251 is unsealed, the sealing member 253 is wound around the unsealing member 254.The user is able to remove the sealing member 253 by pulling the sealing member 253 wound around the unsealing member 254 in the direction indicated by an arrow U1 and then cutting off a dashed line portion Y of the sealing member 253 with a cutter.","The remanufacturing method includes a removing process for removing at least a part of the sealing member 253 in this way before the refilling process.","The user may remove the sealing member 253 from the unsealing member 254 by pulling the sealing member 253 wound around the unsealing member 254 in the direction indicated by the arrow U1.As a shape to make it easy to remove the sealing member 253, for example, the thickness of the sheet of the sealing member 253 in the vicinity of the fixing portions 254b of the unsealing member 254 may be thinner than a portion welded in the vicinity of the openings 251h.","In other words, in the sealing member 253, the film thickness of the portion to which the unsealing member 254 is fixed is thinner than that of the portion at which the openings 251h of the flexible container 251 are sealed.","The force required to separate the sealing member 253 from the fixing portions 254b of the unsealing member 254 is only required to be larger than the force required to detach the sealing member 253 from the flexible container 251.Upon completion of the above-described procedure, the disassembling process of the developing unit 9 is completed.","Then, the openings 251h (251h1 to 251h6) of the flexible container 251 provided in the frame member 29 are exposed, allowing the developer to be refilled into the flexible container 251.In the assembling process after refilling the developer, it is not necessary to reattach the removed sealing member 253.Effects of Sealing Member Removing Process Removing at least a part of the sealing member 253 from the unsealing member 254 can enhance the efficiency of the refilling process for refilling the developer through the openings 251h inside the flexible container 251.Developer Refilling Process Then, the user performs a developer refilling process.","This process is similar to the above-described methods illustrated in FIGS.","6 to 11.Developing Unit Assembling Process and Unit Assembling Process When the refilling of the developer is completed, the user performs the assembling process of the developing unit 9 and the assembling process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.","3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Sixth Embodiment In the fifth embodiment, the unsealing member 254 has a function of a pressing member.","In the sixth embodiment, the description will be given of a case in which the function of the unsealing member 254 is separated from the function of a pressing member.","FIG.","25 is a sectional view illustrating the cartridge P in which the developing unit 9 includes the unsealing member 254 and a pressing member 255.As illustrated in FIG.","25, the pressing member 255 and the unsealing member 254 are configured to receive a driving force from the apparatus body 2 to be rotatable in the direction indicated by the arrow J.","FIG.","26 is a front view illustrating the frame member 29 of the cartridge P in which the developing unit 9 includes the unsealing member 254 and the pressing member 255, viewed from the side of the openings 251h of the flexible container 251.The sealing member 253 is fixed at the fixing portions 254b(254b1 to 254b6) of the unsealing member 254 through ultrasonic welding.","On the drive side of the unsealing member 254, the gear 254a is fitted into the unsealing member 254.The non-drive side of the unsealing member 254 is held by the frame member 29.Similar to the unsealing member 254, on the drive side of the pressing member 255, a gear 255a of the pressing member 255 is fitted into the pressing member 255.The pressing member 255 moves the flexible container 251 to promote the discharge of the developer.","In the remanufactured process cartridge, since an operation for unsealing the flexible container 251 is not required, not only the sealing member 253 but also the unsealing member 254 can be removed as described below.","Sealing Member and Unsealing Member Removing Process The unsealing member 254 and the gear 254a can be separated from each other by pulling the gear 254a in the direction indicated by an arrow U2.Then, the user pulls out the non-drive side of the unsealing member 254 held by the frame member 29.The sealing member 253 and the unsealing member 254 can be thereby separated from the frame member 29.The user may bend the unsealing member 254 to detach the non-drive side from the frame member 29, and then pull out the gear 254a in the direction indicated by the arrow U2.Alternatively, for example, the user may cut off the sealing member 253 and the unsealing member 254 at a dashed line portion Z using a nipper, and then remove the non-drive side of the unsealing member 254 from the frame member 29 to separate the unsealing member 254 and the gear 254a.","The user may separately remove the sealing member 253 and the unsealing member 254.More specifically, the user may pull the sealing member 253 in the direction indicated by the arrow U1 as in the fifth embodiment to remove the sealing member 253, and then remove the unsealing member 254 from the frame member 29 as described above.","Alternatively, as illustrated in FIG.","27, a hole 29r3 for removing the sealing member 253 and the unsealing member 254 may be formed on the non-drive side surface of the frame member 29 holding the sealing member 253 and the unsealing member 254.The hole 29r3 is only required to have a size such that the sealing member 253 and the unsealing member 254 can be pulled out therethrough.","The user pulls out the unsealing member 254 in the direction indicated by an arrow U3 while holding the gear 254a.","Then, the user pulls out the gear 254a in the direction indicated by the arrow U2.Alternatively, while holding the unsealing member 254 through the hole 29r3, the user may first pull out the gear 254a in the direction indicated by the arrow U2, and then pull out the unsealing member 254 in the direction indicated by the arrow U3 through the hole 29r3.To seal the hole 29r3 and the hole from which the gear 254a was pulled out, the user can desirably use an adhesive tape, a plastic plate with an adhesion layer, etc.","In the assembling process after refilling the developer, it is not necessary to reattach the sealing member 253, the unsealing member 254, and the gear 254a that have been removed.","Seventh Embodiment In the fifth embodiment, the detailed description has been given of a case in which a hole for removing the sealing member 253 is not processed on the sealing member 253.In the seventh embodiment, a case in which a perforation is formed at the dashed line portion Y illustrated in FIG.","24, and the sealing member 253 has a perforation is described.","Sealing Member Removing Process As illustrated in FIG.","24, the user pulls the sealing member 253 in the direction indicated by the arrow U1 to release it from the state of being wound around the unsealing member 254.Then, the user pulls the sealing member 253 so as to cut off the perforation.","The sealing member 253 can be thereby cut off.","The force required to separate the sealing member 253 at the perforation of the sealing member 253 is only required to be larger than the force required to detach the sealing member 253 from the flexible container 251.Further, the force required to separate the sealing member 253 from the fixing portions 254b of the unsealing member 254 is only required to be larger than the force required to separate the sealing member 253 at the perforation of the sealing member 253.In the assembling process after refilling the developer, it is not necessary to reattach the removed sealing member 253.Eighth Embodiment In the first embodiment, the detailed description has been given of a case in which the sealing member 253 is formed of one sheet.","In the eighth embodiment, the description will be given of a case in which the sealing member 253 is formed by a fixing member 501 and an opening sealing member 502.As illustrated in FIG.","28, the fixing member 501 is fixed to the fixing portions 254b of the unsealing member 254.The opening sealing member 502 is a member for sealing the openings 251h of the flexible container 251.The fixing member 501 as a “fixing portion” and the opening sealing member 502 as a “sealing portion” are detachably adhered to each other at an adhesion portion R. Thus, the sealing member 253 is formed by the opening sealing member 502 for closing the openings 251h, and the fixing member 501 fixed to the unsealing member 254.The opening sealing member 502 and the fixing member 501 are adhered to each other.","Sealing Member Removing Process As illustrated in FIG.","28, the user pulls out the sealing member 253 wound around the unsealing member 254 in the direction indicated by the arrow U1, and then separates the fixing member 501 and the opening sealing member 502.The force required to separate the fixing member 501 and the opening sealing member 502 is only required to be larger than the force required to detach the opening sealing member 502 from the flexible container 251.Further, the force required to separate the fixing member 501 and the unsealing member 254 is only required to be larger than the force required to separate the fixing member 501 and the opening sealing member 502.In the assembling process after refilling the developer, it is not necessary to reattach the removed opening sealing member 502.Ninth Embodiment In the fifth embodiment, the detailed description has been given of a case in which the developing roller 6 and the developing blade 31 are removed in the disassembling process of the developing unit 9.In the ninth embodiment, a case in which the developing roller 6 and the developing blade 31 are not removed in the disassembling process of the developing unit 9 is described.","First of all, similar to the above descriptions, after the unit separation process, the user separates the developing unit 9 from the cartridge P. In this case, as illustrated in FIG.","22 described above, the user forms, on the frame member 29, the filling port 29r as a hole for removing the sealing member 253 and for refilling the developer.","More specifically, the user forms, on the frame member 29, the filling port 29r as a “frame member communication hole”, and removes at least the sealing member 253 through the filling port 29r.","A hole may be formed anywhere on the frame member 29 as long as the sealing member 253 can be removed and the developer can be refilled through the filling port 29r of the frame member 29 and the openings 251h of the flexible container 251.The filling port 29r may have any shape as long as the sealing member 253 can be taken out therefrom, and as long as the tip portion 201a of the funnel 201 (described below) can be inserted therein.","The method for removing the sealing member 253 is similar to that according to the first embodiment.","Developer Refilling Process As illustrated in FIG.","22, the user inserts the tip portion 201a of the funnel 201 into the flexible container 251 through the filling port 29r and the openings 251h of the flexible container 251, and then refills the developer.","FIG.","23 is a sectional view of the developing unit 9 in which the developer is refilled.","As illustrated in FIG.","23, the user seals the filling port 29r of the frame member 29 using the hole sealing member 300.As the hole sealing member 300, an adhesive tape, a plastic plate with an adhesion layer, etc.","can be desirably used.","In the subsequent processes, the user combines the unit in reverse order of the unit separation process to complete the assembling process.","Tenth Embodiment Developing Unit Assembling Process FIG.","29 is an exploded perspective view illustrating the developing unit 9.Then, the user separates a supply roller 61 from the frame member 29.FIGS.","30A and 30B are enlargement views illustrating the non-drive side portion of the frame member 29 (a portion A illustrated in FIG.","29).","As illustrated in FIG.","30A, a hole 29b into which the shaft of the supply roller 61 is to be fitted is formed on the frame member 29.When the gap between the shaft of the supply roller 61 and the frame member 29 is sealed by the end seals 62, the user removes the end seals 62 and then separates the supply roller 61 from the frame member 29.The user may perform the removing process of both of the respective end seals 62 of the drive side and the non-drive side, the method is not limited thereto.","For example, the user may perform only the removing process of the end seal 62 on the non-drive side and then pull out the supply roller 61 toward the non-drive side to separate it from the frame member 29.Although, in the above descriptions, the shaft of the supply roller 61 is fitted into the hole 29b of the frame member 29, the configuration is not limited thereto.","The supply roller 61 may be fixed to the frame member 29 through a fixing member 28 of the supply roller 61 (refer to FIG.","30B).","In this case, the user separates the fixing member 28 from the frame member 29 and then separates the supply roller 61 from the frame member 29.The user may perform the process for separating the fixing member 28 from the frame member 29 both on the non-drive side and the drive side or only on either one of the non-drive side and the drive side.","For example, when the user performs a removing process of the fixing member 28 only on the non-drive side, the user is able to separate the supply roller 61 from the frame member 29 by pulling out the supply roller 61 toward the non-drive side.","Upon completion of the above-described procedure, the disassembling process of the developing unit 9 is completed, allowing the developer to be refilled.","Opening Enlargement Process FIGS.","31A, 31B, 31C, and 31D are perspective views of the flexible container 251 illustrating an enlargement process for enlarging a plurality of openings 251h1 to 251h10 of the flexible container 251.The remanufacturing method includes an opening processing process for processing the openings 251h so as to enlarge the openings 251h, before the refilling process.","The opening processing process connects the plurality of openings 251h.","As illustrated in FIG.","31A, a certain method cuts off all of connecting portions L1 to L9 between the openings 251h1 to 251h10 of the flexible container 251.As illustrated in FIG.","31B, another method cuts off only the connecting portion L1 among the connecting portions L1 to L9 between the openings 251h1 to 251h10 of the flexible container 251.As illustrated in FIG.","31C, still another method cuts off a large area including the connecting portions L1 and L9 between the openings 251h1 to 251h10 of the flexible container 251 to form an opening L10.As illustrated in FIG.","31D, substantially similar to FIG.","31C, still another method cuts off a large area to form an opening 251h11.In this case, the opening processing process forms the opening 251h11 larger than an area including all of the plurality of openings 251h.","The opening after the processing may have any shape as long as it is enlarged to be larger than the opening before the processing.","In the following descriptions, the opening after the processing is referred to as a refilling opening 251F.","Developer Refilling Process FIG.","32 is a sectional view of the frame member 29 illustrating a process for refilling the developer through the refilling opening 251F.","As illustrated in FIG.","32, when refilling the developer, the frame member 29 is disposed so that the refilling opening 251F is oriented vertically upward.","The funnel 201 used for refilling the developer has such a cross-sectional area of the tip portion 201a as to be fitted into the size of the enlarged refilling opening 251F.","The tip portion 201a of the funnel 201 is inserted into the flexible container 251 through the refilling opening 251F in the direction indicated by an arrow M. The user pours the developer T into the funnel 201 from, for example, a toner bottle (not illustrated) to refill the developer T into the flexible container 251 and into the frame member 29.Although, in the present embodiment, the funnel 201 used has a cross-sectional area of the tip portion 201a according to the size of the refilling opening 251F, the refilling opening 251F may be enlarged according to the size of the funnel 201.As described above, since the refilling opening 251F has a larger opening area than the openings 251h1 to 251h10 of the new flexible container 251, the tip portion 201a of the funnel 201 can have a large cross-sectional area.","This enables efficient refilling of toner in a shorter time.","When the developer T is refilled without enlarging an opening, the user needs to use the funnel 201 having a small cross-sectional area of the tip portion 201a according to the size of the opening.","Therefore, the developer will stagnate in the tip portion 201a of the funnel 201, prolonging the time of refilling.","Further, when refilling the developer T having high cohesiveness, the tip portion 201a of the funnel 201 will be clogged with the developer, making it impossible to refill the developer.","When an opening is extremely small, the tip portion 201a of the funnel 201 cannot be inserted into the flexible container 251.If the user performs the refilling process without inserting the tip portion 201a of the funnel 201 into the flexible container 251, almost none of the refilled developer is filled into the flexible container 251, and only a very small capacity inside the frame member 29 and outside the flexible container 251 is filled with the developer.","As a result, the developer refilling may not be sufficiently completed.","Developing Unit Assembling Process and Unit Combining Process After refilling the developer into the flexible container 251 in this way, the user performs the assembling process of the developing unit 9, and the combining process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.","3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Eleventh Embodiment Opening Enlargement Process FIG.","33A is a perspective view of the flexible container 251 illustrating an enlargement process for enlarging an opening of the flexible container 251 according to the eleventh embodiment.","On the flexible container 251, a cutoff line k1 is preprocessed at the connecting portion L4 between the openings 251h4 and 251h5.In the opening enlargement process, an opening is enlarged by cutting off the cutoff line k1.In the opening processing process, at least one of the plurality of openings 251h is processed.","Further, a plurality of cutoff lines may be processed at connecting portions.","For example, a cutoff line k2 may be processed at the connecting portion L5 between the openings 251h5 and 251h6, in addition to the cutoff line k1.However, the cutoff lines k1 and k2 need to be left uncut when the sealing member 253 is wound up by the unsealing member 254.Therefore, rather than processing the cutoff lines k1 and k2 in the direction perpendicular to the direction indicated by the arrow B in which the sealing member 253 is wound up, it is better to process a cutoff line k4 in such a direction that forms a small angle with respect to the direction of the arrow B in which the sealing member 253 is wound up.","However, the winding direction and the cutoff line direction are not limited thereto.","The tension required to cut off the cutoff lines is only required to be larger than the tension applied to the cutoff lines while the sealing member 253 is being wound up.","FIG.","33B is a perspective view of the flexible container 251 illustrating a cutoff line k3 according to a modification.","As illustrated in FIG.","33B, the cutoff line k3 extending in the direction indicated by the arrow B and connecting with the opening 251h5 may be processed on the surface of the flexible container 251.The cutoff line preprocessed on the flexible container 251 is only required to enlarge an opening by being cut off in the opening enlargement process.","The number and shape of cutoff lines are not limited.","Likewise, an opening can be enlarged by cutting off at least one cutoff line in the opening enlargement process.","Therefore, the user does not need to cut off all of the processed cutoff lines.","The subsequent developer refilling process is similar to that according to the tenth embodiment, and descriptions thereof will be omitted.","Twelfth Embodiment Refilling Opening Processing Process FIGS.","34A, 34B, and 34C are perspective views of the flexible container 251 illustrating a processing process for processing a refilling opening 251G on the flexible container 251 fixed to the inside of the frame member 29.As described above, when the disassembly of the developing unit 9 is completed, the flexible container 251 is exposed.","In this case, the refilling opening 251G is processed on the exposed flexible container 251.This enables the developer to be refilled into the flexible container 251 through the refilling opening 251G.","The refilling opening 251G may be a round through hole 251G1 as illustrated in FIG.","34A, a cross-shaped cut portion 251G2 as illustrated in FIG.","34B, or a U-shaped cut portion 251G3 as illustrated in FIG.","34C.","Further, the refilling opening 251G may have any shape as long as the funnel 201 (described below) can be inserted therein, and may be a through hole such as a square hole, or a cut portion such as a straight line cut portion.","It is desirable to form the refilling opening 251G so large as to allow communication between the inside and the outside of the flexible container 251 more than one of the openings 251h (251h1 to 251h6) on the flexible container 251 does.","Forming the large refilling opening 251G enables a more efficient developer refilling process.","Developer Refilling Process Then, the user performs the developer refilling process, which has been described above with reference to FIGS.","15, 17, and 18.When injecting compressed air into the flexible container 251, any one of the refilling openings 251G illustrated in FIGS.","34A, 34B, and 34C may be used.","As illustrated in FIGS.","34A, 34B, and 34C, the tip portion 201a of the funnel 201 is inserted into the refilling opening 251G of the flexible container 251 (refer to FIG.","16).","The user refills the developer into the flexible container 251 by dropping the developer into the funnel 201 from a developer bottle (not illustrated).","In addition, using a fixed-rate feeding device having an auger in the funnel-shaped main body enables efficient refilling of the developer.","Developing Unit Assembling Process Subsequently, the user performs the assembling process of the developing unit 9 and the unit combining process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.","3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Thirteenth Embodiment In the twelfth embodiment, the detailed description has been given of a case in which the refilling opening 251G is formed on the flexible container 251 without removing the sealing member 253, and then the developer is refilled.","In the thirteenth embodiment, a description will be given of a case in which the refilling opening 251G is formed on the flexible container 251 after removing the sealing member 253, and then the developer is refilled.","Sealing Member Removing Process As described above with reference to FIG.","24, the user may remove the sealing member 253 and then perform the refilling process.","More specifically, at least a part of the sealing member 253 is removed (removing process) before the refilling process.","After removing the sealing member 253, the user forms any one of the refilling openings 251G illustrated in FIGS.","34A, 34B, and 34C on the flexible container 251, and then performs the developer refilling process as illustrated in FIG.","19.More specifically, the refilling opening 251G as “another opening” different from the openings 251h is processed on the flexible container 251 (another opening process) before the refilling process.","In addition, the refilling opening 251G is processed to be larger than the openings 251h.","In the assembling process after refilling the developer, the user does not need to reattach the removed sealing member 253.As in the present embodiment, removing the sealing member 253 enables a more efficient developer refilling process.","Fourteenth Embodiment In the first embodiment, the detailed description has been given of a case in which the developing blade 31 and the like are separated from the frame member 29 to expose the flexible container 251.In the fourteenth embodiment, the description will be given of a case in which only the developing blade 31 is separated from the frame member 29 and then the developer is refilled into the flexible container 251.Developing Blade Disassembling Process To separate only the developing blade 31 from the frame member 29, the user disassembles only the developing blade 31 without disassembling members excluding the developing blade 31 in the disassembling process of the developing unit 9 described with reference to FIG.","29 in the tenth embodiment.","In the developing unit 9 in which the developing blade 31 as a “regulating member” for regulating the layer thickness of the developer on the developing roller 6 is attached to the frame member 29, only the developing blade 31 is separated from the frame member 29 (separation process) before the another opening process.","When the developing blade 31 is fixed to the frame member 29 with the screws 91 and 92, the screws 91 and 92 are removed and then the developing blade 31 is separated from the frame member 29.After separating the developing blade 31 from the frame member 29, any one of the refilling openings 251G as illustrated in FIGS.","34A, 34B, and 34C is formed on the flexible container 251, and then the developer refilling process as illustrated in FIG.","19 is performed.","In addition, the sealing member 253 may be removed after separating the developing blade 31.Alternatively, the unsealing member 254 may be rotated to expose the flexible container 251, without removing the sealing member 253.In the present embodiment, separating only the developing blade 31 from the frame member 29 enables a more simple developer refilling process.","According to the configurations of the first to the fourteenth embodiments, the remanufacturing method of the developing unit 9 is simplified as compared with the conventional technique.","The configurations or processes according to the first to the fourteenth embodiments can be suitably combined.","Although, in the first to the fourteenth embodiments, the description has been given of the cartridge P including the developing unit 9 and the photosensitive unit 8, the configuration is not limited thereto as long as it includes the developing unit 9.In other words, the first to the fourteenth embodiments are also applicable to a developing device, a cartridge, and an image forming apparatus as long as these include the developing unit 9.According to an embodiment of the present invention, it is possible to provide a remanufacturing method of a developer accommodating unit including a flexible container.","While the present invention has been described with reference to embodiments, it is to be understood that the invention is not limited to the disclosed embodiments.","The scope of the following claims is to be accorded the broadest interpretation so as to encompass all such modifications and equivalent structures and functions."]],"string":"[\n [\n \"REMANUFACTURING METHOD OF DEVELOPER ACCOMMODATING UNIT\",\n \"Provided is a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container.\",\n \"The remanufacturing method includes refilling the developer into the flexible container.\"\n ],\n [\n \"1.A remanufacturing method of a cartridge detachably mountable to an image forming apparatus, the cartridge including a used flexible container being configured to accommodate developer and provided with a plurality of openings for discharging developer, the remanufacturing method comprising: filling the used flexible container with developer; and attaching a sealing member to an outside surface of the used flexible container such that the sealing member covers the plurality of openings.\",\n \"2.The remanufacturing method according to claim 1, wherein the used flexible container comprises a developer accommodating portion for accommodating developer, and the used flexible container is deformable to change a capacity of the developer accommodating portion.\",\n \"3.The remanufacturing method according to claim 1, wherein the remanufacturing method comprises removing at least part of a frame member for accommodating the used flexible container such that at least part of the used flexible container is exposed.\",\n \"4.The remanufacturing method according to claim 1, wherein the used flexible container is a flexible container with developer consumed.\",\n \"5.The remanufacturing method according to claim 1, wherein the remanufacturing method comprises attaching an image bearing member for bearing a latent image to the cartridge.\",\n \"6.The remanufacturing method according to claim 1, wherein the remanufacturing method comprises attaching a developer bearing member for developing a latent image to the cartridge.\",\n \"7.A cartridge detachably mountable to an image forming apparatus comprising: an used flexible container configured to accommodate developer and provided with a plurality of openings for discharging developer; developer filled in the used flexible container; and a sealing member bonded to an outside of the used flexible container such that the plurality of the openings are covered by the sealing member.\",\n \"8.The cartridge according to claim 7, wherein the used flexible container comprises a fixed portion being provided with a plurality of the holes.\",\n \"9.The cartridge according to claim 7, wherein the used flexible container comprises a developer accommodating portion for accommodating developer, and the used flexible container is deformable to change a capacity of the developer accommodating portion.\",\n \"10.The cartridge according to claim 7, wherein the used flexible container is a flexible container with developer consumed.\",\n \"11.The cartridge according to claim 7, wherein the cartridge includes an image bearing member for bearing a latent image.\",\n \"12.The cartridge according to claim 7, wherein the cartridge includes a developer bearing member for developing a latent image.\",\n \"13.A cartridge detachably mountable to an image forming apparatus comprising: developer filled in an used flexible container being configured to accommodate developer and provided with a plurality of openings for discharging developer, wherein the plurality of the openings are covered by a sealing member bonded to an outside of the used flexible container.\",\n \"14.The cartridge according to claim 13, wherein the used flexible container comprises a fixed portion being provided with a plurality of holes.\",\n \"15.The cartridge according to claim 13, wherein the used flexible container comprises a developer accommodating portion for accommodating developer, and the used flexible container is deformable to change a capacity of the developer accommodating portion.\",\n \"16.The cartridge according to claim 13, wherein the used flexible container is a flexible container with developer consumed.\",\n \"17.The cartridge according to claim 13, wherein the cartridge includes an image bearing member for bearing a latent image.\",\n \"18.The cartridge according to claim 13, wherein the cartridge includes a developer bearing member for developing a latent image.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is directed to a remanufacturing method of a developer accommodating unit including a flexible container.\",\n \"According to an aspect of the present invention, a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container, includes refilling the developer into the flexible container.\",\n \"Further features of the present invention will become apparent from the following description of embodiments with reference to the attached drawings.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/359,382 filed Nov. 22, 2016, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/920,316 filed Oct. 22, 2015, now U.S. Pat.\",\n \"No.\",\n \"9,535,372 issued Jan. 3, 2017, which claims the benefit of Japanese Patent Application No.\",\n \"2014-218519, filed Oct. 27, 2014, all of which are hereby incorporated by reference herein in their entirety.\",\n \"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a remanufacturing method of a developer accommodating unit for refilling a developer.\",\n \"An image forming apparatus forms an image on a recording medium using an electrophotographic image forming process.\",\n \"Examples of image forming apparatuses include electrophotographic copying machines, electrophotographic printers (for example, laser beam printers and light emitting diode (LED) printers), facsimile apparatuses, and word processors.\",\n \"A developing device includes developer, and a developing roller as a developer bearing member for developing an electrostatic latent image formed on a photosensitive drum as an image bearing member.\",\n \"The developing device is detachably attached to an image forming apparatus or a photosensitive drum unit including a photosensitive drum.\",\n \"A cartridge (process cartridge) integrally includes a photosensitive drum and a developing roller, and is detachably attached to an image forming apparatus.\",\n \"Description of the Related Art Japanese Patent No.\",\n \"3320403 discloses a remanufacturing method of a cartridge having a developing device, more specifically, a remanufacturing method of a cartridge for refilling, using a funnel, toner into a storage container for storing toner, after removing a developing roller and a developing blade.\",\n \"SUMMARY OF THE INVENTION The present invention is directed to a remanufacturing method of a developer accommodating unit including a flexible container.\",\n \"According to an aspect of the present invention, a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container, includes refilling the developer into the flexible container.\",\n \"Further features of the present invention will become apparent from the following description of embodiments with reference to the attached drawings.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a sectional view illustrating an image forming apparatus.\",\n \"FIG.\",\n \"2 is a sectional view illustrating a cartridge.\",\n \"FIG.\",\n \"3 is a perspective view illustrating the cartridge viewed from a drive side.\",\n \"FIG.\",\n \"4 is a perspective view illustrating the cartridge viewed from a non-drive side.\",\n \"FIG.\",\n \"5 is an exploded perspective view illustrating a developing unit.\",\n \"FIG.\",\n \"6 is a sectional view of the cartridge illustrating a process for processing a first communication hole.\",\n \"FIG.\",\n \"7 is a sectional view of the cartridge illustrating a process for processing a second communication hole.\",\n \"FIGS.\",\n \"8A, 8B, and 8C are perspective views of a flexible container illustrating shapes of the second communication hole.\",\n \"FIG.\",\n \"9 is a sectional view illustrating a process for refilling developer into the cartridge through the first and the second communication holes.\",\n \"FIG.\",\n \"10 is a sectional view of the cartridge illustrating a process for sealing the first communication hole.\",\n \"FIG.\",\n \"11 is a sectional view of the cartridge illustrating a process for resealing the second communication hole.\",\n \"FIG.\",\n \"12 is a sectional view of the cartridge illustrating a state before resealing by a sealing member.\",\n \"FIG.\",\n \"13 is a sectional view of the cartridge illustrating a state after resealing by the sealing member.\",\n \"FIGS.\",\n \"14A, 14B, and 14C are perspective views illustrating a process for detaching the sealing member from the flexible container.\",\n \"FIG.\",\n \"15A is a perspective view illustrating a state of the flexible container containing no developer, before the developer is refilled, and FIG.\",\n \"15B is a perspective view illustrating a state of a new flexible container.\",\n \"FIG.\",\n \"16 is a sectional view illustrating a process for refilling the developer.\",\n \"FIG.\",\n \"17 is a perspective view illustrating a process for injecting compressed air into the flexible container to increase a capacity of the flexible container.\",\n \"FIG.\",\n \"18 is a perspective view illustrating a process for refilling the developer into a frame member through an opening of the flexible container, using a funnel.\",\n \"FIG.\",\n \"19 is a sectional view illustrating a process for refilling the developer.\",\n \"FIG.\",\n \"20 is a sectional view illustrating a process for refilling the developer through an opening of the flexible container, using a funnel.\",\n \"FIG.\",\n \"21 is a sectional view illustrating a developing unit.\",\n \"FIG.\",\n \"22 is a sectional view illustrating a process for refilling the developer into the flexible container inside the developing unit.\",\n \"FIG.\",\n \"23 is a sectional view of the developing unit illustrating a state where the developer is refilled.\",\n \"FIG.\",\n \"24 is a front view illustrating the frame member viewed from an opening side of the flexible container.\",\n \"FIG.\",\n \"25 is a sectional view illustrating the cartridge in which the developing unit includes an unsealing member and a pressing member.\",\n \"FIG.\",\n \"26 is a front view illustrating the frame member of the cartridge in which the developing unit includes the unsealing member and the pressing member, viewed from an opening side of the flexible container.\",\n \"FIG.\",\n \"27 is a front view illustrating the frame member of the cartridge in which the developing unit includes the unsealing member and the pressing member, viewed from an opening side of the flexible container.\",\n \"FIG.\",\n \"28 is a side view illustrating the sealing member and the unsealing member.\",\n \"FIG.\",\n \"29 is an exploded perspective view illustrating the developing unit.\",\n \"FIGS.\",\n \"30A and 30B are enlarged views illustrating a non-drive side portion of the frame member (a portion A illustrated in FIG.\",\n \"29).\",\n \"FIGS.\",\n \"31A, 31B, 31C, and 31D are perspective views of the flexible container illustrating an enlargement process for enlarging an opening of the flexible container.\",\n \"FIG.\",\n \"32 is a sectional view of the frame member illustrating a process for refilling the developer through a refilling opening.\",\n \"FIGS.\",\n \"33A and 33B are perspective views of the flexible container illustrating the enlargement process for enlarging an opening of the flexible container according to an eleventh embodiment.\",\n \"FIGS.\",\n \"34A, 34B, and 34C are perspective views of the flexible container illustrating a process for processing a refilling opening on the flexible container fixed to the inside of the frame member.\",\n \"DESCRIPTION OF THE EMBODIMENTS Embodiments of the present invention will be described in detail below with reference to the accompanying drawings.\",\n \"However, sizes, materials, shapes, and relative positions of elements described in the embodiments are not limited thereto, and can be appropriately modified depending on the configuration of an apparatus according to the present invention and other various conditions.\",\n \"Unless otherwise specifically described, the scope of the present invention is not limited to the embodiments described below.\",\n \"Elements in subsequent embodiments that are identical to those in preceding embodiments are assigned the same reference numerals, and descriptions in the preceding embodiments will be incorporated by reference.\",\n \"In the following descriptions, a developer accommodating unit includes at least a frame member and a flexible container.\",\n \"A developing device includes at least a developer bearing member.\",\n \"Further, a process cartridge includes at least an image bearing member.\",\n \"In the embodiments, a developer accommodating unit is equal to a developing device.\",\n \"In the embodiments, a developing unit may be independently configured as a developing device.\",\n \"First Embodiment FIG.\",\n \"1 is a sectional view illustrating an image forming apparatus 1.The image forming apparatus 1 performs full color image formation, and is provided with an apparatus body 2.Inside the apparatus body 2, four cartridges P are detachably attached.\",\n \"In the following descriptions of the image forming apparatus 1, the front surface is on the right side, the rear surface is on the left side, the drive side is on the rear side, and the non-drive side is on the front side, as illustrated in FIG.\",\n \"1.The cartridges P attached to the apparatus body 2 are the following four cartridges: a first cartridge PY, a second cartridge PM, a third cartridge PC, and a fourth cartridge PK.\",\n \"These cartridges P are disposed in a horizontal direction.\",\n \"These cartridges P have an approximately similar configuration expect for different toner colors.\",\n \"The first cartridge PY accommodates yellow developer, the second cartridge PM accommodates magenta developer, the third cartridge PC accommodates cyan developer, and the fourth cartridge PK accommodates black developer.\",\n \"The image forming apparatus 1 performs color image formation on a recording material S. The image forming apparatus 1 is a cartridge type image forming apparatus in which the cartridges P are detachably attached to the apparatus body 2 and a color image is formed on the recording material S. A mechanism inside the cartridge P is driven by a rotational driving force received from a drive output unit (not illustrated) of the apparatus body 2.Internal devices in the cartridge P is supplied with bias voltages (a charging bias voltage, a developing bias voltage, etc.)\",\n \"from the apparatus body 2.An exposure device 200 is disposed above the plurality of cartridges P. The exposure device 200 is a laser scanner unit for irradiating a photosensitive drum 4 with laser light LS based on information transmitted from a controller 50 in the apparatus body 2.This laser light LS passes through an exposure window portion 10 (refer to FIG.\",\n \"2) inside the cartridge P, and the surface of the photosensitive drum 4 is exposed to the laser light LS to be scanned.\",\n \"An intermediate transfer belt unit 11 is disposed below the plurality of cartridges P. The intermediate transfer belt unit 11 includes a transfer belt 12, and a drive roller 13 and tension rollers 14 and 15 for stretching the transfer belt 12.The transfer belt 12 is made of a flexible material.\",\n \"The bottom surface of the photosensitive drum 4 inside the cartridge P contacts the upper surface of the transfer belt 12.The relevant contact portion is a primary transfer portion.\",\n \"Inside the transfer belt 12, primary transfer rollers 16 are disposed to surface respective photosensitive drums 4.A secondary transfer roller 17 is disposed at a position facing the tension roller 14 via the transfer belt 12.The contact portion between the secondary transfer roller 17 and the transfer belt 12 is a secondary transfer portion.\",\n \"A feed unit 18 is disposed below the intermediate transfer belt unit 11.The feed unit 18 includes a tray 19 on which recording materials S are stacked, and a feed roller 20.A fixing unit 21 and a discharge unit 22 are disposed at the upper left position of the cartridge P. A discharge tray 23 is formed on the upper surface of the apparatus body 2.The recording material S is fixed by the fixing unit 21 and then discharged onto the discharge tray 23.FIG.\",\n \"2 is a sectional view illustrating the cartridge P. The cartridge P includes a photosensitive unit 8 and a developing unit 9 as a “developer accommodating unit”.\",\n \"The photosensitive unit 8 includes the photosensitive drum 4 as an “image bearing member”, a charging roller 5, and a cleaning member 7.The charging roller 5 uniformly charges the surface of the photosensitive drum 4.The cleaning member 7 is a blade for removing residual toner that has been developed on the surface of the photosensitive drum 4, but has not been transferred onto the primary transfer roller 16.The developing unit 9 includes a developing roller 6 as a “developer bearing member”, a supply roller 61, and an agitating member 74.The developing roller 6 develops an electrostatic image on the surface of the photosensitive drum 4 using toner.\",\n \"The supply roller 61 supplies developer to the developing roller 6.The agitating member 74 agitates the developer inside the developing unit 9.Operations of the image forming apparatus 1 will be described below with reference to above-described FIGS.\",\n \"1 and 2.The surface of the photosensitive drum 4 is uniformly charged by the charging roller 5 and then is exposed to light by the exposure device 200, so that an electrostatic image is formed on the surface of the photosensitive drum 4.When the electrostatic image is developed by the developing unit 9 using the developer, a developer image is formed.\",\n \"The developer image on the surface of the photosensitive drum 4 is transferred onto the transfer belt 12 rotating in a forward direction (the direction indicated by an arrow C illustrated in FIG.\",\n \"1) of the rotational direction of the photosensitive drum 4.Yellow, magenta, cyan, and black developer images are primarily transferred sequentially from the respective photosensitive drums 4 of the first to the fourth cartridges P onto the transfer belt 12 to be superimposed upon one another.\",\n \"Meanwhile, the recording materials S stacked on the tray 19 are separated and fed one by one according to a predetermined control timing.\",\n \"Each of the recording materials S is conveyed to the secondary transfer portion between the secondary transfer roller 17 and the transfer belt 12.At the secondary transfer portion, the developer image on the surface of the transfer belt 12 is secondarily transferred onto the recording material S. The developing unit 9 includes a flexible container 251 for accommodating (storing) the developer, and a frame member 29 for accommodating (storing) the flexible container 251.The flexible container 251 is provided with openings 251h for discharging the developer.\",\n \"The developing unit 9 further includes a sealing member 253 for sealing the openings 251h, and exposing the openings 251h when being moved, and an unsealing member 254 attached to the sealing member 253 and for unsealing the openings 251h when being moved.\",\n \"In other words, the developing unit 9 refers to a unit including at least the flexible container 251, the sealing member 253, and the unsealing member 254 inside the frame member 29.The flexible container 251 includes an accommodating portion 251b for accommodating (storing) the developer T, and the openings 251h for discharging the developer T. FIG.\",\n \"3 is a perspective view illustrating the cartridge P viewed from the drive side.\",\n \"FIG.\",\n \"4 is a perspective view illustrating the cartridge P viewed from the non-drive side.\",\n \"As illustrated in FIGS.\",\n \"3 and 4, the photosensitive unit 8 and the developing unit 9 are integrally formed by covers 24 and 25.Therefore, the photosensitive unit 8 includes the photosensitive drum 4, the charging roller 5, the cleaning member 7, a cleaning container 26, and the covers 24 and 25.The photosensitive drum 4 is rotatably supported on the cleaning container 26 by the covers 24 and 25.One end side of the photosensitive drum 4 in the longitudinal direction is provided with a coupling member 4a for transmitting a driving force to the photosensitive drum 4.When the coupling member 4a is engaged with a drum drive output unit of the apparatus body 2, the driving force of the drive motor (not illustrated) of the apparatus body 2 is transmitted to the photosensitive drum 4.The charging roller 5 is supported by the cleaning container 26 so that the charging roller 5 can be rotatably driven with being in contact with the photosensitive drum 4.The cleaning member 7 is supported by the cleaning container 26 so that the cleaning member 7 contacts the circumferential surface of the photosensitive drum 4 at a predetermined pressure.\",\n \"Residual developer removed from the circumferential surface of the photosensitive drum 4 by the cleaning member 7 is stored in the cleaning container 26.Holes 24a and 25a for rotatably supporting the developing unit 9 are formed on the covers 24 and 25, respectively.\",\n \"FIG.\",\n \"5 is an exploded perspective view illustrating the developing unit 9.The flexible container 251 is stored in the developing unit 9 illustrated in FIG.\",\n \"5.As illustrated in FIG.\",\n \"5, the developing unit 9 includes the developing roller 6, a developing blade 31, the frame member 29, bearings 45 and 46, and a cover 32.As illustrated in FIG.\",\n \"2, the frame member 29 is provided with a projection 29d as a “fixing member” for fixing a fixed member 251Z of the flexible container 251.The projection 29d is a portion to be inserted into a hole 251a.\",\n \"The flexible container 251 includes the fixed member 251Z on which the hole 251a to be fixed to the frame member 29 is formed, the accommodating portion 251b for accommodating (storing) the developer, and the openings 251h (251h1 to 251h6) for discharging the developer.\",\n \"The hole 251a formed on the fixed member 251Z is a hole different from the openings 251h.\",\n \"When the hole 251a is hooked on the projection 29d, the flexible container 251 is fixed to the frame member 29.When the hole 251a is unhooked from the projection 29d, the flexible container 251 becomes separable from the frame member 29.When the cartridge P is new, since the openings 251h (251h1 to 251h6) (refer to FIGS.\",\n \"15A and 15B) are covered by the sealing member 253 detachably welded to the flexible container 251, the developer is sealed inside the flexible container 251.The sealing member 253 is coupled to the unsealing member 254.The unsealing member 254 is supported so as to be rotatable in the direction indicated by an arrow J by receiving a driving force from the apparatus body 2.When the new cartridge P is used, the cartridge P is attached to the apparatus body 2.Then, the unsealing member 254 receives a driving force from the apparatus body 2 to rotate.\",\n \"At this timing, the sealing member 253 is detached from the flexible container 251 and is rolled up by the unsealing member 254.Thus, the openings 251h (251h1 to 251h6) of the flexible container 251 are exposed, enabling the developer in the flexible container 251 to be discharged into the frame member 29.The developing blade 31 for regulating the layer thickness of the developer on the circumferential surface of the developing roller 6 is fixed to the frame member 29 (refer to FIG.\",\n \"5).\",\n \"The bearings 45 and 46 are fixed at both ends of the frame member 29 in the longitudinal direction.\",\n \"Gears 70, 69, and 68 are disposed on the drive side end.\",\n \"The shaft of the supply roller 61 is fitted into the gear 70.The shaft of the developing roller 6 is fitted into the gear 69.The shaft of the agitating member 74 (FIG.\",\n \"2) is fitted into the gear 68.The gear 69 is set to rotate when the gear 68 rotates.\",\n \"The bearing 45 is provided with the gears 68, 69, and 70.The cover 32 is fixed to the outside of the gears 68, 69, and 70.End seals 62 are disposed at both ends of the shaft of the supply roller 61 to seal between the supply roller 61 and the frame member 29.As illustrated in FIG.\",\n \"5, the cover 32 is provided with a cylindrical portion 32b.\",\n \"A drive transmission portion 68a of the gear 68 is exposed through an opening 32d inside the cylindrical portion 32b.\",\n \"When the cartridge P is attached to the apparatus body 2, the drive transmission portion 68a of the gear 68 is engaged with an apparatus body drive transmission member (not illustrated), so that a driving force from a drive motor (not illustrated) provided in the apparatus body 2 is transmitted.\",\n \"The driving force input from the apparatus body 2 to the gear 68 is transmitted to the developing roller 6 via the gear 69.Photosensitive Unit and Developing Unit Assembling Process As illustrated in FIGS.\",\n \"3 and 4, when assembling the developing unit 9 and the photosensitive unit 8, the outer diameter portion of the cylindrical portion 32b of the cover 32 is fitted into the hole 24a of the cover 24 on one end side.\",\n \"Then, a protruding portion 46b protruding from the bearing 46 is fitted into the hole 25a of the cover 25 on the other end side.\",\n \"Thus, the developing unit 9 is supported so as to be rotatable with respect to the photosensitive unit 8.The developing unit 9 is rotatable around an axis line connecting the hole 24a of the cover 24 and the hole 25a of the cover 25.The rotation center of the developing unit 9 is referred to as a rotation center X.\",\n \"As illustrated in FIG.\",\n \"2, the developing unit 9 is urged by a pressure spring 95 as an elastic member so that the developing roller 6 contacts the photosensitive drum 4 around the rotation center X.\",\n \"More specifically, the developing unit 9 is pressed in the direction indicated by an arrow G illustrated in FIG.\",\n \"2 by an urging force of the pressure spring 95 so that a moment in the direction indicated by an arrow H acts around the rotation center X.\",\n \"Referring to FIG.\",\n \"5, the gear 68 receives a rotational driving force in the direction indicated by the arrow H (refer to FIG.\",\n \"2) from an apparatus body drive transmission member (not illustrated) provided on the apparatus body 2.The gear 69 engaged with the gear 68 thereby rotates in the direction indicated by an arrow E. Likewise, the developing roller 6 thereby rotates in the direction indicated by the arrow E. When a driving force required for rotating the developing roller 6 is input to the gear 68, a rotational moment in the direction indicated by the arrow H arises in the developing unit 9.A pressing force of the above-described pressure spring 95 and a rotational driving force from the apparatus body 2 cause the developing unit 9 to receive a moment in the direction indicated by the arrow H around the rotation center X.\",\n \"Then, the developing roller 6 contacts the photosensitive drum 4 at a predetermined pressure.\",\n \"Although, in the first embodiment, two forces, i.e., the pressing force by the pressure spring 95 and the rotational driving force from the apparatus body 2 are used to press the developing roller 6 against the photosensitive drum 4, only either one force may be used for the relevant purpose.\",\n \"With the cartridge P being attached to the inside of the apparatus body 2, image formation is performed while consuming the developer inside the developing unit 9.The remanufacturing method of the cartridge P of refilling the developer into the developing unit 9 after consuming the developer inside the developing unit 9 will be sequentially described below.\",\n \"Unit Separation Process The remanufacturing method of the developing unit 9 will be described below.\",\n \"A unit separation process for separating the photosensitive unit 8 and the developing unit 9 of the cartridge P will be described below.\",\n \"As illustrated in FIG.\",\n \"3, when the covers 24 and 25 are removed from the cleaning container 26, the developing unit 9 and the photosensitive unit 8 can be separated.\",\n \"As described above, since the covers 24 and 25 and the cleaning container 26 rotatably support the photosensitive drum 4, the above-described unit separation process enables the separation of the photosensitive drum 4 from the photosensitive unit 8.Developing Unit Disassembling Process A process for disassembling the developing unit 9 will be described below with reference to FIG.\",\n \"5.First of all, the cover 32 provided at the drive side end of the developing unit 9 is separated from the frame member 29.When the cover 32 is fixed to the bearing 45 and the frame member 29 with a screw 93, the screw 93 is removed and then the cover 32 is separated from the developing unit 9.Then, on the drive side of the developing unit 9, the gears 68, 69, and 70 disposed inside the cover 32 in the longitudinal direction are separated from the developing unit 9.The gear 68 is slidably supported by the cover 32 and the bearing 45, and the gear 69 is fitted into an end of the shaft of the developing roller 6.The gear 70 is fitted into the shaft of the supply roller 61.Therefore, the gears 68, 69, and 70, the developing roller 6, and the supply roller 61 can be easily separated from the developing unit 9.Then, the bearings 45 and 46 and the developing roller 6 are separated from the developing unit 9.When the bearing 45 is fixed to the frame member 29 with a screw, the screw is removed and then the bearing 45 is separated from the frame member 29.In the present embodiment, the bearing 45 and the cover 32 are fixed together to the frame member 29 with the screw 93.Since the screw 93 has been removed when the cover 32 is separated from the frame member 29, the bearing 45 can be easily separated from the frame member 29.Likewise, when the bearing 46 is fixed to the frame member 29 with a screw, the bearing 46 can be separated from the frame member 29 after the screw is removed.\",\n \"As described above, the developing roller 6 is slidably supported on the frame member 29 by the bearings 45 and 46.Therefore, in a state where the bearings 45 and 46 are separated from the frame member 29, the developing roller 6 can be easily separated from the frame member 29.Although, in the above descriptions, a process for separating both the bearings 45 and 46 from the frame member 29 is performed to separate the developing roller 6 from the frame member 29, the method is not limited thereto.\",\n \"For example, after only the bearing 46 is separated from the frame member 29, the developing roller 6 may be pulled out toward the non-drive side to separate the developing roller 6 from the frame member 29.Then, the developing blade 31 is separated from the frame member 29.When the developing blade 31 is fixed to the frame member 29 with screw 91 and 92, the screws 91 and 92 are removed and then the developing blade 31 is separated from the frame member 29.FIGS.\",\n \"14A, 14B, and 14C are perspective views illustrating a process for detaching the sealing member 253 from the flexible container 251.The flexible container 251 is accommodated (stored) inside the frame member 29.When the unsealing member 254 rotates, the sealing member 253 is separated from an attachment and detachment area around the openings 251h1 to 251h4 of the accommodating portion 251b of the flexible container 251.Although four openings 251h are illustrated in FIGS.\",\n \"14A, 14B, and 14C, there are six openings 251h in the present embodiment.\",\n \"The attachment and detachment area has two different portions on the downstream side in the detachment direction: parallel portions 80b parallel to the axis direction of the developing roller 6, and mountain-shaped portions 80c having a mountain shape toward the downstream side in the detachment direction.\",\n \"The attachment and detachment area further includes a detachment start portion 80a parallel to the axis direction of the developing roller 6, at the upstream side in the detachment direction.\",\n \"The sealing member 253 is pulled in the direction indicated by an arrow O1 and the direction indicated by the arrow O2 to be detached in states illustrated in FIGS.\",\n \"14A, 14B, and 14C in this order.\",\n \"First Communication Hole Processing Process FIG.\",\n \"6 is a sectional view of the cartridge P illustrating a process for processing a first communication hole 101.First of all, a process for processing the first communication hole 101 on the frame member 29 of the developing unit 9 will be described below with reference to FIG.\",\n \"6.A user holds the cartridge P so that the developing unit 9 is disposed on the vertically upper side.\",\n \"Then, the user processes the first communication hole 101 as a “frame member communication hole” on the vertically upper surface of the frame member 29 (frame member processing process).\",\n \"The flexible container 251 fixed to the inside of the frame member 29 is thereby exposed through the first communication hole 101.Second Communication Hole Processing Process FIG.\",\n \"7 is a sectional view of the cartridge P illustrating a process for processing a second communication hole 102.A process for processing the second communication hole 102 on the flexible container 251 fixed to the inside of the frame member 29 will be described below with reference to FIG.\",\n \"7.Since the first communication hole 101 is processed, the flexible container 251 is exposed.\",\n \"The second communication hole 102 as a “container communication hole” is processed on the exposed flexible container 251 (container processing process).\",\n \"The outside of the cartridge P and the inside of the flexible container 251 are thereby communicated with each other, making it possible to refill the developer into the flexible container 251 through the first communication hole 101 and the second communication hole 102.FIGS.\",\n \"8A to 8C are perspective views of the flexible container 251 illustrating possible shapes of the second communication hole 102.As illustrated in FIGS.\",\n \"8A to 8C, the second communication hole 102 may be a through hole such as a round hole (refer to FIG.\",\n \"8A) and a square hole, or a cut portion such as a straight line cut portion, a cross-shaped cut portion (refer to FIG.\",\n \"8B), and a U-shaped cut portion (refer to FIG.\",\n \"8C).\",\n \"Further, the second communication hole 102 may have any shape as long as it enables communication between the inside of the frame member 29 and the inside of the flexible container 251, and a funnel 201 (described below) can be inserted therein.\",\n \"As the second communication hole 102, an opening larger than one of the openings 251h (251h1 to 251h6) of the flexible container 251 can be formed.\",\n \"Developer Refilling Process FIG.\",\n \"9 is a sectional view illustrating a process for refilling the developer into the cartridge P through the first communication hole 101 and the second communication hole 102.As illustrated in FIG.\",\n \"9, the user refills the developer into the flexible container 251 inside the cartridge P in a state where the developing unit 9 is disposed on the vertically upper side.\",\n \"In this case, the user inserts the funnel 201 for refilling the developer, in the direction indicated by an arrow K illustrated in FIG.\",\n \"9.A tip portion 201a of the funnel 201 is inserted into the flexible container 251 inside the frame member 29 from the outside of the frame member 29 through the first communication hole 101 and the second communication hole 102, and the developer is refilled into the flexible container 251 (refilling process).\",\n \"The user pours the developer into the funnel 201 from, for example, a toner bottle (not illustrated) to refill the developer into the flexible container 251 inside the frame member 29.As described above, an opening larger than the openings 251h of the flexible container 251 can be formed as the second communication hole 102.Thus, when the developer is refilled into the flexible container 251 through the second communication hole 102, the funnel 201 having a larger cross-sectional area of the tip portion 201a can be used as compared to the case of refilling the developer into the flexible container 251 through the openings 251h.\",\n \"Therefore, the use of the second communication hole 102 enables more quick and efficient refilling of toner.\",\n \"First Communication Hole Sealing Process FIG.\",\n \"10 is a sectional view of the cartridge P illustrating a process for sealing the first communication hole 101.Then, the user attaches a first resealing member 103 for sealing the first communication hole 101, to the first communication hole 101 using a two-sided tape to prevent leakage of the developer from the frame member 29 (resealing process).\",\n \"As illustrated in FIG.\",\n \"10, the first resealing member 103 is attached in a state where the cartridge P is held so that the developing unit 9 is disposed on the upper side.\",\n \"Then, the first resealing member 103 is attached to the frame member 29 so as to cover the first communication hole 101.The first resealing member 103 may have any shape as long as it covers the first communication hole 101 to prevent leakage of the developer from the frame member 29.Further, the first resealing member 103 may be attached by using an adhesive instead of a two-sided tape.\",\n \"Further, the first resealing member 103 may not necessarily be a member to be attached using a two-sided tape or an adhesive, and may be a member to be fitted into the first communication hole 101, such as a cap.\",\n \"The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P without disassembling the cartridge P. Second Communication Hole Sealing Process (Optional) FIG.\",\n \"11 is a sectional view of the cartridge P illustrating a process for resealing the second communication hole 102.Similar to the first communication hole 101, the resealing process may be applied to the second communication hole 102.This process is performed for attaching a second resealing member 104 for sealing the second communication hole 102, to the second communication hole 102 using a two-sided tape to prevent leakage of the developer from the flexible container 251.The second resealing member 104 is attached in a state where the developing unit 9 is oriented vertically upward.\",\n \"Then, the second resealing member 104 is attached to the flexible container 251 so as to cover the second communication hole 102.The second resealing member 104 may have any shape as long as it covers the second communication hole 102 to prevent leakage of the developer from the flexible container 251.Further, the second resealing member 104 may be attached by using an adhesive instead of a two-sided tape.\",\n \"Then, after performing the second communication hole sealing process for sealing the second communication hole 102, the user performs the first communication hole sealing process for sealing the first communication hole 101 as described above.\",\n \"It is only required to seal at least either one of the above-described first communication hole 101 and the second communication hole 102 to seal the developer refilled in the flexible container 251 (communication hole sealing process).\",\n \"The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P, in which toner is refilled only into the flexible container 251 to reduce the possibility of leakage of toner from the cartridge P. Second Embodiment In the first embodiment, the developer is refilled through the frame member 29 and the flexible container 251 without sealing the openings 251h of the flexible container 251.Alternatively, prior to toner refilling, the user may disassemble the cartridge P until the openings 251h are exposed, seal the openings 251h of the flexible container 251, and then reassemble the cartridge P. After these processes, toner may be refilled only into the flexible container 251.FIG.\",\n \"12 is a sectional view of the cartridge P illustrating a state before resealing by the sealing member 253.FIG.\",\n \"13 is a sectional view of the cartridge P illustrating a state after resealing by the sealing member 253.Unit Separation Process and Developing Unit Disassembling Process In the above-described unit disassembling process, the user performs a separation process of the photosensitive unit 8 and the developing unit 9, and a disassembling process of the developing unit 9.Then, when the separation process of the developing unit 9 is completed, the openings 251h of the flexible container 251 inside the frame member 29 are exposed, allowing the user to refill the developer into the flexible container 251.However, the user does not refill the developer in this process.\",\n \"Then, the user seals the openings 251h of the flexible container 251 without refilling of the developer through openings 251h.\",\n \"This process will be described in detail below with reference to FIGS.\",\n \"12 and 13.Opening Resealing Process As illustrated in FIG.\",\n \"12, in the above-described separation process, the sealing member 253 is detached and the openings 251h are exposed.\",\n \"In this state, the sealing member 253 is accessed from the direction indicated by an arrow V illustrated in FIG.\",\n \"12, the sealing member 253 once used for sealing is welded to the flexible container 251 again, and the sealing member 253 is attached to the openings 251h of the flexible container 251 to reseal the openings 251h.\",\n \"This results in the resealed state illustrated in FIG.\",\n \"13.The leakage of toner from the flexible container 251 can be thereby prevented, and toner can be refilled only into the flexible container 251.The openings 251h are not necessarily sealed by welding, and may be sealed by adhesion by using a two-sided tape.\",\n \"After performing the opening resealing processes, the cartridge P is reassembled.\",\n \"Developing Unit Assembling Process and Unit Combining Process More specifically, the user performs an assembling process of the developing unit 9 and an assembling process of the photosensitive unit 8 and the developing unit 9.After completion of the assembling process of the cartridge P, the user performs the first communication hole processing process, the second communication hole processing process, and the toner refilling process which are similar to the processes according to the above-described embodiment.\",\n \"The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Third Embodiment Developer Refilling Process FIG.\",\n \"15A is a perspective view illustrating a state of the flexible container 251 containing no developer, before refilling of the developer.\",\n \"FIG.\",\n \"15B is a perspective view illustrating a state of the new flexible container 251.As illustrated in FIGS.\",\n \"15A and 15B, the flexible container 251 before refilling of the developer has a different shape from that of the new flexible container 251, and has a smaller capacity than that of the new flexible container 251.The user holds the frame member 29 so that the openings 251h (251h1 to 251h6) of the flexible container 251 are oriented vertically upward, and refills the developer.\",\n \"More specifically, when the size of the flexible container 251 before remanufacturing is represented by H0 in height, D0 in depth, and W0 in width, and the size of the new flexible container 251 is represented by H1 in height, D1 in depth, and W1 in width, a relationship “W1<W0, D1<D0, and H1<H0” may be satisfied.\",\n \"To refill more developer into the flexible container 251, it is desirable to make the capacity of the flexible container 251 approximately equivalent to that of the new flexible container 251.Therefore, for example, before refilling the developer, the user may inject compressed air into the flexible container 251 to increase the capacity of the flexible container 251.FIG.\",\n \"17 is a perspective view illustrating a process for injecting compressed air into the flexible container 251 to increase the capacity of the flexible container 251.The tip portion 201a of the funnel 201 is inserted into the flexible container 251 through the openings 251h (251h1 to 251h6) of the flexible container 251.When the flexible container 251 is provided with a plurality of openings 251h, the tip portion 201a of the funnel 201 may be inserted into any one of the openings 251h1 to 251h6.When compressed air is injected into the flexible container 251 from the funnel 201 in the direction indicated by an arrow A1 as illustrated in FIG.\",\n \"17, compressed air is injected into the flexible container 251 from the tip portion 201a of the funnel 201 in the directions indicated by arrows A2 to A4 (air injection process).\",\n \"Then, the flexible container 251 inflates in the directions indicated by arrows B1 to B3, and accordingly the size (the height H1, the depth D1, and the width W1) of the flexible container 251 recovers to almost the same size as the new flexible container 251.FIG.\",\n \"18 is a perspective view illustrating a process for refilling the developer into the frame member 29 through the openings 251h of the flexible container 251, using the funnel 201.FIG.\",\n \"20 is a sectional view illustrating a process for refilling the developer through the openings 251h (251h1 to 251h6) of the flexible container 251, using the funnel 201.The tip portion 201a of the funnel 201 is inserted through the openings 251h (251h1 to 251h6) of the flexible container 251.The user refills the developer into the flexible container 251 by dropping the developer into the funnel 201 from a developer bottle (not illustrated).\",\n \"In addition, using a fixed-rate feeding device having an auger in the funnel-shaped main body enables efficient refilling of the developer.\",\n \"When the flexible container 251 is provided with a plurality of openings 251h, the tip portion 201a of the funnel 201 may be inserted into any one of the openings 251h1 to 251h6.Developing Unit Assembling Process and Unit Combining Process When the refilling of the developer is completed, the user performs the assembling process of the developing unit 9 and the combining process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.\",\n \"3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Fourth Embodiment FIG.\",\n \"21 is a sectional view illustrating the developing unit 9.In the fourth embodiment, similar to the third embodiment, the user performs a developer refilling process without removing the developing roller 6 and the developing blade 31.Similar to the above descriptions, the user performs a unit separation process and a developing unit separation process to make the developing unit 9 a single unit.\",\n \"As illustrated in FIG.\",\n \"21, the user processes, on the frame member 29, a filling port 29r as a “frame member communication hole” as a hole for refilling the developer (frame member processing process).\",\n \"The filling port 29r may have any shape as long as the tip portion 201a of the funnel 201 (described below) can be inserted therein.\",\n \"FIG.\",\n \"22 is a sectional view illustrating a process for refilling the developer into the flexible container 251 inside the developing unit 9.As illustrated in FIG.\",\n \"22, the user inserts the tip portion 201a of the funnel 201 into the flexible container 251 inside the frame member 29 through the filling port 29r of the frame member 29 and the openings 251h of the flexible container 251, and then refills the developer.\",\n \"FIG.\",\n \"23 is a sectional view of the developing unit 9 illustrating a state where the developer is refilled.\",\n \"As illustrated in FIG.\",\n \"23, the filling port 29r of the frame member 29 is sealed by a hole sealing member 300.As the hole sealing member 300, an adhesive tape, a plastic plate with an adhesion layer, etc.\",\n \"can be desirably used.\",\n \"In the subsequent processes, the user combines the unit in reverse order of the unit separation process to complete the assembling process.\",\n \"Fifth Embodiment Sealing Member Removing Process FIG.\",\n \"24 is a front view illustrating the frame member 29 viewed from the side of the openings 251h of the flexible container 251.The sealing member 253 is fixed at fixing portions 254b (254b1 to 254b6) of the unsealing member 254 through ultrasonic welding.\",\n \"On the drive side of the unsealing member 254, a gear 254a is fitted into the unsealing member 254.The non-drive side of the unsealing member 254 is held by the frame member 29.After the flexible container 251 is unsealed, the sealing member 253 is wound around the unsealing member 254.The user is able to remove the sealing member 253 by pulling the sealing member 253 wound around the unsealing member 254 in the direction indicated by an arrow U1 and then cutting off a dashed line portion Y of the sealing member 253 with a cutter.\",\n \"The remanufacturing method includes a removing process for removing at least a part of the sealing member 253 in this way before the refilling process.\",\n \"The user may remove the sealing member 253 from the unsealing member 254 by pulling the sealing member 253 wound around the unsealing member 254 in the direction indicated by the arrow U1.As a shape to make it easy to remove the sealing member 253, for example, the thickness of the sheet of the sealing member 253 in the vicinity of the fixing portions 254b of the unsealing member 254 may be thinner than a portion welded in the vicinity of the openings 251h.\",\n \"In other words, in the sealing member 253, the film thickness of the portion to which the unsealing member 254 is fixed is thinner than that of the portion at which the openings 251h of the flexible container 251 are sealed.\",\n \"The force required to separate the sealing member 253 from the fixing portions 254b of the unsealing member 254 is only required to be larger than the force required to detach the sealing member 253 from the flexible container 251.Upon completion of the above-described procedure, the disassembling process of the developing unit 9 is completed.\",\n \"Then, the openings 251h (251h1 to 251h6) of the flexible container 251 provided in the frame member 29 are exposed, allowing the developer to be refilled into the flexible container 251.In the assembling process after refilling the developer, it is not necessary to reattach the removed sealing member 253.Effects of Sealing Member Removing Process Removing at least a part of the sealing member 253 from the unsealing member 254 can enhance the efficiency of the refilling process for refilling the developer through the openings 251h inside the flexible container 251.Developer Refilling Process Then, the user performs a developer refilling process.\",\n \"This process is similar to the above-described methods illustrated in FIGS.\",\n \"6 to 11.Developing Unit Assembling Process and Unit Assembling Process When the refilling of the developer is completed, the user performs the assembling process of the developing unit 9 and the assembling process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.\",\n \"3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Sixth Embodiment In the fifth embodiment, the unsealing member 254 has a function of a pressing member.\",\n \"In the sixth embodiment, the description will be given of a case in which the function of the unsealing member 254 is separated from the function of a pressing member.\",\n \"FIG.\",\n \"25 is a sectional view illustrating the cartridge P in which the developing unit 9 includes the unsealing member 254 and a pressing member 255.As illustrated in FIG.\",\n \"25, the pressing member 255 and the unsealing member 254 are configured to receive a driving force from the apparatus body 2 to be rotatable in the direction indicated by the arrow J.\",\n \"FIG.\",\n \"26 is a front view illustrating the frame member 29 of the cartridge P in which the developing unit 9 includes the unsealing member 254 and the pressing member 255, viewed from the side of the openings 251h of the flexible container 251.The sealing member 253 is fixed at the fixing portions 254b(254b1 to 254b6) of the unsealing member 254 through ultrasonic welding.\",\n \"On the drive side of the unsealing member 254, the gear 254a is fitted into the unsealing member 254.The non-drive side of the unsealing member 254 is held by the frame member 29.Similar to the unsealing member 254, on the drive side of the pressing member 255, a gear 255a of the pressing member 255 is fitted into the pressing member 255.The pressing member 255 moves the flexible container 251 to promote the discharge of the developer.\",\n \"In the remanufactured process cartridge, since an operation for unsealing the flexible container 251 is not required, not only the sealing member 253 but also the unsealing member 254 can be removed as described below.\",\n \"Sealing Member and Unsealing Member Removing Process The unsealing member 254 and the gear 254a can be separated from each other by pulling the gear 254a in the direction indicated by an arrow U2.Then, the user pulls out the non-drive side of the unsealing member 254 held by the frame member 29.The sealing member 253 and the unsealing member 254 can be thereby separated from the frame member 29.The user may bend the unsealing member 254 to detach the non-drive side from the frame member 29, and then pull out the gear 254a in the direction indicated by the arrow U2.Alternatively, for example, the user may cut off the sealing member 253 and the unsealing member 254 at a dashed line portion Z using a nipper, and then remove the non-drive side of the unsealing member 254 from the frame member 29 to separate the unsealing member 254 and the gear 254a.\",\n \"The user may separately remove the sealing member 253 and the unsealing member 254.More specifically, the user may pull the sealing member 253 in the direction indicated by the arrow U1 as in the fifth embodiment to remove the sealing member 253, and then remove the unsealing member 254 from the frame member 29 as described above.\",\n \"Alternatively, as illustrated in FIG.\",\n \"27, a hole 29r3 for removing the sealing member 253 and the unsealing member 254 may be formed on the non-drive side surface of the frame member 29 holding the sealing member 253 and the unsealing member 254.The hole 29r3 is only required to have a size such that the sealing member 253 and the unsealing member 254 can be pulled out therethrough.\",\n \"The user pulls out the unsealing member 254 in the direction indicated by an arrow U3 while holding the gear 254a.\",\n \"Then, the user pulls out the gear 254a in the direction indicated by the arrow U2.Alternatively, while holding the unsealing member 254 through the hole 29r3, the user may first pull out the gear 254a in the direction indicated by the arrow U2, and then pull out the unsealing member 254 in the direction indicated by the arrow U3 through the hole 29r3.To seal the hole 29r3 and the hole from which the gear 254a was pulled out, the user can desirably use an adhesive tape, a plastic plate with an adhesion layer, etc.\",\n \"In the assembling process after refilling the developer, it is not necessary to reattach the sealing member 253, the unsealing member 254, and the gear 254a that have been removed.\",\n \"Seventh Embodiment In the fifth embodiment, the detailed description has been given of a case in which a hole for removing the sealing member 253 is not processed on the sealing member 253.In the seventh embodiment, a case in which a perforation is formed at the dashed line portion Y illustrated in FIG.\",\n \"24, and the sealing member 253 has a perforation is described.\",\n \"Sealing Member Removing Process As illustrated in FIG.\",\n \"24, the user pulls the sealing member 253 in the direction indicated by the arrow U1 to release it from the state of being wound around the unsealing member 254.Then, the user pulls the sealing member 253 so as to cut off the perforation.\",\n \"The sealing member 253 can be thereby cut off.\",\n \"The force required to separate the sealing member 253 at the perforation of the sealing member 253 is only required to be larger than the force required to detach the sealing member 253 from the flexible container 251.Further, the force required to separate the sealing member 253 from the fixing portions 254b of the unsealing member 254 is only required to be larger than the force required to separate the sealing member 253 at the perforation of the sealing member 253.In the assembling process after refilling the developer, it is not necessary to reattach the removed sealing member 253.Eighth Embodiment In the first embodiment, the detailed description has been given of a case in which the sealing member 253 is formed of one sheet.\",\n \"In the eighth embodiment, the description will be given of a case in which the sealing member 253 is formed by a fixing member 501 and an opening sealing member 502.As illustrated in FIG.\",\n \"28, the fixing member 501 is fixed to the fixing portions 254b of the unsealing member 254.The opening sealing member 502 is a member for sealing the openings 251h of the flexible container 251.The fixing member 501 as a “fixing portion” and the opening sealing member 502 as a “sealing portion” are detachably adhered to each other at an adhesion portion R. Thus, the sealing member 253 is formed by the opening sealing member 502 for closing the openings 251h, and the fixing member 501 fixed to the unsealing member 254.The opening sealing member 502 and the fixing member 501 are adhered to each other.\",\n \"Sealing Member Removing Process As illustrated in FIG.\",\n \"28, the user pulls out the sealing member 253 wound around the unsealing member 254 in the direction indicated by the arrow U1, and then separates the fixing member 501 and the opening sealing member 502.The force required to separate the fixing member 501 and the opening sealing member 502 is only required to be larger than the force required to detach the opening sealing member 502 from the flexible container 251.Further, the force required to separate the fixing member 501 and the unsealing member 254 is only required to be larger than the force required to separate the fixing member 501 and the opening sealing member 502.In the assembling process after refilling the developer, it is not necessary to reattach the removed opening sealing member 502.Ninth Embodiment In the fifth embodiment, the detailed description has been given of a case in which the developing roller 6 and the developing blade 31 are removed in the disassembling process of the developing unit 9.In the ninth embodiment, a case in which the developing roller 6 and the developing blade 31 are not removed in the disassembling process of the developing unit 9 is described.\",\n \"First of all, similar to the above descriptions, after the unit separation process, the user separates the developing unit 9 from the cartridge P. In this case, as illustrated in FIG.\",\n \"22 described above, the user forms, on the frame member 29, the filling port 29r as a hole for removing the sealing member 253 and for refilling the developer.\",\n \"More specifically, the user forms, on the frame member 29, the filling port 29r as a “frame member communication hole”, and removes at least the sealing member 253 through the filling port 29r.\",\n \"A hole may be formed anywhere on the frame member 29 as long as the sealing member 253 can be removed and the developer can be refilled through the filling port 29r of the frame member 29 and the openings 251h of the flexible container 251.The filling port 29r may have any shape as long as the sealing member 253 can be taken out therefrom, and as long as the tip portion 201a of the funnel 201 (described below) can be inserted therein.\",\n \"The method for removing the sealing member 253 is similar to that according to the first embodiment.\",\n \"Developer Refilling Process As illustrated in FIG.\",\n \"22, the user inserts the tip portion 201a of the funnel 201 into the flexible container 251 through the filling port 29r and the openings 251h of the flexible container 251, and then refills the developer.\",\n \"FIG.\",\n \"23 is a sectional view of the developing unit 9 in which the developer is refilled.\",\n \"As illustrated in FIG.\",\n \"23, the user seals the filling port 29r of the frame member 29 using the hole sealing member 300.As the hole sealing member 300, an adhesive tape, a plastic plate with an adhesion layer, etc.\",\n \"can be desirably used.\",\n \"In the subsequent processes, the user combines the unit in reverse order of the unit separation process to complete the assembling process.\",\n \"Tenth Embodiment Developing Unit Assembling Process FIG.\",\n \"29 is an exploded perspective view illustrating the developing unit 9.Then, the user separates a supply roller 61 from the frame member 29.FIGS.\",\n \"30A and 30B are enlargement views illustrating the non-drive side portion of the frame member 29 (a portion A illustrated in FIG.\",\n \"29).\",\n \"As illustrated in FIG.\",\n \"30A, a hole 29b into which the shaft of the supply roller 61 is to be fitted is formed on the frame member 29.When the gap between the shaft of the supply roller 61 and the frame member 29 is sealed by the end seals 62, the user removes the end seals 62 and then separates the supply roller 61 from the frame member 29.The user may perform the removing process of both of the respective end seals 62 of the drive side and the non-drive side, the method is not limited thereto.\",\n \"For example, the user may perform only the removing process of the end seal 62 on the non-drive side and then pull out the supply roller 61 toward the non-drive side to separate it from the frame member 29.Although, in the above descriptions, the shaft of the supply roller 61 is fitted into the hole 29b of the frame member 29, the configuration is not limited thereto.\",\n \"The supply roller 61 may be fixed to the frame member 29 through a fixing member 28 of the supply roller 61 (refer to FIG.\",\n \"30B).\",\n \"In this case, the user separates the fixing member 28 from the frame member 29 and then separates the supply roller 61 from the frame member 29.The user may perform the process for separating the fixing member 28 from the frame member 29 both on the non-drive side and the drive side or only on either one of the non-drive side and the drive side.\",\n \"For example, when the user performs a removing process of the fixing member 28 only on the non-drive side, the user is able to separate the supply roller 61 from the frame member 29 by pulling out the supply roller 61 toward the non-drive side.\",\n \"Upon completion of the above-described procedure, the disassembling process of the developing unit 9 is completed, allowing the developer to be refilled.\",\n \"Opening Enlargement Process FIGS.\",\n \"31A, 31B, 31C, and 31D are perspective views of the flexible container 251 illustrating an enlargement process for enlarging a plurality of openings 251h1 to 251h10 of the flexible container 251.The remanufacturing method includes an opening processing process for processing the openings 251h so as to enlarge the openings 251h, before the refilling process.\",\n \"The opening processing process connects the plurality of openings 251h.\",\n \"As illustrated in FIG.\",\n \"31A, a certain method cuts off all of connecting portions L1 to L9 between the openings 251h1 to 251h10 of the flexible container 251.As illustrated in FIG.\",\n \"31B, another method cuts off only the connecting portion L1 among the connecting portions L1 to L9 between the openings 251h1 to 251h10 of the flexible container 251.As illustrated in FIG.\",\n \"31C, still another method cuts off a large area including the connecting portions L1 and L9 between the openings 251h1 to 251h10 of the flexible container 251 to form an opening L10.As illustrated in FIG.\",\n \"31D, substantially similar to FIG.\",\n \"31C, still another method cuts off a large area to form an opening 251h11.In this case, the opening processing process forms the opening 251h11 larger than an area including all of the plurality of openings 251h.\",\n \"The opening after the processing may have any shape as long as it is enlarged to be larger than the opening before the processing.\",\n \"In the following descriptions, the opening after the processing is referred to as a refilling opening 251F.\",\n \"Developer Refilling Process FIG.\",\n \"32 is a sectional view of the frame member 29 illustrating a process for refilling the developer through the refilling opening 251F.\",\n \"As illustrated in FIG.\",\n \"32, when refilling the developer, the frame member 29 is disposed so that the refilling opening 251F is oriented vertically upward.\",\n \"The funnel 201 used for refilling the developer has such a cross-sectional area of the tip portion 201a as to be fitted into the size of the enlarged refilling opening 251F.\",\n \"The tip portion 201a of the funnel 201 is inserted into the flexible container 251 through the refilling opening 251F in the direction indicated by an arrow M. The user pours the developer T into the funnel 201 from, for example, a toner bottle (not illustrated) to refill the developer T into the flexible container 251 and into the frame member 29.Although, in the present embodiment, the funnel 201 used has a cross-sectional area of the tip portion 201a according to the size of the refilling opening 251F, the refilling opening 251F may be enlarged according to the size of the funnel 201.As described above, since the refilling opening 251F has a larger opening area than the openings 251h1 to 251h10 of the new flexible container 251, the tip portion 201a of the funnel 201 can have a large cross-sectional area.\",\n \"This enables efficient refilling of toner in a shorter time.\",\n \"When the developer T is refilled without enlarging an opening, the user needs to use the funnel 201 having a small cross-sectional area of the tip portion 201a according to the size of the opening.\",\n \"Therefore, the developer will stagnate in the tip portion 201a of the funnel 201, prolonging the time of refilling.\",\n \"Further, when refilling the developer T having high cohesiveness, the tip portion 201a of the funnel 201 will be clogged with the developer, making it impossible to refill the developer.\",\n \"When an opening is extremely small, the tip portion 201a of the funnel 201 cannot be inserted into the flexible container 251.If the user performs the refilling process without inserting the tip portion 201a of the funnel 201 into the flexible container 251, almost none of the refilled developer is filled into the flexible container 251, and only a very small capacity inside the frame member 29 and outside the flexible container 251 is filled with the developer.\",\n \"As a result, the developer refilling may not be sufficiently completed.\",\n \"Developing Unit Assembling Process and Unit Combining Process After refilling the developer into the flexible container 251 in this way, the user performs the assembling process of the developing unit 9, and the combining process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.\",\n \"3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Eleventh Embodiment Opening Enlargement Process FIG.\",\n \"33A is a perspective view of the flexible container 251 illustrating an enlargement process for enlarging an opening of the flexible container 251 according to the eleventh embodiment.\",\n \"On the flexible container 251, a cutoff line k1 is preprocessed at the connecting portion L4 between the openings 251h4 and 251h5.In the opening enlargement process, an opening is enlarged by cutting off the cutoff line k1.In the opening processing process, at least one of the plurality of openings 251h is processed.\",\n \"Further, a plurality of cutoff lines may be processed at connecting portions.\",\n \"For example, a cutoff line k2 may be processed at the connecting portion L5 between the openings 251h5 and 251h6, in addition to the cutoff line k1.However, the cutoff lines k1 and k2 need to be left uncut when the sealing member 253 is wound up by the unsealing member 254.Therefore, rather than processing the cutoff lines k1 and k2 in the direction perpendicular to the direction indicated by the arrow B in which the sealing member 253 is wound up, it is better to process a cutoff line k4 in such a direction that forms a small angle with respect to the direction of the arrow B in which the sealing member 253 is wound up.\",\n \"However, the winding direction and the cutoff line direction are not limited thereto.\",\n \"The tension required to cut off the cutoff lines is only required to be larger than the tension applied to the cutoff lines while the sealing member 253 is being wound up.\",\n \"FIG.\",\n \"33B is a perspective view of the flexible container 251 illustrating a cutoff line k3 according to a modification.\",\n \"As illustrated in FIG.\",\n \"33B, the cutoff line k3 extending in the direction indicated by the arrow B and connecting with the opening 251h5 may be processed on the surface of the flexible container 251.The cutoff line preprocessed on the flexible container 251 is only required to enlarge an opening by being cut off in the opening enlargement process.\",\n \"The number and shape of cutoff lines are not limited.\",\n \"Likewise, an opening can be enlarged by cutting off at least one cutoff line in the opening enlargement process.\",\n \"Therefore, the user does not need to cut off all of the processed cutoff lines.\",\n \"The subsequent developer refilling process is similar to that according to the tenth embodiment, and descriptions thereof will be omitted.\",\n \"Twelfth Embodiment Refilling Opening Processing Process FIGS.\",\n \"34A, 34B, and 34C are perspective views of the flexible container 251 illustrating a processing process for processing a refilling opening 251G on the flexible container 251 fixed to the inside of the frame member 29.As described above, when the disassembly of the developing unit 9 is completed, the flexible container 251 is exposed.\",\n \"In this case, the refilling opening 251G is processed on the exposed flexible container 251.This enables the developer to be refilled into the flexible container 251 through the refilling opening 251G.\",\n \"The refilling opening 251G may be a round through hole 251G1 as illustrated in FIG.\",\n \"34A, a cross-shaped cut portion 251G2 as illustrated in FIG.\",\n \"34B, or a U-shaped cut portion 251G3 as illustrated in FIG.\",\n \"34C.\",\n \"Further, the refilling opening 251G may have any shape as long as the funnel 201 (described below) can be inserted therein, and may be a through hole such as a square hole, or a cut portion such as a straight line cut portion.\",\n \"It is desirable to form the refilling opening 251G so large as to allow communication between the inside and the outside of the flexible container 251 more than one of the openings 251h (251h1 to 251h6) on the flexible container 251 does.\",\n \"Forming the large refilling opening 251G enables a more efficient developer refilling process.\",\n \"Developer Refilling Process Then, the user performs the developer refilling process, which has been described above with reference to FIGS.\",\n \"15, 17, and 18.When injecting compressed air into the flexible container 251, any one of the refilling openings 251G illustrated in FIGS.\",\n \"34A, 34B, and 34C may be used.\",\n \"As illustrated in FIGS.\",\n \"34A, 34B, and 34C, the tip portion 201a of the funnel 201 is inserted into the refilling opening 251G of the flexible container 251 (refer to FIG.\",\n \"16).\",\n \"The user refills the developer into the flexible container 251 by dropping the developer into the funnel 201 from a developer bottle (not illustrated).\",\n \"In addition, using a fixed-rate feeding device having an auger in the funnel-shaped main body enables efficient refilling of the developer.\",\n \"Developing Unit Assembling Process Subsequently, the user performs the assembling process of the developing unit 9 and the unit combining process of the photosensitive unit 8 and the developing unit 9.Upon completion of the above-described procedure, the assembling process of the cartridge P is completed as illustrated in FIG.\",\n \"3.The above-described remanufacturing method of the cartridge P enables achievement of a simplified remanufacturing method of the cartridge P. Thirteenth Embodiment In the twelfth embodiment, the detailed description has been given of a case in which the refilling opening 251G is formed on the flexible container 251 without removing the sealing member 253, and then the developer is refilled.\",\n \"In the thirteenth embodiment, a description will be given of a case in which the refilling opening 251G is formed on the flexible container 251 after removing the sealing member 253, and then the developer is refilled.\",\n \"Sealing Member Removing Process As described above with reference to FIG.\",\n \"24, the user may remove the sealing member 253 and then perform the refilling process.\",\n \"More specifically, at least a part of the sealing member 253 is removed (removing process) before the refilling process.\",\n \"After removing the sealing member 253, the user forms any one of the refilling openings 251G illustrated in FIGS.\",\n \"34A, 34B, and 34C on the flexible container 251, and then performs the developer refilling process as illustrated in FIG.\",\n \"19.More specifically, the refilling opening 251G as “another opening” different from the openings 251h is processed on the flexible container 251 (another opening process) before the refilling process.\",\n \"In addition, the refilling opening 251G is processed to be larger than the openings 251h.\",\n \"In the assembling process after refilling the developer, the user does not need to reattach the removed sealing member 253.As in the present embodiment, removing the sealing member 253 enables a more efficient developer refilling process.\",\n \"Fourteenth Embodiment In the first embodiment, the detailed description has been given of a case in which the developing blade 31 and the like are separated from the frame member 29 to expose the flexible container 251.In the fourteenth embodiment, the description will be given of a case in which only the developing blade 31 is separated from the frame member 29 and then the developer is refilled into the flexible container 251.Developing Blade Disassembling Process To separate only the developing blade 31 from the frame member 29, the user disassembles only the developing blade 31 without disassembling members excluding the developing blade 31 in the disassembling process of the developing unit 9 described with reference to FIG.\",\n \"29 in the tenth embodiment.\",\n \"In the developing unit 9 in which the developing blade 31 as a “regulating member” for regulating the layer thickness of the developer on the developing roller 6 is attached to the frame member 29, only the developing blade 31 is separated from the frame member 29 (separation process) before the another opening process.\",\n \"When the developing blade 31 is fixed to the frame member 29 with the screws 91 and 92, the screws 91 and 92 are removed and then the developing blade 31 is separated from the frame member 29.After separating the developing blade 31 from the frame member 29, any one of the refilling openings 251G as illustrated in FIGS.\",\n \"34A, 34B, and 34C is formed on the flexible container 251, and then the developer refilling process as illustrated in FIG.\",\n \"19 is performed.\",\n \"In addition, the sealing member 253 may be removed after separating the developing blade 31.Alternatively, the unsealing member 254 may be rotated to expose the flexible container 251, without removing the sealing member 253.In the present embodiment, separating only the developing blade 31 from the frame member 29 enables a more simple developer refilling process.\",\n \"According to the configurations of the first to the fourteenth embodiments, the remanufacturing method of the developing unit 9 is simplified as compared with the conventional technique.\",\n \"The configurations or processes according to the first to the fourteenth embodiments can be suitably combined.\",\n \"Although, in the first to the fourteenth embodiments, the description has been given of the cartridge P including the developing unit 9 and the photosensitive unit 8, the configuration is not limited thereto as long as it includes the developing unit 9.In other words, the first to the fourteenth embodiments are also applicable to a developing device, a cartridge, and an image forming apparatus as long as these include the developing unit 9.According to an embodiment of the present invention, it is possible to provide a remanufacturing method of a developer accommodating unit including a flexible container.\",\n \"While the present invention has been described with reference to embodiments, it is to be understood that the invention is not limited to the disclosed embodiments.\",\n \"The scope of the following claims is to be accorded the broadest interpretation so as to encompass all such modifications and equivalent structures and functions.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874741"}}},{"rowIdx":4494682,"cells":{"text":{"kind":"list like","value":[["SMART STORAGE OF TEMPERATURE SENSITIVE PHARMACEUTICALS","A refrigerator and/or freezer unit and system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products in compliance with regulatory requirements.","The unit contains compartments for each product type in multiple controlled temperature zones with sensors to track product status and content.","In a system, each unit communicates with an application service provider to provide remote inventory management capability."],["1.A smart refrigerator and/or freezer unit for temperature sensitive pharmaceutical products, comprising: (a) a plurality of location- and temperature-monitored compartments to store temperature sensitive pharmaceutical products and disposed in at least one temperature-controlled temperature zone, wherein each such compartment is associated with at least one temperature sensor, is configured to store a plurality of units of a temperature sensitive pharmaceutical product type, and is maintained at substantially the same temperature as the one or more other compartment(s in the same temperature-controlled temperature zone; and (b) one or more processors configured for unit operation and to electronically communicate wirelessly or via a hard wire link with an application service provider (ASP).","2.The smart refrigerator and/or freezer unit of claim 1, wherein the temperature zone comprises a temperature between about 2° C. and about 8° C. or between about −50° C. and about −15° C. 3.The smart refrigerator and/or freezer unit of claim 1, wherein temperature zone temperature is monitored by the one or more temperature sensors associated with the temperature-monitored compartments in the temperature zone, and wherein the temperature of each temperature zone is displayed on an external portion of the refrigerator, optionally on a touch screen interface.","4.The smart refrigerator and/or freezer unit of claim 3 that further comprises a backup power supply 5.The smart refrigerator and/or freezer unit of claim 1 that further comprises a reader, optionally a barcode reader.","6.The smart refrigerator and/or freezer unit of claim 1 that is wirelessly or connected via a hard wire to a computer network, optionally the Internet.","7.The smart refrigerator and/or freezer unit of claim 1 that is in electronic communication with an ASP.","8.The smart refrigerator and/or freezer unit of claim 1, wherein temperature monitoring of the compartments in the at least one temperature zone is continuous.","9.The smart refrigerator and/or freezer unit of claim 1 configured for secure access, optionally via entry of a user login code or biometric data.","10.The smart refrigerator and/or freezer unit of claim 1 that further comprises a touch screen interface configured displays information on the unit and its contents.","11.The smart refrigerator and/or freezer unit of claim 10, wherein the information displayed on the touch screen interface comprises one or more of: temperature sensitive pharmaceutical product type name or names; temperature sensitive pharmaceutical product type dosage or dosages; temperature sensitive pharmaceutical product type quantity or quantities in the smart refrigerator and/or freezer unit; nearest temperature sensitive pharmaceutical product expiration date; current temperature of temperature-controlled temperature zone(s); alerts; and temperature sensitive pharmaceutical product type order status.","12.The smart refrigerator and/or freezer unit of claim 10, wherein a user, by selecting the name of a specific temperature sensitive pharmaceutical product type on the touch screen display, is provided further information about the temperature sensitive pharmaceutical product type, which further information is optionally selected from the group consisting of location by compartment and/or temperature zone, temperature history, lot number or numbers with associated expiration date or dates of current inventory of the temperature sensitive pharmaceutical product type, and an Internet link to the temperature sensitive pharmaceutical product type.","13.The smart refrigerator and/or freezer unit of claim 1, wherein each of the plurality of compartments is capable of holding a plurality of units of one temperature sensitive pharmaceutical product type, which units optionally have the same expiration date.","14.The smart refrigerator and/or freezer unit of claim 1, wherein the plurality of compartments holds one temperature sensitive pharmaceutical product unit per temperature-monitored compartment.","15.The smart refrigerator and/or freezer unit of claim 1 that further comprises a plurality of temperature-controlled temperature zones, each of which is optionally maintained at a temperature different from the temperature of the at least one other temperature zone.","16.The smart refrigerator and/or freezer unit of claim 15 that comprises first and second temperature-controlled temperature zones, wherein the first temperature-controlled temperature zone is maintained at a temperature between about 2° C. and about 8° C. and the second temperature-controlled temperature zone is maintained at a temperature between about −50° C. and about −15° C. 17.A system to manage temperature sensitive pharmaceutical products, comprising a plurality of smart refrigerator and/or freezer units each according to claim 1 connected to an application service provider (ASP).","18.A system according to claim 17, wherein the ASP provides one or more services selected from the group consisting of inventory management and system administration.","19.A method of managing a temperature sensitive pharmaceutical product inventory comprising: storing a temperature sensitive pharmaceutical product inventory in a refrigerator and/or freezer unit according to claim 1; collecting data related to the unit and the product inventory stored within; providing a user interface at the unit; and providing via the ASP inventory management services.","20.A method of storing a temperature sensitive pharmaceutical product inventory comprising: storing a temperature sensitive pharmaceutical product inventory in a refrigerator and/or freezer unit according to claim 1 that is connected wirelessly or via a hard wire connection to a computer network, optionally the Internet, hosting the ASP, wherein the ASP provides inventory management services for the product inventory stored in the unit; collecting data related to the unit and the stored product inventory; and communicating at least a portion of such data to the ASP."],["<SOH> BACKGROUND OF THE INVENTION <EOH>Many pharmaceutical products are dependent upon proper storage of the product with temperature being one of the key parameters that determines if a product is to be administered or discarded as spoiled.","Some pharmaceutical product formulations require a storage temperature of about 5° C. and lose effectiveness and potency when stored at temperatures below freezing while others require sub zero storage.","Generally, effectiveness and potency are decreased with every freeze thaw cycle.","This is especially true for immunobiologics such as vaccines.","Concern over the proper storage of vaccines and awareness that exposure of vaccines to temperatures outside the recommended ranges can have adverse effect on potency, thereby reducing protection from vaccine-preventable diseases, prompted the Centers for Disease Control and Prevention (CDC) to establish “Guidelines for Maintaining and Managing the Vaccine Cold Chain” (www.cdc.gov/mmwr/preview/mmwrhtml/mm5242a6.htm).","The CDC emphasizes that administration of potent immunobiologics is not only dependent on an effective cold storage unit it also requires maintaining accurate temperature logs.","Due to significant variability of temperatures within a compartment of a refrigerator it is recommended that temperatures be recorded near the actual container of the pharmaceutical several times per day.","Vaccines stored outside of a recommended temperature range are to be immediately separated from the stock of effective vaccines so to avoid dispensing of ineffective product.","The high cost of biologic pharmaceuticals further highlights the need of a refrigerator/freezer unit for the storage of pharmaceuticals with accurately maintained temperature zones, sensors for the recordation of temperatures surrounding the pharmaceutical product, and an alert system that assures responsive transfer of product to alternate site in case of a unit malfunction or power failure and removal of expired and ineffective product.","A further need arises to simplify the management of the unit and its contents and to maintain an optimal inventory of the pharmaceuticals.","Therefore it is an object herein to provide a smart refrigerator system that ascertains proper storage of pharmaceuticals in compliance with regulatory requirements, simplifies management protocols, and further utilizing the data and information thus gained to maintain optimal levels of pharmaceutical stock."],["<SOH> SUMMARY OF THE INVENTION <EOH>Provided herein are a refrigerator and/or freezer unit and an inventory management system for the storage of pharmaceuticals in compliance with regulatory requirements.","Provided herein are a refrigerator and/or freezer unit and a system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products.","Also provided herein are a plurality of compartments for each temperature sensitive pharmaceutical product type located in at least one controlled, sensor monitored, temperature zone of the unit, a reader for the identification of the product, and a user interface device (UID), in communications with an application service provider (ASP).","The unit, system and methods provided herein include a data collection system wherein the UID and/or the ASP capture and store data, related to the refrigerator and/or freezer unit and the temperature sensitive pharmaceutical products stored within that includes: unit content, a product descriptor, product dispense and refill transactions, a reader scan of product, reader scan of compartments, compartment camera images, temperature sensor data, lock sensor data, login codes, biometric scans, system security and function status, and/or manually entered data.","Also provided herein is a user interface at the unit that provides a user with secure access, via the UID, to the unit, unit content, and status and information including: product name, dosage, location, quantity, lot numbers, and expiration dates; compartment temperatures; alerts and order status; and/or internet access to further product information.","The user can also manually enter information at the user interface.","Further provided herein is an ASP, in a cloud based hosted environment that provides services including: server space for data and information storage; software for the management of the unit, its content, and information related to the unit and the products stored within; product and regulatory information resource; and/or unit maintenance resource.","The ASP provided software includes software to manage the inventory of temperature sensitive pharmaceuticals in compliance with regulatory requirements wherein the pharmaceuticals are selected from among a biologic, an immunobiologic, an antibody, a peptide, a protein, an enzyme, a hormone, a nucleic acid, a lipid, and a formulation and/or combination of any of the preceding thereof.","The refrigerator and/or freezer unit provided herein may be a smaller unit, equal to, less than about 34 inches tall, or a larger unit, above about 34 in tall, and include controlled temperature zones below and/or above 0° C. For example the at least one controlled temperature zone can be maintained between 2° C. and 8° C. or between minus 50° C. and minus 15° C., In some examples the unit includes a first temperature zone maintained between 2° C. and 8° C. and a second temperature zone maintained between minus 50° C. and minus 15° C. wherein preferably the first temperature zone maintained between 4° C. and 6° C. and a second temperature zone maintained between minus 40° C. and minus 17° C. The temperature is monitored within each compartment of the plurality of compartments and the temperature within each compartment is recorded in compliance with regulatory requirements and displayed on an external portion of the refrigerator.","The temperature is monitored by temperature sensors located within the compartments and connected to a backup power supply wherein in the event or a power outage the temperature data is transmitted to the UID and when full power is restored to the ASP.","In yet another embodiment the temperature zone temperature is monitored by a plurality of temperature sensors to ascertain that the temperature within each compartment is maintained at the designated temperature.","In one exemplary embodiment, the refrigerator and/or freezer unit is equal to or less than about 34″ tall and at least 4 compartments are located in the sub 0.degree.","C. temperature zone and at least 8 compartments are located in the above 0.degree.","C. temperature zone.","Further provided herein is refrigerator and/or freezer unit wherein the plurality of compartments fill each temperature zone and vary in size and number providing customization of the compartment configuration.","The compartments may be available in at least two standard sizes, very in number from at least two containers per temperature zone, may contain only one type of product, one product type with one expiration date, or one product, and may be optionally labeled and/or color coded to denote differences between the products contained within.","The reader used to identify a pharmaceutical product can be implemented using a variety of technologies including, but not limited to, optical device, a magnetic device, a camera, RFID, barcodes reader, and a magnetic strip reader.","In one exemplary embodiment the reader device may be implemented with a barcode reader wherein the barcode reader optically scans a product, decodes the signal, and transfers the product information to the UID.","In yet another embodiment the reader is a camera wherein identification of product includes the following steps: the camera captures an image of the pharmaceutical product with barcode label; the image is transmitted to the UID; the UID transmits the image to the ASP; the ASP provided product identification software analyzes the image and generates a product descriptor; the product descriptor is stored within the ASP provided product database and is transmitted to the UID; the UID receives and adds the product descriptor to its current inventory database and updates the UID product information display.","The product descriptor may include information contained in the barcode and manufacturer provided product information.","The product descriptor record thus may include product name and dosage, lot numbers and associated expiration date, recommended temperature for storage, compartment location, storage temperature history, and internet links to manufacturer and/or Center for Disease Control and Prevention (CDC) information on the product.","In yet another embodiment the reader is a camera associated with each compartment and is used to capture an image of all products within a compartment wherein the analysis of the image captured by the camera reader provides a count of the product within the compartment.","The refrigerator and/or freezer unit may be implemented with a UID that is a touch screen computing device, such as a tablet computer, connected to the refrigerator via a docking station, and may be connected to or embedded within the outer surface of the unit.","The UID can maintain a connection to the internet via multiple routes such as a local internet, a wireless network (WIFI) and/or cell phone card embedded in the refrigerator unit.","A UID home screen displays information on the status of the unit and its content.","Exemplary information displayed includes product name, product quantity, nearest expiration date, current temperature of product compartment, alerts, and/or product order status.","Further information about the product may be displayed by selecting the name of a specific product on the UID display and includes location by compartment, temperature history, lot numbers with associated expiration dates of current inventory, and links to product information on the internet that includes manufacturer and/or Centre for Disease Control and Prevention (CDC) product information.","At the user interface the user completes the capture of product transactional information by confirming a successful reader scan of the product being added to the unit, entering the product information manually, or by selecting on the UID screen, product to be removed from the unit.","In yet another embodiment an optionally activated security interface is provided wherein access to the UID and the refrigerator unit includes a login code verification and/or a biometric sensor scan wherein a biometric scan device may be a finger print identification device, a retinal scan identification device, a facial recognition device or a voice identification device.","Provided herein is a system wherein the ASP provided software functions include: analysis and storage of data, records, and information related to the unit; communicating with the UID and select recipients; generating alerts related to temperature, expiration dates, system health, network disruption, power disruption/loss and low stock; and providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, inventory management, wherein the access is via a secure website customizable based on user profile.","A service provider, using ASP provided software and servers in a cloud based hosted environment may include inventory management in compliance with regulatory requirements, system administration, alerting, and reporting.","The inventory management may include tracking of the inventory of products within the refrigerator and/or freezer unit and all product dispense and refill transactions, tracking the expiration date of each product, providing re-order messages, providing remove expired product messages; providing product is about to expire messages; and providing a product and regulatory information resource.","The system administration may include monitoring the refrigerator and/or freezer unit location information; monitoring information related to the physical status of the unit comprising: function; power, temperature or latches sensor data; maintaining communication between UID, ASP, and cell card application layers; maintaining select user an optionally secure access to the unit and ASP; and facilitating unit maintenance.","The alerting provides the delivery of alerting messages, to select recipients and/or the UID, related to events comprising: temperature of a compartment approaches or exceeds allowed temperature limits; a product stock is depleted or reached a low limit; a product expired or is to expire within select number of days; and power outage.","Further embodiments of the system provides alert, delivery to the UID and other customizable pre-determined locations such as specified phone numbers, computers and email addresses.","The alert delivered to the UID on the refrigerator indicates the location of the deviation and generate a customizable audio and/or visual alert.","In yet another embodiment the ASP inventory management software determines if a product has reached its expiration date or is deemed to have lost potency due to compartment temperature fluctuations outside of the recommended range, and sends an alert that product has expired, instructing the user to remove the expired and/or ineffective product.","Determining if product has reached its expiration date and/or lost potency includes: comparing current date to expiration date of product and if current date is on or post the expiration date, the product is expired; and determining if the temperature of compartment holding product exceeded allowed temperature limits for a time period greater than a select number of minutes the product is deemed to have lost potency.","Further the ASP inventory management software identifies product within select number of days prior to the expiration date and sends an alert to the UID and select recipients to prioritize use of the product or exchange/return the product for fresher product.","In a particular embodiment the ASP inventory management software monitors inventory levels of product within each compartment and when one or more products approach a predetermined re-order count of product a low stock alert is generated wherein a first customizable and unique audio and/or visual alert is generated when product stock is low and a second customizable and unique audio and/or visual alert is generated when a product reaches a zero inventory count.","The predetermined re-order count of product is determined by the user or the ASP service using dispense rate data, quantity of product contained in manufacturer packaging and number of days required to receive ordered product.","In a further embodiment the ASP provided software analyzes the reader data received from the UID and in combination with information available from product manufacturer generates a product descriptor record that includes for example: product name and dosage; lot numbers with associated expiration date; recommended temperature for storage; and compartment number.","Also provided herein are ASP provided software applications related to product potency and inventory management including: product potency assessment based on storage temperature history and product expiration date; product potency review in compliance with regulatory requirements; current product inventory assessment based on reader captured data and UID manually entered data; product inventory dispensing assessment; product order requests, status and recommendations; and reports and data analytics including: stock and dispense transactions, product loss due to expiration or spoilage, and frequency of refills.","Further embodiment of the software applications function is customization of refrigerator unit variables including: unit size and refrigerator and/or freezer option; compartment number, size and label and/or color coding per product and temperature zone; secure or free access to unit; selection of users; establishing user profiles with customized level of access; unit alert message signal type, audio and or visual option; and recipients of alert messages.","In yet another embodiment the ASP secure website software generates a user profile for each user and provides each user with customized levels of access to the information and data associated with each unit.","A user that includes refrigerator unit user, refrigerator unit managers, and refrigerator unit owners may have the following level of access: a user with access to unit content only; a user with access to unit content and order related information on the ASP web site; a user with access to unit content and all information related to the unit on the ASP web site; and a user with access to select product reports.","Provided herein are reports generated by the ASP provided software, available based on a user's profile and permission status, wherein user group includes: refrigerator unit users, managers, and owners; manufacturers; distributors; product representatives; physicians; and pharmacists.","Reporting includes: providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, or inventory management, wherein the access is via a secure website and customizable based on user profile.","For example a refrigerator unit user, manager and owner have access to reports related to their unit and the reports may include: current inventory of product with expiration dates; quantity of product used, by type of use and/or total use, for a selected time period such as day, week month year; product dispense rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; and alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.","The refrigerator unit user, manager and owner also have access to reports related to other units serviced by the ASP including: type and quantity of product dispensed to patient by location such as a local region defined by community or city, a state, and/or country within a selected time period; product usage rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.","A manufacturer of exemplary product A may have access to reports including: quantity of product A dispensed to patient by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit for a selected location; number of units within select location or region distributing product “A”; and low stock of product “A” alerts per unit and/or region.","A distributor and a product representative may have access to reports on their products including reports on: quantity of product dispensed to patient, expired, and or spoiled by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.","And a pharmacist may have access to reports on their products and refrigerator and/or freezer unit stocked by their pharmacy wherein reports included are: quantity of product dispensed to patient, expired, and or spoiled by date and by refrigerator and/or freezer unit stocked by their pharmacy; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.","Other features and advantages of the invention will be apparent from the following description, drawings and claims."],["RELATED APPLICATIONS This application is a continuation of allowed U.S. non-provisional patent application Ser.","No.","15/675,618 filed on Aug. 11, 2017, which is a continuation of U.S. non-provisional patent application Ser.","No.","13/974,793 filed on Aug. 23, 2013 (now U.S. Pat.","No.","9,733,012), which claimed the benefit of and priority to now-expired U.S. provisional patent application Ser.","No.","61/692,659 filed on Aug. 23, 2012, all of which are/were entitled “Smart Storage of Temperature Sensitive Pharmaceuticals”.","Each of these foregoing applications is hereby incorporated by reference in its entirety.","FIELD OF THE INVENTION The present invention relates generally to storage and inventory management of temperature sensitive pharmaceuticals.","BACKGROUND OF THE INVENTION Many pharmaceutical products are dependent upon proper storage of the product with temperature being one of the key parameters that determines if a product is to be administered or discarded as spoiled.","Some pharmaceutical product formulations require a storage temperature of about 5° C. and lose effectiveness and potency when stored at temperatures below freezing while others require sub zero storage.","Generally, effectiveness and potency are decreased with every freeze thaw cycle.","This is especially true for immunobiologics such as vaccines.","Concern over the proper storage of vaccines and awareness that exposure of vaccines to temperatures outside the recommended ranges can have adverse effect on potency, thereby reducing protection from vaccine-preventable diseases, prompted the Centers for Disease Control and Prevention (CDC) to establish “Guidelines for Maintaining and Managing the Vaccine Cold Chain” (www.cdc.gov/mmwr/preview/mmwrhtml/mm5242a6.htm).","The CDC emphasizes that administration of potent immunobiologics is not only dependent on an effective cold storage unit it also requires maintaining accurate temperature logs.","Due to significant variability of temperatures within a compartment of a refrigerator it is recommended that temperatures be recorded near the actual container of the pharmaceutical several times per day.","Vaccines stored outside of a recommended temperature range are to be immediately separated from the stock of effective vaccines so to avoid dispensing of ineffective product.","The high cost of biologic pharmaceuticals further highlights the need of a refrigerator/freezer unit for the storage of pharmaceuticals with accurately maintained temperature zones, sensors for the recordation of temperatures surrounding the pharmaceutical product, and an alert system that assures responsive transfer of product to alternate site in case of a unit malfunction or power failure and removal of expired and ineffective product.","A further need arises to simplify the management of the unit and its contents and to maintain an optimal inventory of the pharmaceuticals.","Therefore it is an object herein to provide a smart refrigerator system that ascertains proper storage of pharmaceuticals in compliance with regulatory requirements, simplifies management protocols, and further utilizing the data and information thus gained to maintain optimal levels of pharmaceutical stock.","SUMMARY OF THE INVENTION Provided herein are a refrigerator and/or freezer unit and an inventory management system for the storage of pharmaceuticals in compliance with regulatory requirements.","Provided herein are a refrigerator and/or freezer unit and a system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products.","Also provided herein are a plurality of compartments for each temperature sensitive pharmaceutical product type located in at least one controlled, sensor monitored, temperature zone of the unit, a reader for the identification of the product, and a user interface device (UID), in communications with an application service provider (ASP).","The unit, system and methods provided herein include a data collection system wherein the UID and/or the ASP capture and store data, related to the refrigerator and/or freezer unit and the temperature sensitive pharmaceutical products stored within that includes: unit content, a product descriptor, product dispense and refill transactions, a reader scan of product, reader scan of compartments, compartment camera images, temperature sensor data, lock sensor data, login codes, biometric scans, system security and function status, and/or manually entered data.","Also provided herein is a user interface at the unit that provides a user with secure access, via the UID, to the unit, unit content, and status and information including: product name, dosage, location, quantity, lot numbers, and expiration dates; compartment temperatures; alerts and order status; and/or internet access to further product information.","The user can also manually enter information at the user interface.","Further provided herein is an ASP, in a cloud based hosted environment that provides services including: server space for data and information storage; software for the management of the unit, its content, and information related to the unit and the products stored within; product and regulatory information resource; and/or unit maintenance resource.","The ASP provided software includes software to manage the inventory of temperature sensitive pharmaceuticals in compliance with regulatory requirements wherein the pharmaceuticals are selected from among a biologic, an immunobiologic, an antibody, a peptide, a protein, an enzyme, a hormone, a nucleic acid, a lipid, and a formulation and/or combination of any of the preceding thereof.","The refrigerator and/or freezer unit provided herein may be a smaller unit, equal to, less than about 34 inches tall, or a larger unit, above about 34 in tall, and include controlled temperature zones below and/or above 0° C. For example the at least one controlled temperature zone can be maintained between 2° C. and 8° C. or between minus 50° C. and minus 15° C., In some examples the unit includes a first temperature zone maintained between 2° C. and 8° C. and a second temperature zone maintained between minus 50° C. and minus 15° C. wherein preferably the first temperature zone maintained between 4° C. and 6° C. and a second temperature zone maintained between minus 40° C. and minus 17° C. The temperature is monitored within each compartment of the plurality of compartments and the temperature within each compartment is recorded in compliance with regulatory requirements and displayed on an external portion of the refrigerator.","The temperature is monitored by temperature sensors located within the compartments and connected to a backup power supply wherein in the event or a power outage the temperature data is transmitted to the UID and when full power is restored to the ASP.","In yet another embodiment the temperature zone temperature is monitored by a plurality of temperature sensors to ascertain that the temperature within each compartment is maintained at the designated temperature.","In one exemplary embodiment, the refrigerator and/or freezer unit is equal to or less than about 34″ tall and at least 4 compartments are located in the sub 0.degree.","C. temperature zone and at least 8 compartments are located in the above 0.degree.","C. temperature zone.","Further provided herein is refrigerator and/or freezer unit wherein the plurality of compartments fill each temperature zone and vary in size and number providing customization of the compartment configuration.","The compartments may be available in at least two standard sizes, very in number from at least two containers per temperature zone, may contain only one type of product, one product type with one expiration date, or one product, and may be optionally labeled and/or color coded to denote differences between the products contained within.","The reader used to identify a pharmaceutical product can be implemented using a variety of technologies including, but not limited to, optical device, a magnetic device, a camera, RFID, barcodes reader, and a magnetic strip reader.","In one exemplary embodiment the reader device may be implemented with a barcode reader wherein the barcode reader optically scans a product, decodes the signal, and transfers the product information to the UID.","In yet another embodiment the reader is a camera wherein identification of product includes the following steps: the camera captures an image of the pharmaceutical product with barcode label; the image is transmitted to the UID; the UID transmits the image to the ASP; the ASP provided product identification software analyzes the image and generates a product descriptor; the product descriptor is stored within the ASP provided product database and is transmitted to the UID; the UID receives and adds the product descriptor to its current inventory database and updates the UID product information display.","The product descriptor may include information contained in the barcode and manufacturer provided product information.","The product descriptor record thus may include product name and dosage, lot numbers and associated expiration date, recommended temperature for storage, compartment location, storage temperature history, and internet links to manufacturer and/or Center for Disease Control and Prevention (CDC) information on the product.","In yet another embodiment the reader is a camera associated with each compartment and is used to capture an image of all products within a compartment wherein the analysis of the image captured by the camera reader provides a count of the product within the compartment.","The refrigerator and/or freezer unit may be implemented with a UID that is a touch screen computing device, such as a tablet computer, connected to the refrigerator via a docking station, and may be connected to or embedded within the outer surface of the unit.","The UID can maintain a connection to the internet via multiple routes such as a local internet, a wireless network (WIFI) and/or cell phone card embedded in the refrigerator unit.","A UID home screen displays information on the status of the unit and its content.","Exemplary information displayed includes product name, product quantity, nearest expiration date, current temperature of product compartment, alerts, and/or product order status.","Further information about the product may be displayed by selecting the name of a specific product on the UID display and includes location by compartment, temperature history, lot numbers with associated expiration dates of current inventory, and links to product information on the internet that includes manufacturer and/or Centre for Disease Control and Prevention (CDC) product information.","At the user interface the user completes the capture of product transactional information by confirming a successful reader scan of the product being added to the unit, entering the product information manually, or by selecting on the UID screen, product to be removed from the unit.","In yet another embodiment an optionally activated security interface is provided wherein access to the UID and the refrigerator unit includes a login code verification and/or a biometric sensor scan wherein a biometric scan device may be a finger print identification device, a retinal scan identification device, a facial recognition device or a voice identification device.","Provided herein is a system wherein the ASP provided software functions include: analysis and storage of data, records, and information related to the unit; communicating with the UID and select recipients; generating alerts related to temperature, expiration dates, system health, network disruption, power disruption/loss and low stock; and providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, inventory management, wherein the access is via a secure website customizable based on user profile.","A service provider, using ASP provided software and servers in a cloud based hosted environment may include inventory management in compliance with regulatory requirements, system administration, alerting, and reporting.","The inventory management may include tracking of the inventory of products within the refrigerator and/or freezer unit and all product dispense and refill transactions, tracking the expiration date of each product, providing re-order messages, providing remove expired product messages; providing product is about to expire messages; and providing a product and regulatory information resource.","The system administration may include monitoring the refrigerator and/or freezer unit location information; monitoring information related to the physical status of the unit comprising: function; power, temperature or latches sensor data; maintaining communication between UID, ASP, and cell card application layers; maintaining select user an optionally secure access to the unit and ASP; and facilitating unit maintenance.","The alerting provides the delivery of alerting messages, to select recipients and/or the UID, related to events comprising: temperature of a compartment approaches or exceeds allowed temperature limits; a product stock is depleted or reached a low limit; a product expired or is to expire within select number of days; and power outage.","Further embodiments of the system provides alert, delivery to the UID and other customizable pre-determined locations such as specified phone numbers, computers and email addresses.","The alert delivered to the UID on the refrigerator indicates the location of the deviation and generate a customizable audio and/or visual alert.","In yet another embodiment the ASP inventory management software determines if a product has reached its expiration date or is deemed to have lost potency due to compartment temperature fluctuations outside of the recommended range, and sends an alert that product has expired, instructing the user to remove the expired and/or ineffective product.","Determining if product has reached its expiration date and/or lost potency includes: comparing current date to expiration date of product and if current date is on or post the expiration date, the product is expired; and determining if the temperature of compartment holding product exceeded allowed temperature limits for a time period greater than a select number of minutes the product is deemed to have lost potency.","Further the ASP inventory management software identifies product within select number of days prior to the expiration date and sends an alert to the UID and select recipients to prioritize use of the product or exchange/return the product for fresher product.","In a particular embodiment the ASP inventory management software monitors inventory levels of product within each compartment and when one or more products approach a predetermined re-order count of product a low stock alert is generated wherein a first customizable and unique audio and/or visual alert is generated when product stock is low and a second customizable and unique audio and/or visual alert is generated when a product reaches a zero inventory count.","The predetermined re-order count of product is determined by the user or the ASP service using dispense rate data, quantity of product contained in manufacturer packaging and number of days required to receive ordered product.","In a further embodiment the ASP provided software analyzes the reader data received from the UID and in combination with information available from product manufacturer generates a product descriptor record that includes for example: product name and dosage; lot numbers with associated expiration date; recommended temperature for storage; and compartment number.","Also provided herein are ASP provided software applications related to product potency and inventory management including: product potency assessment based on storage temperature history and product expiration date; product potency review in compliance with regulatory requirements; current product inventory assessment based on reader captured data and UID manually entered data; product inventory dispensing assessment; product order requests, status and recommendations; and reports and data analytics including: stock and dispense transactions, product loss due to expiration or spoilage, and frequency of refills.","Further embodiment of the software applications function is customization of refrigerator unit variables including: unit size and refrigerator and/or freezer option; compartment number, size and label and/or color coding per product and temperature zone; secure or free access to unit; selection of users; establishing user profiles with customized level of access; unit alert message signal type, audio and or visual option; and recipients of alert messages.","In yet another embodiment the ASP secure website software generates a user profile for each user and provides each user with customized levels of access to the information and data associated with each unit.","A user that includes refrigerator unit user, refrigerator unit managers, and refrigerator unit owners may have the following level of access: a user with access to unit content only; a user with access to unit content and order related information on the ASP web site; a user with access to unit content and all information related to the unit on the ASP web site; and a user with access to select product reports.","Provided herein are reports generated by the ASP provided software, available based on a user's profile and permission status, wherein user group includes: refrigerator unit users, managers, and owners; manufacturers; distributors; product representatives; physicians; and pharmacists.","Reporting includes: providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, or inventory management, wherein the access is via a secure website and customizable based on user profile.","For example a refrigerator unit user, manager and owner have access to reports related to their unit and the reports may include: current inventory of product with expiration dates; quantity of product used, by type of use and/or total use, for a selected time period such as day, week month year; product dispense rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; and alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.","The refrigerator unit user, manager and owner also have access to reports related to other units serviced by the ASP including: type and quantity of product dispensed to patient by location such as a local region defined by community or city, a state, and/or country within a selected time period; product usage rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.","A manufacturer of exemplary product A may have access to reports including: quantity of product A dispensed to patient by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit for a selected location; number of units within select location or region distributing product “A”; and low stock of product “A” alerts per unit and/or region.","A distributor and a product representative may have access to reports on their products including reports on: quantity of product dispensed to patient, expired, and or spoiled by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.","And a pharmacist may have access to reports on their products and refrigerator and/or freezer unit stocked by their pharmacy wherein reports included are: quantity of product dispensed to patient, expired, and or spoiled by date and by refrigerator and/or freezer unit stocked by their pharmacy; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.","Other features and advantages of the invention will be apparent from the following description, drawings and claims.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 shows an exemplary interior view of a refrigerator with a compartment configuration for two temperature zones.","FIG.","2 shows an exemplary front exterior view of refrigerator.","FIG.","3 shows an exemplary view of a UID display.","FIG.","4 is a block diagram overview of refrigerator system components.","FIG.","5 is a flow diagram illustrating communication between refrigerator, UID and ASP.","FIG.","6 is a flow diagram illustrating steps of an exemplary product intake process using external camera reader 2.FIG.","7 is a flow diagram illustrating steps of an exemplary product dispense process using internal camera reader 1.FIG.","8 is a flow diagram illustrating steps of an exemplary product intake process using a barcode reader.","FIG.","9 is a flow diagram illustrating steps performed by the system in generating temperature deviation alert.","FIG.","10 is a flow diagram illustrating steps performed by the system in generating expiration of product alert.","FIG.","11 is a flow diagram illustrating steps performed by the system in generating low stock of product alert.","FIG.","12 is a flow diagram illustrating steps performed by the system in determining a product dispense rate.","FIGS.","13A and 13B is a flow diagram illustrating access to inventory reports based on user profile.","FIG.","14 is a block diagram illustrating the various functions provided by the Application Service Provider.","DETAILED DESCRIPTION OF THE INVENTION The following detailed description illustrates an embodiment of the invention by way of example, not by way of limitation of the principles of the invention.","Various embodiments of the invention will be described by way of illustration with reference to various software tools, but it should be understood that other software tools that have comparable capabilities of the mentioned tools may be used.","The contents of this Detailed Description are organized under the following headings: Definitions; Overview; Refrigerator Unit; User Interface device (UID); Reader; Application Service Provider (ASP); Alerts; and Inventory Management.","Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs.","All patents and publications referred to herein are, unless noted otherwise, incorporated by reference in their entirety.","In the event a definition in this section is not consistent with definitions elsewhere, the definition set forth in this section will control.","As used herein, “refrigerator” refers to an appliance that cools the interior compartments to temperatures below the ambient temperature of the room, is designed for the storage of temperature sensitive pharmaceuticals in compliance with regulatory requirements, and is fitted with sensors, devices and a computer as described hereinafter.","The refrigerator contains compartments above zero .degree.","C. and may or may not provide a freezer compartment with temperatures below zero .degree.","C. It is a low humidity, frost free, refrigerator with calibrated temperature monitoring sensors located at a point or points within the compartments which most accurately represents the temperature profile of the pharmaceutical product, is equipped with alarms to indicate temperature excursions and/or refrigeration failure, and has lockable doors meeting the guidelines of the World Health Organization (WHO), as described in “WHO Expert Committee on Specifications for Pharmaceutical Preparations”, WHO technical Report Series 961, 2011 (Report found on www.who.int/en/) As used herein, “freezer” refers to an appliance defined as is the refrigerator noted above with the exception of the inside of the unit cooled to a temperature below zero ° C. As used herein, “smart refrigerator” refers to a refrigerator and/or freezer unit which contains a computer in communication with an ASP and is designed for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products as described herein.","As used herein, “compartment” refers to a holding container for a product designed to securely fit into the refrigerator and/or freezer unit and may take on a plurality of shapes including for example; a sliding drawer like structure wherein a drawer may contain further subdivisions forming smaller compartments; a tray like structure further holding individual trays designed to hold one product type which may come for example in the form of a vial, two vials, a syringe, or a package.","The compartment design meets regulatory requirements and provides for a consistent temperature profile throughout the storage compartments when empty and in a normal filled condition.","As used herein, “cleanable surface” of a refrigerator is made of materials that are acceptable in a medical environment and can be cleaned and/or wiped with sterilization and/or cleaning chemicals and cloths as required by WHO regulation or best practice methods.","The material is a durable, corrosion free material such as stainless steel, hard plastic or resin, and the surface is smooth with minimal number of seams.","As used herein, “Automatic Identification and Data Capture” (AIDC) refers to methods of automatically identifying objects using a device which collects data about the object and transfers the data directly into computer systems.","Technologies typically considered as part of AIDC include bar code readers, Radio Frequency Identification (RFID), biometric scanners, magnetic strip reader, Optical Character Recognition (OCR), smart cards, and voice recognition.","As used herein, “reader” is a device used to obtain the identity of, and information related to, a specific product, using a method referred to as Automatic Identification and Data Capture (AIDC), by scanning, detecting, or capturing an image of a product in order to identify embedded information on the product.","As used herein, a “camera” may be used as a reader device to capture an image of a product with the portion displaying a barcode.","The camera transfers the data to the ASP database via the UID computer, for analysis by barcode recognition software (see, e.g.","Barcode Xpress available from accusoft at www.acusoft.com).","The camera may also be used to capture an image of a compartment which is analyzed by the ASP provided software for the number of objects stored in a compartment using image recognition software available and known to those of skill in the art.","As used herein, “barcode” refers to an optical symbol, machine readable, containing information about the product on which it is displayed.","The barcode may be one dimensional, a collection of bars of various widths representing the descriptive characters, two dimensional collection of symbols for example known as a Quick Response Code (QR), or three dimensional, where for example a 2D image includes color and further expands the amount of information captured.","As used herein, “barcode reader” refers to an electronic device specifically designed for reading printed barcodes.","It consists of a light source, a lens and a light sensor translating optical impulses into electrical ones.","Additionally, nearly all barcode readers contain decoder circuitry analyzing the barcode's image data provided by the sensor and sending the barcode's content to the scanner's output port (see, e.g., The LS3008 rugged handheld scanner by Motorola designed for the healthcare industry or the Motorola SE330X which can be integrated into a device, on the Motorola web site at www.motorola.com).","As used herein, “Radio-frequency identification” (RFID) refers to a reader that uses radio-frequency electromagnetic fields to transfer data from a tag attached to a product for the purposes of automatic identification and tracking.","The tag does not require a battery as it is powered by the electromagnetic fields used to read them.","The tag contains electronically stored information which can be read from up to several meters away.","Unlike a bar code, the tag does not need to be within line of sight of the reader and may be embedded in the tracked object (see, e.g.","UHF Mobile RFID Reader for Smartphones and Tablets, by IDBLUE at www.idblue.com).","As used herein, “magnetic strip reader” or “magnetic card reader” refers to a device with a guide for swiping and reading a magnetic card for example containing an access identification code of the designated user.","Exemplary devices include MagTek Mini Swipe Magnetic Strip Reader, available from MAGTEK.®.","(see, e.g.","magtek.com) where data is sent to the UID via a USB port and may be viewed in applications such as Windows.RTM.","Notepad without requiring additional drivers or application programming.","As used herein, “biometricreader” refers to a reader that uses for example a finger print or a retinal or facial recognition scan as a security measure to identify an authorized user of a refrigerator unit.","For example a finger print recognition controlled access implements a finger print scanner, embedded in the user interface device, and software to analyze the scan.","Scanners and software are readily available (see e.g.","Mercury.™ Series OEM Module from Lumidigm at www.lumidigm.com).","As used herein, “docking station” refers to a device that receives the user interface device.","The docking station may serve only as a power source or may also be integrated directly into the other devices or systems such as temperature sensor, a reader, a camera, a biometric sensor or a central processing unit (CPU).","As used herein, “cell phone card” refers to a cellular network card which provides access to the internet.","Cell phone cards are available and known to those of skill in the art.","As used herein, “user interface device” (UID) is a computer in communication with the refrigerator unit components and an ASP and is docked, or mounted, in a docking station connected to or embedded in the unit.","The UID contains wired and wireless network adapter cards and remains fully functional when docked or undocked maintaining communications with the unit via a short range wireless communication device embedded in the unit.","The UID, preferably a touch screen computer with a virtual onscreen keyboard, can access the internet via a wireless link to a local wireless network, a wireless communication through a cell phone card embedded in the unit, or a cable connection through a docking station.","The UID contains an operating system and software required to capture data from sensors and readers on or within the refrigerator unit, send and receive data from an ASP, capture manually entered data, and display information.","As used herein, “tablet” refers to a self contained computer with a wireless internet connectivity that uses a touch screen with virtual keyboard capabilities for data access and entry.","As used herein, “Wireless” refers to a type of communication in which power and/or data is transferred over a distance without the use of electrical conductors or wires.","For example, electromagnetic waves, light waves, or acoustic waves can be used to carry power and/or data over a distance without using electrical conductors or wires.","As used herein, “cloud-based host” refers to a third party provider server farm located in a centralized location, away from the individual refrigerator units, implemented as a service, maintaining communications with individual computers and users via the web.","The data, software and programming are centralized on the server farm.","As used herein, “Application Service Provider” (“ASP”) refers to a cloud-based hosted environment business that provides computer-based services to customers over a network.","A user requires only a browser and an internet/intranet connection on their desktop, laptop, or other network access appliance to obtain substantially complete secure access to that system.","Software offered using an ASP model is also sometimes called on-demand software or software as a service (SaaS) and may be accessed using standard protocol such as Hypertext Transfer Protocol (HTTP), foundation of data communication for the World Wide Web (see, e.g., ASP hosted services provided by NetSuite, Inc. of San Mateo, Calif. such as NetSuite.™., Oracle.®.","Small Business Suite, NetCRM.™., and NetERP.™., descriptions of which can be found at www.netsuite.com).","The ASP utilizes one or more software application programs, routines or modules configured to be executed by a general purpose microprocessor, in one or more hardware devices, such as a programmable logic controller (PLC).","The user benefits from having access to highly specialized software without the cost of purchasing, servicing and upgrading the software as well as access to ASP provided information and resources related to the products.","A used herein, “service provider” refers to a business that oversees and maintains the refrigerator/freezer system in all its functions as described herein.","As used herein a “product descriptor”, refers to product information generated by the ASP provided software that combines the reader data received from the UID and information available from product manufacturer, information includes for example: product name and dosage, lot numbers and associated expiration date, recommended temperature for storage, and compartment location.","As used herein, “HL7” refers to a data format adapted by the healthcare industry for sharing information within the health care field.","The document format is developed by Health Level Seven (HL7), a non-profit organization involved in the development of international healthcare informatics interoperability standards.","As used herein, “Electronic data interchange” or “EDI” refers to a data format adapted for communication between a healthcare provider and a vendor for example.","EDI is the structured transmission of data between organizations by electronic means and without human intervention as defined by the National Institute of Standards and Technology.","As used herein, a “HIPPA” refers to “The Health Insurance Portability and Accountability Act of 1996” wherein it protects the privacy of individually identifiable health information; the HIPAA Security Rule, which sets national standards for the security of electronic protected health information.","As used herein, “regulatory requirements” refers to the regulations related to a refrigerator unit for storage of temperature sensitive pharmaceutical products as defined by the World Health Organization (WHO) qualification requirements for cold storage of Time and Temperature Sensitive Pharmaceutical Products (TTSPP) (see, “WHO Expert Committee on Specifications for Pharmaceutical Preparations”, WHO technical Report Series 961, 2011 available at www.who.int/).","As used herein, a “web site” is a set of related web pages containing content such as text, images, video, audio, etc.","A website is hosted on at least one web server, accessible via a network such as the Internet or a private local area network through an Internet address known as a Uniform Resource Locator.","All publicly accessible websites collectively constitute the World Wide Web.","As used herein, “product type” refers to products of the same pharmaceutical composition and dosage and its packaging may come for example, in the form of a vial, two vials, a syringe, or a package.","As used herein, “par level” is a predetermined inventory level of a specific product.","When ordering or re-ordering product the goal is to increase inventory to the predetermined par level.","The predetermined par level takes into consideration the physical maximum quantity of the specific product that can be physically accommodated by the storage unit, the shelf life of the product, and historical product dispense records.","As used herein, “re-order point” is the inventory level at which a re-order message is generated.","The re-order point takes into account lead time for dispense rate, order processing, and product delivery in order to avoid stocking out of the product.","The re-order point quantity of product to be ordered is determined by the difference between current inventory and the predetermined par level.","As used herein, “critical low” is an inventory level whereby a re-order would not arrive in time to avoid a zero count of stock, “stock-out”, based on expected dispense rate, and manual intervention such as placing an overnight shipping order may be required.","As used herein, “biologic” is a pharmaceutical product composed of sugars, lipids, peptides, proteins, nucleic acids or combinations of these substances and may be a vaccine, blood or a blood component, allergenic, somatic cell, gene therapeutic product, recombinant therapeutic protein or nucleic acid, or living cells that are used as therapeutics to treat diseases.","As used herein, “potency” is a measure of the pharmaceutical product activity expressed in terms of the amount required to produce an effect of given intensity.","Exposure to improper storage temperatures may decrease potency of a pharmaceutical product due to decomposition and/or denaturation of the product and/or by destabilizing the formulation of the product.","As used herein, “effectiveness” refers to the ability of a pharmaceutical to produce a beneficial effect.","The “Centers for Disease Control and Prevention” (CDC), a division of Department of Health and Human Services, which among its many roles also provides guidelines for proper handling and storage of vaccines.","The guidelines may be found at www.cdc.gov/mmwr/preview/mmwrhtml/mm5242a6.htm.","As used herein, “point of care” is a location at or near the location where the pharmaceutical product is administered to a patient.","Locations may include a physician's office, a physicians practice group suite, a clinic, a pharmacy, and a hospital.","As used herein, “business hours” refer to a time period of the day when pharmaceuticals are administered to patients and the refrigerator unit is likely to be opened frequently.","Overview Provided herein is a smart refrigerator unit and system for the secure storage of temperature sensitive pharmaceuticals at optimal temperatures designed to identify, track and maintain an inventory of the temperature sensitive pharmaceuticals at optimal levels and potency in compliance with regulatory requirements.","The refrigerator unit compartments are dedicated to one product type and expiration date, or a single product, and may be customized by size and number.","The compartments may be located within several temperature zones which may include zones above and below freezing, zero ° C. The refrigerator unit devices such as temperature sensors, readers, locking mechanism, and security features communicate with a user interface device, docked on the unit, via a direct hard wire link or a wireless connection.","The UID controls access to the unit, collects data related to the status of the refrigerator and its inventory content, and communicates with an ASP provided software in a cloud based hosted environment for inventory and information management.","Refrigerator and/or Freezer Unit A smart refrigerator unit in one exemplary embodiment is a smaller unit, under 34 inches tall, designed to fit under a counter within a point of care facility such as a physician's office, a clinic or an onsite pharmacy.","The exemplary unit contains two temperature zones commonly recommended for the storage of biologic pharmaceuticals, a first cold temperature zone maintained between 2° C. and 8° C., and a second frozen temperature zone maintained between minus 15° C. and minus 50° C. The first temperature zone is maintained preferably between 3° C. and 7° C. and more preferably between 4° C. and 6° C. The second temperature zone is maintained preferably between minus 15° C. and minus 30° C., and more preferably between minus 15° C. and minus 25° C. Each temperature zone is filled with compartments for holding product, customizable in number and size, from at least one compartments in the frozen temperature zone to at least four compartments in the cold temperature zone.","The compartments slide in and out for ease of access, come in at least 2 standard sizes, and vary in width and height to accommodate various quantities and sizes of product.","FIG.","1 shows an exemplary layout of an arrangement of customizable compartments 102 with 4 compartments located in the below 0° C. temperature zone 104 and 13 compartments located in the above 0° C. temperature zones 103.Each compartment is dedicated to one type of product and expiration date and may be optionally labeled and/or color coded to denote differences between products contained within.","The smaller unit described above, may further be implemented by dedicating the unit to only one temperature zone, for example above 0° C. storage or below 0° C. storage, to meet the needs of a point of care facility.","Larger units, above a 34 in height in yet another implementation of the invention may be a preferred size for point of care facilities including for example, a hospital, a clinic and pharmacy.","The larger unit may also be dedicated to above 0° C. storage, below 0° C. storage or a combination of multiple temperature zones.","In one exemplary embodiment each compartment within the unit contains at least one temperature sensor which, in communication with the user interface device, provides a historical record of temperature for each product assigned to the compartment.","The temperature of each compartment is monitored at a customizable frequency that meets regulatory requirements and may vary throughout the day based on the frequency of opening and closing of the unit.","For example, the temperature may be monitored at least once every 10 minutes during regular office hours and at least every 30 minutes outside of regular business hours.","The sensor is connected to a back-up power source, a battery, or optionally if the sensor is a wireless sensor it is powered by a battery.","In yet another embodiment the temperature of a plurality of small compartments, designed to hold one or several products, is monitored by a plurality of temperature sensors positioned throughout a unit temperature zone to ascertain temperature measurement is representative of the compartment temperature.","The temperature within each temperature zone is pre-set to a temperature within the recommended storage temperature range for the products stored within and is maintained within several degrees of that point.","In the event of a power failure the temperature sensors have a back-up power source, a battery, and will continue to record and store temperature data.","Temperatures of the various compartments are displayed on the UID docked on the external portion of the refrigerator.","The compartment temperatures may also be displayed using a secondary device, for example a digital or LED display, embedded or mounted on the external portion of the refrigerator.","During a power outage the locks to the unit may be disabled and a user may choose to transfer products to another cold storage device in the event of temperature deviations outside of the recommended range.","Each compartment may further have a designated camera used to capture an image of the compartment content.","Analysis of the image using ASP provided reader software generates a count of the number of products contained in the compartment, wherein the image analysis is based on the number of objects in the image.","Each compartment is dedicated to one product type and expiration date and therefore the count of products within a compartment also provides an accurate inventory count.","The unit is fully compliant with the World Health Organization (WHO) qualification requirements for cold storage of Time and Temperature Sensitive Pharmaceutical Products (TTSPP) (see, “WHO Expert Committee on Specifications for Pharmaceutical Preparations”, WHO technical Report Series 961, 2011 available at www.who.int/).","The unit is specifically designed for storage of TTSPP, is capable of maintaining the temperature range over the full range of annual ambient temp at a point of care facility, is equipped with alarms to indicate temperature excursions and/or refrigeration failure and is fitted with lockable doors and an access control system.","The exterior and interior of the unit is made of materials that are cleanable with sterilization solutions.","The unit has a consistent temperature profile throughout the storage compartments when empty and in a normal filled condition and is equipped with calibrated temperature sensors, accurate to±0.5° C., capable of continuous recording.","The sensors are located at points within the unit which most accurately represents the temperature profile of the TTSPP.","The WHO specifications for a refrigerator unit address the physical requirements, noted above, as well as protocols and methods that validate the potency of the administered TTSPP.","The WHO protocol specifications include keeping records of the temperature profile of each TTSPP stored, providing alerts when deviations occur and scheduling and completing regular maintenance of the unit.","The smart refrigerator system provided software follows, performs and/or schedules the specified protocols.","User Interface Device (UID) A UID 203, preferably a tablet computer with a touchpad incorporated into the display, is docked in a docking station 201 embedded or connected to the front of the refrigerator unit.","See FIG.","2.Communications between the UID and refrigerator unit is maintained via a hard wire connection to the central processing unit (CPU) of the smart refrigerator unit.","The UID is the primary security interface providing a secure access to the unit and may use login code verification and/or a biometric image capture such as finger print identification, a retinal scan, a facial recognition, or a voice identification.","A log in code may be a simple alphanumeric password that the user is either given or is provided an opportunity to enter a password that will be stored in the authentication server, located in the ASP database, in conjunction with the user account name.","The user may also be prompted to enter a security question in the event the user forgets the password and needs to be issued a new password.","The security feature may be optionally disabled The UID communicates with a cloud-based ASP via an internet connection through a local internet router, a wired or wireless network adapter card, or via a cellular network using a cell phone card, embedded in the unit.","When the cell phone card is activated it updates information to the ASP at customizable number of minute intervals which may vary for periods during business hours, a period of frequent use of the unit, and periods outside of business hours when the unit remains closed.","A docking station connected to or embedded on the external portion of the unit provides a port for the UID and will primarily function as a link to the CPU and a power source for the UID.","Other devices and sensors associated with the unit may communicate with or deliver data to the UID via the CPU or wirelessly.","The docking station may in yet another embodiment provide a wired internet connection, a power source, and may integrate any wired sensors and devices, such as the temperature sensor and compartment cameras, with the UID.","An RFID reader, a biometric sensor, a barcode or magnetic strip reader are other exemplary devices that can communicate with the UID wirelessly or be integrated with the UID via the docking station.","The UID uses a touch screen to display, enter and access information on the unit and its content.","The default UID display includes: current temperatures, current product content with name and quantity of pharmaceuticals, nearest expiration date, alerts, and order status.","By selecting the name of a specific pharmaceutical product on the UID screen further information about the pharmaceutical product is displayed including location by compartment, temperature history, lot numbers with associated expiration dates of current inventory; and links to manufacturer and/or Centers for Disease Control and Prevention (CDC) information on the pharmaceutical.","FIG.","3 shows an exemplary display on the UID.","Reader A reader in one embodiment is a device used to identify and/or count products present in the unit or being added to or removed from the unit.","The reader device is embedded in, attached, and/or unattached to the unit and is in communication with the UID via a wired or wireless connection.","Suitable reader devices are known to those skilled in the art and may be selected from various technologies including a camera, a radio frequency identification (RFID), barcode scanner, and or magnetic strip reader.","Most pharmaceutical products, packaged individually or in groups by lot number, are labeled with a barcode by the manufacturer and therefore a barcode reader is preferred.","An exemplary reader is a camera which captures the image of a product, including a barcode label, and via the internet, wired or wireless, sends the image to the ASP for analysis.","An ASP provided software analyzes the image obtaining product descriptor information which includes product name, dosage, lot number, and expiration date.","The camera may be located on the UID and/or within or above the refrigerator compartment.","A camera reader is a technology readily available, simple to use, and does not require special labeling of the product In yet another embodiment of the invention a barcode reader may also be utilized to identify a product.","The barcode reader in this case contains decoder circuitry analyzing the barcode's image sending the information directly to the UID wherein the UID stores and also send the product information to the ASP to be added to a product database.","The on-site user may scan the product being added to the unit with a handheld or an embedded reader wherein the information is transmitting to the UID via a wireless or a wired connection.","The smart refrigerator unit may also be implemented with RFID technology by placement of an RFID reader, a two way radio transmitter-receiver wired to a transmitter, in communications with the UID which transfers the signal to the ASP provided RFID software to generate a product descriptor.","The product in this case must be labeled with an RFID tag.","A reader in yet another embodiment is a biometric or magnetic strip device used as a security measure to identify an authorized user of the unit.","In embodiments using biometric authentication, some biometric information, such as a fingerprint image, is obtained and stored in the authentication server for use as the authentication credential.","Such biometric information may be, but are not limited to, finger print images, spoken phrases for use in voice recognition, and facial images for use in facial recognition.","In embodiments using finger print biometric information, users will have a fingerprint scanned to generate a fingerprint template that is stored in the authentication server.","For other forms of biometric authentication, users may record a voice sample or have their retina scanned, with the resulting recording (or voice print) or image stored in the authentication server.","For embodiments using facial recognition as a form of authentication, a camera may be employed to take detailed photographs of a user's face.","FIG.","4 contains a block diagram overview of an exemplary refrigerator system and components.","The unit 100 includes docking station 201, an exemplary compartment 410 further including an internal reader 1415 and temperature sensors 420 connected to a backup power source 425, a cell phone card 430 in communication with a central processing unit (435).","A UID 203 can be docked in the docking station includes a touch pad 440, a camera 445, a biometric sensor 450, a speaker 455, a microphone 460, and is connected to or in communication with an external reader 2 465.The UID is connected to a local internet router 470 which provides access to the cloud based ASP 475.FIG.","5 contains a block diagram overview of communication lines between components of an exemplary refrigerator system.","Reader 1415 and temperature sensor 420 communicate with CPU 435, The cell phone card 430 and CPU 435 in refrigerator unit 100 communicate with the UID 203 that also communicates with reader 2465, biometric sensor 450, and ASP 475.Reader 1415 and temperature sensor 420 may also communicate directly with and cell phone card 430 that is in communications with the ASP 475.The ASP 475 communicates, via a secure web site, with authorized users that include the unit user 500 and other non-unit users for example, a sales representative 505, a pharmacist 510 and a manufacture 515.Application Service Provider (ASP) The ASP, a cloud-based hosted environment, provides server space, to store and securely access data and information related to the unit, and software required to analyze and manage the data, information, and inventory.","The refrigerator unit data captured by the ASP inventory management software includes product dispense and refill transactions, product reader scans, temperature sensor data, manually entered information via the UID, camera images, and bioscans.","The ASP software analyses and stores the data.","The ASP product identification software provides a product descriptor record for each product which includes product name, dosage, lot number, expiration date, quantity of the product in the unit, recommended temperature for storage, unit/compartment location, special handling requirements and links to manufacturer and/or CDC information.","The ASP further generates records related to dispense rate of product, spoilage frequency, historical temperature records, and product order frequency including average number of days required to receive new product.","An ASP inventory management function includes the tracking of add/dispense transactions of product to and from the unit.","FIG.","6 provides an exemplary protocol flow diagram for addition of product to the unit using a camera as the reader device.","An on-site user logs into (step 615) or directly accesses (step 620) the unit via the UID and scans the product using a reader device on the unit (step 625), for example a camera embedded in the UID.","The camera reader in communication with the UID send image to the ASP product identification software (step 630) that analyzes the image (step 640) and, using additional manufacturer information stored in its database, generates a product descriptor (step 645) which includes product name, dosage, lot number, expiration date, recommended temperature of storage, and any special handling requirements such as for example light sensitivity.","The ASP product management software compares the product descriptor to those of product already in the unit (step 650) and if the product has an assigned compartment in the unit the compartment identifier is included with the product descriptor (step 660).","If the product does not have an assigned compartment the ASP product management software will assign one in the temperature zone required for the storage of that product (step 655).","The product descriptor and instructions for placement and handling are delivered to the on-site user via the UID where the information is displayed and can be verified by the on-site user (step 665).","If any information is missing, for example the expiration date, the on-site user can use the UID keypad to manually enter the information (steps 670, 675, 680).","The product is placed in the compartment (step 685), the user logs out (step 690) and the UID product content is updated (step 695).","The product descriptor is stored in both the ASP and the UID product database.","Dispensing of product in one embodiment may be captured by the unit when the on-site user selects the product to dispense on the unit content listing, displayed on the UID, and further selects the reason for dispensing including for example: dispense to patient, expired, spoiled in unit, transferred from unit, and discontinued.","Optionally the user may also select, or enter manually, the name of the patient to receive the product.","The “dispense to patient” reason may be changed to post dispense spoilage if product is deemed to have spoiled prior to being administered to a to patient.","FIG.","7 provides an exemplary protocol flow diagram for dispensing of product from the unit using a camera associated with a compartment as the reader 1 device.","An on-site user access the unit and UID (step 700) and views the unit content listing on the UID display (step 705).","The compartment holding product is identified (step 715) and the user removes product (step 720) The user logs out and closes unit (step 725).","The compartment camera takes and image of the compartment (step 730), the image is sent to the ASP provided software for analysis (step 735), and the unit content is updated (step 740).","FIG.","8 provides and exemplary protocol for addition of product to the unit using an external barcode reader 2.An on-site user scans the product barcode label with a barcode reader (step 805) and the reader transmits the information to the UID (step 815) which transmits the information to the ASP (step 820) wherein the ASP inventory management software generates a product descriptor with assigned compartment (step 825).","The product descriptor is sent to the UID (step 830) and user confirms correct identification of the product (step 835).","If product is not correctly identified the user enters information (step 840), ASP software confirms receipt of data and compartment assignment (step 845) and the user places product in the designated compartment (step 850).","If the product is correctly identified at step 835 the user places the product in the designated compartment (step 850).","The user logs out, closes unit (step 850) and the UID product data base is updated (step 860).","Alerts Alerting activities will emanate from the ASP hosted system and alerts will be delivered to pre-determined locations including the physical unit and/or specified phones, computers and email addresses.","Alerts are generated by events associated with the physical unit including: temperature deviations from allowed temperature range, loss of power to the physical unit in the event of a power outage, lock malfunction, and cooling system failure.","Alerts are further generated by the inventory management software based on inventory deviations including expiration of product, about to expire product and low or depleted stock warnings.","The ASP unit management software records and keeps historical data on the temperature of each compartment and the product contained within the compartment.","FIG.","9 shows an exemplary flow diagram illustrating the steps taken to monitor temperature and send out alerts.","The temperature is, recorded by the temperature sensors associated with each compartment and or temperature zone (step 900) and is sent to and displayed on the UID (step 905).","The temperature data is further sent by the UID via the internet (step 910) or a cell phone card (step 915), if internet access is not available, to the ASP unit management software, the temperature data is compared to the allowed storage temperature limits for that product (step 925).","If the temperature falls within these limits no action is taken (step 930).","If the temperature falls outside these limits an alert is generated (step 935) and delivered to the UID and selected recipients emails and/or phone numbers (step 940).","The alert, which may include a visual and/or audio signal, received by the UID will display a temperature deviation warning with name and location of product and instruct the user to confirm the temperature deviation by comparing to temperature readout at the unit, and take action to transfer product to an alternate storage device if necessary.","The alert is emailed or telephoned to the customized list of user contacts and includes all information on the nature of the deviation and instruct the recipient to follow user established protocol and take action to confirm product is properly stored.","The ASP database stores expiration date for each product within a unit and generates an alert when a product is within a select number of days from the expiration date or has expired.","When a product expires it is critical to remove the product from the unit, not only to comply with TTSPP storage regulation, but to avoid the ultimate error of administering an ineffective product to a patient and endangering the patients well being.","FIG.","10 shows an exemplary flow diagram illustrating the steps taken to monitor the expiration dates of products and send out alerts.","The ASP inventory management software accesses expiration date data in database (step 1000), comparing current date to expiration date (step 1010).","If the expiration date is equal to or prior to the current date, the product is expired and an alert is sent to the UID and select recipients (step 1015), with optional audio and or visual alerts, instructing user to remove and dispose of expired product, providing product name, expiration date, lot number and unit/compartment location (step 1020).","If a product expiration date is a select number of days post current date (step 1025) a different alert is sent to the UID and select users (step 1030), for example instructing the user to prioritize use of the product (step 1035) if products with later expiration dates are also present in the unit and to verify stock status and consider ordering more product.","The select number of days post current date is customizable by the unit user and is based on the dispense rate of the product.","The ASP inventory management software further sends out low stock alerts and reorder recommendations based on the captured data related to current inventory status of each unit, expiration dates of the products, and pre-determined re-order levels.","FIG.","11 shown an exemplary flow diagram illustrating the steps taken to monitor product stock in the unit and send out alerts.","The ASP inventory management software updates the inventory levels of each compartment every time a compartment is accessed and the unit is reclosed (step 1100).","Inventory is decremented as product is dispensed and upon reaching or falling below a predetermined re-order level (step 1105), an order for additional product will be processed.","If product count is greater than the re-order level count (step 1105) no action is required (step 1115).","Should inventory levels fall to or below the predetermined re-order level a reorder message is sent (step 1110) to place or confirm if an order has been placed (step 1120).","If the re-order message is not successful, an order was not placed, the system will determine if the product count is below a critical level (step 1130) and will generate a low stock alert if it is not below the critical level (step 1135) or a critical low stock alert (step 1140) if it is below the critical level.","No action is required (step 1125) if an order is in place.","A critical low may occur for a variety of reasons including: expected shipment has been delayed, sudden surge in usage in a single day that reduces inventory past the reorder point, and failure to process a re-order.","The quantity of product that is re-ordered is calculated based on the difference between current inventory and the predetermined par level of inventory.","The ASP inventory management software can be configured to reorder stock automatically.","Inventory Management All inventory management functions are managed centrally by the ASP in a cloud based hosted environment.","Communication with individual units occurs via the Internet and all authorized users have secure access to their designated units via the ASP website.","The ASP inventory management software captures transactions related to inventory of the refrigerator unit and include stock and dispense transactions with reason for dispending of product.","The dispense transactions may include for example: dispensed to patient, expired, spoiled in unit due to unit temperature deviations outside of recommended range, transferred from unit, and discontinued.","Post a transaction the “dispensed to patient” transaction may be changed by user to “post dispense spoilage” if product was not administered to patient and product has been deemed to have spoiled.","The data is further used to establish historical records of product demand, to ascertain adequate stock is available as needed, avoid loss of product due to expiration/spoilage, and to optimize the frequency and timing for ordering product and the quantity of product to be ordered.","A product dispense rate is determined by the ASP provided inventory management software to establish historical trends in use of product.","Shown in FIG.","12 is an exemplary flow diagram for the process of determining dispense rates of a product.","The ASP stored transaction data (step 1200) is first selected for dispensing transaction data (step 1205) which is then sorted by type (step 1210).","The dispense rate for each type of dispensing transaction per calendar week (step 1215) and the average weekly rate for each type of dispensing transaction (step 1220) are determined.","A comparison is made between the average dispense rate/week for each type of transaction to each weekly rate and one time anomalies in dispensing of product are excluded (step 1225).","A corrected average dispense rate/week for each type of transaction is determined (step 1230) and a combined average of dispense rate/week for all transactions is established (step 1235).","The exemplary dispense rates above are determined as a weekly rate.","Further implementations of the dispense rate may be based on rates calculated for various time segments including a single day, several days, a month or year.","To ascertain a unit does not run out of stock and the optimal quantity of stock is ordered, par levels, re-order levels and critical lows of stock are determined and low stock alert are generated.","The determination of the physical maximum inventory level, par level, re-order level and critical low inventory level may be made by an authorized administrator of the unit.","Typically, these inventory points will be determined by an individual with access to information and reports on transaction statistics for the unit.","As historical trends of product use are established for a specific unit the determination of the par levels may be adjusted to reflect the historical use of the product within a given time period and may also be adjusted for seasonal variations.","The unit user may choose to adjust the rates based on their review of the historical transaction data or may request that the ASP provide estimated values as a service.","The quantity of product to be ordered is based on the predetermined par level which is a function of the number of products that can physically fit within the allotted compartments (physical maximum) in the unit, the shelf life of the product, a desired re-order frequency and the dispense rate of the product.","For example a product with a shelf life of 90 days (i.e.","expiration date is 90 days from the date of manufacture) and a dispense rate of 5 products per 10 days would allow the storage of a maximum of 45 products without having some of the product expire prior to use.","Although the unit can physically accommodate 45 product units, the par level may be set significantly lower than 45 in order to have a desired shipment of product every two weeks.","In this example, the par level may be set at 15, allowing room for variations in dispenses rate and product delivery.","If the unit compartment can only accommodate 10 product units, the maximum par level in this exemplary case is set at 10.The re-order level is used to trigger a product order.","If the order is not placed for whatever reason, there is a chance that the product could completely stock out and reach an inventory count of zero generating a stock-out alert.","For example if it takes two days to order and receive product and the current dispense rate for product is 5 per day, a re-order level of 10 would be the lowest product count to trigger re-order.","If an order has not been placed and inventory is at or below the set re-order level of 10, a low stock alert will be issued.","Further, if the inventory level has reached a predetermined critical low level ( )a low stock alert would be issued.","In keeping with the example, if the critical low level is determined to be 4 (less than a day's supply of product) and that inventory level is reached prior to the new shipment arriving, a low stock alert is issued.","Preferably the re-order level will be set at a higher count, for example 20 in this exemplary case, to adjust for delays in placement of order and dispense rate variations.","The authorized user of a unit has access to reports, provided by the ASP inventory management software, HIPPA compliant, that ascertain compliance with regulatory requirements, and allow the user to review and optimize protocols of handling and ordering of product.","The reports may include: current inventory of product with expiration dates; quantity of product dispensed, by type of dispensing and/or total dispensed, for a selected time period such as day, week month year; dispense rate and type by date, percentages of product administered and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.","An authorized user further has access to reports on regional inventory data available through the ASP database wherein the report may include: type and quantity of product administered by location such as a local region defined by community or city, a state, and/or country within a selected time period; and dispense rate and type by date, percentages of product administered and percent product lost due to expiration, spoilage in unit, spoilage outside of unit.","Fluctuating supply demands for time and temperature sensitive pharmaceuticals (TTSPS) give rise to a need for timely communication between the unit user, a point of care provider, manufacturers, distributors, sales representatives and others managing the flow of the TTSPS.","The ASP inventory management software provides such a communications network, via a web interface, delivering user profile customized access to reports related to TTSPS inventory transactions.","A manufacture of product “A”, for example, can have access to product “A” reports.","Reports may include: quantity of product administered in by date and/or by location such as a local region defined by community or city, a state, and/or country within a selected time period; percentages of product administered and percent product lost due to expiration, spoilage in unit, spoilage outside of unit for a selected location; number of units within select location or region distributing product “A”; and low stock of product “A” alerts per unit and/or region.","A distributor and/or product representative can have access to reports on products that they distribute and/or represent.","Reports may include: quantity of product dispensed to patient by date and/or by location such as a local region defined by community or city, a state, and/or country within a selected time period; percentages of product dispensed to patient and percent product lost due to spoilage or expiration.","FIG.","13A and FIG.","13B illustrate by way of an example the generation of, and user access to, reports on products A and B based on a time period of one week.","Unit 1 and Unit 2 transaction data (steps 1300 and 1305) is used to generate a report for each unit, Unit 1 Report 1 and Unit 2 Report 2 accessible to the unit's users, 1312 and 1317, and includes the number of products stocked or dispensed per week by transaction type.","The reports and data are merged in a regional database 1320 and provide unit user, 1312 and 1317, with regional data report, Report 4 1325.The regional data is broken down by product type, Report 5 for exemplary product A, 1330, and Report 6 for exemplary product B 6, 1335, for reporting to for example manufactures and sales representatives, of product A, 1340, and of product B, 1345.FIG.","14 illustrates by way of example some of the functions provided by the ASP.","The ASP 1400 utilizes the Inventory Management Software 1410 and Product Recognition Software 1420 to capture and analyze data received from the Unit 1405 to generate Reports 1430 made available by report type (1432, 1434, and 1446) to the Unit User 1440, Sales Representative 1442, and Manufacturer 1444.The Unit 1405 UID 1407 captures data from a Temperature Sensor 1409, Readers 1 and 2 1411, Biometric Sensor 1413 and manually entered data 1415.The Product Recognition Software 1420 captures and analyze the Product Reader Data 1422 and generates a Product Identifier 1424 that is used in combination with the Temperature Sensor & Stock/Dispense Data 1412 by the Inventory Management Software 1410 to generate Unit Content/Status and Alerts 1426 also displayed on the UID 1407.In further embodiments of the ASP provided inventory management software an automatic customizable product order/reorder protocol may be implemented in response to low stock alerts.","Re-order messages will be directed to one or more parties depending on customized preferences.","These messages for example could flow to a manufacturer, a distributor, a physician's re-ordering system or some combination of two or more.","Re-order messages are available in a variety of message formats including, but not limited to, EDI and HL7.The ASP hosted system will provide an interface to other computer systems that require information directly.","A doctor's office may desire an interface to provide dispense data to confirm the product dispensed and/or re-ordering information to process through an existing re-order process.","Interface messages are available in a variety of message formats including (but not limited to) EDI and HL 7.Since modifications will be apparent to those of skill in this art, it is intended that this invention be limited only by the scope of the appended claims."]],"string":"[\n [\n \"SMART STORAGE OF TEMPERATURE SENSITIVE PHARMACEUTICALS\",\n \"A refrigerator and/or freezer unit and system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products in compliance with regulatory requirements.\",\n \"The unit contains compartments for each product type in multiple controlled temperature zones with sensors to track product status and content.\",\n \"In a system, each unit communicates with an application service provider to provide remote inventory management capability.\"\n ],\n [\n \"1.A smart refrigerator and/or freezer unit for temperature sensitive pharmaceutical products, comprising: (a) a plurality of location- and temperature-monitored compartments to store temperature sensitive pharmaceutical products and disposed in at least one temperature-controlled temperature zone, wherein each such compartment is associated with at least one temperature sensor, is configured to store a plurality of units of a temperature sensitive pharmaceutical product type, and is maintained at substantially the same temperature as the one or more other compartment(s in the same temperature-controlled temperature zone; and (b) one or more processors configured for unit operation and to electronically communicate wirelessly or via a hard wire link with an application service provider (ASP).\",\n \"2.The smart refrigerator and/or freezer unit of claim 1, wherein the temperature zone comprises a temperature between about 2° C. and about 8° C. or between about −50° C. and about −15° C. 3.The smart refrigerator and/or freezer unit of claim 1, wherein temperature zone temperature is monitored by the one or more temperature sensors associated with the temperature-monitored compartments in the temperature zone, and wherein the temperature of each temperature zone is displayed on an external portion of the refrigerator, optionally on a touch screen interface.\",\n \"4.The smart refrigerator and/or freezer unit of claim 3 that further comprises a backup power supply 5.The smart refrigerator and/or freezer unit of claim 1 that further comprises a reader, optionally a barcode reader.\",\n \"6.The smart refrigerator and/or freezer unit of claim 1 that is wirelessly or connected via a hard wire to a computer network, optionally the Internet.\",\n \"7.The smart refrigerator and/or freezer unit of claim 1 that is in electronic communication with an ASP.\",\n \"8.The smart refrigerator and/or freezer unit of claim 1, wherein temperature monitoring of the compartments in the at least one temperature zone is continuous.\",\n \"9.The smart refrigerator and/or freezer unit of claim 1 configured for secure access, optionally via entry of a user login code or biometric data.\",\n \"10.The smart refrigerator and/or freezer unit of claim 1 that further comprises a touch screen interface configured displays information on the unit and its contents.\",\n \"11.The smart refrigerator and/or freezer unit of claim 10, wherein the information displayed on the touch screen interface comprises one or more of: temperature sensitive pharmaceutical product type name or names; temperature sensitive pharmaceutical product type dosage or dosages; temperature sensitive pharmaceutical product type quantity or quantities in the smart refrigerator and/or freezer unit; nearest temperature sensitive pharmaceutical product expiration date; current temperature of temperature-controlled temperature zone(s); alerts; and temperature sensitive pharmaceutical product type order status.\",\n \"12.The smart refrigerator and/or freezer unit of claim 10, wherein a user, by selecting the name of a specific temperature sensitive pharmaceutical product type on the touch screen display, is provided further information about the temperature sensitive pharmaceutical product type, which further information is optionally selected from the group consisting of location by compartment and/or temperature zone, temperature history, lot number or numbers with associated expiration date or dates of current inventory of the temperature sensitive pharmaceutical product type, and an Internet link to the temperature sensitive pharmaceutical product type.\",\n \"13.The smart refrigerator and/or freezer unit of claim 1, wherein each of the plurality of compartments is capable of holding a plurality of units of one temperature sensitive pharmaceutical product type, which units optionally have the same expiration date.\",\n \"14.The smart refrigerator and/or freezer unit of claim 1, wherein the plurality of compartments holds one temperature sensitive pharmaceutical product unit per temperature-monitored compartment.\",\n \"15.The smart refrigerator and/or freezer unit of claim 1 that further comprises a plurality of temperature-controlled temperature zones, each of which is optionally maintained at a temperature different from the temperature of the at least one other temperature zone.\",\n \"16.The smart refrigerator and/or freezer unit of claim 15 that comprises first and second temperature-controlled temperature zones, wherein the first temperature-controlled temperature zone is maintained at a temperature between about 2° C. and about 8° C. and the second temperature-controlled temperature zone is maintained at a temperature between about −50° C. and about −15° C. 17.A system to manage temperature sensitive pharmaceutical products, comprising a plurality of smart refrigerator and/or freezer units each according to claim 1 connected to an application service provider (ASP).\",\n \"18.A system according to claim 17, wherein the ASP provides one or more services selected from the group consisting of inventory management and system administration.\",\n \"19.A method of managing a temperature sensitive pharmaceutical product inventory comprising: storing a temperature sensitive pharmaceutical product inventory in a refrigerator and/or freezer unit according to claim 1; collecting data related to the unit and the product inventory stored within; providing a user interface at the unit; and providing via the ASP inventory management services.\",\n \"20.A method of storing a temperature sensitive pharmaceutical product inventory comprising: storing a temperature sensitive pharmaceutical product inventory in a refrigerator and/or freezer unit according to claim 1 that is connected wirelessly or via a hard wire connection to a computer network, optionally the Internet, hosting the ASP, wherein the ASP provides inventory management services for the product inventory stored in the unit; collecting data related to the unit and the stored product inventory; and communicating at least a portion of such data to the ASP.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>Many pharmaceutical products are dependent upon proper storage of the product with temperature being one of the key parameters that determines if a product is to be administered or discarded as spoiled.\",\n \"Some pharmaceutical product formulations require a storage temperature of about 5° C. and lose effectiveness and potency when stored at temperatures below freezing while others require sub zero storage.\",\n \"Generally, effectiveness and potency are decreased with every freeze thaw cycle.\",\n \"This is especially true for immunobiologics such as vaccines.\",\n \"Concern over the proper storage of vaccines and awareness that exposure of vaccines to temperatures outside the recommended ranges can have adverse effect on potency, thereby reducing protection from vaccine-preventable diseases, prompted the Centers for Disease Control and Prevention (CDC) to establish “Guidelines for Maintaining and Managing the Vaccine Cold Chain” (www.cdc.gov/mmwr/preview/mmwrhtml/mm5242a6.htm).\",\n \"The CDC emphasizes that administration of potent immunobiologics is not only dependent on an effective cold storage unit it also requires maintaining accurate temperature logs.\",\n \"Due to significant variability of temperatures within a compartment of a refrigerator it is recommended that temperatures be recorded near the actual container of the pharmaceutical several times per day.\",\n \"Vaccines stored outside of a recommended temperature range are to be immediately separated from the stock of effective vaccines so to avoid dispensing of ineffective product.\",\n \"The high cost of biologic pharmaceuticals further highlights the need of a refrigerator/freezer unit for the storage of pharmaceuticals with accurately maintained temperature zones, sensors for the recordation of temperatures surrounding the pharmaceutical product, and an alert system that assures responsive transfer of product to alternate site in case of a unit malfunction or power failure and removal of expired and ineffective product.\",\n \"A further need arises to simplify the management of the unit and its contents and to maintain an optimal inventory of the pharmaceuticals.\",\n \"Therefore it is an object herein to provide a smart refrigerator system that ascertains proper storage of pharmaceuticals in compliance with regulatory requirements, simplifies management protocols, and further utilizing the data and information thus gained to maintain optimal levels of pharmaceutical stock.\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>Provided herein are a refrigerator and/or freezer unit and an inventory management system for the storage of pharmaceuticals in compliance with regulatory requirements.\",\n \"Provided herein are a refrigerator and/or freezer unit and a system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products.\",\n \"Also provided herein are a plurality of compartments for each temperature sensitive pharmaceutical product type located in at least one controlled, sensor monitored, temperature zone of the unit, a reader for the identification of the product, and a user interface device (UID), in communications with an application service provider (ASP).\",\n \"The unit, system and methods provided herein include a data collection system wherein the UID and/or the ASP capture and store data, related to the refrigerator and/or freezer unit and the temperature sensitive pharmaceutical products stored within that includes: unit content, a product descriptor, product dispense and refill transactions, a reader scan of product, reader scan of compartments, compartment camera images, temperature sensor data, lock sensor data, login codes, biometric scans, system security and function status, and/or manually entered data.\",\n \"Also provided herein is a user interface at the unit that provides a user with secure access, via the UID, to the unit, unit content, and status and information including: product name, dosage, location, quantity, lot numbers, and expiration dates; compartment temperatures; alerts and order status; and/or internet access to further product information.\",\n \"The user can also manually enter information at the user interface.\",\n \"Further provided herein is an ASP, in a cloud based hosted environment that provides services including: server space for data and information storage; software for the management of the unit, its content, and information related to the unit and the products stored within; product and regulatory information resource; and/or unit maintenance resource.\",\n \"The ASP provided software includes software to manage the inventory of temperature sensitive pharmaceuticals in compliance with regulatory requirements wherein the pharmaceuticals are selected from among a biologic, an immunobiologic, an antibody, a peptide, a protein, an enzyme, a hormone, a nucleic acid, a lipid, and a formulation and/or combination of any of the preceding thereof.\",\n \"The refrigerator and/or freezer unit provided herein may be a smaller unit, equal to, less than about 34 inches tall, or a larger unit, above about 34 in tall, and include controlled temperature zones below and/or above 0° C. For example the at least one controlled temperature zone can be maintained between 2° C. and 8° C. or between minus 50° C. and minus 15° C., In some examples the unit includes a first temperature zone maintained between 2° C. and 8° C. and a second temperature zone maintained between minus 50° C. and minus 15° C. wherein preferably the first temperature zone maintained between 4° C. and 6° C. and a second temperature zone maintained between minus 40° C. and minus 17° C. The temperature is monitored within each compartment of the plurality of compartments and the temperature within each compartment is recorded in compliance with regulatory requirements and displayed on an external portion of the refrigerator.\",\n \"The temperature is monitored by temperature sensors located within the compartments and connected to a backup power supply wherein in the event or a power outage the temperature data is transmitted to the UID and when full power is restored to the ASP.\",\n \"In yet another embodiment the temperature zone temperature is monitored by a plurality of temperature sensors to ascertain that the temperature within each compartment is maintained at the designated temperature.\",\n \"In one exemplary embodiment, the refrigerator and/or freezer unit is equal to or less than about 34″ tall and at least 4 compartments are located in the sub 0.degree.\",\n \"C. temperature zone and at least 8 compartments are located in the above 0.degree.\",\n \"C. temperature zone.\",\n \"Further provided herein is refrigerator and/or freezer unit wherein the plurality of compartments fill each temperature zone and vary in size and number providing customization of the compartment configuration.\",\n \"The compartments may be available in at least two standard sizes, very in number from at least two containers per temperature zone, may contain only one type of product, one product type with one expiration date, or one product, and may be optionally labeled and/or color coded to denote differences between the products contained within.\",\n \"The reader used to identify a pharmaceutical product can be implemented using a variety of technologies including, but not limited to, optical device, a magnetic device, a camera, RFID, barcodes reader, and a magnetic strip reader.\",\n \"In one exemplary embodiment the reader device may be implemented with a barcode reader wherein the barcode reader optically scans a product, decodes the signal, and transfers the product information to the UID.\",\n \"In yet another embodiment the reader is a camera wherein identification of product includes the following steps: the camera captures an image of the pharmaceutical product with barcode label; the image is transmitted to the UID; the UID transmits the image to the ASP; the ASP provided product identification software analyzes the image and generates a product descriptor; the product descriptor is stored within the ASP provided product database and is transmitted to the UID; the UID receives and adds the product descriptor to its current inventory database and updates the UID product information display.\",\n \"The product descriptor may include information contained in the barcode and manufacturer provided product information.\",\n \"The product descriptor record thus may include product name and dosage, lot numbers and associated expiration date, recommended temperature for storage, compartment location, storage temperature history, and internet links to manufacturer and/or Center for Disease Control and Prevention (CDC) information on the product.\",\n \"In yet another embodiment the reader is a camera associated with each compartment and is used to capture an image of all products within a compartment wherein the analysis of the image captured by the camera reader provides a count of the product within the compartment.\",\n \"The refrigerator and/or freezer unit may be implemented with a UID that is a touch screen computing device, such as a tablet computer, connected to the refrigerator via a docking station, and may be connected to or embedded within the outer surface of the unit.\",\n \"The UID can maintain a connection to the internet via multiple routes such as a local internet, a wireless network (WIFI) and/or cell phone card embedded in the refrigerator unit.\",\n \"A UID home screen displays information on the status of the unit and its content.\",\n \"Exemplary information displayed includes product name, product quantity, nearest expiration date, current temperature of product compartment, alerts, and/or product order status.\",\n \"Further information about the product may be displayed by selecting the name of a specific product on the UID display and includes location by compartment, temperature history, lot numbers with associated expiration dates of current inventory, and links to product information on the internet that includes manufacturer and/or Centre for Disease Control and Prevention (CDC) product information.\",\n \"At the user interface the user completes the capture of product transactional information by confirming a successful reader scan of the product being added to the unit, entering the product information manually, or by selecting on the UID screen, product to be removed from the unit.\",\n \"In yet another embodiment an optionally activated security interface is provided wherein access to the UID and the refrigerator unit includes a login code verification and/or a biometric sensor scan wherein a biometric scan device may be a finger print identification device, a retinal scan identification device, a facial recognition device or a voice identification device.\",\n \"Provided herein is a system wherein the ASP provided software functions include: analysis and storage of data, records, and information related to the unit; communicating with the UID and select recipients; generating alerts related to temperature, expiration dates, system health, network disruption, power disruption/loss and low stock; and providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, inventory management, wherein the access is via a secure website customizable based on user profile.\",\n \"A service provider, using ASP provided software and servers in a cloud based hosted environment may include inventory management in compliance with regulatory requirements, system administration, alerting, and reporting.\",\n \"The inventory management may include tracking of the inventory of products within the refrigerator and/or freezer unit and all product dispense and refill transactions, tracking the expiration date of each product, providing re-order messages, providing remove expired product messages; providing product is about to expire messages; and providing a product and regulatory information resource.\",\n \"The system administration may include monitoring the refrigerator and/or freezer unit location information; monitoring information related to the physical status of the unit comprising: function; power, temperature or latches sensor data; maintaining communication between UID, ASP, and cell card application layers; maintaining select user an optionally secure access to the unit and ASP; and facilitating unit maintenance.\",\n \"The alerting provides the delivery of alerting messages, to select recipients and/or the UID, related to events comprising: temperature of a compartment approaches or exceeds allowed temperature limits; a product stock is depleted or reached a low limit; a product expired or is to expire within select number of days; and power outage.\",\n \"Further embodiments of the system provides alert, delivery to the UID and other customizable pre-determined locations such as specified phone numbers, computers and email addresses.\",\n \"The alert delivered to the UID on the refrigerator indicates the location of the deviation and generate a customizable audio and/or visual alert.\",\n \"In yet another embodiment the ASP inventory management software determines if a product has reached its expiration date or is deemed to have lost potency due to compartment temperature fluctuations outside of the recommended range, and sends an alert that product has expired, instructing the user to remove the expired and/or ineffective product.\",\n \"Determining if product has reached its expiration date and/or lost potency includes: comparing current date to expiration date of product and if current date is on or post the expiration date, the product is expired; and determining if the temperature of compartment holding product exceeded allowed temperature limits for a time period greater than a select number of minutes the product is deemed to have lost potency.\",\n \"Further the ASP inventory management software identifies product within select number of days prior to the expiration date and sends an alert to the UID and select recipients to prioritize use of the product or exchange/return the product for fresher product.\",\n \"In a particular embodiment the ASP inventory management software monitors inventory levels of product within each compartment and when one or more products approach a predetermined re-order count of product a low stock alert is generated wherein a first customizable and unique audio and/or visual alert is generated when product stock is low and a second customizable and unique audio and/or visual alert is generated when a product reaches a zero inventory count.\",\n \"The predetermined re-order count of product is determined by the user or the ASP service using dispense rate data, quantity of product contained in manufacturer packaging and number of days required to receive ordered product.\",\n \"In a further embodiment the ASP provided software analyzes the reader data received from the UID and in combination with information available from product manufacturer generates a product descriptor record that includes for example: product name and dosage; lot numbers with associated expiration date; recommended temperature for storage; and compartment number.\",\n \"Also provided herein are ASP provided software applications related to product potency and inventory management including: product potency assessment based on storage temperature history and product expiration date; product potency review in compliance with regulatory requirements; current product inventory assessment based on reader captured data and UID manually entered data; product inventory dispensing assessment; product order requests, status and recommendations; and reports and data analytics including: stock and dispense transactions, product loss due to expiration or spoilage, and frequency of refills.\",\n \"Further embodiment of the software applications function is customization of refrigerator unit variables including: unit size and refrigerator and/or freezer option; compartment number, size and label and/or color coding per product and temperature zone; secure or free access to unit; selection of users; establishing user profiles with customized level of access; unit alert message signal type, audio and or visual option; and recipients of alert messages.\",\n \"In yet another embodiment the ASP secure website software generates a user profile for each user and provides each user with customized levels of access to the information and data associated with each unit.\",\n \"A user that includes refrigerator unit user, refrigerator unit managers, and refrigerator unit owners may have the following level of access: a user with access to unit content only; a user with access to unit content and order related information on the ASP web site; a user with access to unit content and all information related to the unit on the ASP web site; and a user with access to select product reports.\",\n \"Provided herein are reports generated by the ASP provided software, available based on a user's profile and permission status, wherein user group includes: refrigerator unit users, managers, and owners; manufacturers; distributors; product representatives; physicians; and pharmacists.\",\n \"Reporting includes: providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, or inventory management, wherein the access is via a secure website and customizable based on user profile.\",\n \"For example a refrigerator unit user, manager and owner have access to reports related to their unit and the reports may include: current inventory of product with expiration dates; quantity of product used, by type of use and/or total use, for a selected time period such as day, week month year; product dispense rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; and alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.\",\n \"The refrigerator unit user, manager and owner also have access to reports related to other units serviced by the ASP including: type and quantity of product dispensed to patient by location such as a local region defined by community or city, a state, and/or country within a selected time period; product usage rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.\",\n \"A manufacturer of exemplary product A may have access to reports including: quantity of product A dispensed to patient by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit for a selected location; number of units within select location or region distributing product “A”; and low stock of product “A” alerts per unit and/or region.\",\n \"A distributor and a product representative may have access to reports on their products including reports on: quantity of product dispensed to patient, expired, and or spoiled by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.\",\n \"And a pharmacist may have access to reports on their products and refrigerator and/or freezer unit stocked by their pharmacy wherein reports included are: quantity of product dispensed to patient, expired, and or spoiled by date and by refrigerator and/or freezer unit stocked by their pharmacy; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.\",\n \"Other features and advantages of the invention will be apparent from the following description, drawings and claims.\"\n ],\n [\n \"RELATED APPLICATIONS This application is a continuation of allowed U.S. non-provisional patent application Ser.\",\n \"No.\",\n \"15/675,618 filed on Aug. 11, 2017, which is a continuation of U.S. non-provisional patent application Ser.\",\n \"No.\",\n \"13/974,793 filed on Aug. 23, 2013 (now U.S. Pat.\",\n \"No.\",\n \"9,733,012), which claimed the benefit of and priority to now-expired U.S. provisional patent application Ser.\",\n \"No.\",\n \"61/692,659 filed on Aug. 23, 2012, all of which are/were entitled “Smart Storage of Temperature Sensitive Pharmaceuticals”.\",\n \"Each of these foregoing applications is hereby incorporated by reference in its entirety.\",\n \"FIELD OF THE INVENTION The present invention relates generally to storage and inventory management of temperature sensitive pharmaceuticals.\",\n \"BACKGROUND OF THE INVENTION Many pharmaceutical products are dependent upon proper storage of the product with temperature being one of the key parameters that determines if a product is to be administered or discarded as spoiled.\",\n \"Some pharmaceutical product formulations require a storage temperature of about 5° C. and lose effectiveness and potency when stored at temperatures below freezing while others require sub zero storage.\",\n \"Generally, effectiveness and potency are decreased with every freeze thaw cycle.\",\n \"This is especially true for immunobiologics such as vaccines.\",\n \"Concern over the proper storage of vaccines and awareness that exposure of vaccines to temperatures outside the recommended ranges can have adverse effect on potency, thereby reducing protection from vaccine-preventable diseases, prompted the Centers for Disease Control and Prevention (CDC) to establish “Guidelines for Maintaining and Managing the Vaccine Cold Chain” (www.cdc.gov/mmwr/preview/mmwrhtml/mm5242a6.htm).\",\n \"The CDC emphasizes that administration of potent immunobiologics is not only dependent on an effective cold storage unit it also requires maintaining accurate temperature logs.\",\n \"Due to significant variability of temperatures within a compartment of a refrigerator it is recommended that temperatures be recorded near the actual container of the pharmaceutical several times per day.\",\n \"Vaccines stored outside of a recommended temperature range are to be immediately separated from the stock of effective vaccines so to avoid dispensing of ineffective product.\",\n \"The high cost of biologic pharmaceuticals further highlights the need of a refrigerator/freezer unit for the storage of pharmaceuticals with accurately maintained temperature zones, sensors for the recordation of temperatures surrounding the pharmaceutical product, and an alert system that assures responsive transfer of product to alternate site in case of a unit malfunction or power failure and removal of expired and ineffective product.\",\n \"A further need arises to simplify the management of the unit and its contents and to maintain an optimal inventory of the pharmaceuticals.\",\n \"Therefore it is an object herein to provide a smart refrigerator system that ascertains proper storage of pharmaceuticals in compliance with regulatory requirements, simplifies management protocols, and further utilizing the data and information thus gained to maintain optimal levels of pharmaceutical stock.\",\n \"SUMMARY OF THE INVENTION Provided herein are a refrigerator and/or freezer unit and an inventory management system for the storage of pharmaceuticals in compliance with regulatory requirements.\",\n \"Provided herein are a refrigerator and/or freezer unit and a system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products.\",\n \"Also provided herein are a plurality of compartments for each temperature sensitive pharmaceutical product type located in at least one controlled, sensor monitored, temperature zone of the unit, a reader for the identification of the product, and a user interface device (UID), in communications with an application service provider (ASP).\",\n \"The unit, system and methods provided herein include a data collection system wherein the UID and/or the ASP capture and store data, related to the refrigerator and/or freezer unit and the temperature sensitive pharmaceutical products stored within that includes: unit content, a product descriptor, product dispense and refill transactions, a reader scan of product, reader scan of compartments, compartment camera images, temperature sensor data, lock sensor data, login codes, biometric scans, system security and function status, and/or manually entered data.\",\n \"Also provided herein is a user interface at the unit that provides a user with secure access, via the UID, to the unit, unit content, and status and information including: product name, dosage, location, quantity, lot numbers, and expiration dates; compartment temperatures; alerts and order status; and/or internet access to further product information.\",\n \"The user can also manually enter information at the user interface.\",\n \"Further provided herein is an ASP, in a cloud based hosted environment that provides services including: server space for data and information storage; software for the management of the unit, its content, and information related to the unit and the products stored within; product and regulatory information resource; and/or unit maintenance resource.\",\n \"The ASP provided software includes software to manage the inventory of temperature sensitive pharmaceuticals in compliance with regulatory requirements wherein the pharmaceuticals are selected from among a biologic, an immunobiologic, an antibody, a peptide, a protein, an enzyme, a hormone, a nucleic acid, a lipid, and a formulation and/or combination of any of the preceding thereof.\",\n \"The refrigerator and/or freezer unit provided herein may be a smaller unit, equal to, less than about 34 inches tall, or a larger unit, above about 34 in tall, and include controlled temperature zones below and/or above 0° C. For example the at least one controlled temperature zone can be maintained between 2° C. and 8° C. or between minus 50° C. and minus 15° C., In some examples the unit includes a first temperature zone maintained between 2° C. and 8° C. and a second temperature zone maintained between minus 50° C. and minus 15° C. wherein preferably the first temperature zone maintained between 4° C. and 6° C. and a second temperature zone maintained between minus 40° C. and minus 17° C. The temperature is monitored within each compartment of the plurality of compartments and the temperature within each compartment is recorded in compliance with regulatory requirements and displayed on an external portion of the refrigerator.\",\n \"The temperature is monitored by temperature sensors located within the compartments and connected to a backup power supply wherein in the event or a power outage the temperature data is transmitted to the UID and when full power is restored to the ASP.\",\n \"In yet another embodiment the temperature zone temperature is monitored by a plurality of temperature sensors to ascertain that the temperature within each compartment is maintained at the designated temperature.\",\n \"In one exemplary embodiment, the refrigerator and/or freezer unit is equal to or less than about 34″ tall and at least 4 compartments are located in the sub 0.degree.\",\n \"C. temperature zone and at least 8 compartments are located in the above 0.degree.\",\n \"C. temperature zone.\",\n \"Further provided herein is refrigerator and/or freezer unit wherein the plurality of compartments fill each temperature zone and vary in size and number providing customization of the compartment configuration.\",\n \"The compartments may be available in at least two standard sizes, very in number from at least two containers per temperature zone, may contain only one type of product, one product type with one expiration date, or one product, and may be optionally labeled and/or color coded to denote differences between the products contained within.\",\n \"The reader used to identify a pharmaceutical product can be implemented using a variety of technologies including, but not limited to, optical device, a magnetic device, a camera, RFID, barcodes reader, and a magnetic strip reader.\",\n \"In one exemplary embodiment the reader device may be implemented with a barcode reader wherein the barcode reader optically scans a product, decodes the signal, and transfers the product information to the UID.\",\n \"In yet another embodiment the reader is a camera wherein identification of product includes the following steps: the camera captures an image of the pharmaceutical product with barcode label; the image is transmitted to the UID; the UID transmits the image to the ASP; the ASP provided product identification software analyzes the image and generates a product descriptor; the product descriptor is stored within the ASP provided product database and is transmitted to the UID; the UID receives and adds the product descriptor to its current inventory database and updates the UID product information display.\",\n \"The product descriptor may include information contained in the barcode and manufacturer provided product information.\",\n \"The product descriptor record thus may include product name and dosage, lot numbers and associated expiration date, recommended temperature for storage, compartment location, storage temperature history, and internet links to manufacturer and/or Center for Disease Control and Prevention (CDC) information on the product.\",\n \"In yet another embodiment the reader is a camera associated with each compartment and is used to capture an image of all products within a compartment wherein the analysis of the image captured by the camera reader provides a count of the product within the compartment.\",\n \"The refrigerator and/or freezer unit may be implemented with a UID that is a touch screen computing device, such as a tablet computer, connected to the refrigerator via a docking station, and may be connected to or embedded within the outer surface of the unit.\",\n \"The UID can maintain a connection to the internet via multiple routes such as a local internet, a wireless network (WIFI) and/or cell phone card embedded in the refrigerator unit.\",\n \"A UID home screen displays information on the status of the unit and its content.\",\n \"Exemplary information displayed includes product name, product quantity, nearest expiration date, current temperature of product compartment, alerts, and/or product order status.\",\n \"Further information about the product may be displayed by selecting the name of a specific product on the UID display and includes location by compartment, temperature history, lot numbers with associated expiration dates of current inventory, and links to product information on the internet that includes manufacturer and/or Centre for Disease Control and Prevention (CDC) product information.\",\n \"At the user interface the user completes the capture of product transactional information by confirming a successful reader scan of the product being added to the unit, entering the product information manually, or by selecting on the UID screen, product to be removed from the unit.\",\n \"In yet another embodiment an optionally activated security interface is provided wherein access to the UID and the refrigerator unit includes a login code verification and/or a biometric sensor scan wherein a biometric scan device may be a finger print identification device, a retinal scan identification device, a facial recognition device or a voice identification device.\",\n \"Provided herein is a system wherein the ASP provided software functions include: analysis and storage of data, records, and information related to the unit; communicating with the UID and select recipients; generating alerts related to temperature, expiration dates, system health, network disruption, power disruption/loss and low stock; and providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, inventory management, wherein the access is via a secure website customizable based on user profile.\",\n \"A service provider, using ASP provided software and servers in a cloud based hosted environment may include inventory management in compliance with regulatory requirements, system administration, alerting, and reporting.\",\n \"The inventory management may include tracking of the inventory of products within the refrigerator and/or freezer unit and all product dispense and refill transactions, tracking the expiration date of each product, providing re-order messages, providing remove expired product messages; providing product is about to expire messages; and providing a product and regulatory information resource.\",\n \"The system administration may include monitoring the refrigerator and/or freezer unit location information; monitoring information related to the physical status of the unit comprising: function; power, temperature or latches sensor data; maintaining communication between UID, ASP, and cell card application layers; maintaining select user an optionally secure access to the unit and ASP; and facilitating unit maintenance.\",\n \"The alerting provides the delivery of alerting messages, to select recipients and/or the UID, related to events comprising: temperature of a compartment approaches or exceeds allowed temperature limits; a product stock is depleted or reached a low limit; a product expired or is to expire within select number of days; and power outage.\",\n \"Further embodiments of the system provides alert, delivery to the UID and other customizable pre-determined locations such as specified phone numbers, computers and email addresses.\",\n \"The alert delivered to the UID on the refrigerator indicates the location of the deviation and generate a customizable audio and/or visual alert.\",\n \"In yet another embodiment the ASP inventory management software determines if a product has reached its expiration date or is deemed to have lost potency due to compartment temperature fluctuations outside of the recommended range, and sends an alert that product has expired, instructing the user to remove the expired and/or ineffective product.\",\n \"Determining if product has reached its expiration date and/or lost potency includes: comparing current date to expiration date of product and if current date is on or post the expiration date, the product is expired; and determining if the temperature of compartment holding product exceeded allowed temperature limits for a time period greater than a select number of minutes the product is deemed to have lost potency.\",\n \"Further the ASP inventory management software identifies product within select number of days prior to the expiration date and sends an alert to the UID and select recipients to prioritize use of the product or exchange/return the product for fresher product.\",\n \"In a particular embodiment the ASP inventory management software monitors inventory levels of product within each compartment and when one or more products approach a predetermined re-order count of product a low stock alert is generated wherein a first customizable and unique audio and/or visual alert is generated when product stock is low and a second customizable and unique audio and/or visual alert is generated when a product reaches a zero inventory count.\",\n \"The predetermined re-order count of product is determined by the user or the ASP service using dispense rate data, quantity of product contained in manufacturer packaging and number of days required to receive ordered product.\",\n \"In a further embodiment the ASP provided software analyzes the reader data received from the UID and in combination with information available from product manufacturer generates a product descriptor record that includes for example: product name and dosage; lot numbers with associated expiration date; recommended temperature for storage; and compartment number.\",\n \"Also provided herein are ASP provided software applications related to product potency and inventory management including: product potency assessment based on storage temperature history and product expiration date; product potency review in compliance with regulatory requirements; current product inventory assessment based on reader captured data and UID manually entered data; product inventory dispensing assessment; product order requests, status and recommendations; and reports and data analytics including: stock and dispense transactions, product loss due to expiration or spoilage, and frequency of refills.\",\n \"Further embodiment of the software applications function is customization of refrigerator unit variables including: unit size and refrigerator and/or freezer option; compartment number, size and label and/or color coding per product and temperature zone; secure or free access to unit; selection of users; establishing user profiles with customized level of access; unit alert message signal type, audio and or visual option; and recipients of alert messages.\",\n \"In yet another embodiment the ASP secure website software generates a user profile for each user and provides each user with customized levels of access to the information and data associated with each unit.\",\n \"A user that includes refrigerator unit user, refrigerator unit managers, and refrigerator unit owners may have the following level of access: a user with access to unit content only; a user with access to unit content and order related information on the ASP web site; a user with access to unit content and all information related to the unit on the ASP web site; and a user with access to select product reports.\",\n \"Provided herein are reports generated by the ASP provided software, available based on a user's profile and permission status, wherein user group includes: refrigerator unit users, managers, and owners; manufacturers; distributors; product representatives; physicians; and pharmacists.\",\n \"Reporting includes: providing an authorized user access to information and reports related to unit status, product information, regulatory requirements, or inventory management, wherein the access is via a secure website and customizable based on user profile.\",\n \"For example a refrigerator unit user, manager and owner have access to reports related to their unit and the reports may include: current inventory of product with expiration dates; quantity of product used, by type of use and/or total use, for a selected time period such as day, week month year; product dispense rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; and alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.\",\n \"The refrigerator unit user, manager and owner also have access to reports related to other units serviced by the ASP including: type and quantity of product dispensed to patient by location such as a local region defined by community or city, a state, and/or country within a selected time period; product usage rate and type by date, percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.\",\n \"A manufacturer of exemplary product A may have access to reports including: quantity of product A dispensed to patient by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient and percent product lost due to expiration, spoilage in unit, spoilage outside of unit for a selected location; number of units within select location or region distributing product “A”; and low stock of product “A” alerts per unit and/or region.\",\n \"A distributor and a product representative may have access to reports on their products including reports on: quantity of product dispensed to patient, expired, and or spoiled by date and/or by location such as a local region defined by community or city, a state, and/or country; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.\",\n \"And a pharmacist may have access to reports on their products and refrigerator and/or freezer unit stocked by their pharmacy wherein reports included are: quantity of product dispensed to patient, expired, and or spoiled by date and by refrigerator and/or freezer unit stocked by their pharmacy; percentages of product dispensed to patient, expired, and spoiled; and low stock alerts.\",\n \"Other features and advantages of the invention will be apparent from the following description, drawings and claims.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 shows an exemplary interior view of a refrigerator with a compartment configuration for two temperature zones.\",\n \"FIG.\",\n \"2 shows an exemplary front exterior view of refrigerator.\",\n \"FIG.\",\n \"3 shows an exemplary view of a UID display.\",\n \"FIG.\",\n \"4 is a block diagram overview of refrigerator system components.\",\n \"FIG.\",\n \"5 is a flow diagram illustrating communication between refrigerator, UID and ASP.\",\n \"FIG.\",\n \"6 is a flow diagram illustrating steps of an exemplary product intake process using external camera reader 2.FIG.\",\n \"7 is a flow diagram illustrating steps of an exemplary product dispense process using internal camera reader 1.FIG.\",\n \"8 is a flow diagram illustrating steps of an exemplary product intake process using a barcode reader.\",\n \"FIG.\",\n \"9 is a flow diagram illustrating steps performed by the system in generating temperature deviation alert.\",\n \"FIG.\",\n \"10 is a flow diagram illustrating steps performed by the system in generating expiration of product alert.\",\n \"FIG.\",\n \"11 is a flow diagram illustrating steps performed by the system in generating low stock of product alert.\",\n \"FIG.\",\n \"12 is a flow diagram illustrating steps performed by the system in determining a product dispense rate.\",\n \"FIGS.\",\n \"13A and 13B is a flow diagram illustrating access to inventory reports based on user profile.\",\n \"FIG.\",\n \"14 is a block diagram illustrating the various functions provided by the Application Service Provider.\",\n \"DETAILED DESCRIPTION OF THE INVENTION The following detailed description illustrates an embodiment of the invention by way of example, not by way of limitation of the principles of the invention.\",\n \"Various embodiments of the invention will be described by way of illustration with reference to various software tools, but it should be understood that other software tools that have comparable capabilities of the mentioned tools may be used.\",\n \"The contents of this Detailed Description are organized under the following headings: Definitions; Overview; Refrigerator Unit; User Interface device (UID); Reader; Application Service Provider (ASP); Alerts; and Inventory Management.\",\n \"Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs.\",\n \"All patents and publications referred to herein are, unless noted otherwise, incorporated by reference in their entirety.\",\n \"In the event a definition in this section is not consistent with definitions elsewhere, the definition set forth in this section will control.\",\n \"As used herein, “refrigerator” refers to an appliance that cools the interior compartments to temperatures below the ambient temperature of the room, is designed for the storage of temperature sensitive pharmaceuticals in compliance with regulatory requirements, and is fitted with sensors, devices and a computer as described hereinafter.\",\n \"The refrigerator contains compartments above zero .degree.\",\n \"C. and may or may not provide a freezer compartment with temperatures below zero .degree.\",\n \"C. It is a low humidity, frost free, refrigerator with calibrated temperature monitoring sensors located at a point or points within the compartments which most accurately represents the temperature profile of the pharmaceutical product, is equipped with alarms to indicate temperature excursions and/or refrigeration failure, and has lockable doors meeting the guidelines of the World Health Organization (WHO), as described in “WHO Expert Committee on Specifications for Pharmaceutical Preparations”, WHO technical Report Series 961, 2011 (Report found on www.who.int/en/) As used herein, “freezer” refers to an appliance defined as is the refrigerator noted above with the exception of the inside of the unit cooled to a temperature below zero ° C. As used herein, “smart refrigerator” refers to a refrigerator and/or freezer unit which contains a computer in communication with an ASP and is designed for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products as described herein.\",\n \"As used herein, “compartment” refers to a holding container for a product designed to securely fit into the refrigerator and/or freezer unit and may take on a plurality of shapes including for example; a sliding drawer like structure wherein a drawer may contain further subdivisions forming smaller compartments; a tray like structure further holding individual trays designed to hold one product type which may come for example in the form of a vial, two vials, a syringe, or a package.\",\n \"The compartment design meets regulatory requirements and provides for a consistent temperature profile throughout the storage compartments when empty and in a normal filled condition.\",\n \"As used herein, “cleanable surface” of a refrigerator is made of materials that are acceptable in a medical environment and can be cleaned and/or wiped with sterilization and/or cleaning chemicals and cloths as required by WHO regulation or best practice methods.\",\n \"The material is a durable, corrosion free material such as stainless steel, hard plastic or resin, and the surface is smooth with minimal number of seams.\",\n \"As used herein, “Automatic Identification and Data Capture” (AIDC) refers to methods of automatically identifying objects using a device which collects data about the object and transfers the data directly into computer systems.\",\n \"Technologies typically considered as part of AIDC include bar code readers, Radio Frequency Identification (RFID), biometric scanners, magnetic strip reader, Optical Character Recognition (OCR), smart cards, and voice recognition.\",\n \"As used herein, “reader” is a device used to obtain the identity of, and information related to, a specific product, using a method referred to as Automatic Identification and Data Capture (AIDC), by scanning, detecting, or capturing an image of a product in order to identify embedded information on the product.\",\n \"As used herein, a “camera” may be used as a reader device to capture an image of a product with the portion displaying a barcode.\",\n \"The camera transfers the data to the ASP database via the UID computer, for analysis by barcode recognition software (see, e.g.\",\n \"Barcode Xpress available from accusoft at www.acusoft.com).\",\n \"The camera may also be used to capture an image of a compartment which is analyzed by the ASP provided software for the number of objects stored in a compartment using image recognition software available and known to those of skill in the art.\",\n \"As used herein, “barcode” refers to an optical symbol, machine readable, containing information about the product on which it is displayed.\",\n \"The barcode may be one dimensional, a collection of bars of various widths representing the descriptive characters, two dimensional collection of symbols for example known as a Quick Response Code (QR), or three dimensional, where for example a 2D image includes color and further expands the amount of information captured.\",\n \"As used herein, “barcode reader” refers to an electronic device specifically designed for reading printed barcodes.\",\n \"It consists of a light source, a lens and a light sensor translating optical impulses into electrical ones.\",\n \"Additionally, nearly all barcode readers contain decoder circuitry analyzing the barcode's image data provided by the sensor and sending the barcode's content to the scanner's output port (see, e.g., The LS3008 rugged handheld scanner by Motorola designed for the healthcare industry or the Motorola SE330X which can be integrated into a device, on the Motorola web site at www.motorola.com).\",\n \"As used herein, “Radio-frequency identification” (RFID) refers to a reader that uses radio-frequency electromagnetic fields to transfer data from a tag attached to a product for the purposes of automatic identification and tracking.\",\n \"The tag does not require a battery as it is powered by the electromagnetic fields used to read them.\",\n \"The tag contains electronically stored information which can be read from up to several meters away.\",\n \"Unlike a bar code, the tag does not need to be within line of sight of the reader and may be embedded in the tracked object (see, e.g.\",\n \"UHF Mobile RFID Reader for Smartphones and Tablets, by IDBLUE at www.idblue.com).\",\n \"As used herein, “magnetic strip reader” or “magnetic card reader” refers to a device with a guide for swiping and reading a magnetic card for example containing an access identification code of the designated user.\",\n \"Exemplary devices include MagTek Mini Swipe Magnetic Strip Reader, available from MAGTEK.®.\",\n \"(see, e.g.\",\n \"magtek.com) where data is sent to the UID via a USB port and may be viewed in applications such as Windows.RTM.\",\n \"Notepad without requiring additional drivers or application programming.\",\n \"As used herein, “biometricreader” refers to a reader that uses for example a finger print or a retinal or facial recognition scan as a security measure to identify an authorized user of a refrigerator unit.\",\n \"For example a finger print recognition controlled access implements a finger print scanner, embedded in the user interface device, and software to analyze the scan.\",\n \"Scanners and software are readily available (see e.g.\",\n \"Mercury.™ Series OEM Module from Lumidigm at www.lumidigm.com).\",\n \"As used herein, “docking station” refers to a device that receives the user interface device.\",\n \"The docking station may serve only as a power source or may also be integrated directly into the other devices or systems such as temperature sensor, a reader, a camera, a biometric sensor or a central processing unit (CPU).\",\n \"As used herein, “cell phone card” refers to a cellular network card which provides access to the internet.\",\n \"Cell phone cards are available and known to those of skill in the art.\",\n \"As used herein, “user interface device” (UID) is a computer in communication with the refrigerator unit components and an ASP and is docked, or mounted, in a docking station connected to or embedded in the unit.\",\n \"The UID contains wired and wireless network adapter cards and remains fully functional when docked or undocked maintaining communications with the unit via a short range wireless communication device embedded in the unit.\",\n \"The UID, preferably a touch screen computer with a virtual onscreen keyboard, can access the internet via a wireless link to a local wireless network, a wireless communication through a cell phone card embedded in the unit, or a cable connection through a docking station.\",\n \"The UID contains an operating system and software required to capture data from sensors and readers on or within the refrigerator unit, send and receive data from an ASP, capture manually entered data, and display information.\",\n \"As used herein, “tablet” refers to a self contained computer with a wireless internet connectivity that uses a touch screen with virtual keyboard capabilities for data access and entry.\",\n \"As used herein, “Wireless” refers to a type of communication in which power and/or data is transferred over a distance without the use of electrical conductors or wires.\",\n \"For example, electromagnetic waves, light waves, or acoustic waves can be used to carry power and/or data over a distance without using electrical conductors or wires.\",\n \"As used herein, “cloud-based host” refers to a third party provider server farm located in a centralized location, away from the individual refrigerator units, implemented as a service, maintaining communications with individual computers and users via the web.\",\n \"The data, software and programming are centralized on the server farm.\",\n \"As used herein, “Application Service Provider” (“ASP”) refers to a cloud-based hosted environment business that provides computer-based services to customers over a network.\",\n \"A user requires only a browser and an internet/intranet connection on their desktop, laptop, or other network access appliance to obtain substantially complete secure access to that system.\",\n \"Software offered using an ASP model is also sometimes called on-demand software or software as a service (SaaS) and may be accessed using standard protocol such as Hypertext Transfer Protocol (HTTP), foundation of data communication for the World Wide Web (see, e.g., ASP hosted services provided by NetSuite, Inc. of San Mateo, Calif. such as NetSuite.™., Oracle.®.\",\n \"Small Business Suite, NetCRM.™., and NetERP.™., descriptions of which can be found at www.netsuite.com).\",\n \"The ASP utilizes one or more software application programs, routines or modules configured to be executed by a general purpose microprocessor, in one or more hardware devices, such as a programmable logic controller (PLC).\",\n \"The user benefits from having access to highly specialized software without the cost of purchasing, servicing and upgrading the software as well as access to ASP provided information and resources related to the products.\",\n \"A used herein, “service provider” refers to a business that oversees and maintains the refrigerator/freezer system in all its functions as described herein.\",\n \"As used herein a “product descriptor”, refers to product information generated by the ASP provided software that combines the reader data received from the UID and information available from product manufacturer, information includes for example: product name and dosage, lot numbers and associated expiration date, recommended temperature for storage, and compartment location.\",\n \"As used herein, “HL7” refers to a data format adapted by the healthcare industry for sharing information within the health care field.\",\n \"The document format is developed by Health Level Seven (HL7), a non-profit organization involved in the development of international healthcare informatics interoperability standards.\",\n \"As used herein, “Electronic data interchange” or “EDI” refers to a data format adapted for communication between a healthcare provider and a vendor for example.\",\n \"EDI is the structured transmission of data between organizations by electronic means and without human intervention as defined by the National Institute of Standards and Technology.\",\n \"As used herein, a “HIPPA” refers to “The Health Insurance Portability and Accountability Act of 1996” wherein it protects the privacy of individually identifiable health information; the HIPAA Security Rule, which sets national standards for the security of electronic protected health information.\",\n \"As used herein, “regulatory requirements” refers to the regulations related to a refrigerator unit for storage of temperature sensitive pharmaceutical products as defined by the World Health Organization (WHO) qualification requirements for cold storage of Time and Temperature Sensitive Pharmaceutical Products (TTSPP) (see, “WHO Expert Committee on Specifications for Pharmaceutical Preparations”, WHO technical Report Series 961, 2011 available at www.who.int/).\",\n \"As used herein, a “web site” is a set of related web pages containing content such as text, images, video, audio, etc.\",\n \"A website is hosted on at least one web server, accessible via a network such as the Internet or a private local area network through an Internet address known as a Uniform Resource Locator.\",\n \"All publicly accessible websites collectively constitute the World Wide Web.\",\n \"As used herein, “product type” refers to products of the same pharmaceutical composition and dosage and its packaging may come for example, in the form of a vial, two vials, a syringe, or a package.\",\n \"As used herein, “par level” is a predetermined inventory level of a specific product.\",\n \"When ordering or re-ordering product the goal is to increase inventory to the predetermined par level.\",\n \"The predetermined par level takes into consideration the physical maximum quantity of the specific product that can be physically accommodated by the storage unit, the shelf life of the product, and historical product dispense records.\",\n \"As used herein, “re-order point” is the inventory level at which a re-order message is generated.\",\n \"The re-order point takes into account lead time for dispense rate, order processing, and product delivery in order to avoid stocking out of the product.\",\n \"The re-order point quantity of product to be ordered is determined by the difference between current inventory and the predetermined par level.\",\n \"As used herein, “critical low” is an inventory level whereby a re-order would not arrive in time to avoid a zero count of stock, “stock-out”, based on expected dispense rate, and manual intervention such as placing an overnight shipping order may be required.\",\n \"As used herein, “biologic” is a pharmaceutical product composed of sugars, lipids, peptides, proteins, nucleic acids or combinations of these substances and may be a vaccine, blood or a blood component, allergenic, somatic cell, gene therapeutic product, recombinant therapeutic protein or nucleic acid, or living cells that are used as therapeutics to treat diseases.\",\n \"As used herein, “potency” is a measure of the pharmaceutical product activity expressed in terms of the amount required to produce an effect of given intensity.\",\n \"Exposure to improper storage temperatures may decrease potency of a pharmaceutical product due to decomposition and/or denaturation of the product and/or by destabilizing the formulation of the product.\",\n \"As used herein, “effectiveness” refers to the ability of a pharmaceutical to produce a beneficial effect.\",\n \"The “Centers for Disease Control and Prevention” (CDC), a division of Department of Health and Human Services, which among its many roles also provides guidelines for proper handling and storage of vaccines.\",\n \"The guidelines may be found at www.cdc.gov/mmwr/preview/mmwrhtml/mm5242a6.htm.\",\n \"As used herein, “point of care” is a location at or near the location where the pharmaceutical product is administered to a patient.\",\n \"Locations may include a physician's office, a physicians practice group suite, a clinic, a pharmacy, and a hospital.\",\n \"As used herein, “business hours” refer to a time period of the day when pharmaceuticals are administered to patients and the refrigerator unit is likely to be opened frequently.\",\n \"Overview Provided herein is a smart refrigerator unit and system for the secure storage of temperature sensitive pharmaceuticals at optimal temperatures designed to identify, track and maintain an inventory of the temperature sensitive pharmaceuticals at optimal levels and potency in compliance with regulatory requirements.\",\n \"The refrigerator unit compartments are dedicated to one product type and expiration date, or a single product, and may be customized by size and number.\",\n \"The compartments may be located within several temperature zones which may include zones above and below freezing, zero ° C. The refrigerator unit devices such as temperature sensors, readers, locking mechanism, and security features communicate with a user interface device, docked on the unit, via a direct hard wire link or a wireless connection.\",\n \"The UID controls access to the unit, collects data related to the status of the refrigerator and its inventory content, and communicates with an ASP provided software in a cloud based hosted environment for inventory and information management.\",\n \"Refrigerator and/or Freezer Unit A smart refrigerator unit in one exemplary embodiment is a smaller unit, under 34 inches tall, designed to fit under a counter within a point of care facility such as a physician's office, a clinic or an onsite pharmacy.\",\n \"The exemplary unit contains two temperature zones commonly recommended for the storage of biologic pharmaceuticals, a first cold temperature zone maintained between 2° C. and 8° C., and a second frozen temperature zone maintained between minus 15° C. and minus 50° C. The first temperature zone is maintained preferably between 3° C. and 7° C. and more preferably between 4° C. and 6° C. The second temperature zone is maintained preferably between minus 15° C. and minus 30° C., and more preferably between minus 15° C. and minus 25° C. Each temperature zone is filled with compartments for holding product, customizable in number and size, from at least one compartments in the frozen temperature zone to at least four compartments in the cold temperature zone.\",\n \"The compartments slide in and out for ease of access, come in at least 2 standard sizes, and vary in width and height to accommodate various quantities and sizes of product.\",\n \"FIG.\",\n \"1 shows an exemplary layout of an arrangement of customizable compartments 102 with 4 compartments located in the below 0° C. temperature zone 104 and 13 compartments located in the above 0° C. temperature zones 103.Each compartment is dedicated to one type of product and expiration date and may be optionally labeled and/or color coded to denote differences between products contained within.\",\n \"The smaller unit described above, may further be implemented by dedicating the unit to only one temperature zone, for example above 0° C. storage or below 0° C. storage, to meet the needs of a point of care facility.\",\n \"Larger units, above a 34 in height in yet another implementation of the invention may be a preferred size for point of care facilities including for example, a hospital, a clinic and pharmacy.\",\n \"The larger unit may also be dedicated to above 0° C. storage, below 0° C. storage or a combination of multiple temperature zones.\",\n \"In one exemplary embodiment each compartment within the unit contains at least one temperature sensor which, in communication with the user interface device, provides a historical record of temperature for each product assigned to the compartment.\",\n \"The temperature of each compartment is monitored at a customizable frequency that meets regulatory requirements and may vary throughout the day based on the frequency of opening and closing of the unit.\",\n \"For example, the temperature may be monitored at least once every 10 minutes during regular office hours and at least every 30 minutes outside of regular business hours.\",\n \"The sensor is connected to a back-up power source, a battery, or optionally if the sensor is a wireless sensor it is powered by a battery.\",\n \"In yet another embodiment the temperature of a plurality of small compartments, designed to hold one or several products, is monitored by a plurality of temperature sensors positioned throughout a unit temperature zone to ascertain temperature measurement is representative of the compartment temperature.\",\n \"The temperature within each temperature zone is pre-set to a temperature within the recommended storage temperature range for the products stored within and is maintained within several degrees of that point.\",\n \"In the event of a power failure the temperature sensors have a back-up power source, a battery, and will continue to record and store temperature data.\",\n \"Temperatures of the various compartments are displayed on the UID docked on the external portion of the refrigerator.\",\n \"The compartment temperatures may also be displayed using a secondary device, for example a digital or LED display, embedded or mounted on the external portion of the refrigerator.\",\n \"During a power outage the locks to the unit may be disabled and a user may choose to transfer products to another cold storage device in the event of temperature deviations outside of the recommended range.\",\n \"Each compartment may further have a designated camera used to capture an image of the compartment content.\",\n \"Analysis of the image using ASP provided reader software generates a count of the number of products contained in the compartment, wherein the image analysis is based on the number of objects in the image.\",\n \"Each compartment is dedicated to one product type and expiration date and therefore the count of products within a compartment also provides an accurate inventory count.\",\n \"The unit is fully compliant with the World Health Organization (WHO) qualification requirements for cold storage of Time and Temperature Sensitive Pharmaceutical Products (TTSPP) (see, “WHO Expert Committee on Specifications for Pharmaceutical Preparations”, WHO technical Report Series 961, 2011 available at www.who.int/).\",\n \"The unit is specifically designed for storage of TTSPP, is capable of maintaining the temperature range over the full range of annual ambient temp at a point of care facility, is equipped with alarms to indicate temperature excursions and/or refrigeration failure and is fitted with lockable doors and an access control system.\",\n \"The exterior and interior of the unit is made of materials that are cleanable with sterilization solutions.\",\n \"The unit has a consistent temperature profile throughout the storage compartments when empty and in a normal filled condition and is equipped with calibrated temperature sensors, accurate to±0.5° C., capable of continuous recording.\",\n \"The sensors are located at points within the unit which most accurately represents the temperature profile of the TTSPP.\",\n \"The WHO specifications for a refrigerator unit address the physical requirements, noted above, as well as protocols and methods that validate the potency of the administered TTSPP.\",\n \"The WHO protocol specifications include keeping records of the temperature profile of each TTSPP stored, providing alerts when deviations occur and scheduling and completing regular maintenance of the unit.\",\n \"The smart refrigerator system provided software follows, performs and/or schedules the specified protocols.\",\n \"User Interface Device (UID) A UID 203, preferably a tablet computer with a touchpad incorporated into the display, is docked in a docking station 201 embedded or connected to the front of the refrigerator unit.\",\n \"See FIG.\",\n \"2.Communications between the UID and refrigerator unit is maintained via a hard wire connection to the central processing unit (CPU) of the smart refrigerator unit.\",\n \"The UID is the primary security interface providing a secure access to the unit and may use login code verification and/or a biometric image capture such as finger print identification, a retinal scan, a facial recognition, or a voice identification.\",\n \"A log in code may be a simple alphanumeric password that the user is either given or is provided an opportunity to enter a password that will be stored in the authentication server, located in the ASP database, in conjunction with the user account name.\",\n \"The user may also be prompted to enter a security question in the event the user forgets the password and needs to be issued a new password.\",\n \"The security feature may be optionally disabled The UID communicates with a cloud-based ASP via an internet connection through a local internet router, a wired or wireless network adapter card, or via a cellular network using a cell phone card, embedded in the unit.\",\n \"When the cell phone card is activated it updates information to the ASP at customizable number of minute intervals which may vary for periods during business hours, a period of frequent use of the unit, and periods outside of business hours when the unit remains closed.\",\n \"A docking station connected to or embedded on the external portion of the unit provides a port for the UID and will primarily function as a link to the CPU and a power source for the UID.\",\n \"Other devices and sensors associated with the unit may communicate with or deliver data to the UID via the CPU or wirelessly.\",\n \"The docking station may in yet another embodiment provide a wired internet connection, a power source, and may integrate any wired sensors and devices, such as the temperature sensor and compartment cameras, with the UID.\",\n \"An RFID reader, a biometric sensor, a barcode or magnetic strip reader are other exemplary devices that can communicate with the UID wirelessly or be integrated with the UID via the docking station.\",\n \"The UID uses a touch screen to display, enter and access information on the unit and its content.\",\n \"The default UID display includes: current temperatures, current product content with name and quantity of pharmaceuticals, nearest expiration date, alerts, and order status.\",\n \"By selecting the name of a specific pharmaceutical product on the UID screen further information about the pharmaceutical product is displayed including location by compartment, temperature history, lot numbers with associated expiration dates of current inventory; and links to manufacturer and/or Centers for Disease Control and Prevention (CDC) information on the pharmaceutical.\",\n \"FIG.\",\n \"3 shows an exemplary display on the UID.\",\n \"Reader A reader in one embodiment is a device used to identify and/or count products present in the unit or being added to or removed from the unit.\",\n \"The reader device is embedded in, attached, and/or unattached to the unit and is in communication with the UID via a wired or wireless connection.\",\n \"Suitable reader devices are known to those skilled in the art and may be selected from various technologies including a camera, a radio frequency identification (RFID), barcode scanner, and or magnetic strip reader.\",\n \"Most pharmaceutical products, packaged individually or in groups by lot number, are labeled with a barcode by the manufacturer and therefore a barcode reader is preferred.\",\n \"An exemplary reader is a camera which captures the image of a product, including a barcode label, and via the internet, wired or wireless, sends the image to the ASP for analysis.\",\n \"An ASP provided software analyzes the image obtaining product descriptor information which includes product name, dosage, lot number, and expiration date.\",\n \"The camera may be located on the UID and/or within or above the refrigerator compartment.\",\n \"A camera reader is a technology readily available, simple to use, and does not require special labeling of the product In yet another embodiment of the invention a barcode reader may also be utilized to identify a product.\",\n \"The barcode reader in this case contains decoder circuitry analyzing the barcode's image sending the information directly to the UID wherein the UID stores and also send the product information to the ASP to be added to a product database.\",\n \"The on-site user may scan the product being added to the unit with a handheld or an embedded reader wherein the information is transmitting to the UID via a wireless or a wired connection.\",\n \"The smart refrigerator unit may also be implemented with RFID technology by placement of an RFID reader, a two way radio transmitter-receiver wired to a transmitter, in communications with the UID which transfers the signal to the ASP provided RFID software to generate a product descriptor.\",\n \"The product in this case must be labeled with an RFID tag.\",\n \"A reader in yet another embodiment is a biometric or magnetic strip device used as a security measure to identify an authorized user of the unit.\",\n \"In embodiments using biometric authentication, some biometric information, such as a fingerprint image, is obtained and stored in the authentication server for use as the authentication credential.\",\n \"Such biometric information may be, but are not limited to, finger print images, spoken phrases for use in voice recognition, and facial images for use in facial recognition.\",\n \"In embodiments using finger print biometric information, users will have a fingerprint scanned to generate a fingerprint template that is stored in the authentication server.\",\n \"For other forms of biometric authentication, users may record a voice sample or have their retina scanned, with the resulting recording (or voice print) or image stored in the authentication server.\",\n \"For embodiments using facial recognition as a form of authentication, a camera may be employed to take detailed photographs of a user's face.\",\n \"FIG.\",\n \"4 contains a block diagram overview of an exemplary refrigerator system and components.\",\n \"The unit 100 includes docking station 201, an exemplary compartment 410 further including an internal reader 1415 and temperature sensors 420 connected to a backup power source 425, a cell phone card 430 in communication with a central processing unit (435).\",\n \"A UID 203 can be docked in the docking station includes a touch pad 440, a camera 445, a biometric sensor 450, a speaker 455, a microphone 460, and is connected to or in communication with an external reader 2 465.The UID is connected to a local internet router 470 which provides access to the cloud based ASP 475.FIG.\",\n \"5 contains a block diagram overview of communication lines between components of an exemplary refrigerator system.\",\n \"Reader 1415 and temperature sensor 420 communicate with CPU 435, The cell phone card 430 and CPU 435 in refrigerator unit 100 communicate with the UID 203 that also communicates with reader 2465, biometric sensor 450, and ASP 475.Reader 1415 and temperature sensor 420 may also communicate directly with and cell phone card 430 that is in communications with the ASP 475.The ASP 475 communicates, via a secure web site, with authorized users that include the unit user 500 and other non-unit users for example, a sales representative 505, a pharmacist 510 and a manufacture 515.Application Service Provider (ASP) The ASP, a cloud-based hosted environment, provides server space, to store and securely access data and information related to the unit, and software required to analyze and manage the data, information, and inventory.\",\n \"The refrigerator unit data captured by the ASP inventory management software includes product dispense and refill transactions, product reader scans, temperature sensor data, manually entered information via the UID, camera images, and bioscans.\",\n \"The ASP software analyses and stores the data.\",\n \"The ASP product identification software provides a product descriptor record for each product which includes product name, dosage, lot number, expiration date, quantity of the product in the unit, recommended temperature for storage, unit/compartment location, special handling requirements and links to manufacturer and/or CDC information.\",\n \"The ASP further generates records related to dispense rate of product, spoilage frequency, historical temperature records, and product order frequency including average number of days required to receive new product.\",\n \"An ASP inventory management function includes the tracking of add/dispense transactions of product to and from the unit.\",\n \"FIG.\",\n \"6 provides an exemplary protocol flow diagram for addition of product to the unit using a camera as the reader device.\",\n \"An on-site user logs into (step 615) or directly accesses (step 620) the unit via the UID and scans the product using a reader device on the unit (step 625), for example a camera embedded in the UID.\",\n \"The camera reader in communication with the UID send image to the ASP product identification software (step 630) that analyzes the image (step 640) and, using additional manufacturer information stored in its database, generates a product descriptor (step 645) which includes product name, dosage, lot number, expiration date, recommended temperature of storage, and any special handling requirements such as for example light sensitivity.\",\n \"The ASP product management software compares the product descriptor to those of product already in the unit (step 650) and if the product has an assigned compartment in the unit the compartment identifier is included with the product descriptor (step 660).\",\n \"If the product does not have an assigned compartment the ASP product management software will assign one in the temperature zone required for the storage of that product (step 655).\",\n \"The product descriptor and instructions for placement and handling are delivered to the on-site user via the UID where the information is displayed and can be verified by the on-site user (step 665).\",\n \"If any information is missing, for example the expiration date, the on-site user can use the UID keypad to manually enter the information (steps 670, 675, 680).\",\n \"The product is placed in the compartment (step 685), the user logs out (step 690) and the UID product content is updated (step 695).\",\n \"The product descriptor is stored in both the ASP and the UID product database.\",\n \"Dispensing of product in one embodiment may be captured by the unit when the on-site user selects the product to dispense on the unit content listing, displayed on the UID, and further selects the reason for dispensing including for example: dispense to patient, expired, spoiled in unit, transferred from unit, and discontinued.\",\n \"Optionally the user may also select, or enter manually, the name of the patient to receive the product.\",\n \"The “dispense to patient” reason may be changed to post dispense spoilage if product is deemed to have spoiled prior to being administered to a to patient.\",\n \"FIG.\",\n \"7 provides an exemplary protocol flow diagram for dispensing of product from the unit using a camera associated with a compartment as the reader 1 device.\",\n \"An on-site user access the unit and UID (step 700) and views the unit content listing on the UID display (step 705).\",\n \"The compartment holding product is identified (step 715) and the user removes product (step 720) The user logs out and closes unit (step 725).\",\n \"The compartment camera takes and image of the compartment (step 730), the image is sent to the ASP provided software for analysis (step 735), and the unit content is updated (step 740).\",\n \"FIG.\",\n \"8 provides and exemplary protocol for addition of product to the unit using an external barcode reader 2.An on-site user scans the product barcode label with a barcode reader (step 805) and the reader transmits the information to the UID (step 815) which transmits the information to the ASP (step 820) wherein the ASP inventory management software generates a product descriptor with assigned compartment (step 825).\",\n \"The product descriptor is sent to the UID (step 830) and user confirms correct identification of the product (step 835).\",\n \"If product is not correctly identified the user enters information (step 840), ASP software confirms receipt of data and compartment assignment (step 845) and the user places product in the designated compartment (step 850).\",\n \"If the product is correctly identified at step 835 the user places the product in the designated compartment (step 850).\",\n \"The user logs out, closes unit (step 850) and the UID product data base is updated (step 860).\",\n \"Alerts Alerting activities will emanate from the ASP hosted system and alerts will be delivered to pre-determined locations including the physical unit and/or specified phones, computers and email addresses.\",\n \"Alerts are generated by events associated with the physical unit including: temperature deviations from allowed temperature range, loss of power to the physical unit in the event of a power outage, lock malfunction, and cooling system failure.\",\n \"Alerts are further generated by the inventory management software based on inventory deviations including expiration of product, about to expire product and low or depleted stock warnings.\",\n \"The ASP unit management software records and keeps historical data on the temperature of each compartment and the product contained within the compartment.\",\n \"FIG.\",\n \"9 shows an exemplary flow diagram illustrating the steps taken to monitor temperature and send out alerts.\",\n \"The temperature is, recorded by the temperature sensors associated with each compartment and or temperature zone (step 900) and is sent to and displayed on the UID (step 905).\",\n \"The temperature data is further sent by the UID via the internet (step 910) or a cell phone card (step 915), if internet access is not available, to the ASP unit management software, the temperature data is compared to the allowed storage temperature limits for that product (step 925).\",\n \"If the temperature falls within these limits no action is taken (step 930).\",\n \"If the temperature falls outside these limits an alert is generated (step 935) and delivered to the UID and selected recipients emails and/or phone numbers (step 940).\",\n \"The alert, which may include a visual and/or audio signal, received by the UID will display a temperature deviation warning with name and location of product and instruct the user to confirm the temperature deviation by comparing to temperature readout at the unit, and take action to transfer product to an alternate storage device if necessary.\",\n \"The alert is emailed or telephoned to the customized list of user contacts and includes all information on the nature of the deviation and instruct the recipient to follow user established protocol and take action to confirm product is properly stored.\",\n \"The ASP database stores expiration date for each product within a unit and generates an alert when a product is within a select number of days from the expiration date or has expired.\",\n \"When a product expires it is critical to remove the product from the unit, not only to comply with TTSPP storage regulation, but to avoid the ultimate error of administering an ineffective product to a patient and endangering the patients well being.\",\n \"FIG.\",\n \"10 shows an exemplary flow diagram illustrating the steps taken to monitor the expiration dates of products and send out alerts.\",\n \"The ASP inventory management software accesses expiration date data in database (step 1000), comparing current date to expiration date (step 1010).\",\n \"If the expiration date is equal to or prior to the current date, the product is expired and an alert is sent to the UID and select recipients (step 1015), with optional audio and or visual alerts, instructing user to remove and dispose of expired product, providing product name, expiration date, lot number and unit/compartment location (step 1020).\",\n \"If a product expiration date is a select number of days post current date (step 1025) a different alert is sent to the UID and select users (step 1030), for example instructing the user to prioritize use of the product (step 1035) if products with later expiration dates are also present in the unit and to verify stock status and consider ordering more product.\",\n \"The select number of days post current date is customizable by the unit user and is based on the dispense rate of the product.\",\n \"The ASP inventory management software further sends out low stock alerts and reorder recommendations based on the captured data related to current inventory status of each unit, expiration dates of the products, and pre-determined re-order levels.\",\n \"FIG.\",\n \"11 shown an exemplary flow diagram illustrating the steps taken to monitor product stock in the unit and send out alerts.\",\n \"The ASP inventory management software updates the inventory levels of each compartment every time a compartment is accessed and the unit is reclosed (step 1100).\",\n \"Inventory is decremented as product is dispensed and upon reaching or falling below a predetermined re-order level (step 1105), an order for additional product will be processed.\",\n \"If product count is greater than the re-order level count (step 1105) no action is required (step 1115).\",\n \"Should inventory levels fall to or below the predetermined re-order level a reorder message is sent (step 1110) to place or confirm if an order has been placed (step 1120).\",\n \"If the re-order message is not successful, an order was not placed, the system will determine if the product count is below a critical level (step 1130) and will generate a low stock alert if it is not below the critical level (step 1135) or a critical low stock alert (step 1140) if it is below the critical level.\",\n \"No action is required (step 1125) if an order is in place.\",\n \"A critical low may occur for a variety of reasons including: expected shipment has been delayed, sudden surge in usage in a single day that reduces inventory past the reorder point, and failure to process a re-order.\",\n \"The quantity of product that is re-ordered is calculated based on the difference between current inventory and the predetermined par level of inventory.\",\n \"The ASP inventory management software can be configured to reorder stock automatically.\",\n \"Inventory Management All inventory management functions are managed centrally by the ASP in a cloud based hosted environment.\",\n \"Communication with individual units occurs via the Internet and all authorized users have secure access to their designated units via the ASP website.\",\n \"The ASP inventory management software captures transactions related to inventory of the refrigerator unit and include stock and dispense transactions with reason for dispending of product.\",\n \"The dispense transactions may include for example: dispensed to patient, expired, spoiled in unit due to unit temperature deviations outside of recommended range, transferred from unit, and discontinued.\",\n \"Post a transaction the “dispensed to patient” transaction may be changed by user to “post dispense spoilage” if product was not administered to patient and product has been deemed to have spoiled.\",\n \"The data is further used to establish historical records of product demand, to ascertain adequate stock is available as needed, avoid loss of product due to expiration/spoilage, and to optimize the frequency and timing for ordering product and the quantity of product to be ordered.\",\n \"A product dispense rate is determined by the ASP provided inventory management software to establish historical trends in use of product.\",\n \"Shown in FIG.\",\n \"12 is an exemplary flow diagram for the process of determining dispense rates of a product.\",\n \"The ASP stored transaction data (step 1200) is first selected for dispensing transaction data (step 1205) which is then sorted by type (step 1210).\",\n \"The dispense rate for each type of dispensing transaction per calendar week (step 1215) and the average weekly rate for each type of dispensing transaction (step 1220) are determined.\",\n \"A comparison is made between the average dispense rate/week for each type of transaction to each weekly rate and one time anomalies in dispensing of product are excluded (step 1225).\",\n \"A corrected average dispense rate/week for each type of transaction is determined (step 1230) and a combined average of dispense rate/week for all transactions is established (step 1235).\",\n \"The exemplary dispense rates above are determined as a weekly rate.\",\n \"Further implementations of the dispense rate may be based on rates calculated for various time segments including a single day, several days, a month or year.\",\n \"To ascertain a unit does not run out of stock and the optimal quantity of stock is ordered, par levels, re-order levels and critical lows of stock are determined and low stock alert are generated.\",\n \"The determination of the physical maximum inventory level, par level, re-order level and critical low inventory level may be made by an authorized administrator of the unit.\",\n \"Typically, these inventory points will be determined by an individual with access to information and reports on transaction statistics for the unit.\",\n \"As historical trends of product use are established for a specific unit the determination of the par levels may be adjusted to reflect the historical use of the product within a given time period and may also be adjusted for seasonal variations.\",\n \"The unit user may choose to adjust the rates based on their review of the historical transaction data or may request that the ASP provide estimated values as a service.\",\n \"The quantity of product to be ordered is based on the predetermined par level which is a function of the number of products that can physically fit within the allotted compartments (physical maximum) in the unit, the shelf life of the product, a desired re-order frequency and the dispense rate of the product.\",\n \"For example a product with a shelf life of 90 days (i.e.\",\n \"expiration date is 90 days from the date of manufacture) and a dispense rate of 5 products per 10 days would allow the storage of a maximum of 45 products without having some of the product expire prior to use.\",\n \"Although the unit can physically accommodate 45 product units, the par level may be set significantly lower than 45 in order to have a desired shipment of product every two weeks.\",\n \"In this example, the par level may be set at 15, allowing room for variations in dispenses rate and product delivery.\",\n \"If the unit compartment can only accommodate 10 product units, the maximum par level in this exemplary case is set at 10.The re-order level is used to trigger a product order.\",\n \"If the order is not placed for whatever reason, there is a chance that the product could completely stock out and reach an inventory count of zero generating a stock-out alert.\",\n \"For example if it takes two days to order and receive product and the current dispense rate for product is 5 per day, a re-order level of 10 would be the lowest product count to trigger re-order.\",\n \"If an order has not been placed and inventory is at or below the set re-order level of 10, a low stock alert will be issued.\",\n \"Further, if the inventory level has reached a predetermined critical low level ( )a low stock alert would be issued.\",\n \"In keeping with the example, if the critical low level is determined to be 4 (less than a day's supply of product) and that inventory level is reached prior to the new shipment arriving, a low stock alert is issued.\",\n \"Preferably the re-order level will be set at a higher count, for example 20 in this exemplary case, to adjust for delays in placement of order and dispense rate variations.\",\n \"The authorized user of a unit has access to reports, provided by the ASP inventory management software, HIPPA compliant, that ascertain compliance with regulatory requirements, and allow the user to review and optimize protocols of handling and ordering of product.\",\n \"The reports may include: current inventory of product with expiration dates; quantity of product dispensed, by type of dispensing and/or total dispensed, for a selected time period such as day, week month year; dispense rate and type by date, percentages of product administered and percent product lost due to expiration, spoilage in unit, spoilage outside of unit; alert reports detailing any inventory and/or temperature alerts that have been generated over a given period of time.\",\n \"An authorized user further has access to reports on regional inventory data available through the ASP database wherein the report may include: type and quantity of product administered by location such as a local region defined by community or city, a state, and/or country within a selected time period; and dispense rate and type by date, percentages of product administered and percent product lost due to expiration, spoilage in unit, spoilage outside of unit.\",\n \"Fluctuating supply demands for time and temperature sensitive pharmaceuticals (TTSPS) give rise to a need for timely communication between the unit user, a point of care provider, manufacturers, distributors, sales representatives and others managing the flow of the TTSPS.\",\n \"The ASP inventory management software provides such a communications network, via a web interface, delivering user profile customized access to reports related to TTSPS inventory transactions.\",\n \"A manufacture of product “A”, for example, can have access to product “A” reports.\",\n \"Reports may include: quantity of product administered in by date and/or by location such as a local region defined by community or city, a state, and/or country within a selected time period; percentages of product administered and percent product lost due to expiration, spoilage in unit, spoilage outside of unit for a selected location; number of units within select location or region distributing product “A”; and low stock of product “A” alerts per unit and/or region.\",\n \"A distributor and/or product representative can have access to reports on products that they distribute and/or represent.\",\n \"Reports may include: quantity of product dispensed to patient by date and/or by location such as a local region defined by community or city, a state, and/or country within a selected time period; percentages of product dispensed to patient and percent product lost due to spoilage or expiration.\",\n \"FIG.\",\n \"13A and FIG.\",\n \"13B illustrate by way of an example the generation of, and user access to, reports on products A and B based on a time period of one week.\",\n \"Unit 1 and Unit 2 transaction data (steps 1300 and 1305) is used to generate a report for each unit, Unit 1 Report 1 and Unit 2 Report 2 accessible to the unit's users, 1312 and 1317, and includes the number of products stocked or dispensed per week by transaction type.\",\n \"The reports and data are merged in a regional database 1320 and provide unit user, 1312 and 1317, with regional data report, Report 4 1325.The regional data is broken down by product type, Report 5 for exemplary product A, 1330, and Report 6 for exemplary product B 6, 1335, for reporting to for example manufactures and sales representatives, of product A, 1340, and of product B, 1345.FIG.\",\n \"14 illustrates by way of example some of the functions provided by the ASP.\",\n \"The ASP 1400 utilizes the Inventory Management Software 1410 and Product Recognition Software 1420 to capture and analyze data received from the Unit 1405 to generate Reports 1430 made available by report type (1432, 1434, and 1446) to the Unit User 1440, Sales Representative 1442, and Manufacturer 1444.The Unit 1405 UID 1407 captures data from a Temperature Sensor 1409, Readers 1 and 2 1411, Biometric Sensor 1413 and manually entered data 1415.The Product Recognition Software 1420 captures and analyze the Product Reader Data 1422 and generates a Product Identifier 1424 that is used in combination with the Temperature Sensor & Stock/Dispense Data 1412 by the Inventory Management Software 1410 to generate Unit Content/Status and Alerts 1426 also displayed on the UID 1407.In further embodiments of the ASP provided inventory management software an automatic customizable product order/reorder protocol may be implemented in response to low stock alerts.\",\n \"Re-order messages will be directed to one or more parties depending on customized preferences.\",\n \"These messages for example could flow to a manufacturer, a distributor, a physician's re-ordering system or some combination of two or more.\",\n \"Re-order messages are available in a variety of message formats including, but not limited to, EDI and HL7.The ASP hosted system will provide an interface to other computer systems that require information directly.\",\n \"A doctor's office may desire an interface to provide dispense data to confirm the product dispensed and/or re-ordering information to process through an existing re-order process.\",\n \"Interface messages are available in a variety of message formats including (but not limited to) EDI and HL 7.Since modifications will be apparent to those of skill in this art, it is intended that this invention be limited only by the scope of the appended claims.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874742"}}},{"rowIdx":4494683,"cells":{"text":{"kind":"list like","value":[["PLASMA ETCHING DEVICE WITH PLASMA ETCH RESISTANT COATING","A method for coating a part body for use in a plasma processing chamber is provided.","The part body is received into a chamber.","At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor deposition with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride."],["1.A method for coating a part body for use in a plasma processing chamber, comprising: receiving the part body; and coating by physical vapor deposition or chemical vapor deposition at least part of a surface of the part body with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.","2.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a porosity of less than 1%.","3.The method, as recited in claim 1, wherein the part body is made of ceramic.","4.The method, as recited in claim 1, wherein the part body includes at least one of a RF window and/or a gas injector.","5.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition comprises coating by electron beam physical vapor deposition.","6.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition comprises coating by ion assisted electron beam deposition.","7.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating consisting essentially of yttrium oxyfluoride.","8.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a thickness of 2-18 μm.","9.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating consisting essentially of yttrium, lanthanum, zirconium, samarium (Sm), gadolinium (Gd), dysprosium (Dy), erbium (Er), ytterbium (Yb), or thulium (Tm) in an oxyfluoride.","10.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a thickness of 15-16 μm.","11.The method, as recited in claim 1, wherein the receiving the part body comprises receiving a RF window, and further comprising mounting the part body in a processing chamber comprising a substrate support for supporting a substrate within the processing chamber and a gas inlet for providing gas into the processing chamber.","12.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a density of at least 5 g/cm3.13.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition coats without cracking.","14.A method of forming an edge ring for use in a plasma processing chamber, comprising: forming a green edge ring consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride; and sintering the green edge ring.","15.The method, as recited in claim 14, wherein the green edge ring consisting essentially of yttrium oxyfluoride."],["<SOH> BACKGROUND <EOH>The present disclosure relates to the manufacturing of semiconductor devices.","More specifically, the disclosure relates to coating chamber surfaces used in manufacturing semiconductor devices.","During semiconductor wafer processing, plasma processing chambers are used to process semiconductor devices.","Coatings are used to protect chamber surfaces."],["<SOH> SUMMARY <EOH>To achieve the foregoing and in accordance with the purpose of the present disclosure, a method for coating a part body for use in a plasma processing chamber is provided.","The part body is received into a chamber.","At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor deposition with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.","These and other features of the present invention will be described in more detail below in the detailed description of the invention and in conjunction with the following figures."],["CLAIM OF PRIORITY This application is a Continuation of U.S. application Ser.","No.","14/817,115 filed on Aug. 3, 2015 entitled “PLASMA ETCHING DEVICE WITH PLASMA RESISTANT COATING.” The entire contents of the application noted above are hereby incorporated by reference.","BACKGROUND The present disclosure relates to the manufacturing of semiconductor devices.","More specifically, the disclosure relates to coating chamber surfaces used in manufacturing semiconductor devices.","During semiconductor wafer processing, plasma processing chambers are used to process semiconductor devices.","Coatings are used to protect chamber surfaces.","SUMMARY To achieve the foregoing and in accordance with the purpose of the present disclosure, a method for coating a part body for use in a plasma processing chamber is provided.","The part body is received into a chamber.","At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor deposition with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.","These and other features of the present invention will be described in more detail below in the detailed description of the invention and in conjunction with the following figures.","BRIEF DESCRIPTION OF THE DRAWINGS The present disclosure is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements and in which: FIG.","1 is a schematic view of an etch reactor that may be used in an embodiment.","FIG.","2 is an enlarged cross-sectional view of a power window.","FIG.","3 is an enlarged cross-sectional view of the gas injector.","FIG.","4 is an enlarged cross-sectional view of part of an edge ring.","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will now be described in detail with reference to a few preferred embodiments thereof as illustrated in the accompanying drawings.","In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention.","It will be apparent, however, to one skilled in the art, that the present invention may be practiced without some or all of these specific details.","In other instances, well known process steps and/or structures have not been described in detail in order to not unnecessarily obscure the present invention.","To facilitate understanding, FIG.","1 schematically illustrates an example of a plasma processing chamber 100 which may be used in an embodiment.","The plasma processing chamber 100 includes a plasma reactor 102 having a plasma processing confinement chamber 104 therein.","A plasma power supply 106, tuned by a match network 108, supplies power to a TCP coil 110 located near a power window 112 to create a plasma 114 in the plasma processing confinement chamber 104 by providing an inductively coupled power.","The TCP coil (upper power source) 110 may be configured to produce a uniform diffusion profile within the plasma processing confinement chamber 104.For example, the TCP coil 110 may be configured to generate a toroidal power distribution in the plasma 114.The power window 112 is provided to separate the TCP coil 110 from the plasma processing confinement chamber 104 while allowing energy to pass from the TCP coil 110 to the plasma processing confinement chamber 104.A wafer bias voltage power supply 116 tuned by a match network 118 provides power to an electrode 120 to set the bias voltage on the substrate 164 which is supported by the electrode 120.A controller 124 sets points for the plasma power supply 106, gas source/gas supply mechanism 130, and the wafer bias voltage power supply 116.The plasma power supply 106 and the wafer bias voltage power supply 116 may be configured to operate at specific radio frequencies such as, for example, 13.56 MHz, 27 MHz, 2 MHz, 60 MHz, 400 kHz, 2.54 GHz, or combinations thereof.","Plasma power supply 106 and wafer bias voltage power supply 116 may be appropriately sized to supply a range of powers in order to achieve desired process performance.","For example, in one embodiment of the present invention, the plasma power supply 106 may supply the power in a range of 50 to 5000 Watts, and the wafer bias voltage power supply 116 may supply a bias voltage of in a range of 20 to 2000 V. In addition, the TCP coil 110 and/or the electrode 120 may be comprised of two or more sub-coils or sub-electrodes, which may be powered by a single power supply or powered by multiple power supplies.","As shown in FIG.","1, the plasma processing chamber 100 further includes a gas source/gas supply mechanism 130.The gas source 130 is in fluid connection with plasma processing confinement chamber 104 through a gas inlet, such as a gas injector 140.The gas injector 140 may be located in any advantageous location in the plasma processing confinement chamber 104, and may take any form for injecting gas.","Preferably, however, the gas inlet may be configured to produce a “tunable” gas injection profile, which allows independent adjustment of the respective flow of the gases to multiple zones in the plasma process confinement chamber 104.The process gases and byproducts are removed from the plasma process confinement chamber 104 via a pressure control valve 142 and a pump 144, which also serve to maintain a particular pressure within the plasma processing confinement chamber 104.The pressure control valve 142 can maintain a pressure of less than 1 Torr during processing.","An edge ring 160 is placed around the wafer 164.The gas source/gas supply mechanism 130 is controlled by the controller 124.A Kiyo by Lam Research Corp. of Fremont, Calif., may be used to practice an embodiment.","FIG.","2 is an enlarged cross-sectional view of the power window 112.The power window 112 comprises a window body 204 and a coating 208 covering at least one surface of the window body 204.In this example, the coating 208 is only on one surface of the window body 204.The window body 204 may be of one or more different materials.","Preferably, the window body 204 is ceramic.","More preferably, the window body 204 comprises at least one of silicon (Si), quartz, silicon carbide (SiC), silicon nitride (SiN), aluminum oxide (AlO), aluminum nitride (AlC), or aluminum carbide (AlC).","The coating 208 consists essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.","More preferably, the coating consists essentially of yttrium, lanthanum, zirconium, samarium (Sm), gadolinium (Gd), dysprosium (Dy), erbium (Er), ytterbium (Yb), or thulium (Tm) in an oxyfluoride.","More preferably, the coating 208 consists essentially of yttrium oxyfluoride.","Preferably, the coating 208 is no more than 30 μm thick.","More preferably, the coating 208 is 5-20 μm thick.","Most preferably, the coating 208 is 10-18 μm thick.","Preferably, the coating 208 is 99.7% pure.","Preferably, the coating 208 is high density with a porosity of less than 1%.","More preferably, the coating 208 has a porosity of less than 0.5%.","To provide such a uniform, high density, low porosity, and thin coating, preferably the coating 208 is formed by physical vapor deposition.","More preferably, the physical vapor deposition is electron beam physical vapor deposition.","Most preferably, the physical vapor deposition is ion assisted electron beam deposition.","Preferably, the coating has a density of at least 5 g/cm3.FIG.","3 is an enlarged cross-sectional view of the gas injector 140.The gas injector 140 comprises an injector body 304 and a coating 308 covering at least one surface of the injector body 304.In this example, the coating 308 is on at least two surfaces of the injector body 304.The injector body 304 has a bore hole 312, through which the gas flows.","In some embodiments, the coating 308 may line the bore hole 312.The gas injector 140 may also have a mount 316 for fixing the gas injector 140 to the power window 112.The injector body 304 may be of one or more different materials.","Preferably, the injector body 304 is ceramic.","More preferably, the injector body 304 comprises at least one of silicon (Si), quartz, silicon carbide (SiC), silicon nitride (SiN), aluminum oxide (AlO), aluminum nitride (AlC), or aluminum carbide (AlC).","The coating 308 consists essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.","More preferably, the coating 308 consists essentially of yttrium oxyfluoride.","Preferably, the coating 308 is no more than 30 μm thick.","More preferably, the coating 308 is 2-20 μm thick.","Most preferably, the coating 308 is 10-18 μm thick.","Preferably, the coating 308 is 99.7% pure.","Preferably, the coating 308 is high density with a porosity of less than 1%.","To provide such a uniform, high density, low porosity, and thin coating, preferably the coating 308 is formed by physical vapor deposition or chemical vapor deposition.","More preferably, the physical vapor deposition is electron beam physical vapor deposition.","Most preferably, the physical vapor deposition is ion assisted electron beam deposition.","FIG.","4 is an enlarged cross-sectional view of part of the edge ring 160.The edge ring 160 comprises a ring body 404.A method of making the edge ring 160 would form a ceramic consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride into a green edge ring.","The green edge ring is sintered to fuse ceramic particles together.","Preferably, the ceramic consists essentially of yttrium oxyfluoride.","The density of the ring body is at least 5 g/cm3.In some embodiments, the gas source provides a halogen containing gas, which is formed into a halogen containing plasma.","It has been unexpectedly found that coatings comprising at least one of a Group III or Group IV element in an oxyfluoride are highly etch resistant.","It has been found that providing a porosity of less than 1% increases etch resistance.","In other embodiments, other components such as the chamber walls or the electrostatic chuck may also have an etch resistant coating or body.","In other embodiments, the plasma processing chamber may be a capacitively coupled plasma processing chamber.","In such chambers components such as confinement rings and upper electrodes may have the etch resistant coatings.","If parts of the chamber only have an yttrium oxide coating, a fluorine containing plasma would convert some of the yttrium oxide coating into yttrium oxyfluoride particles.","The yttrium oxyfluoride particles would flake off, becoming contaminants.","It has been unexpectedly found that a high density and low porosity yttrium oxyfluoride coating would not produce such particles and would be more etch resistant to fluorine containing plasmas.","In addition, it has been unexpectedly found that a coating of yttrium oxyfluoride may be deposited with a thickness of 15-16 μm without cracking caused by stress, allowing for a coating that would be much thicker than an yttrium oxide coating, and would allow the production of a coating that would have more than twice the life expectancy of an yttrium oxide coating.","While this disclosure has been described in terms of several preferred embodiments, there are alterations, permutations, modifications, and various substitute equivalents, which fall within the scope of this disclosure.","It should also be noted that there are many alternative ways of implementing the methods and apparatuses of the present disclosure.","It is therefore intended that the following appended claims be interpreted as including all such alterations, permutations, and various substitute equivalents as fall within the true spirit and scope of the present disclosure."]],"string":"[\n [\n \"PLASMA ETCHING DEVICE WITH PLASMA ETCH RESISTANT COATING\",\n \"A method for coating a part body for use in a plasma processing chamber is provided.\",\n \"The part body is received into a chamber.\",\n \"At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor deposition with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.\"\n ],\n [\n \"1.A method for coating a part body for use in a plasma processing chamber, comprising: receiving the part body; and coating by physical vapor deposition or chemical vapor deposition at least part of a surface of the part body with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.\",\n \"2.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a porosity of less than 1%.\",\n \"3.The method, as recited in claim 1, wherein the part body is made of ceramic.\",\n \"4.The method, as recited in claim 1, wherein the part body includes at least one of a RF window and/or a gas injector.\",\n \"5.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition comprises coating by electron beam physical vapor deposition.\",\n \"6.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition comprises coating by ion assisted electron beam deposition.\",\n \"7.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating consisting essentially of yttrium oxyfluoride.\",\n \"8.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a thickness of 2-18 μm.\",\n \"9.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating consisting essentially of yttrium, lanthanum, zirconium, samarium (Sm), gadolinium (Gd), dysprosium (Dy), erbium (Er), ytterbium (Yb), or thulium (Tm) in an oxyfluoride.\",\n \"10.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a thickness of 15-16 μm.\",\n \"11.The method, as recited in claim 1, wherein the receiving the part body comprises receiving a RF window, and further comprising mounting the part body in a processing chamber comprising a substrate support for supporting a substrate within the processing chamber and a gas inlet for providing gas into the processing chamber.\",\n \"12.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition provides a coating with a density of at least 5 g/cm3.13.The method, as recited in claim 1, wherein the coating by physical vapor deposition or chemical vapor deposition coats without cracking.\",\n \"14.A method of forming an edge ring for use in a plasma processing chamber, comprising: forming a green edge ring consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride; and sintering the green edge ring.\",\n \"15.The method, as recited in claim 14, wherein the green edge ring consisting essentially of yttrium oxyfluoride.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>The present disclosure relates to the manufacturing of semiconductor devices.\",\n \"More specifically, the disclosure relates to coating chamber surfaces used in manufacturing semiconductor devices.\",\n \"During semiconductor wafer processing, plasma processing chambers are used to process semiconductor devices.\",\n \"Coatings are used to protect chamber surfaces.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>To achieve the foregoing and in accordance with the purpose of the present disclosure, a method for coating a part body for use in a plasma processing chamber is provided.\",\n \"The part body is received into a chamber.\",\n \"At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor deposition with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.\",\n \"These and other features of the present invention will be described in more detail below in the detailed description of the invention and in conjunction with the following figures.\"\n ],\n [\n \"CLAIM OF PRIORITY This application is a Continuation of U.S. application Ser.\",\n \"No.\",\n \"14/817,115 filed on Aug. 3, 2015 entitled “PLASMA ETCHING DEVICE WITH PLASMA RESISTANT COATING.” The entire contents of the application noted above are hereby incorporated by reference.\",\n \"BACKGROUND The present disclosure relates to the manufacturing of semiconductor devices.\",\n \"More specifically, the disclosure relates to coating chamber surfaces used in manufacturing semiconductor devices.\",\n \"During semiconductor wafer processing, plasma processing chambers are used to process semiconductor devices.\",\n \"Coatings are used to protect chamber surfaces.\",\n \"SUMMARY To achieve the foregoing and in accordance with the purpose of the present disclosure, a method for coating a part body for use in a plasma processing chamber is provided.\",\n \"The part body is received into a chamber.\",\n \"At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor deposition with a coating with a thickness of no more than 30 microns consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.\",\n \"These and other features of the present invention will be described in more detail below in the detailed description of the invention and in conjunction with the following figures.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The present disclosure is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements and in which: FIG.\",\n \"1 is a schematic view of an etch reactor that may be used in an embodiment.\",\n \"FIG.\",\n \"2 is an enlarged cross-sectional view of a power window.\",\n \"FIG.\",\n \"3 is an enlarged cross-sectional view of the gas injector.\",\n \"FIG.\",\n \"4 is an enlarged cross-sectional view of part of an edge ring.\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will now be described in detail with reference to a few preferred embodiments thereof as illustrated in the accompanying drawings.\",\n \"In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention.\",\n \"It will be apparent, however, to one skilled in the art, that the present invention may be practiced without some or all of these specific details.\",\n \"In other instances, well known process steps and/or structures have not been described in detail in order to not unnecessarily obscure the present invention.\",\n \"To facilitate understanding, FIG.\",\n \"1 schematically illustrates an example of a plasma processing chamber 100 which may be used in an embodiment.\",\n \"The plasma processing chamber 100 includes a plasma reactor 102 having a plasma processing confinement chamber 104 therein.\",\n \"A plasma power supply 106, tuned by a match network 108, supplies power to a TCP coil 110 located near a power window 112 to create a plasma 114 in the plasma processing confinement chamber 104 by providing an inductively coupled power.\",\n \"The TCP coil (upper power source) 110 may be configured to produce a uniform diffusion profile within the plasma processing confinement chamber 104.For example, the TCP coil 110 may be configured to generate a toroidal power distribution in the plasma 114.The power window 112 is provided to separate the TCP coil 110 from the plasma processing confinement chamber 104 while allowing energy to pass from the TCP coil 110 to the plasma processing confinement chamber 104.A wafer bias voltage power supply 116 tuned by a match network 118 provides power to an electrode 120 to set the bias voltage on the substrate 164 which is supported by the electrode 120.A controller 124 sets points for the plasma power supply 106, gas source/gas supply mechanism 130, and the wafer bias voltage power supply 116.The plasma power supply 106 and the wafer bias voltage power supply 116 may be configured to operate at specific radio frequencies such as, for example, 13.56 MHz, 27 MHz, 2 MHz, 60 MHz, 400 kHz, 2.54 GHz, or combinations thereof.\",\n \"Plasma power supply 106 and wafer bias voltage power supply 116 may be appropriately sized to supply a range of powers in order to achieve desired process performance.\",\n \"For example, in one embodiment of the present invention, the plasma power supply 106 may supply the power in a range of 50 to 5000 Watts, and the wafer bias voltage power supply 116 may supply a bias voltage of in a range of 20 to 2000 V. In addition, the TCP coil 110 and/or the electrode 120 may be comprised of two or more sub-coils or sub-electrodes, which may be powered by a single power supply or powered by multiple power supplies.\",\n \"As shown in FIG.\",\n \"1, the plasma processing chamber 100 further includes a gas source/gas supply mechanism 130.The gas source 130 is in fluid connection with plasma processing confinement chamber 104 through a gas inlet, such as a gas injector 140.The gas injector 140 may be located in any advantageous location in the plasma processing confinement chamber 104, and may take any form for injecting gas.\",\n \"Preferably, however, the gas inlet may be configured to produce a “tunable” gas injection profile, which allows independent adjustment of the respective flow of the gases to multiple zones in the plasma process confinement chamber 104.The process gases and byproducts are removed from the plasma process confinement chamber 104 via a pressure control valve 142 and a pump 144, which also serve to maintain a particular pressure within the plasma processing confinement chamber 104.The pressure control valve 142 can maintain a pressure of less than 1 Torr during processing.\",\n \"An edge ring 160 is placed around the wafer 164.The gas source/gas supply mechanism 130 is controlled by the controller 124.A Kiyo by Lam Research Corp. of Fremont, Calif., may be used to practice an embodiment.\",\n \"FIG.\",\n \"2 is an enlarged cross-sectional view of the power window 112.The power window 112 comprises a window body 204 and a coating 208 covering at least one surface of the window body 204.In this example, the coating 208 is only on one surface of the window body 204.The window body 204 may be of one or more different materials.\",\n \"Preferably, the window body 204 is ceramic.\",\n \"More preferably, the window body 204 comprises at least one of silicon (Si), quartz, silicon carbide (SiC), silicon nitride (SiN), aluminum oxide (AlO), aluminum nitride (AlC), or aluminum carbide (AlC).\",\n \"The coating 208 consists essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.\",\n \"More preferably, the coating consists essentially of yttrium, lanthanum, zirconium, samarium (Sm), gadolinium (Gd), dysprosium (Dy), erbium (Er), ytterbium (Yb), or thulium (Tm) in an oxyfluoride.\",\n \"More preferably, the coating 208 consists essentially of yttrium oxyfluoride.\",\n \"Preferably, the coating 208 is no more than 30 μm thick.\",\n \"More preferably, the coating 208 is 5-20 μm thick.\",\n \"Most preferably, the coating 208 is 10-18 μm thick.\",\n \"Preferably, the coating 208 is 99.7% pure.\",\n \"Preferably, the coating 208 is high density with a porosity of less than 1%.\",\n \"More preferably, the coating 208 has a porosity of less than 0.5%.\",\n \"To provide such a uniform, high density, low porosity, and thin coating, preferably the coating 208 is formed by physical vapor deposition.\",\n \"More preferably, the physical vapor deposition is electron beam physical vapor deposition.\",\n \"Most preferably, the physical vapor deposition is ion assisted electron beam deposition.\",\n \"Preferably, the coating has a density of at least 5 g/cm3.FIG.\",\n \"3 is an enlarged cross-sectional view of the gas injector 140.The gas injector 140 comprises an injector body 304 and a coating 308 covering at least one surface of the injector body 304.In this example, the coating 308 is on at least two surfaces of the injector body 304.The injector body 304 has a bore hole 312, through which the gas flows.\",\n \"In some embodiments, the coating 308 may line the bore hole 312.The gas injector 140 may also have a mount 316 for fixing the gas injector 140 to the power window 112.The injector body 304 may be of one or more different materials.\",\n \"Preferably, the injector body 304 is ceramic.\",\n \"More preferably, the injector body 304 comprises at least one of silicon (Si), quartz, silicon carbide (SiC), silicon nitride (SiN), aluminum oxide (AlO), aluminum nitride (AlC), or aluminum carbide (AlC).\",\n \"The coating 308 consists essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride.\",\n \"More preferably, the coating 308 consists essentially of yttrium oxyfluoride.\",\n \"Preferably, the coating 308 is no more than 30 μm thick.\",\n \"More preferably, the coating 308 is 2-20 μm thick.\",\n \"Most preferably, the coating 308 is 10-18 μm thick.\",\n \"Preferably, the coating 308 is 99.7% pure.\",\n \"Preferably, the coating 308 is high density with a porosity of less than 1%.\",\n \"To provide such a uniform, high density, low porosity, and thin coating, preferably the coating 308 is formed by physical vapor deposition or chemical vapor deposition.\",\n \"More preferably, the physical vapor deposition is electron beam physical vapor deposition.\",\n \"Most preferably, the physical vapor deposition is ion assisted electron beam deposition.\",\n \"FIG.\",\n \"4 is an enlarged cross-sectional view of part of the edge ring 160.The edge ring 160 comprises a ring body 404.A method of making the edge ring 160 would form a ceramic consisting essentially of a Lanthanide series or Group III or Group IV element in an oxyfluoride into a green edge ring.\",\n \"The green edge ring is sintered to fuse ceramic particles together.\",\n \"Preferably, the ceramic consists essentially of yttrium oxyfluoride.\",\n \"The density of the ring body is at least 5 g/cm3.In some embodiments, the gas source provides a halogen containing gas, which is formed into a halogen containing plasma.\",\n \"It has been unexpectedly found that coatings comprising at least one of a Group III or Group IV element in an oxyfluoride are highly etch resistant.\",\n \"It has been found that providing a porosity of less than 1% increases etch resistance.\",\n \"In other embodiments, other components such as the chamber walls or the electrostatic chuck may also have an etch resistant coating or body.\",\n \"In other embodiments, the plasma processing chamber may be a capacitively coupled plasma processing chamber.\",\n \"In such chambers components such as confinement rings and upper electrodes may have the etch resistant coatings.\",\n \"If parts of the chamber only have an yttrium oxide coating, a fluorine containing plasma would convert some of the yttrium oxide coating into yttrium oxyfluoride particles.\",\n \"The yttrium oxyfluoride particles would flake off, becoming contaminants.\",\n \"It has been unexpectedly found that a high density and low porosity yttrium oxyfluoride coating would not produce such particles and would be more etch resistant to fluorine containing plasmas.\",\n \"In addition, it has been unexpectedly found that a coating of yttrium oxyfluoride may be deposited with a thickness of 15-16 μm without cracking caused by stress, allowing for a coating that would be much thicker than an yttrium oxide coating, and would allow the production of a coating that would have more than twice the life expectancy of an yttrium oxide coating.\",\n \"While this disclosure has been described in terms of several preferred embodiments, there are alterations, permutations, modifications, and various substitute equivalents, which fall within the scope of this disclosure.\",\n \"It should also be noted that there are many alternative ways of implementing the methods and apparatuses of the present disclosure.\",\n \"It is therefore intended that the following appended claims be interpreted as including all such alterations, permutations, and various substitute equivalents as fall within the true spirit and scope of the present disclosure.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874744"}}},{"rowIdx":4494684,"cells":{"text":{"kind":"list like","value":[["PREPARATION OF (R,R)-FENOTEROL AND (R,R)- OR (R,S)-FENOTEROL ANALOGUES AND THEIR USE IN TREATING CONGESTIVE HEART FAILURE","This disclosure concerns the discovery of (R,R)- and (R,S)-fenoterol analogues which are highly effective at binding β2-adrenergic receptors.","Exemplary chemical structures for these analogues are provided.","Also provided are pharmaceutical compositions including the disclosed (R,R)-fenoterol and fenoterol analogues, and methods of using such compounds and compositions for the treatment of cardiac disorders such as congestive heart failure and pulmonary disorders such as asthma or chronic obstructive pulmonary disease."],["1.A method for treating a pulmonary or cardiovascular disorder in a subject, comprising: administering to the subject with the pulmonary or cardiovascular disorder a therapeutically effective amount of a compound having the formula wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl or a combination thereof; R4 is H or lower alkyl; R5 is X is H, —OR6, or —NR7R8; R6 is lower alkyl; and R7 and R8 independently are H or lower alkyl, wherein the compound is optically active.","2.The method of claim 1, wherein R5 is where X is H or —OR6 and R6 is lower alkyl.","3.The method of claim 1, wherein R4 is lower alkyl.","4.The method of claim 1, wherein the compound is a (R,R)- or (R,S)-compound.","5.The method of claim 4, wherein R5 is where X is H or —OCH3.6.The method of claim 5, wherein R4 is methyl, ethyl, n-propyl, or isopropyl.","7.The method of claim 5, wherein R4 is methyl.","8.The method of claim 6, wherein R1-R3 are hydrogen.","9.The method of claim 1, wherein the compound is 10.The method of claim 9, wherein the compound is a (R,R)- or (R,S)-compound.","11.The method of claim 1, wherein the compound is 12.The method of claim 1, wherein the disorder is a cardiovascular disorder.","13.The method of claim 12, wherein the cardiovascular disorder is congestive heart failure.","14.The method of claim 1, wherein the disorder is a pulmonary disorder.","15.The method of claim 14, wherein the pulmonary disorder is at least one of asthma or chronic pulmonary obstructive disease.","16.The method of claim 1, wherein administering a therapeutically effective amount of the compound comprises administering a pharmaceutical composition comprising the therapeutically effective amount of the compound and at least one pharmaceutically acceptable carrier.","17.A method of increasing cardiomyocyte contractility, comprising: contacting cardiomyocytes with a therapeutically effective amount of a compound having the formula wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl or a combination thereof; R4 is H or lower alkyl; R5 is X is H, —OR6, or —NR7R8; R6 is lower alkyl; and R7 and R8 independently are H or lower alkyl, wherein the compound is optically active.","18.The method of claim 17, wherein: R4 is lower alkyl; and R5 is where X is H or —OR6 and R6 is lower alkyl.","19.The method of claim 17, wherein the compound is 20.The method of claim 19, wherein the compound is a (R,R)- or (R,S)-compound."],["<SOH> BACKGROUND <EOH>Fenoterol, 5-[1-hydroxy-2[[2-(4-hydroxyphenyl)-1-methylethyl]-amino] ethyl]1,2-benzenediol, is a β2-adrenergic receptor agonist that has traditionally been used for the treatment of pulmonary disorders such as asthma.","This drug has two chiral (asymmetric) carbons that can each be independently arranged in an R or S configuration, so that the drug exists in distinct (R,R), (R,S), (S,R) and (S,S) forms known as stereoisomers.","Fenoterol is commercially available as a racemic mixture of the (R,R)- and (S,S)-compounds.","Fenoterol is known to act as an agonist that binds to and activates the β2-adrenergic receptor.","This activity has led to its clinical use in the treatment of asthma because this agonist's activity dilates constricted airways.","Additional therapeutic uses for fenoterol remain to be thoroughly explored.","Pharmacological studies of the class of drugs that includes fenoterol have shown that only one of the enantiomers is responsible for generating brochodilation.","For example, studies have demonstrated that the primary bronchodilatory activity for racemic (±)-fenoterol resides in the (R,R)-isomer of fenoterol.","Further, it has recently become apparent that the inactive enantiomer may be associated with adverse effects.","For instance, the diastereomer (S,S)-fenoterol has been demonstrated to cause adverse side effects or development of tolerance often associated with β2-adrenergic receptor agonist treatment.","It would therefore be advantageous to provide fenoterol compositions that were effective at treating disorders such as asthma, chronic obstructive pulmonary disease, or congestive heart failure, but had reduced side effects such as hypersensitivity and drug resistance (tolerance)."],["<SOH> SUMMARY <EOH>This disclosure concerns the discovery of fenoterol analogues that are highly effective at binding β2-adrenergic receptors.","Exemplary chemical structures for these analogues are provided throughout the disclosure.","By way of example, such compounds are represented by the following general formula: wherein R 1 -R 3 independently are hydrogen, acyl, alkoxy carbonyl, amino carbonyl (carbamoyl) or a combination thereof; R 4 is H or lower alkyl; R 5 is lower alkyl, wherein X, Y 1 , Y 2 and Y 3 independently are hydrogen, —OR 6 and —NR 7 R 8 ; R 6 is independently hydrogen, lower alkyl, acyl, alkoxy carbonyl or amino carbonyl; and R 7 and R 8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl.","Pharmaceutical compositions containing, and methods of using (R,R)-fenoterol and fenoterol analogues are also provided.","For example, the disclosed (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues (e.g., (R,R)-methoxyfenoterol, (R,R)-napthylfenoterol, and (R,S)-napthylfenoterol) are effective at treating cardiac disorders or pulmonary disorders.","The foregoing and other features and advantages will become more apparent from the following detailed description of several embodiments, which proceeds with reference to the accompanying figures."],["CROSS REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. patent application Ser.","No.","15/347,354, filed Nov. 9, 2016, which is a continuation of U.S. patent application Ser.","No.","14/199,208, filed Mar.","6, 2014, now issued as U.S. Pat.","No.","9,522,871, which is a divisional of U.S. patent application Ser.","No.","13/333,866, filed Dec. 21, 2011, now issued as U.S. Pat.","No.","8,703,826, which is a continuation of U.S. patent application Ser.","No.","12/376,945, filed Feb. 9, 2009, now abandoned, which is a § 371 U.S. National Stage of International Application No.","PCT/US2007/075731, filed Aug. 10, 2007, which in turn claims the benefit of U.S.","Provisional Patent Application No.","60/927,825, filed May 3, 2007, and U.S.","Provisional Application No.","60/837,161, filed Aug. 10, 2006, all of which are incorporated herein in their entirety by reference.","FIELD The present disclosure relates to the field of pharmaceutical compositions and in particular, to the preparation of (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues and their use in treating congestive heart failure.","BACKGROUND Fenoterol, 5-[1-hydroxy-2[[2-(4-hydroxyphenyl)-1-methylethyl]-amino] ethyl]1,2-benzenediol, is a β2-adrenergic receptor agonist that has traditionally been used for the treatment of pulmonary disorders such as asthma.","This drug has two chiral (asymmetric) carbons that can each be independently arranged in an R or S configuration, so that the drug exists in distinct (R,R), (R,S), (S,R) and (S,S) forms known as stereoisomers.","Fenoterol is commercially available as a racemic mixture of the (R,R)- and (S,S)-compounds.","Fenoterol is known to act as an agonist that binds to and activates the β2-adrenergic receptor.","This activity has led to its clinical use in the treatment of asthma because this agonist's activity dilates constricted airways.","Additional therapeutic uses for fenoterol remain to be thoroughly explored.","Pharmacological studies of the class of drugs that includes fenoterol have shown that only one of the enantiomers is responsible for generating brochodilation.","For example, studies have demonstrated that the primary bronchodilatory activity for racemic (±)-fenoterol resides in the (R,R)-isomer of fenoterol.","Further, it has recently become apparent that the inactive enantiomer may be associated with adverse effects.","For instance, the diastereomer (S,S)-fenoterol has been demonstrated to cause adverse side effects or development of tolerance often associated with β2-adrenergic receptor agonist treatment.","It would therefore be advantageous to provide fenoterol compositions that were effective at treating disorders such as asthma, chronic obstructive pulmonary disease, or congestive heart failure, but had reduced side effects such as hypersensitivity and drug resistance (tolerance).","SUMMARY This disclosure concerns the discovery of fenoterol analogues that are highly effective at binding β2-adrenergic receptors.","Exemplary chemical structures for these analogues are provided throughout the disclosure.","By way of example, such compounds are represented by the following general formula: wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl, amino carbonyl (carbamoyl) or a combination thereof; R4 is H or lower alkyl; R5 is lower alkyl, wherein X, Y1, Y2 and Y3 independently are hydrogen, —OR6 and —NR7R8; R6 is independently hydrogen, lower alkyl, acyl, alkoxy carbonyl or amino carbonyl; and R7 and R8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl.","Pharmaceutical compositions containing, and methods of using (R,R)-fenoterol and fenoterol analogues are also provided.","For example, the disclosed (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues (e.g., (R,R)-methoxyfenoterol, (R,R)-napthylfenoterol, and (R,S)-napthylfenoterol) are effective at treating cardiac disorders or pulmonary disorders.","The foregoing and other features and advantages will become more apparent from the following detailed description of several embodiments, which proceeds with reference to the accompanying figures.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 illustrates the chromatographic separation of (S,S)- and (R,R)-fenoterol.","FIG.","2A provides an ultraviolet spectra of (R,R)- and (S,S)-fenoterol.","FIG.","2B illustrates a circular dichroism spectra of (R,R)- and (S,S)-fenoterol.","FIG.","3 provides frontal chromatographic elution profiles of [+H]-(±)-fenoterol produced by the addition of (R,R)-fenoterol to the running buffer.","FIG.","4A is a graph including dose-response curves generated by treating freshly isolated rat ventricular myocytes with (±)-fenoterol, (R,R)-fenoterol or (S,S)-fenoterol.","FIG.","4B is a graph including dose-response curves of T50% relaxation in freshly isolated rat ventricular myocytes generated by treatment with (±)-fenoterol, (R,R)-fenoterol or (S,S)-fenoterol.","FIG.","5 illustrates the chemical structures of the stereoisomers of fenoterol and fenoterol analogs (compounds 2-7).","FIG.","6 illustrates the chemical structures of compounds 47-51.FIG.","7 illustrates the effect of fenoterol and fenoterol analogs on cell contraction in single ventricular myocytes.","FIG.","8 is a graph illustrating time-dependent mean plasma concentration of (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-napthylfenoterol after administration (5 mg/mL).","DETAILED DESCRIPTION OF SEVERAL EMBODIMENTS I.","Introduction This disclosure provides fenoterol analogues that bind the β2-adrenergic receptor with comparable or greater activity than fenoterol.","In one embodiment, the optically active fenoterol analogues are substantially purified from a racemic mixture.","For example, an optically active fenoterol analogue is purified to represent greater than 90%, often greater than 95% of the composition.","These analogues can be used to treat pulmonary disorders such as asthma and chronic obstructive pulmonary disease that have previously been treated with (±)-fenoterol.","Use of the disclosed fenoterol analogues with an equal to higher efficacy than (±)-fenoterol can possibly reduce adverse effects previously observed with (±)-fenoterol.","For example, use of a lower concentration of the fenoterol analogues to obtain a therapeutic effective response is expected to reduce side-effects such as hypersensitivity and drug resistance (tolerance) observed with the commercially available (±)-fenoterol.","Also, purification of the analogues removes contaminants such as the inactive enantiomer which can be responsible for these adverse effects.","The present disclosure also demonstrates that (R,R)-fenoterol is the active component of commercially available (±)-fenoterol.","It is specifically contemplated that (R,R)-fenoterol as well as disclosed (R,R)- and (R,S)-fenoterol analogues can be used to treat cardiac disorders such as congestive heart failure.","Use of substantially optically pure (R,R)-fenoterol or (R,R)- or (R,S)-fenoterol analogues to treat congestive heart failure is expected to reduce the incidence of side-effects caused by physiologically less active forms of the drug.","II.","Abbreviations and Terms AR: adrenergic receptor CD: circular dichroism CoMFA: comparative molecular field analysis HPLC: high performance liquid chromatography IAM-PC: immobilized artificial membrane chromatographic support ICYP: [125I]cyanopindolol UV: ultraviolet Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed subject matter belongs.","Definitions of common terms in chemistry terms may be found in The McGraw-Hill Dictionary of Chemical Terms, 1985, and The Condensed Chemical Dictionary, 1981.As used herein, the singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise.","Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise.","Also, as used herein, the term “comprises” means “includes.” Hence “comprising A or B” means including A, B, or A and B.","Except as otherwise noted, any quantitative values are approximate whether the word “about” or “approximately” or the like are stated or not.","The materials, methods, and examples described herein are illustrative only and not intended to be limiting.","Any molecular weight or molecular mass values are approximate and are provided only for description.","Except as otherwise noted, the methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification.","See, e.g., Loudon, Organic Chemistry, Fourth Edition, New York: Oxford University Press, 2002, pp.","360-361, 1084-1085; Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fifth Edition, Wiley-Interscience, 2001; or Vogel, A Textbook of Practical Organic Chemistry, Including Qualitative Organic Analysis, Fourth Edition, New York: Longman, 1978.In order to facilitate review of the various embodiments disclosed herein, the following explanations of specific terms are provided: Acyl: A group of the formula RC(O)— wherein R is an organic group.","Acyloxy: A group having the structure —OC(O)R, where R may be an optionally substituted alkyl or optionally substituted aryl.","“Lower acyloxy” groups are those where R contains from 1 to 10 (such as from 1 to 6) carbon atoms.","Alkoxy: A radical (or substituent) having the structure —O—R, where R is a substituted or unsubstituted alkyl.","Methoxy (—OCH3) is an exemplary alkoxy group.","In a substituted alkoxy, R is alkyl substituted with a non-interfering substituent.","“Thioalkoxy” refers to —S—R, where R is substituted or unsubstituted alkyl.","“Haloalkyloxy” means a radical —OR where R is a haloalkyl.","Alkoxy carbonyl: A group of the formula —C(O)OR, where R may be an optionally substituted alkyl or optionally substituted aryl.","“Lower alkoxy carbonyl” groups are those where R contains from 1 to 10 (such as from 1 to 6) carbon atoms.","Alkyl: An acyclic, saturated, branched- or straight-chain hydrocarbon radical, which, unless expressly stated otherwise, contains from one to fifteen carbon atoms; for example, from one to ten, from one to six, or from one to four carbon atoms.","This term includes, for example, groups such as methyl, ethyl, n-propyl, isopropyl, isobutyl, t-butyl, pentyl, heptyl, octyl, nonyl, decyl, or dodecyl.","The term “lower alkyl” refers to an alkyl group containing from one to ten carbon atoms.","Unless expressly referred to as an “unsubstituted alkyl,” alkyl groups can either be unsubstituted or substituted.","An alkyl group can be substituted with one or more substituents (for example, up to two substituents for each methylene carbon in an alkyl chain).","Exemplary alkyl substituents include, for instance, amino groups, amide, sulfonamide, halogen, cyano, carboxy, hydroxy, mercapto, trifluoromethyl, alkyl, alkoxy (such as methoxy), alkylthio, thioalkoxy, arylalkyl, heteroaryl, alkylamino, dialkylamino, alkylsulfano, keto, or other functionality.","Amino carbonyl (carbamoyl): A group of the formula —OCN(R)R′—, wherein R and R′ are independently of each other hydrogen or a lower alkyl group.","Asthma: Asthma is a disease of the respiratory system in which the airways constrict, become inflamed, and are lined with excessive amounts of mucus, often in response to one or more “triggers,” such as exposure to an environmental stimulant (or allergen), cold air, exercise, or emotional stress.","This airway narrowing causes symptoms such as wheezing, shortness of breath, chest tightness, and coughing.","The disorder is a chronic or recurring inflammatory condition in which the airways develop increased responsiveness to the various stimuli, characterized by bronchial hyper-responsiveness, inflammation, increased mucus production, and intermittent airway obstruction.","Carbamate: A group of the formula —OC(O)N(R)—, wherein R is H, or an aliphatic group, such as a lower alkyl group or an aralkyl group Cardiac Disorder or Disease: In general, a cardiac disorder/disease is a class of disorders/diseases that involve the heart and/or blood vessels (arteries and veins).","In a particular example, cardiac disorder/disease includes congestive heart failure.","Chronic Obstructive Pulmonary Disease: A group of respiratory tract diseases including chronic bronchitis, emphysema and bronchiectasis that are characterized by airflow obstruction or limitation that is not fully reversible.","The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.","Congestive Heart Failure: Heart failure in which the heart is unable to maintain an adequate circulation of blood in the bodily tissues or to pump out the venous blood returned to it by the veins.","Derivative: A chemical substance that differs from another chemical substance by one or more functional groups.","Preferably, a derivative (such as a fenoterol analogue) retains a biological activity (such as β2-adrenergic receptor stimulation) of a molecule from which it was derived (such as a fenoterol).","Isomers: Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”.","Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”.","Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers.” When a compound has an asymmetric center, for example, if a carbon atom is bonded to four different groups, a pair of enantiomers is possible.","An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (−) isomers, respectively).","A chiral compound can exist as either an individual enantiomer or as a mixture thereof.","A mixture containing equal proportions of the enantiomers is called a “racemic mixture.” The compounds described herein may possess one or more asymmetric centers; such compounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof.","Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof.","The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see, e.g., March, Advanced Organic Chemistry, 4th edition, New York: John Wiley and Sons, 1992, Chapter 4).","Optional: “Optional” or “optionally” means that the subsequently described event or circumstance can but need not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.","Pharmaceutically Acceptable Carriers: The pharmaceutically acceptable carriers (vehicles) useful in this disclosure are conventional.","Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 19th Edition (1995), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compounds or molecules, such as one or more nucleic acid molecules, proteins or antibodies that bind these proteins, and additional pharmaceutical agents.","In general, the nature of the carrier will depend on the particular mode of administration being employed.","For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle.","For solid compositions (for example, powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate.","In addition to biologically-neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.","Phenyl: Phenyl groups may be unsubstituted or substituted with one, two or three substituents, with substituent(s) independently selected from alkyl, heteroalkyl, aliphatic, heteroaliphatic, thioalkoxy, halo, haloalkyl (such as —CF3), nitro, cyano, —OR (where R is hydrogen or alkyl), —N(R)R′ (where R and R′ are independently of each other hydrogen or alkyl), —COOR (where R is hydrogen or alkyl) or —C(O)N(R′)R″ (where R′ and R″ are independently selected from hydrogen or alkyl).","Pulmonary Disorder or Disease: In general, pulmonary disorder/disease includes any disorder/disease pertaining to the lungs.","In a particular example, pulmonary disorder/disease includes asthma and chronic obstructive pulmonary disease.","Purified: The term “purified” does not require absolute purity; rather, it is intended as a relative term.","Thus, for example, a purified preparation is one in which a desired component such as an (R,R)-enantiomer of fenoterol is more enriched than it was in a preceding environment such as in a (±)-fenoterol mixture.","A desired component such as (R,R)-enantiomer of fenoterol is considered to be purified, for example, when at least about 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% of a sample by weight is composed of the desired component.","Purity of a compound may be determined, for example, by high performance liquid chromatography (HPLC) or other conventional methods.","In an example, the specific fenoterol analogue enantiomers are purified to represent greater than 90%, often greater than 95% of the other enantiomers present in a purified preparation.","In other cases, the purified preparation may be essentially homogeneous, wherein other stereoisomers are less than 1%.","Compounds described herein may be obtained in a purified form or purified by any of the means known in the art, including silica gel and/or alumina chromatography.","See, e.g., Introduction to Modern Liquid Chromatography, 2nd Edition, ed.","by Snyder and Kirkland, New York: John Wiley and Sons, 1979; and Thin Layer Chromatography, ed.","by Stahl, New York: Springer Verlag, 1969.In an example, a compound includes purified fenoterol or fenoterol analogue with a purity of at least about 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% of a sample by weight relative to other contaminants.","In a further example, a compound includes at least two purified stereoisomers each with a purity of at least about 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% of a sample by weight relative to other contaminants.","For instance, a compound can include a substantially purified (R,R)-fenoterol analogue and a substantially purified (R,S)-fenoterol analogue.","Subject: The term “subject” includes both human and veterinary subjects, for example, humans, non-human primates, dogs, cats, horses, rats, mice, and cows.","Similarly, the term mammal includes both human and non-human mammals.","Treating or treatment: With respect to disease, either term includes (1) preventing the disease, e.g., causing the clinical symptoms of the disease not to develop in a subject that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease, (2) inhibiting the disease, e.g., arresting the development of the disease or its clinical symptoms, or (3) relieving the disease, e.g., causing regression of the disease or its clinical symptoms.","Therapeutically Effective Amount: A quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent.","For example, this may be the amount of (R,R)-fenoterol or (R,R)- or (R,S)-fenoterol analogue useful in preventing, reducing, and/or inhibiting, and/or treating a cardiac disorder such as congestive heart failure.","Ideally, a therapeutically effective amount of an agent is an amount sufficient to prevent, reduce, and/or inhibit, and/or treat the disorder in a subject without causing a substantial cytotoxic effect in the subject.","The effective amount of an agent useful for preventing, reducing, and/or inhibiting, and/or treating a disorder in a subject will be dependent on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition.","III.","(R,R)-Fenoterol and Fenoterol Analogues A.","Chemical Structure Some exemplary fenoterol analogues disclosed herein have the formula: wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl, amino carbonyl or a combination thereof; R4 is H or lower alkyl; R5 is lower alkyl, wherein X and Y independently are selected from hydrogen, lower —OR6 and —NR7R8; R6 is lower alkyl or acyl; and R7 and R8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl.","With continued reference to the general formula for fenoterol analogues above, Y may be —OH In one embodiment, R5 is a 1- or 2-napthyl derivative optionally having 1, 2 or 3 substituents.","Examples of such R5 groups are represented by the formula wherein Y1, Y2 and Y3 independently are hydrogen, lower —OR6 and —NR7R8; R6 is independently for each occurrence selected from lower alkyl and acyl; and R7 and R8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl (carbamoyl).","In particular compounds at least one of Y1, Y2 and Y3 is —OCH3.Particular R5 groups include those represented by the formulas wherein R6 is lower alkyl, such as methyl, ethyl, propyl or isopropyl or acyl, such as acetyl.","Exemplary R5 groups include In one example, R4 is lower alkyl and R5 is wherein X and Y independently are selected from H, lower alkyl —OR6 and —NR7R8; R6 is lower alkyl; and R7 and R8 independently are hydrogen or lower alkyl.","In a further example, R4 is selected from ethyl, n-propyl, and isopropyl and R5 has the formula wherein X is H, —OR6 or —NR7R8.For example, R6 may be methyl or R7 and R8 are hydrogen.","In an additional example, R5 has the formula In further embodiments, R4 is selected from methyl, ethyl, n-propyl and isopropyl and R5 represents Examples of suitable groups for R1-R3 that can be cleaved in vivo to provide a hydroxy group include, without limitation, acyl, acyloxy and alkoxy carbonyl groups.","Compounds having such cleavable groups are referred to as “prodrugs.” The term “prodrug,” as used herein, means a compound which includes a substituent that is convertible in vivo (e.g., by hydrolysis) to a hydroxyl group.","Various forms of prodrugs are known in the art, for example, as discussed in Bundgaard, (ed.","), Design of Prodrugs, Elsevier (1985); Widder, et al.","(ed.","), Methods in Enzymology, Vol.","4, Academic Press (1985); Krogsgaard-Larsen, et al., (ed), Design and Application of Prodrugs, Textbook of Drug Design and Development, Chapter 5, 113 191 (1991); Bundgaard, et al., Journal of Drug Delivery Reviews, 8:1 38 (1992); Bundgaard, Pharmaceutical Sciences, 77:285 et seq.","(1988); and Higuchi and Stella (eds.)","Prodrugs as Novel Drug Delivery Systems, American Chemical Society (1975).","An exemplary (R,R)-compound has the chemical structure of: X and R1-R3 are as described above.","An additional exemplary (R,R)-compound has the chemical structure: An exemplary (R,S)-compound has the chemical structure: wherein X and R1-R3 are as described above.","An additional exemplary (R,S)-compound has the chemical structure: An exemplary (S,R)-compound has the chemical structure: wherein X and R1-R3 are as described above.","An exemplary (S,S)-compound has the chemical structure: wherein X and R1-R3 are as described above.","Examples of chemical structures illustrating the various stereoisomers of fenoterol are provided below.","Particular method embodiments contemplate the use of solvates (such as hydrates), pharmaceutically acceptable salts and/or different physical forms of (R,R)-fenoterol or any of the fenoterol analogues herein described.","1.Solvates, Salts and Physical Forms “Solvate” means a physical association of a compound with one or more solvent molecules.","This physical association involves varying degrees of ionic and covalent bonding, including by way of example covalent adducts and hydrogen bonded solvates.","In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid.","“Solvate” encompasses both solution-phase and isolable solvates.","Representative solvates include ethanol associated compound, methanol associated compounds, and the like.","“Hydrate” is a solvate wherein the solvent molecule(s) is/are H2O.","The disclosed compounds also encompass salts including, if several salt-forming groups are present, mixed salts and/or internal salts.","The salts are generally pharmaceutically-acceptable salts that are non-toxic.","Salts may be of any type (both organic and inorganic), such as fumarates, hydrobromides, hydrochlorides, sulfates and phosphates.","In an example, salts include non-metals (e.g., halogens) that form group VII in the periodic table of elements.","For example, compounds may be provided as a hydrobromide salt.","Additional examples of salt-forming groups include, but are not limited to, a carboxyl group, a phosphonic acid group or a boronic acid group, that can form salts with suitable bases.","These salts can include, for example, nontoxic metal cations which are derived from metals of groups IA, IB, IIA and IIB of the periodic table of the elements.","In one embodiment, alkali metal cations such as lithium, sodium or potassium ions, or alkaline earth metal cations such as magnesium or calcium ions can be used.","The salt can also be a zinc or an ammonium cation.","The salt can also be formed with suitable organic amines, such as unsubstituted or hydroxyl-substituted mono-, di- or tri-alkylamines, in particular mono-, di- or tri-alkylamines, or with quaternary ammonium compounds, for example with N-methyl-N-ethylamine, diethylamine, triethylamine, mono-, bis- or tris-(2-hydroxy-lower alkyl)amines, such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine or tris(hydroxymethyl)methylamine, N,N-di-lower alkyl-N-(hydroxy-lower alkyl)amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine, or N-methyl-D-glucamine, or quaternary ammonium compounds such as tetrabutylammonium salts.","Exemplary compounds disclosed herein possess at least one basic group that can form acid-base salts with inorganic acids.","Examples of basic groups include, but are not limited to, an amino group or imino group.","Examples of inorganic acids that can form salts with such basic groups include, but are not limited to, mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid.","Basic groups also can form salts with organic carboxylic acids, sulfonic acids, sulfo acids or phospho acids or N-substituted sulfamic acid, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid, and, in addition, with amino acids, for example with α-amino acids, and also with methanesulfonic acid, ethanesulfonic acid, 2-hydroxymethanesulfonic acid, ethane-1,2-disulfonic acid, benzenedisulfonic acid, 4-methylbenzenesulfonic acid, naphthalene-2-sulfonic acid, 2- or 3-phosphoglycerate, glucose-6-phosphate or N-cyclohexylsulfamic acid (with formation of the cyclamates) or with other acidic organic compounds, such as ascorbic acid.","In a currently preferred embodiment, fenoterol is provided as a hydrobromide salt and exemplary fenoterol analogues are provided as their fumarate salts.","Additional counterions for forming pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, 19th Edition, Mack Publishing Company, Easton, Pa., 1995.In one aspect, employing a pharmaceutically acceptable salt may also serve to adjust the osmotic pressure of a composition.","In certain embodiments the compounds used in the method are provided are polymorphous.","As such, the compounds can be provided in two or more physical forms, such as different crystal forms, crystalline, liquid crystalline or non-crystalline (amorphous) forms.","2.Use for the Manufacture of a Medicament Any of the above described compounds (e.g., (R,R)-fenoterol or fenoterol analogues or a hydrate or pharmaceutically acceptable salt thereof) or combinations thereof are intended for use in the manufacture of a medicament for β2-adrenergic receptor stimulation in a subject or for the treatment of pulmonary and cardiac disorders (e.g., asthma and congestive heart failure).","Formulations suitable for such medicaments, subjects who may benefit from same and other related features are described elsewhere herein.","B.","Methods of Synthesis The disclosed fenoterol analogues can be synthesized by any method known in the art.","Many general references providing commonly known chemical synthetic schemes and conditions useful for synthesizing the disclosed compounds are available (see, e.g., Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fifth Edition, Wiley-Interscience, 2001; or Vogel, A Textbook of Practical Organic Chemistry, Including Qualitative Organic Analysis, Fourth Edition, New York: Longman, 1978).","Compounds as described herein may be purified by any of the means known in the art, including chromatographic means, such as HPLC, preparative thin layer chromatography, flash column chromatography and ion exchange chromatography.","Any suitable stationary phase can be used, including normal and reversed phases as well as ionic resins.","Most typically the disclosed compounds are purified via open column chromatography or prep chromatography.","Suitable exemplary syntheses of fenoterol analogues are provided below: Scheme III describes an exemplary synthesis for the chiral building blocks used in Scheme II.","The (R)- and (S)-3′,5′-dibenzyloxyphenyl-bromohydrin enantiomers were obtained by the enantiospecific reduction of 3,5-dibenzyloxy-α-bromoacetophenone using boron-methyl sulfide complex (BH3SCH3) and either (1R,2S)- or (1S,2R)-cis-1-amino-2-indanol.","The required (R)- and (S)-2-benzylaminopropanes were prepared by enantioselective crystallization of the rac-2-benzylaminopropanes using either (R)- or (S)-mandelic acid as the counter ion.","IV.","Pharmaceutical Compositions The disclosed (R,R)-fenoterol and fenoterol analogues can be useful, at least, for the treatment of pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD) and cardiac disorders such as congestive heart failure.","Accordingly, pharmaceutical compositions comprising at least one disclosed fenoterol compound or analogue are also described herein.","Formulations for pharmaceutical compositions are well known in the art.","For example, Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 19th Edition, 1995, describes exemplary formulations (and components thereof) suitable for pharmaceutical delivery of (R,R)-fenoterol and disclosed fenoterol analogues.","Pharmaceutical compositions comprising at least one of these compounds can be formulated for use in human or veterinary medicine.","Particular formulations of a disclosed pharmaceutical composition may depend, for example, on the mode of administration (e.g., oral or parenteral) and/or on the disorder to be treated (e.g., pulmonary disorder or cardiac disorder such as congestive heart failure).","In some embodiments, formulations include a pharmaceutically acceptable carrier in addition to at least one active ingredient, such as a fenoterol compound.","Pharmaceutically acceptable carriers useful for the disclosed methods and compositions are conventional in the art.","The nature of a pharmaceutical carrier will depend on the particular mode of administration being employed.","For example, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle.","For solid compositions such as powder, pill, tablet, or capsule forms conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate.","In addition to biologically neutral carriers, pharmaceutical compositions to be administered can optionally contain minor amounts of non-toxic auxiliary substances or excipients, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like; for example, sodium acetate or sorbitan monolaurate.","Other non-limiting excipients include, nonionic solubilizers, such as cremophor, or proteins, such as human serum albumin or plasma preparations.","The disclosed pharmaceutical compositions may be formulated as a pharmaceutically acceptable salt.","Pharmaceutically acceptable salts are non-toxic salts of a free base form of a compound that possesses the desired pharmacological activity of the free base.","These salts may be derived from inorganic or organic acids.","Non-limiting examples of suitable inorganic acids are hydrochloric acid, nitric acid, hydrobromic acid, sulfuric acid, hydriodic acid, and phosphoric acid.","Non-limiting examples of suitable organic acids are acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, methyl sulfonic acid, salicylic acid, formic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, asparagic acid, aspartic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, and the like.","Lists of other suitable pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, 19th Edition, Mack Publishing Company, Easton, Pa., 1995.A pharmaceutically acceptable salt may also serve to adjust the osmotic pressure of the composition.","The dosage form of a disclosed pharmaceutical composition will be determined by the mode of administration chosen.","For example, in addition to injectable fluids, oral dosage forms may be employed.","Oral formulations may be liquid such as syrups, solutions or suspensions or solid such as powders, pills, tablets, or capsules.","Methods of preparing such dosage forms are known, or will be apparent, to those skilled in the art.","Certain embodiments of the pharmaceutical compositions comprising a disclosed compound may be formulated in unit dosage form suitable for individual administration of precise dosages.","The amount of active ingredient such as (R,R)-fenoterol administered will depend on the subject being treated, the severity of the disorder, and the manner of administration, and is known to those skilled in the art.","Within these bounds, the formulation to be administered will contain a quantity of the extracts or compounds disclosed herein in an amount effective to achieve the desired effect in the subject being treated.","In particular examples, for oral administration the compositions are provided in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.0 mg, about 2.5 mg, 5 mg, about 10 mg, or about 50 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.","In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg (such as about 2 mg to about 10 mg) active ingredient is administered two to four times a day, such as two times, three times or four times.","V. Methods of Use The present disclosure includes methods of treating disorders including pulmonary and cardiac disorders.","In some examples, the pulmonary disorder is asthma or chronic obstructive pulmonary disease.","In other examples, the cardiac disorder is congestive heart failure.","Disclosed methods includes administering (R,R)-fenoterol or a disclosed fenoterol analogue (and, optionally, one or more other pharmaceutical agents) to a subject in a pharmaceutically acceptable carrier and in an amount effective to treat the pulmonary and/or cardiac disorder.","Routes of administration useful in the disclosed methods include but are not limited to oral and parenteral routes, such as intravenous (iv), intraperitoneal (ip), rectal, topical, ophthalmic, nasal, and transdermal.","Formulations for these dosage forms are described above.","An effective amount of (R,R)-fenoterol or a disclosed fenoterol analogue will depend, at least, on the particular method of use, the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition.","A “therapeutically effective amount” of a composition is a quantity of a specified compound sufficient to achieve a desired effect in a subject being treated.","For example, this may be the amount of a (R,R)-fenoterol necessary to prevent, inhibit, reduce or relieve the pulmonary and/or cardiac disorder and/or one or more symptoms of disorder in a subject.","Ideally, a therapeutically effective amount of (R,R)-fenoterol or a disclosed fenoterol analogue is an amount sufficient to prevent, inhibit, reduce or relieve the pulmonary and/or cardiac disorder and/or one or more symptoms of the disorder without causing a substantial cytotoxic effect on host cells.","Therapeutically effective doses of a disclosed fenoterol compound or pharmaceutical composition can be determined by one of skill in the art, with a goal of achieving concentrations that are at least as high as the EC50 of the applicable compound disclosed in the examples herein.","An example of a dosage range is from about 0.001 to about 10 mg/kg body weight orally in single or divided doses.","In particular examples, a dosage range is from about 0.005 to about 5 mg/kg body weight orally in single or divided doses (assuming an average body weight of approximately 70 kg; values adjusted accordingly for persons weighing more or less than average).","For oral administration, the compositions are, for example, provided in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.5 mg, about 5 mg, about 10 mg, or about 50 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.","In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg active ingredient is administered two to four times a day, such as two times, three times or four times.","The specific dose level and frequency of dosage for any particular subject may be varied and will depend upon a variety of factors, including the activity of the specific compound, the metabolic stability and length of action of that compound, the age, body weight, general health, sex and diet of the subject, mode and time of administration, rate of excretion, drug combination, and severity of the condition of the subject undergoing therapy.","The subject matter of the present disclosure is further illustrated by the following non-limiting Examples.","EXAMPLES Example 1 Materials and Methods Reagents.","Phenylmethylsulfonyl fluoride (PMSF), benzamidine, leupeptin, pepstatin A, MgCl2, EDTA, Trizma-Hydrochloride (Tris-HCl), (±)-propranolol and minimal essential medium (MEM) were obtained from Sigma Aldrich (St. Louis, Mo.).","Egg phosphatidylcholine lipids (PC) were obtained from Avanti Polar Lipids (Alabaster, Ala.).","(±)-fenoterol was purchased from Sigma Aldrich and [3H]-(±)-fenoterol was acquired from Amersham Biosciences (Boston, Mass.).","The organic solvents n-hexane, 2-propanol and triethylamine were obtained as ultra pure HPLC grade solvents from Carlo Erba (Milan, Italy).","Fetal bovine serum and penicillin-streptomycin were purchased from Life Technologies (Gaithersburg, Md.","), and [125I]-(±)-iodocyanopindolol (ICYP) was purchased from NEN Life Science Products, Inc. (Boston, Mass.).","Preparation and Identification of (R,R)-Fenoterol and (S,S)-Fenoterol.","(R,R)-fenoterol and (S,S)-fenoterol were prepared from (±)-fenoterol using chiral HPLC techniques employing an HPLC column (25 cm×0.46 cm i.d.)","containing the amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase (CHIRALPAK® AD CSP, Chiral Technologies, West Chester, Pa.; CHIRALPAK is a registered trademark of Daicel Chemical Industries Ltd., Exton, Pa.).","The chromatographic system consisted of a JASCO® PU-980 solvent delivery system, and a JASCO® MD-910 multi-wavelength detector set at λ=230 nm, connected to a computer workstation; JASCO is a registered trademark of JASCO, Inc., Tokyo, Japan).","A Rheodyne model 7125 injector with 20 μl sample loop was used to inject 0.2-0.3 mg (±)-fenoterol onto the chromatographic system.","The mobile phase was n-hexane/2-propanol (88/12 v/v) with 0.1% triethylamine, the flow rate was 1 mL/minute and the temperature of the system was maintained at 25° C. using a column heater/chiller (Model 7955, Jones Chromatography Ltd., UK).","The separated (R,R)-fenoterol and (S,S)-fenoterol were collected in 10-mL fractions as the respective peaks eluted from the chromatographic column.","A 2-mL intermediate fraction was collected and discarded to improve the enantiomeric purity of the collected isomers.","The stereochemical configurations of the resolved (R,R)-fenoterol and (S,S)-fenoterol were established using circular dichroism (CD) measurements obtained with a JASCO® J-800 spectropolarimeter.","The (R,R)-fenoterol and (S,S)-fenoterol were dissolved in 2-propanol and the measurements were obtained using 1 cm path length at room temperature.","Immobilized β2-AR Frontal Chromatography.","The liquid chromatography column containing the immobilized β2-AR was prepared using a previously described technique (Beigi et al., Anal.","Chem., 76: 7187-7193, 2004).","In brief, cellular membranes were obtained from a HEK 293 cell line that had been transfected with cDNA encoding human β2-AR.","An aliquot of a cell pellet suspension corresponding to 5-7 mg total protein, as determined by the micro BCA method, was used to create the column.","The membranes were prepared in 10 mL buffer composed of Tris-HCl [50 mM, pH 7.4] containing MgCl2 (2 mM), benzamidine (1 mM), leupeptin (0.03 mM) pepstatin A (0.005 mM) and EDTA (1 mM).","A 180 mg aliquot of immobilized artificial membrane chromatographic support (IAM-PC, 12 micron particle size, 300 {acute over (Å)} pore size obtained from Regis Chemical Co., Morton Grove, Ill.) and 80 μM PC were added to the membrane preparation and the resulting mixture was stirred at room temperature for 3 hours, transferred into (5 cm length) nitrocellulose dialysis membrane (MW cutoff 10,000 Da, Pierce Chemical, Rockford, Ill.) and placed in 1 L of dialysis buffer composed of Tris-HCl [50 mM, pH 7.4] containing EDTA (1 mM), MgCl2 (2 mM), NaCl (300 mM) and PMSF (0.2 mM) at 4° C. for 24 hours.","The dialysis step was repeated twice using fresh buffer.","After dialysis, the mixture was centrifuged at 120×g for 3 minutes, the supernatant was discarded and the pellet of IAM support containing the immobilized receptor-bearing membranes was collected.","The pellet was resuspended in 2 mL chromatographic running buffer, composed of Tris-HCl [10 mM, pH 7.4] containing EDTA (1 mM) and MgCl2 (2 mM) and the suspension was pumped through a HR 5/2 chromatographic glass column (Amersham Pharmacia Biotech, Uppsala, Sweden) at a flow rate of 0.3 mL/minutes using a peristaltic pump.","The end adaptors were assembled producing a total gel-bed volume of 0.4 mL.","The column was stored at 4° C. when not in use.","The column containing the immobilized β2-AR stationary phase was placed in a chromatographic system composed of a HPLC pump (10-AD, Shimadzu Inc., Columbia, Md.","), a manually controlled FPLC injector (Amersham Biotechnology, Uppsala, Sweden) with a 50 μL sample loop, the packed immobilized receptor column and an on-line radioactive flow detector (IN/US, Tampa, Fla.), all connected sequentially.","In the frontal chromatographic studies, sample volumes of 5-7 mL were applied continuously until the elution profile showed a plateau region.","The running buffer was composed of Tris-HCl [10 mM, pH 7.4] containing EDTA (1 mM) and MgCl2 (2 mM) and 0.05 nM [3H]-(±)-fenoterol, the marker ligand.","(R,R)-fenoterol or (S,S)-fenoterol was added to the running buffer in sequential concentrations of 0.1, 80.0, 240, and 700 nM, and applied to the column.","The immobilized receptor column was equilibrated with about 80 mL of running buffer, without the added (R,R)-fenoterol or (S,S)-fenoterol respectively, in between each sample injection.","All chromatographic studies were carried out at room temperature at a flow rate of 0.2 mL/minutes.","The data were analyzed to determine the number of binding sites and dissociation constant using the non-linear equation (1), [ M ] ( Vi - V min ) = P [ M ] Kd + [ M ] ( Eq ."," 1 ) where Vi is the solute elution volume, Vmin is the elution volume at the saturation point, P is the number of available binding sites, M is the concentration of the marker ligand and Kd is the dissociation constant of the ligand.","Ligand-Displacement Binding.","Twenty-four hours after adenoviral infection with human β2-AR, HEK293 cells were harvested in lysis buffer, Tris-HCl [5 mM, pH 7.4] containing EGTA [5 mM], and homogenized with 15 strokes on ice.","Samples were centrifuged at 30,000×g for 15 minutes to pellet membranes.","Membranes were resuspended in binding buffer, Tris-HCl [20 mM, pH 7.4] containing NaCl (120 mM), KCl (5.4 mM), CaCl2 (1.8 mM), MgCl2 (0.8 mM), and glucose (5 mM) and stored in aliquots at −80° C. Binding assays were performed on 5-10 μg of membrane protein using saturating amounts (1-300 pM) of the β-AR-specific ligand [125I]cyanopindolol (ICYP).","For competition binding, the 5-10 μg of membrane protein were pretreated with 50 μM of GTPγs (non-hydrolyzable guanosine triphosphate) and then incubated with 125ICYP (50 pM) and different concentrations of fenoterol or its isomers in a total volume of 250 μL.","Nonspecific binding was determined in the presence of 20 μM propranolol.","Reactions were conducted in 250 μL of binding buffer at 37° C. for 1 hour.","The binding reaction was terminated by addition of ice-cold Tris-HCl [10 mM, pH 7.4] to the membrane suspension, followed by rapid vacuum filtration through glass-fiber filters (Whatman GF/C).","Each filter was washed three times with an additional 7 mL of ice-cold Tris-HCl [10 mM, pH 7.4].","The radioactivity of the wet filters was determined in a gamma counter.","All assays were performed in duplicate, and receptor density was normalized to milligrams of membrane protein.","Kd and the maximal number of binding sites (Bmax) for ICYP were determined by Scatchard analysis of saturation binding isotherms.","Data from competition studies were analyzed using 1- or 2-site competition binding curves with GRAPHPAD PRISM® Software (GRAPHPAD PRISM is a registered trademark of GraphPad Software, Inc., San Diego, Calif.).","Example 2 Purification and Identification of (R,R)-Fenoterol and (S,S)-Fenoterol This example demonstrates the resolution of (R,R)-fenoterol and (S,S)-fenoterol from (±)-fenoterol to a high degree of enantiomeric purity.","Using the chromatographic conditions described in Example 1, (±)-fenoterol was separated into its component enantiomers, (R,R)-fenoterol and (S,S)-fenoterol, on the AD-CSP.","As illustrated in FIG.","1, the two stereoisomers were resolved with enantioselectivity factor (α) of 1.21 and a resolution factor (RS) of 1.06.Because of the observed tailing of the chromatographic peaks, a 2-mL intermediate fraction was collected and discarded.","The collected peaks were analyzed using the same chromatographic conditions and the data demonstrated that both enantiomers had been prepared with >97% stereochemical purity.","The assignment of the absolute configuration of the isolated fractions was accomplished using their chiroptical properties.","The ultraviolet (UV) spectra of both fractions contained identical maxima at about 280 and 230, indicating the same UV chromophores for the two enantiomers.","The circular dichroism (CD) spectrum shows, for the less retained enantiomeric fraction, negative CD bands at about 280 and 215 nm, while the spectrum is positive at 230 and 200 nm.","The sign of the CD bands is reversed for the most retained fenoterol fraction, this confirming the enantiomeric nature of the two fractions.","The lowest energy UV and CD spectra of the two enantiomeric fractions are presented in FIGS.","2A and 2B, respectively.","The less retained chromatographic fraction showed a negative CD band at about 280 nm, while the CD spectrum of the most retained chromatographic fraction contained a positive CD band at the same wavelength (FIG.","2B).","These results indicate that each of the fractions contained one of the fenoterol enantiomers.","The sign of the lowest energy CD band can be used to assign the absolute configuration to the separated fenoterol enantiomers, by applying the Brewster-Buta/Smith-Fontana sector rule for chiral benzylic derivatives (Brewster and Buta, J.","Am.","Chem.","Soc., 88: 2233-2240, 1996).","This sector rule is used to predict the sign of the CD band related to the 1Lb electronic transition of the benzylic compounds, with either hydroxyl or amine moieties and has been primarily applied to conformationally mobile aromatic compounds containing a single stereogenic center.","In the case of fenoterol, there are two stereogenic centers.","However, it is believed that the observed optical activity is mainly determined by the arylcarbinol moiety, because of the distance between the aromatic ring and the stereogenic center.","The application of this rule permitted the assignment of the absolute configuration of (S,S) to the fenoterol enantiomer contained in the less retained fraction that showed a negative CD band at 280 nm, and the absolute configuration of (R,R) to the fenoterol enantiomer contained in the most retained fraction that showed a positive CD band at 280 nm.","This assignment was confirmed by the independent synthesis of (S,S)-fenoterol and (R,R)-fenoterol.","These studies indicate that (R,R)-fenoterol and (S,S)-fenoterol can be separated from (±)-fenoterol to a high degree of enantiomeric purity.","Example 3 Chromatographic Determination of the Binding of (R,R)-Fenoterol and (S,S)-Fenoterol to the Immobilized β2-AR This example demonstrates that (R,R)-fenoterol is responsible for the β2-AR binding of the clinically used drug (±)-fenoterol.","The preparation, characterization and application of a liquid chromatographic stationary phase containing immobilized membranes obtained from the β2-AR HEK-293 cell line have been previously reported (Beigi et al., Anal.","Chem., 76: 7187-7193, 2004).","For example, Beigi et al.","(Anal.","Chem., 76: 7187-7193, 2004) demonstrated that frontal displacement chromatography could be used to determine the dissociation constants (Kd) for the binding of two β2-AR antagonists, (S)-propranolol and CGP 12177A, to the immobilized β2-AR.","Zonal displacement chromatography using CGP 12177A as the marker ligand demonstrated that the immobilized β2-AR had retained its enantioselectivity as the addition of (S)-propranolol to the mobile phase produced a greater displacement than the addition of (R)-propranolol (Id.).","The addition of (±)-fenoterol to the mobile phase was also shown to produce a conformation change in the immobilized β2-AR (Id.).","Agonist-induced conformational changes of the β2-AR, as well as most G-protein coupled receptors, from a resting to active state have been documented (Ghanoui et al., Proc.","Natl.","Acad.","Sci.","U.S.A., 98: 5997-6002, 2001).","Presently, the immobilized β2-AR column was equilibrated with the running buffer containing the [3H]-fenoterol, the marker ligand, before the initiation of the displacement studies.","It was assumed that the binding data calculated using frontal displacement chromatography reflects the binding of (R,R)-fenoterol and (S,S)-fenoterol to the active state of the receptor.","In frontal chromatography, the initial flat portion of the chromatographic trace represents the binding of a marker ligand that is specific for the immobilized target, in this study the β2-AR, as well as non-specific binding to other sites on the immobilized membrane fragments.","Saturation of specific binding sites produces a breakthrough front followed by a plateau representing the establishment of a new equilibrium.","The addition of a second compound into the mobile phase will produce a shift of the chromatographic trace to the left if the compound competes with the marker for binding to the β2-AR.","The relationship between the magnitude of this shift and the concentration of the marker ligand can be used to calculate the binding affinity of the displacer for the target and the number of active binding sites.","This approach has been recently reviewed (Moaddel and Wainer, Anal.","Chem.","Acata, 546: 97-105, 2006).","As shown in FIG.","3 (curve 1), the addition of [3H]-fenoterol to the running buffer produced the expected frontal chromatography trace.","Sequential addition of increasing concentrations of (R,R)-fenoterol to the running buffer produced a corresponding shift in the chromatographic traces towards smaller retention volumes (FIG.","3, curves 2-4).","The magnitude and the shift and the corresponding concentrations of (R,R)-fenoterol were analyzed using Eqn 1 and the calculated dissociation constant, Kd, was 472 nM and the amount of available binding sites [P] was 176 pmoles per column, r2=0.9999 (n=2).","The sequential addition of increasing concentrations of (S,S)-fenoterol to the running buffer produced no corresponding shift in the chromatographic traces toward shorter retention times.","Thus, (S,S)-fenoterol had no significant affinity for the immobilized β2-AR.","In order to validate the chromatographic results, a standard membrane binding study was conducted using membranes obtained from the same HEK-293 cell line used to create the immobilized β2-AR column.","The data reflected the presence of a single binding site with (mean±SD) Kd=457±55 nM (n=4) for (R,R)-fenoterol and 109,000±10,400 nM (n=4) for (S,S)-fenoterol.","These data indicate that frontal affinity chromatography on immobilized cellular membrane columns can be used to determine the magnitude and enantioselectivity of ligand binding to the target receptor.","Further, the results from the frontal affinity chromatography and ligand competition binding studies both demonstrate that (R,R)-fenoterol is responsible for the β2-AR binding of the clinically used drug (±)-fenoterol.","Example 4 The Effect of (R,R)-Fenoterol and (S,S)-Fenoterol on Cardiomyocyte Contractility This example demonstrates that (R,R)-fenoterol and (S,S)-fenoterol differentially activate β2-adrenergic receptor/stimulatory heterotrimeric G protein (AR/Gs) signaling in regards to cell contractility.","To determine if (R,R)-fenoterol and (S,S)-fenoterol differentially activate β2-AR/Gs signaling in the regulation of cell contractility, freshly isolated adult rat cardiomyocytes were perfused with various concentrations of either (R,R)-fenoterol or (S,S)-fenoterol.","These studies were carried out using a previously described approach (Thou et al., Mol.","Pharmacol., 200, 58: 887-894).","In brief, single ventricular myocytes were isolated from 2-4 month old rat hearts by a standard enzymatic technique.","The isolated cells were resuspended in HEPES buffer solution [20 mM, pH 7.4] containing, NaCl (137 mM), KCl (5.4 mM), MgCl2 (1.2 mM), NaH2PO4 (1.0 mM), CaCl2 (1.0 mM), and glucose (20 mM).","All studies were performed within 8 hours of cell isolation.","The cells were placed on the stage of an inverted microscope (Zeiss model IM-35, Zeiss, Thornwood, N.Y.), perfused with the HEPES-buffered solution at a flow rate of 1.8 mL/minutes, and electrically stimulated at 0.5 Hz at 23° C. Cell length was monitored by an optical edge-tracking method using a photodiode array (Model 1024 SAQ, Reticon, Boston, Mass.)","with a 3 ms time resolution.","Cell contraction was measured by the percent shortening of cell length following electrical stimulation.","The addition of (R,R)-fenoterol (10−8 to 10−5 M) produced a markedly elevated positive inotropic effect and a significant upward shift of the dose-response curve compared to (±)-fenoterol (FIG.","4A).","This was demonstrated by an increase in the maximum contractile response from 265±11.6% to 306±11.8% resting cell length (p<0.05) and a reduction in EC50 from −7.0±0.2 to −7.1±0.2 log [M](p<0.05).","In contrast, (S,S)-fenoterol had only a minor positive inotropic effect (FIG.","4B).","The cardiomyocyte contractility studies indicate that (R,R)-fenoterol is responsible for the observed β2-AR agonist activity in cardiomyocytes.","Example 5 Synthesis General Procedures: All reactions were carried out using commercial grade reagents and solvents.","Tetrahydrofuran (THF) was dried by refluxing over sodium and benzophenone.","Dichloromethane was dried by refluxing over calcium hydride.","Ultraviolet spectra were recorded on a Cary 50 Concentration spectrophotometer.","Optical rotations were done on a Rudolph Research Autopol IV.","NMR Spectra were recorded on a Varian Mercury VMX 300-MHz spectrophotometer using tetramethylsilane as the internal standard.","NMR multiplicities were reported by using the following abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; p, pentet; m, multiplet; apt., apparent; and br, broad.","Low resolution mass spectra were obtained on a Finnigan LCQDuo LC MS/MS atmospheric pressure chemical ionization (API) quadrupole ion trap MS system equipped with both electrospray (ESI) and atmospheric pressure chemical ionization (APCI) probes.","Analytical HPLC data was obtained using a Waters 2690 Separations Module with PDA detection.","Method (a): ThermoHypersil BDS 100×4.6 mm C18 column, H2O/CH3CN/TFA.","Method (b): Brownlee Phenyl Spheri-5 100×4.6 mm, water/acetonitrile/TFA.","Method (c): Vydac 150×4 mm C18 column, H2O/isopropanol/TFA.","Method (d): CHIRALPAK® AD-H 250×10 mm, 95/5/0.05 CH3CN/isopropanol/diethylamine.","Merck silica gel (230-400 mesh) was used for open column chromatography.","3′,5′-Dibenzyloxy-α-bromoacetophenone (46).","A solution of 2.4 mL (46 mmol) of Br2 in 45 mL of CHCl3 was added dropwise over 1 h to a chilled, stirring solution of 9.66 g (29 mmol) of 3′,5′-dibenzyloxyacetophenone (45) in 40 mL of CHCl3.The resulting solution was allowed to warm to room temperature over 1 hour with good stirring, then poured into 100 mL of cold H2O and transferred to a separatory funnel where the CHCl3 fraction was isolated, washed with brine solution, dried (Na2SO4), filtered, and concentrated to 10.8 g. This material was applied to 500 g of silica gel, eluting with CHCl3 to obtain 2.65 g (22%) of compound 46 as a white solid.","1H NMR (CDCl3) δ 4.39 (s, 2H), 5.08 (s, 4H), 6.85 (t, 1H, J=2.1 Hz), 7.20 (d, 2H, J=2.4 Hz), 7.31-7.44 (m, 10H).","General Procedure for the Enantioselective Reduction of Compound 46 to 3′,5′-Dibenzyloxyphenylbromohydrins [(R)-8, (S)-/3].","Under argon atmosphere, 0.06 mL (0.316 mmol, 10 mol %) of 5.0 M boron-methyl sulfide complex (BH3SCH3) in diethyl ether was added in one portion to a solution of 25 mg (0.16 mmol, 5 mol %) of the appropriate cis-1-amino-2-indanol in 3 mL of dry THF.","This material under argon was added over 30 minutes to a solution of 1.3 g (3.16 mmol) of 3′,5′-dibenzyloxy-α-bromoacetophenone in 20 mL of dry THF, while at the same time adding in ˜0.05 mL pulses, 0.45 mL of 5.0 M boron-methyl sulfide complex.","The resulting solution was stirred under argon for 2 hours, and then quenched with 3 mL of methanol, controlling gas evolution.","Solvents were removed in vacuo and the resulting residue taken up in 30 mL of CHCl3 and washed with 25 mL of 0.2 M sulfuric acid followed by 20 mL of brine, then dried (Na2SO4), filtered, and evaporated.","(R)-(−)-3′,5′-Dibenzyloxyphenylbromohydrin [(R)-8].","Prepared with (1R,2D)-(+)-cis-1-amino-2-indanol as the enantioselective reduction catalyst to give 1.02 g (78%) of (R)-8 as a fine white powder.","1H NMR (CDCl3) δ 3.44 (dd, 1H, J=9.0, 10.5 Hz), 3.55 (dd, 1H, J=3.3, 10.5 Hz), 4.79 (dd, 1H, J=3.3, 8.7 Hz), 4.97 (s, 4H), 6.51 (t, 1H, J=2.4 Hz), 6.57 (d, 2H, J=1.8 Hz), 7.21-7.38 (m, 10H); [α]D=−12.1° (c=1.0 MeOH).","(S)-(+)-3′,5′-Dibenzyloxyphenylbromohydrin [(S)-8].","Prepared with (1S,2R)-(−)-cis-1-amino-2-indanol as the enantioselective reduction catalyst to give 1.07 g (82%) of (S)-8 as a fine white powder.","1H NMR (CDCl3) δ 3.43 (dd, 1H, J=9.0, 10.5 Hz), 3.55 (dd, 1H, J=3.3, 10.5 Hz), 4.78 (dd, 1H, J=3.3, 8.7 Hz), 4.96 (s, 4H), 6.50 (t, 1H, J=2.4 Hz), 6.57 (d, 2H, J=1.8 Hz), 7.21-7.39 (m, 10H); [α]D=+11.8° (c=0.90 MeOH).","4-Benzyloxyphenylacetone (34).","To 10.0 g (41.3 mmol) of 4-benzyloxyphenylacetic acid (31) was added, 20 mL of acetic anhydride and 20 mL of pyridine, which was heated to reflux with stirring under argon atmosphere for 6 hours.","Solvents were evaporated and residue dissolved in CHCl3 (50 mL) and washed with 1N NaOH (2×50 mL).","Dried organic layer (MgSO4), filtered, and evaporated to 11.8 g of an amber oil.","Vacuum distillation at 0.1 mm Hg in an oil-bath set to 170° C. followed by silica gel chromatography eluting with 8/2 CH2Cl2-hexanes gave 2.68 g (27%).","1H NMR (CDCl3) δ 2.14 (s, 3H), 3.63 (s, 2H), 5.05 (s, 2H), 6.94 (d, 2H, J=8.7 Hz), 7.10 (d, 2H, J=8.7 Hz), 7.26-7.47 (m, 5H).","Phenylacetone (35).","A solution of 20.4 g (0.15 mol) of phenylacetic acid, acetic anhydride (70 mL) and pyridine (70 mL) was heated to reflux with stirring under argon atmosphere for 6 hours.","Solvents were evaporated and residue dissolved in CHCl3 (100 mL), washed with 1N NaOH (2×100 mL) and dried the organic layer (MgSO4), filtered, and evaporated to give 20.4 g. Vacuum distillation at 0.1 mm Hg in an oil bath set to 160° C., followed by silica gel chromatography eluting with 1/1 hexanes/CH2Cl2 gave 5.5 g (27%).","1H (CDCl3) δ 2.15 (s, 3H), 3.70 (s, 2H), 7.20-7.36 (m, 5H).","1-Naphthalen-1-yl-propan-2-one (36).","A solution of 37.2 g (20 mmol) of naphthoic acid (33), acetic anhydride (100 mL) and pyridine (100 mL) was heated to reflux with stirring under argon atmosphere for 6 hours.","Evaporated solvents, dissolved residue in CHCl3 (200 mL) and washed with 1N NaOH (2×150 mL), dried organic layer (MgSO4), filtered, and evaporated to give 34.6 g. Distillation at 0.5 mm Hg in an oil bath set to 170° C., followed silica gel chromatography eluting with 1/1 hexanes/CH2Cl2 gave 9.7 g (26%).","1H (CDCl3) δ 2.11 (s, 3H), 4.12 (s, 2H), 7.40-7.53 (m, 4H), 7.81 (d, 1H, J=8.4 Hz), 7.87-7.90 (m, 2H).","General Procedure for Preparation of 2-benzylaminopropanes (37-39, 42, 43).","To the appropriate ketone (1 eq) in CH2Cl2 (c=0.5 M), cooled to 0° C. was added glacial HOAc (1 eq), followed by benzylamine (1 eq) and NaBH(AcO)3 (1.4 eq).","The reaction mixture was warmed to room temperature and stirred under argon for 20 hours.","The reaction mixture was cooled (ice bath), 10% NaOH (5 eq) was added dropwise and then extracted into CH2Cl2, washed with brine.","The product was then dried (Na2SO4), filtered and evaporated.","1-(4-benzyloxy)-2-benzylaminopropane (37).","Prepared from 4-benzyloxyphenylacetone (34; 2.0 g, 8.3 mmol) to afford 2.61 g (95%) as a tan solid.","1H (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.50-2.58 (m, 1H).","2.68-2.77 (m, 1H), 2.82-2.89 (m, 1H), 3.75 (dd, 2H, J=12 Hz, J=30 Hz), 5.05 (s, 2H), 6.90 (d, 2H, J=8.7 Hz), 7.04 (d, 2H, J=8.7 Hz), 7.17-7.42 (m, 10H); MS (APCI+) m/z (rel): 332 (100).","1-Phenyl-2-benzylaminopropane (38).","Prepared from phenylacetone (35; 5.5 g, 41 mmol) to afford 8.4 g (91%) as a tan solid.","1H (CDCl3) δ 1.09 (d, 3H, J=6.3 Hz), 2.61-2.81 (m, 2H), 2.92 (m, 1H), 3.80 (dd, 2H), 7.14-7.30 (m, 10H); MS (APCI+) m/z (rel): 226 (100).","1-(1′-Naphthyl)-2-benzylaminopropane (39).","Prepared from 1-naphthalen-1-yl-propan-2-one (36; 5.0 g, 27.1 mmol) to afford 7.0 g (94%) as a tan solid.","1H (CDCl3) δ 1.14 (d, 3H, J=6.0 Hz), 3.02-3.18 (m, 2H), 3.27 (m, 1H), 3.80 (dd, 2H, J=13.2, 43.8 Hz), 7.13-7.23 (m, 5H), 7.31-7.48 (m, 4H), 7.73 (d, 1H, J=7.8 Hz), 7.83-7.86 (m, 1H), 7.96-7.99 (m, 1H); MS (APCI+) m/z (rel): 276 (100).","1-(4′-Methoxyphenyl)-2-benzylaminopropane (42).","Prepared from 4-methoxyphenyl-acetone (40; 2.75 g, 13.1 mmol) to afford 2.31 g (97%).","1H (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.56-2.75 (m, 2H), 2.90 (m, 1H), 3.79 (s, 1H), 3.79 (m, 2H, J=13.2 Hz), 6.82 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.7 Hz), 7.18-7.32 (m, 5H); MS (APCI+) m/z (rel): 256 (100).","1-(4′-nitrophenyl)-2-benzylaminopropane (43).","Prepared from 4-nitrophenyl-acetone (41; 4.95 g, 28 mmol) to afford 7.32 g (98%) as an amber oil.","1H (CDCl3) δ 1.60 (d, 3H, J=6.3 Hz), 2.73-2.85 (m, 1H), 3.00-3.12 (m, 2H), 3.86 (dd, 2H, J=26 Hz, J=60 Hz), 7.23-7.40 (m, 5H), 7.30 (d, 2H, J=9.0 Hz), 8.14 (d, 2H, J=8.7 Hz).","MS (APCI+) m/z (rel): 271 (100).","General Procedure for Enantiomeric Separation of 2-benzylaminopropanes [(R)-10-14, (S)-10-14].","The appropriate racemic 2-benzylaminopropane (1 eq) was combined with the appropriate optically active mandelic acid (1 eq) in methanol (c=0.5 M) and refluxed until the solution homogenized, then cooled to RT.","The crystals were filtered, collected, and recrystallized twice from methanol (c=0.3 M) to afford the optically active 2-benzylaminopropane.mandelic acid salt.","The salts were converted to the free amine for the purpose of collecting NMR and rotation data by partitioning the mandelic acid salt between 10% K2CO3 and CHCl3, drying organic extracts (Na2SO4) and evaporating.","(R)-(−)-1-(4′-benzyloxy)-2-benzylaminopropane [(R)-10].","A sample of 2.13 g (6.42 mmol) of 1-(4-benzyloxy)-2-benzylaminopropane (37) was reacted with 972 mg (6.42 mmol) of (R)-(−)-mandelic acid to give 295 mg (28% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.12 (d, 3H, J=6.3 Hz), 2.58-2.78 (m, 2H), 2.82-2.91 (m, 1H), 3.75 (dd, 2H, J=12 Hz, J=30 Hz)), 5.07 (s, 2H), 6.93 (d, 2H, J=8.7 Hz), 7.10 (d, 2H, J=8.7 Hz), 7.21-7.42 (m, 10H); MS (APCI+) m/z (rel): 332 (100); [α]D=−19.1° (c=1.4, MeOH).","(S)-(+)-1-(4′-benzyloxy)-2-benzylaminopropane [(S)-10].","The washes from the separation of (R)-10 were concentrated and partitioned between 50 mL of chloroform and 50 mL of 10% K2CO3 in water.","Washed organics with brine, dried (Na2SO4), filtered and evaporated to 1.70 g (5.1 mmol).","The organics were brought to reflux with 782 mg (5.1 mmol) of (S)-(+)-mandelic acid (as previously described) and crystallized 3 times to obtain 670 mg of the (S)-amine.","(S)-mandelic acid salt.","The (S)-amine.","(S)-mandelic acid salt was triturated in ether then partitioned between 30 mL of chloroform and 20 mL of 10% K2CO3 in water.","The organic partition was washed with brine, then dried (Na2SO4), filtered and evaporated to give 366 mg of the free amine (33% based on enantiomeric abundance).","1H NMR (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.58-2.78 (m, 2H), 2.82-2.91 (m, 1H), 3.76 (dd, 2H, J=12, 30 Hz), 5.06 (s, 2H), 6.93 (d, 2H, J=8.7 Hz), 7.09 (d, 2H, J=8.7 Hz), 7.21-7.42 (m, 10H); MS (APCI+) m/z (rel): 332 (100); [α]D=+19.2° (c=1.5 MeOH).","(R)-(−)-1-(4′-Methoxyphenyl)-2-benzylaminopropane [(R)-11].","A sample of 3.02 g (11.8 mmol) of 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 1.8 g (11.8 mmol) (S)-(+)-mandelic acid to give 530 mg (35% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.57-2.76 (m, 2H), 2.88-2.94 (m, 1H), 3.79 (s, 3H), 3.72-3.88 (m, 2H), 6.82 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.15-7.31 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=−30.4° (c=1.25 MeOH).","(S)-(+)-1-(4′-Methoxyphenyl)-2-benzylaminopropane [(S)-11].","A sample of 3.36 g (13.2 mmol) of the racemate 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 2.0 g (13.2 mmol) of (R)-(−)-mandelic acid to give 740 mg (44% based on enantiomeric abundance) of the free amine after workup.","1H NMR, (CDCl3) δ 1.10 (d, 3H, J=6.2 Hz), 2.55-2.76 (m, 2H), 2.88-2.95 (m, 1H), 3.73-3.88 (m, 2H), 3.79 (s, 3H), 6.80 (d, 2H, J=8.7 Hz), 7.08 (d, 2H, J=8.4 Hz), 7.15-7.30 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=+30.5° (c=1.1 MeOH).","(R)-(−)-1-(4′-nitrophenyl)-2-benzylaminopropane [(R)-12].","A sample of 2.0 g (7.3 mmol) of 1-(4′-nitrophenyl)-2-benzylaminopropane (43) was reacted with 1.13 g (7.3 mmol) of (S)-(+)-mandelic acid to give 486 mg (49% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.60 (d, 3H, J=6.3 Hz), 2.73-2.85 (m, 1H), 3.00-3.12 (m, 2H), 3.86 (dd, 2H, J=26 Hz, J=60 Hz), 7.23-7.40 (m, 5H), 7.30 (d, 2H, J=9.0 Hz), 8.14 (d, 2H, J=8.7 Hz); MS (APCI+) m/z (rel): 271 (100); [α]D=−9.3° (c=1.0 MeOH).","(S)-(+)-1-(4′-nitrophenyl)-2-benzylaminopropane [(S)-12].","A sample of 2.0 g (7.3 mmol) of 1-(4′-nitrophenyl)-2-benzylaminopropane (43) was reacted with 1.13 g (7.3 mmol) of (R)-(−)-mandelic acid to give 640 mg (65% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.60 (d, 3H, J=6.3 Hz), 2.73-2.85 (m, 1H), 3.00-3.12 (m, 2H), 3.86 (dd, 2H, J=26, 60 Hz), 7.23-7.40 (m, 5H), 7.30 (d, 2H, J=9.0 Hz), 8.14 (d, 2H, J=8.7 Hz); MS (APCI+) m/z (rel): 271 (100); [α]D=+8.2° (c=1.0 MeOH).","(R)-(−)-1-Phenyl-2-benzylaminopropane [(R)-13].","A sample of 2.62 g (11.6 mmol) of 1-phenyl-2-benzylaminopropane (38) was reacted with 1.77 g (11.6 mmol) of (S)-(+)-mandelic acid to give 747 mg (57% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.13 (d, 3H, J=6.0 Hz), 2.62-2.84 (m, 2H), 2.92-2.99 (m, 1H), 3.81 (dd, 2H, J=13.2, 34.5 Hz) 7.14-7.29 (m, 10H); MS (APCI+) m/z (rel): 226 (100); [α]D=−24.5° (c=1.10 MeOH).","(S)-(+)-1-Phenyl-2-benzylaminopropane [(S)-13].","A sample of 5.0 g (22.2 mmol) of racemic 1-phenyl-2-benzylaminopropane (38) was reacted with 3.4 g (22.2 mmol) of (R)-(−)-mandelic acid to give 2.15 g (86% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.11 (d, 3H, J=6.0 Hz), 2.62-2.84 (m, 2H), 2.92-2.99 (m, 1H), 3.81 (dd, 2H, J=13.2, 34.5 Hz), 7.14-7.29 (m, 5H); MS (APCI+) m/z (rel): 226 (100); [α]D=+18.2° (c=0.85 MeOH).","(R)-(−)-1-(1′-Naphthyl)-2-benzylaminopropane [(R)-14].","The washes recovered from the separation of (S)-14 were concentrated and partitioned between 40 mL of choroform and 40 mL of 10% K2CO3 in water.","The organic partition was washed with 20 mL of brine then dried (Na2SO4) to afford 1.16 g (4.2 mmol) of the free amine, which was reacted with 640 mg (4.2 mmol) of (S)-(+)-mandelic acid.","588 mg (46% based on enantiomeric abundance) of the free amine was obtained.","1H NMR (CDCl3) δ 1.07 (d, 3H, J=6.0 Hz), 3.02-3.18 (m, 2H), 3.27 (m, 1H), 3.74 (dd, 2H, J=13.2, 30.9 Hz), 7.13-7.23 (m, 5H), 7.31-7.48 (m, 4H), 7.73 (d, 1H, J=7.8 Hz), 7.83-7.86 (m, 1H), 7.96-7.99 (m, 1H); MS (APCI+) m/z (rel): 276 (100); [α]D=−5.8° (c=1.0 MeOH).","(S)-(+)-1-(1′-Naphthyl)-2-benzylaminopropane [(S)-14].","A sample of 2.6 g (9.4 mmol) of 1-(1′-naphthyl)-2-benzylaminopropane (39) was reacted with 1.44 g (9.4 mmol) of (R)-(−)-mandelic acid to give 420 mg (21% based on enantiomeric abundance) of the free amine after workup.","1H NMR (CDCl3) δ 1.07 (d, 3H, J=6.0 Hz), 3.02-3.18 (m, 2H), 3.27 (m, 1H), 3.74 (dd, 2H, J=13.2, 30.9 Hz), 7.13-7.23 (m, 5H), 7.31-7.48 (m, 4H), 7.73 (d, 1H, J=7.8 Hz), 7.83-7.86 (m, 1H), 7.96-7.99 (m, 1H); MS (APCI+) m/z (rel): 276 (100); [α]D=+6.3° (c=1.0 MeOH).","(R)-(−)-2-Benzylaminoheptane [(R)-15].","A sample of 0.65 mL (4.4 mmol) of (R)-(−)-2-aminoheptane (R-44) 0.44 mL (4.4 mmol) of benzaldehyde and 0.1 mL of HOAc were combined in 40 mL of CH2Cl2 and then cooled to 0° C. To the reaction mixture was added 2.75 mg (13 mmol) of sodium triacetoxyborohydride in one portion, which was stirred under argon at room temperature for 28 hours.","The reaction mixture was diluted with 30 mL of CH2Cl2, cooled in an ice bath and 80 mL of 5% NaOH (in water) was added.","Fractions were separated, organics (Na2SO4) dried and evaporated to 638 mg (71%) of (R)-15.1H NMR (CDCl3) δ 0.88 (m, 3H), 1.08 (d, 3H J=6.6 Hz), 1.20-1.39 (m, 6H), 1.41-1.67 (m, 2H), 3.62-3.77 (m, 1H), 3.75 (p, 2H, J=12 Hz), 7.17-7.41 (m, 5H); MS (APCI+) m/z (rel): 206 (100); [α]D=+6.9° (c=1.0, MeOH).","(S)-(+)-2-Benzylaminoheptane [(S)-15].","A sample of 0.15 mL (1 mmol) of (S)-(+)-2-aminoheptane ((S)-44) 0.1 mL (1 mmol) of benzaldehyde and 0.1 mL of HOAc were combined in 10 mL of CH2Cl2 and cooled to 0° C., then added 650 mg (3 mmol) of sodium triacetoxyborohydride in one portion.","The reaction mixture was stirred under argon at room temperature for 28 hours.","The mixture was diluted with 10 mL of dichloromethane, cooled in an ice bath and 20 mL of 5% NaOH (in water) was added.","Fractions were separated, organics were dried (Na2SO4) and evaporated to 154 mg (70%).","1H NMR (CDCl3) δ 0.88 (m, 3H), 1.08 (d, 3H J=6.6 Hz), 1.19-1.37 (m, 6H), 1.41-1.67 (m, 2H), 3.62-3.77 (m, 1H), 3.75 (p, 2H, J=12 Hz), 7.17-7.41 (m, 5H); MS (APCI+) m/z (rel): 206 (100); [α]D=+7.8° (c=1.0, MeOH).","Preparation of Fenoterol Analogs, Procedure A.","To form the epoxide, the appropriate 3′,5′-dibenzyloxyphenylbromohydrin ((R)-8) or (S)-8 (1 eq) was combined with K2CO3 (1.4 eq) in 1:1 THF/MeOH (c=0.3 M) and stirred for 2 hours under argon at room temperature.","The solvent was removed and the residue partitioned between toluene and H2O.","The toluene fraction was isolated, dried (Na2SO4), filtered, and evaporated.","The residue was dissolved with the appropriate free benzylamine (R)- or (S)-10-15, 28 (0.95 eq) in a good amount of toluene and evaporated again under high vacuum to remove trace H2O.","The resulting colorless residue was heated to 120° C. under argon for 20 hours, cooled and checked by 1H NMR and mass spectrometry to confirm coupling.","The residue was dissolved in EtOH (c=0.07 M) with heat and transferred to a Parr flask, where it was hydrogenated at 50 psi of hydrogen over 10% (wt) Pd/C (10 mg cat/65 mg bromohydrin) for 24 hours.","Complete debenzylation was confirmed by mass spectrometry.","The mixture was filtered through Celite, the filter cake rinsed with isopropanol, and the filtrate concentrated.","The residue was dissolved in 1:1 isopropanol/EtOH (c=0.2 M) and brought to reflux for 30 minutes with 0.5 eq of fumaric acid.","The reaction was cooled and the solvent removed.","The crude material was purified by open column chromatograph or preparative chromatograph.","Column Separation of (R,R)-1 and (S,S)-1, Procedure B.","A sample of 75 mg of fenoterol HBr was dissolved in 1.5 mL of 95/5/0.05 CH3CN/isopropanol/HNEt2 and applied in 100 μL injections to a CHIRALPAK® AD-H 10×250 mm 5 μm semi-preparative column using a waters 2690 Separations Module, PDA set to 280 nm.","The eluting solvent was 95/5/0.05 CH3CN/isopropanol/HNEt2, 5 mL/min.","Retention times for (S,S) and (R,R) isomers were 4.8 min and 7.8 min, respectively.","(R,R)-(−)-Fenoterol [(R,R)-1].","Obtained according to Procedure B to give 40 mg collected after evaporation.","1H NMR (CD3OD) δ 1.05 (d, 3H, J=6.3 Hz), 2.49 (q, 1H, J=6.9 Hz), 2.62-2.74 (m, 2H), 2.80-2.91 (m, 2H), 4.55 (dd, 1H, J=5.1, J=3.3 Hz), 6.16 (t, 1H, J=2.4 Hz), 6.27 (d, 2H, J=2.1 Hz), 6.68 (d, 2H, J=8.4 Hz), 6.94 (d, 2H, J=8.4 Hz); 13C NMR (CD3CN) δ 20.3, 43.2, 55.1, 55.2, 72.4, 102.2, 105.4, 116.0, 131.3, 131.8, 147.4, 156.2, 159.0; UV (MeOH) λmax 279 nm (ε 2,760), 225 (12,900), 204 (32,600); MS (APCI+) m/z (rel): 304 (100, M+H); [α]D=−29.0° (conc=0.2% MeOH); HPLC: (a) 0.1% diethylamine in H2O, 0.50 mL/min, 254 nm, tR 2.90 min, 99% pure; (d) tR 7.8 min, >99% pure.","(S,S)-(+)-Fenoterol [(S,S)-1].","Obtained according to Procedure B to give 35 mg after evaporation.","1H NMR (CD3OD) δ 1.05 (d, 3H, J=6.6 Hz), 2.49 (q, 1H, J=7.2 Hz), 2.62-2.76 (m, 2H), 2.80-2.94 (m, 2H), 4.55 (dd, 1H, J=4.8, J=3.3 Hz), 6.16 (t, 1H, J=2.1 Hz), 6.27 (d, 2H, J=2.4 Hz), 6.68 (d, 2H, J=8.4 Hz), 6.94 (d, 2H, J=8.4 Hz); 13C (CD3CN) δ 20.3, 43.2, 55.0, 55.2, 72.4, 102.2, 105.4, 116.0, 131.3, 131.8, 147.4, 156.2, 159.0; UV (MeOH) λmax 279 nm (ε 2,680), 224 (12,700), 204 (32,800); MS (APCI+) m/z (rel): 304 (100, M+H); [α]D=+28.5° (conc=0.20% MeOH); HPLC: (a) 0.1% diethylamine in H2O, 0.50 mL/min, 254 nm, tR 2.72 min, >99% pure; (d) tR 4.8 min, >99% pure.","(R,S)-(−)-Fenoterol Fumarate [(R,S)-1].","Prepared from (R)-8 and (S)-10 according to Procedure A to give 168 mg (64%).","1H NMR (CD3OD) δ 1.22 (d, 3H, J=6.6 Hz), 2.64 (dd, 1H, J=9.9 Hz, J=13.2 Hz), 3.01-3.51 (m, 4H), 4.79 (dd, 1H, J=3.0 Hz, J=9.9 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.1 Hz), 6.75 (s, 1H), 6.76 (d, 2H, J=8.4 Hz), 7.05 (d, 2H, J=8.1 Hz); 13C NMR (CD3OD) δ 16.2, 39.1, 52.5, 57.4, 70.4, 103.4, 105.3, 116.7, 127.8, 131.4, 135.2, 144.6, 157.7, 160.0, 168.2; UV (MeOH) λmax 278 nm (ε 2,520), 205 (27,900); MS (ESI+) m/z (rel): 304 (100, M+H); [α]D=−7.5° (cone=0.75% MeOH); HPLC: (a) 70/30/0.05.1.00 mL/min, 282 nm, tR 1.35 min, >99% pure; (b) 50/50/0.05.1.0 ml, 0.50 mL/min, 254 nm, tR 2.72 min, >99% pure; (d) tR 4.8 min, 1.00 mL/min, 280 nm, tR 2.10 min, 97.5% pure.","(S,R)-(+)-Fenoterol Fumarate [(S,R)-1].","Prepared from (S)-8 and (R)-10 according to Procedure A to give 104 mg (39%).","1H NMR (CD3OD) δ 1.22 (d, 3H, J=6.6 Hz), 2.64 (dd, 1H, J=9.9 Hz, J=13.5 Hz), 3.47-3.04 (m, 4H), 4.80 (dd, 1H, J=2.7, J=9.6 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.1 Hz), 6.75 (s, 1H), 6.76 (d, 2H, J=8.4 Hz), 7.05 (d, 2H, J=8.4 Hz); 13C NMR (CD3OD) δ 16.2, 39.1, 52.5, 57.4, 70.4, 103.4, 105.3, 116.7, 127.8, 131.4, 135.2, 144.6, 157.7, 159.9, 168.2; UV (MeOH) λmax 278 nm (ε 2,640), 202 (36,600); MS (ESI+) m/z (rel): 304 (100, M+H), 413 (10); [α]D=+6.4° (conc=0.50% MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 282 nm, tR 1.35 min, 95.9% pure; (b) 50/50/0.05, 1.0 mL/min, 280 nm, tR 2.06 min, 99% pure.","(R,R)-(−)-1-p-Methoxyphenyl-2-(β-3′,5′-dihydroxy-phenyl-β-oxy)ethylamino-propane Fumarate [(R,R)-2].","Prepared from (R)-8 and (R)-11 according to Procedure A to give 172 mg (38%).","1H NMR (CD3OD) δ 1.08 (d, 3H, J=6.3 Hz), 3.05-2.56 (m, 5H), 4.57 (dd.","1H, J=8.4, 5.4 Hz), 6.16 (m, 1H), 6.26 (d, 2H, J=2.7 Hz), 6.81 (d, 2H, J=8.7 Hz), 7.03 (d, 2H J=8.7 Hz); 13C NMR (CD3OD) δ 18.8, 42.3, 54.5, 55.6, 56.0, 72.6, 103.0, 105.4, 115.0, 131.1, 131.2, 131.3, 146.2, 159.8, 159.9; UV (MeOH) λmax 277 nm (ε 3,590), 224 (17,700), 207 (29,500); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=−24.9° (c=0.8 MeOH); HPLC: (a) 70/30/0.05, 1.0 mL/min, 282 nm, tR 1.54 min, 96.5% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.51 min, 95.9% pure.","(S,S)-(+)-1-p-Methoxyphenyl-2-(β-3′,5′-dihydroxy-phenyl-(β-oxy)ethylamino-propane Fumarate [(S,S)-2].","Prepared from (S)-8 and (S)-11 according to Procedure A to give 318 mg (53%).","1H NMR (CD3OD) δ 1.15 (d, 3H, J=6.0 Hz), 2.58-3.22 (m, 5H), 3.77 (s, 3H), 4.68 (dd, 1H, J=4.8, 8.4 Hz), 6.18 (t, 1H, J=2.1 Hz), 6.31 (d, 2H, J=2.1 Hz), 2.23 (s, 0.5 H, fumarate), 6.84 (d, 2H, J=8.7 Hz), 7.10 (d, 2H, J=9.0 Hz); 13C NMR (CD3OD) δ 16.1, 39.9, 52.4, 54.5, 55.3, 70.4, 101.9, 104.2, 114.0, 129.2, 130.1, 144.4, 158.7, 158.9; UV (MeOH) λmax 277 nm (ε 2,100), 224 (11,00), 205 (22,700); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=+28.6° (c=0.95 MeOH); HPLC: (a) 70/30/0.05, 1.0 mL/min, 282 nm, tR 1.67 min, 96.0% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.51 min, 97.1% pure.","(R,S)-(+1p-Methoxyphenyl-2-(β-3′,5′-dihydroxy-phenyl-(β-oxy)ethylaminopropane Fumarate [(R,S)-2].","Prepared from (R)-8 and (S)-11 according to Procedure A to give 160 mg (38%).","1H NMR (CD3OD) δ 1.20 (d, 3H, J=6.6 Hz), 2.62-2.71 (m, 1H), 2.98-3.20 (m, 3H), 3.30-3.42 (m, 2H), 4.73-4.81 (m, 1H), 6.21 (m, 2H), 3.35 (m, 2H), 6.71 (s, 0.5H, fumarate), 6.56-6.89 (m, 2H), 7.11-7.19 (m, 2H); 13C NMR (CD3OD) δ 15.6, 38.5, 51.8, 54.5, 55.9, 69.7, 102.1, 104.1, 114.1, 128.5, 130.2, 136.0, 143.8, 158.8, 159.1; UV (MeOH) λmax 277 nm (ε 4,100), 224 (21,400), 203 (50,600); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=−7.2° (c=1.5 MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 282 nm, tR 1.40 min, 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.51 min, 96.1% pure.","(S,R)-(+)-1-p-Methoxyphenyl-2-(β-3′,5′-dihydroxyphenyl-β-oxy)ethylaminopropane Fumarate [(S,R)-2].","Prepared from (S)-8 and (R)-11 according to Procedure A to give 200 mg (51%).","1H NMR (CD3OD) δ 1.12 (d, 3H, J=6.0 Hz), 2.58-3.13 (m, 5H), 3.77 (s, 3H), 4.62 (dd, 1H, J=3.6, 9.0 Hz), 6.15 (m, 1H), 6.30 (d, 2H, J=1.8 Hz), 6.85 (d, 2H, J=8.7 Hz), 7.11 (d, 2H, J=8.7 Hz); 13C NMR (CD3OD) δ 18.2, 41.4, 54.1, 55.7, 56.5, 64.7, 103.0, 105.3, 115.1, 130.7, 131.3, 145.9, 159.8, 160.0; UV (MeOH) λmax 277 nm (ε 3,150), 224 (3,310), 205 (30,600); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=+14.1° (c=0.95 MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 282 nm, tR 1.42 min, 97.7% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.52 min, 97.8% pure.","(R,R)-(+5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(R,R)-3].","Prepared from (R)-8 and (R)-12 according to Procedure A to give 88 mg (42%).","1H NMR (CD3OD) δ 1.23 (m, 3H), 2.70-3.24 (m, 4H), 3.54 (m, 1H), 4.84 (dd, 1H, J=3.3, 9.6 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.38 (d, 2H, J=2.1 Hz), 6.75 (s, 2H, fumarate), 7.35 (dd, 4H, J=8.1, 21.0 Hz); 13C (CD3OD) δ 15.5, 39.6, 52.7, 56.6, 70.3, 103.4, 105.3, 123.8, 132.0, 132.1, 135.2, 137.5, 144.7, 160.0, 168.1; UV (MeOH) λmax 284 nm (ε 1,520), 206 (21,700); MS (ESI+) m/z (rel): 303 (100, M+H); [α]D=−6.8° (conc=1.0% MeOH); HPLC: (a) 80/20/0.05, 0.70 mL/min, 276 nm, tR 2.07 min, 95.5% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.60, 97.16% pure.","(S,S)-(+)-5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(S,S)-3].","Prepared from (S)-8 and (S)-12 according to Procedure A to give 56 mg (25%).","1H NMR (CD3OD) δ 1.23 (m, 3H), 2.62-3.27 (m, 4H), 3.55 (m, 1H), 4.74-4.88 (m, 1H), 6.22 (t, 1H, J=1.8 Hz), 6.37 (d, 2H, J=2.4 Hz), 6.75 (s, 2H, fumarate), 7.32 (dd, 4H, J=8.7, 25.8 Hz); 13C NMR (CD3OD) δ 15.5, 39.6, 52.5, 56.7, 70.7, 103.4, 105.3, 123.3, 131.8, 132.0, 135.2, 136.9, 144.7, 160.0, 168.1; UV (MeOH) λmax 284 nm (ε 1,720), 207 (28,400); MS (ESI+) m/z (rel): 303 (100, M+H), 329 (20); [α]D=+11.1° (conc=0.50% MeOH); HPLC: (a) 80/20/0.05, 0.7 mL/min, 276 nm, tR 2.01 min, <99% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.50 min, 99.4% pure.","(R,S)-(+5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(R,S)-3].","Prepared from (R)-8 and (S)-12 according to Procedure A to give 72 mg (35%).","1H NMR (CD3OD) δ 1.23 (m, 3H), 2.73-3.24 (m, 4H), 3.51 (m, 1H), 4.80 (dd, 1H, J=2.7, 9.6 Hz), 6.22 (t, 1H, J=2.1 Hz), 6.36 (d, 2H, J=2.4 Hz), 6.75 (s, 2H, fumarate), 7.32 (dd, 4H, J=8.4, 25.2 Hz); 13C NMR (CD3OD) δ 16.1, 39.12, 5.16, 56.9, 70.4, 103.4, 105.3, 123.4, 132.0, 132.0, 135.2, 136.8, 144.6, 160, 168.10; UV (MeOH) λmax 284 nm (ε 1,620), 205 (27,200); MS (ESI+) m/z (rel): 303 (100, M+H), 134 (14); [α]D=−7.5° (conc=0.50% MeOH); HPLC: (a) 80/20/0.05, 0.7 mL/min, 276 nm, tR 2.08 min, 95.0% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.51 min, 97.4% pure.","(S,R)-(+)-5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(S,R)-3].","Prepared from (S)-8 and (R)-12 according to Procedure A to give 93 mg (42%).","1H NMR (CD3OD) δ 1.23 (d, 3H, J=6.3 Hz), 2.70-3.78 (m, 4H), 3.42-3.62 (m, 1H), 4.80 (dd, 1H, J=3.0, 9.9 Hz), 6.22 (t, 1H, J=2.1 Hz), 6.37 (d, 2H, J=2.1 Hz), 6.75 (s, 2H, fumarate), 7.33 (dd, 4H, J=8.4, 26.7 Hz); 13C NMR (CD3OD) δ 16.2, 39.1, 52.6, 56.9, 70.5, 103.4, 105.3, 123.5, 132.1, 133.7, 135.2, 137.1, 144.7, 160.0, 168.1 UV (MeOH) λmax 284 nm (ε 8,230), 207 (100,000); MS (ESI+) m/z (rel): 303 (100, M+H), 134 (18); [α]D=+11.4° (conc=0.50% MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 280 nm, tR 1.45 min, 99% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.63 min, 95.33% pure.","(R,R)-(+5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(R,R)-4].","Prepared from (R)-8 and (R)-13 according to Procedure A to give 92 mg (26%).","1H NMR (CD3OD) δ 1.22 (m, 3H), 2.68-3.28 (m, 2H), 3.10-3.28 (m, 2H), 3.53 (br-m, 1H), 4.75-4.80 (m, 1H), 6.24 (t, 1H, J=2.4 Hz), 6.38 (d, 2H, J=2.1 Hz), 6.75 (s, 1H, fumarate), 7.22-7.33 (m, 5H); 13C NMR (CD3OD) δ 15.5, 40.3, 56.9, 70.2, 103.4, 105.3, 128.3, 129.9, 130.3, 135.2, 137.3, 144.6, 144.6, 159.9, 168.1; UV (MeOH) λmax 277 nm (ε 926), 204 (18,700); MS (APCI+) m/z 288 (100, M+H); [α]D=−21.2° (conc=0.85% MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm; tR 1.73 min; 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.46 min, 97.5% pure.","(S,S)-(+)-5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(S,S)-4].","Prepared from (S)-8 and (S)-13 according to Procedure A to give 184 mg (51%).","1H NMR (CD3OD) δ 1.21 (m, 3H), 2.70-3.13 (m, 2H), 3.15-3.23 (m, 2H), 3.54 (br-m, 1H), 4.79-4.86 (m, 1H), 6.24 (t, 1H, J=2.1 Hz), 6.39 (t, 2H, J=2.7 Hz), 6.76 (s, 1H, fumarate), 7.22-7.32 (m, 5H); 13C NMR (CD3OD) δ 15.5, 40.3, 56.9, 70.2, 103.4, 105.3, 128.3, 129.9, 130.3, 135.1, 137.3, 144.6, 144.6, 159.9, 168.1 UV (MeOH) λmax 278 nm (ε 1,510), 207 (26,600); MS (APCI+) m/z 288 (100, M+H); [α]D=+19.3° (conc=0.90% MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm, tR 1.49 min; 98.4% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.35 min, 99% pure.","(R,S)-(+5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(R,S)-4].","Prepared from (R)-8 and (S)-13 according to Procedure A to give 170 mg (45%).","1H NMR (CD3OD) δ 1.22 (m, 3H), 2.68-3.28 (m, 2H), 3.13-3.28 (m, 2H), 3.53 (br-m, 1H), 4.76-4.80 (m, 1H), 6.23 (t, 1H, J=2.1 Hz), 6.37 (t, 2H, J=3.0 Hz), 6.75 (s, 1H, fumarate), 7.24-7.37 (m, 5H); 13C NMR (CD3OD) δ 16.3, 24.2, 39.8, 57.2, 70.5, 103.4, 105.3, 128.4, 130.0, 130.4, 135.2, 137.4, 144.6, 160.1 UV (MeOH) λmax 278 nm (ε 1,110), 205 (31,000); MS (APCI+) m/z (rel): 288 (100, M+H); [α]D=−6.9° (conc=0.85% MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm, tR 1.53 min, 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.46 min, 98.5% pure.","(S,R)-(+)-5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(S,R)-4].","Prepared from (S)-8 and (R)-13 according to Procedure A to give 212 mg (59%).","1H NMR (CD3OD) δ 1.22 (m, 3H), 2.72 (dd, 1H J=10.2, 13.2 Hz), 3.11 (dd, 1H, J=10.2, 12.6 Hz), 3.18-3.27 (m, 2H), 3.48-3.61 (m, 1H), 4.83 (dd, 1H, J=3.3, 9.9 Hz), 6.22 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.4 Hz), 6.75 (s, 1H, fumarate), 7.24-7.37 (m, 5H); 13C NMR (CD3OD) δ 16.3, 24.2, 39.8, 57.2, 70.5, 103.4, 105.3, 128.4, 130.0, 130.4, 135.2, 137.4, 144.6, 160.1; UV (MeOH) λmax 278 nm (ε 1,680), 206 (35,500); MS (APCI+) m/z (rel): 288 (100, M+H), 270 (19, M-OH); [α]D=+9.1° (conc=1.1%, MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm, tR 1.51 min, 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.43 min, 99% pure.","(R,R)-(+5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(R,R)-5].","Prepared from (R)-8 and (R)-14 according to Procedure A to give 135 mg (46%).","1H NMR (CD3OD) δ 1.18-1.23 (m, 3H), 3.16-3.34 (m, 1H, 2H), 3.69-3.74 (m, 2H), 4.78-4.80 (m, 1H), 6.23 (t, 1H, J=2.4 Hz), 6.38 (m, 2H), 7.41-7.61 (m, 4H), 7.83 (d, 1H, J=7.5 Hz), 7.90 (d, 1H, J=7.8 Hz), 8.10 (m, 1H); 13C NMR (CD3OD) δ 16.2, 37.2, 54.5, 56.1, 70.3, 103.4, 105.3, 124.3, 126.5, 127.0, 127.7, 129.3, 130.1, 133.2, 135.2, 135.6, 144.7, 160.1, 168.2; UV (MeOH) λmax 282 nm (ε 5,860), 224 (50,900), 208 (35,500); MS (APCI+) m/z (rel): 338 (100, M+H), 169 (15, fragment); [α]D=−20.4 (conc=0.50% MeOH); HPLC: (a) 60/40/0.05, 1.00 mL/min, 282 nm, tR 2.08 min, 95.7% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.20 min, 99% pure.","(S,S)-(+)-5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(S,S)-5].","Prepared from (S)-8 and (S)-14 according to Procedure A to give 118 mg (40%)1H NMR (CD3OD) δ 1.13-1.17 (m, 3H), 3.14-3.26 (m, 1H, 2H), 3.61-3.76 (m, 2H), 4.44-4.75 (m, 1H), 6.18 (t, 1H, J=2.4 Hz), 6.33 (m, 2H), 7.36-7.52 (m, 4H), 7.77 (dd, 1H, J=1.8, 7.5 Hz), 7.84 (d, 1H, J=8.1 Hz), 8.04 (t, 1H, J=8.4 Hz); 13C NMR (CD3OD) δ 16.1, 37.1, 54.4, 56.0, 70.3, 103.3, 105.3, 124.3, 126.5, 127.0, 127.7, 129.2, 130.0, 133.2, 135.2, 135.7, 144.5, 160.0, 168.1; UV (MeOH) λmax 282 nm (ε 6,210), 223 (56,400), 208 (42,700); MS (APCI+) m/z (rel): 338 (100, M+H), 169 (8, fragment); [α]D=+20.0° (conc=1.1% MeOH); HPLC: (a) 60/40/0.05, 1.00 mL/min, 282 nm, tR 2.35 min, 98.9% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.26 min, 97.2% pure.","(R,S)-(+5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(R,S)-5].","Prepared from (R)-8 and (S)-14 according to Procedure A to give 114 mg (39%).","1H NMR (CD3OD) δ 1.08-1.11 (m, 3H), 3.02-3.24 (m, 1H, 2H), 3.54-3.68 (m, 2H), 4.45-4.75 (m, 1H), 6.11 (t, 1H, J=1.8 Hz), 6.26 (m, 2H), 6.63 (s, 2H fumarate), 7.28-7.48 (m, 4H), 7.70 (d, 1H, J=7.5 Hz), 7.77 (d, 1H, J=7.8 Hz), 7.97 (t, 1H, J=7.8 Hz); 13C NMR (CD3OD) δ 16.0, 37.1, 52.5, 56.0, 70.4, 103.4, 105.3, 124.4, 126.5, 127.0, 127.6, 129.2, 130.1, 133.1, 135.2, 135.5, 144.7, 159.9, 168.2; UV (MeOH) λmax 281 nm (ε 12,600), 224 (61,900), 204 (47,200); MS (APCI+) m/z (rel): 338 (100, M+H), 190 (15, fragment); [α]D=−11.3° (conc=0.85% MeOH); HPLC: (a) 60/40/0.05, 1.00 mL/min, 282 nm, tr 2.30 min, 98.6% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.36 min, 99% pure.","(S,R)-(+)-5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(S,R)-5].","Prepared from (S)-8 and (R)-14 according to Procedure A to give 123 mg (42%).","1H NMR (CD3OD) δ 1.18-1.22 (m, 3H), 3.10-3.28 (m, 1H, 2H), 3.69-3.78 (m, 2H), 4.45-4.75 (m, 1H), 6.23 (t, 1H, J=2.1 Hz), 6.39 (m, 2H), 6.73 (s, 2H fumarate), 7.39-7.59 (m, 4H), 7.80 (d, 1H, J=7.5 Hz), 7.88 (d, 1H, J=7.8 Hz), 8.01 (t, 1H, J=9.0 Hz); 13C NMR (CD3OD) δ 16.4, 37.4, 52.5, 56.2, 70.6, 103.4, 105.3, 124.4, 126.5, 127.0, 129.3, 130.1, 133.1, 133.4, 135.6, 136.3, 144.8, 160.0, 171.4; UV (MeOH) λmax 282 nm (ε 7,740), 224 (70,900), 206 (55,800); MS (ESI+) m/z (rel): 338 (100, M+H); [α]D=+15.5 (conc=1.0% MeOH) HPLC: (a) 60/40/0.05, 1.0 mL/min, 282 nm, tR 1.95, 95.7% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.29 min, 95.7% pure.","(R,R)-(+5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(R,R)-6].","Prepared from (R)-8 and (R)-15 according to Procedure A to give 45 mg (29%).","1H NMR (CD3OD) δ 0.920 (t, 3H, J=6.9 Hz), 1.30 (d, 3H, J=6.9 Hz), 1.29-1.64 (m, 8H), 3.01-3.18 (m, 2H), 3.14-3.30 (m, 1H), 4.80 (dd, 1H, J=3.3, 9.6 Hz), 6.22 (t, 1H, J=2.1 Hz), 6.36 (d, 2H, J=2.4 Hz), 6.75 (s, 1H, fumarate); 13C NMR (CD3OD) δ 14.3, 16.0, 23.5, 26.2, 32.6, 34.2, 52.1, 55.7, 70.2, 103.3, 105.3, 135.2, 144.7, 160.0, 168.0; UV (MeOH) λmax 278 nm (ε 931), 203 nm (20,100); MS (ESI+) m/z (rel): 268 (100, M+H); [α]D=−8.8° (conc=1.1% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.18 min, 96.6% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.06 min, 98.9% pure.","(S,S)-(+)-5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(S,S)-6].","Prepared from (S)-8 and (S)-15 according to Procedure A to give 96 mg (43%).","1H NMR (CD3OD) δ 0.923 (t, 3H, J=6.6 Hz); 1.31 (d, 3H, J=6.6 Hz), 1.26-1.84 (m, 8H), 2.01-3.18 (m, 2H), 3.14-3.30 (m, 1H), 4.81 (dd, 1H, J=3.3, 9.6 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.39 (d, 2H, J=2.1 Hz), 6.76 (s, 1H, fumarate): 13C NMR (CD3OD) δ 14.2, 16.0, 23.4, 26.3, 32.6, 34.1, 52.1, 55.8, 70.2, 103.4, 105.3, 135.2, 144.7, 159.9, 168.2; UV (MeOH) λmax 278 nm (ε 1,340), 203 (28,800); MS (APCI+) m/z (rel): 268 (100, M+H); [α]D=+10.8° (conc=0.50% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.16 min, 97.0% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.11 min, 99% pure.","(R,S)-(+5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(R,S)-6].","Prepared from (R)-8 and (S)-15 according to Procedure A to give 83 mg (38%).","1H NMR (CD3OD) δ 0.924 (m, 3H); 1.32 (d, 3H, J=6.6 Hz), 1.26-1.84 (m, 8H), 2.98-3.20 (m, 2H), 3.32-3.22 (m, 1H), 4.78 (dd, 1H, J=3.0, 9.9 Hz), 6.23 (t, 1H, J=2.1 Hz), 6.37 (d, 2H, J=1.8 Hz), 6.76 (s, 1H, fumarate); 13C NMR (CD3OD) δ 14.2, 16.4, 23.4, 26.2, 32.6, 33.5, 52.2, 56.0, 70.4, 103.4, 105.3, 135.2, 144.7, 160.0, 168.1; UV (MeOH) λmax 276 nm (ε 2,770), 203 (35,900); MS (APCI+) m/z (rel): 268 (100, M+H); [α]D=−15.9° (conc=0.70% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.16 min, 97.0% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.07 min, 96.2% pure.","(S,R)-(+)-5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(S,R)-6].","Prepared from (S)-8 and (R)-15 according to Procedure A to give 81 mg (38%).","1H NMR (CD3OD) δ 0.920 (t, 3H, J=6.3 Hz), 1.32 (d, 3H, J=6.9 Hz), 1.30-1.77 (m, 8H), 2.99-3.17 (m, 2H), 3.23-3.26 (m, 1H), 4.76 (dd, 1H, J=3.0, 9.6 Hz), 6.22 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.1 Hz), 6.75 (s, 1H, fumarate); 13C NMR (CD3OD) δ 14.2, 16.5, 23.5, 26.2, 32.6, 39.5, 52.2, 56.0, 70.4, 103.4, 105.3, 135.2, 144.7, 160.0, 168.0; UV (MeOH) λmax 278 nm (ε 1,440), 204 (29,900); MS (APCI+) m/z (rel): 268 (100, M+H); [α]D=+12.7° (conc=1.0% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.16 min, 99% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.02 min, 95.7% pure.","(R)-(+5-(1-Hydroxy-2-phenethylaminoethyl)-1,3-benzenediol fumarate [(R)-7].","Prepared from (R)-8 and 28 to give 37 mg (15%).","1H NMR (CD3OD) δ 2.94-3.23 (m, 6H), 4.73 (dd, 1H, J=3.3, 9.9 Hz), 6.15 (t, 1H, J=2.4 Hz), 6.29 (d, 2H, J=1.8 Hz), 7.19-7.28 (m, 5H), 6.69 (s, 1H); UV (MeOH) λmax 278 nm (ε 1,360), 205 (32,600); MS (APCI+) m/z (rel): 274 (100, M+H); [α]D=−13.0° (conc=1.0% MeOH); HPLC: (a) 80/20/0.05, 1.00 mL/min, 282 nm, tR 1.47 min, 96.7% pure; (b) 50/50/0.05, 1.0 mL/min, 272 nm, tR 2.78 min, 95.1% pure.","(S)-(+)-5-(1-hydroxy-2-phenethylaminoethyl)-1,3-benzenediol fumarate [(S)-7].","Prepared from (S)-8 and 28 to give 51 mg (17%).","1H NMR (CD3OD) δ 2.87-3.21 (m, 6H), 4.68 (dd, 1H, J=3.6, 9.9 Hz), 6.10 (t, 1H, J=2.4 Hz), 6.24 (d, 2H, J=2.1 Hz), 6.63 (s, 1H), 7.12-7.21 (m, 5H); UV (MeOH) λmax 278 nm (ε 1,280), 204 (33,700); MS (APCI+) m/z (rel): 274 (100, M+H); [α]D=+14.64° (conc=1.1% MeOH); HPLC: (a) 80/20/0.05, 1.00 mL/min, 282 nm, tR 1.47 min, 98.6% pure; (b) 50/50/0.05, 1.0 mL/min, 272 nm, tR 2.74 min, 98.8% pure.","(R,R)-(−)-ethylfenoterol.","1H NMR: (300 MHz, CD3OD): δ 0.950 (t, 3H, J=7.5 Hz), 1.67 (m, 2H), 2.83-3.18 (m, 4H), 3.33-3.40 (m, 1H), 3.37 (s, 4H), 4.82 (m, 1H), 6.24 (d, 1H, J=2.1 Hz), 6.37 (d, 2H, J=1.8 Hz), 6.73 (s, 2H, fum), 6.76 (d, 2H, J=8.4 Hz), 7.05 (d, 2H, J=8.7 Hz) ppm.","CMR: 13C (75 MHz, CD3OD): δ 9.43, 23.28, 36.56, 52.29, 62.16, 70.02, 103.4, 105.3, 116.7, 127.8, 131.3, 136.5, 144.6, 157.6, 159.9, 172.3 ppm.","UV: (Methanol), λmax (ε): 206 nm (22,500), 223 (12,300), 278 (2,460).","MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 318 (100, M+H).","HPLC 1: Column: Varian Sunfire C18 100×4.6; 70/30/0.1 water/acetonitrile/TFA; 1.0 mL/min; Det: 278 nm; 2.76 min (fumarate, 6.99%), 3.57 min (90.11%); Purity: 97.1%.","HPLC 2: Column: Chiralpak IA 250×10; 90/10/0.05 acetonitrile/methanol/TFA; 2.0 mL/min; Det: 278 nm; 5.26 (RR isomer, 92.37%), 7.11 min (fumarate, 5.02%); Purity 97.5%.","Specific Rotation: [α]D=−15.6 (free amine, 0.5% MeOH).","(R,S)-(−)-ethylfenoterol.","1H NMR: (300 MHz, CD3OD): δ 0.972 (t, 3H, J=7.5 Hz), 1.70 (p, 2H, J=6.9 Hz)), 2.86-3.22 (m, 4H), 3.32-3.37 (m, 1H), 3.34 (s, 4H), 4.82 (m, 1H), 6.25 (t, 1H, J=2.1 Hz), 6.36 (d, 2H, J=1.8 Hz), 6.74 (s, 2H, fum), 6.77 (d, 2H, J=8.4 Hz), 7.08 (d, 2H, J=8.7 Hz) ppm.","CMR: 13C (75 MHz, CD3OD): δ 9.820, 24.16, 36.48, 52.30, 62.32, 69.92, 103.3, 105.3, 116.8, 127.7, 131.3, 136.1, 144.4, 157.6, 159.8, 171.3 ppm.","UV: (Methanol), λmax (c): 204 nm (26,900), 224 (11,500), 278 (2,320).","MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 318 (100, M+H).","HPLC 1: Column: Varian Sunfire C18 100×4.6; 70/30/0.1 water/acetonitrile/TFA; 1.0 mL/min; Det: 278 nm; 2.79 min (fumarate, 3.34%), 3.56 min (96.11%); Purity: 99.5% HPLC 2: Column: Chiralpak IA 250×10; 90/10/0.05 acetonitrile/methanol/TFA; 2.0 mL/min; Det: 278 nm; 5.88 (RS isomer, 97.08%), 7.12 min (fumarate, 2.92%); Purity >99%.","Specific Rotation: [α]D=−7.2 (free amine, 0.5% MeOH).","C22H25NO4.0.5C4H4O4 1H NMR: (300 MHz, CD3OD): δ 1.22 (t, 3H, J=6.6 Hz), 3.09-3.21 (m, 3H), 3.59-3.69 (m, 2H), 3.99 (s, 3H), 4.74-4.83 (m, 1H), 6.23 (t, 1H, J=2.4 Hz), 6.37 (dd, 2H, J=2.4, 5.7 Hz), 6.74 (s, 1H), 6.86 (d, 1H, J=7.8 Hz), 7.32 (d, 1H, J=7.8 Hz), 7.48 (t, 1H, J=6.9 Hz), 7.56 (t, 1H, J=6.9 Hz), 8.02 (dd, 1H, J=8.4, 12.0 Hz), 8.27 (d, 1H, J=8.7 Hz) ppm.","CMR: 13C (75 MHz, CD3OD): δ 15.78, 36.66, 52.39, 55.96, 70.20, 103.4, 104.5, 105.3, 123.8, 124.3, 124.9, 126.2, 127.4, 128.1, 129.5, 133.8, 135.2, 144.6, 156.6, 160.0, 168.3 ppm.","UV: (Methanol), λmax (c): 298 nm (4,970), 286 (9,920), 234 (22,600), 210 (42,500).","MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 368 (100, M+H).","Specific Rotation: [α]D=−28.8 (Free Amine; 0.5% MeOH).","C22H25NO4.0.5C4H4O4 1H NMR: (300 MHz, CD3OD): δ 1.20 (t, 3H, J=6.6 Hz), 3.07-3.21 (m, 3H), 3.52-3.75 (m, 2H), 3.97 (s, 3H), 4.69-4.83 (m, 1H), 6.24 (t, 1H, J=2.1 Hz), 6.39 (dd, 2H, J=2.4, 5.4 Hz), 6.74 (s, 1H), 6.84 (d, 1H, J=7.8 Hz), 7.31 (d, 1H, J=8.1 Hz), 7.48 (t, 1H, J=6.9 Hz), 7.56 (t, 1H, J=6.9 Hz), 8.01 (dd, 1H, J=8.4, 13.5 Hz), 8.27 (d, 1H, J=7.8 Hz) ppm.","CMR: 13C (75 MHz, CD3OD): δ 15.77, 36.64, 52.37, 55.94, 70.46, 103.4, 104.5, 105.3, 123.8, 124.3, 124.9, 126.2, 127.4, 128.1, 129.4, 133.8, 135.5, 144.7, 156.6, 160.0, 169.0 ppm.","UV: (Methanol), λmax (c): 298 nm (5,430), 286 (5,710), 233 (25,100), 210 (43,200).","MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 368 (100, M+H).","Specific Rotation: [α]D=−15.8 (Free Amine; 0.5% MeOH).","A step in the synthesis of the 4 stereoisomers of 1-6 was the coupling of the epoxide formed from either (R)- or (S)-3′,5′-dibenzyloxyphenylbromohydrin with the (R)- or (S)-enantiomer of the appropriate benzyl-protected 2-amino-3-benzylpropane (1-5) or the (R)- or (S)-enantiomer of N-benzyl-2-aminoheptane (6), Scheme I.","The synthesis of (R)-7 and (S)-7 was accomplished using 2-phenethylamine, Scheme II.","This approach was similar to the one developed by Trofast et al.","(Chirality 3: 443-450, 1991) for the synthesis of the stereoisomers of formoterol, compound 47, FIG.","6.The resulting compounds were then deprotected by hydrogenation over Pd/C and purified as the fumarate salts.","The chiral building blocks used in the syntheses were produced using Scheme III.","The (R)- and (S)-3′,5′-dibenzyloxyphenyl-bromohydrin enantiomers were obtained by the enantiospecific reduction of 3,5-dibenzyloxya-bromoacetophenone using boron-methyl sulfide complex (BH3SCH3) and either (1R,2S)- or (1S,2R)-cis-1-amino-2-indanol.","The required (R)- and (S)-2-benzylaminopropanes were prepared by enantioselective crystallization of the rac-2-benzylaminopropanes using either (R)- or (S)-mandelic acid as the counter ion.","Example 6 Binding Affinities of Exemplary Fenoterol Analogues for β1 and β2 Adrenergic Receptors This example demonstrates that fenoterol analogues have an equivalent if not greater binding affinity for β2-adrenergic receptors than fenoterol.","Compounds were tested up to three times each to determine their binding affinities at the β□- and β2-adrenergic receptors.","Competition curves with standard and unknown compounds included at least six concentrations (in triplicate).","For each compound, graphs were prepared containing individual competition curves obtained for that test compound.","IC50 values and Hill coefficients were calculated using GraphPad Prism® software.","Ki values were calculated using the Cheng-Prusoff transformation (Biochem Pharmacol 22: 3099-3108, 1973).","In each experiment, a standard compound was simultaneously run on the 96-well plate.","If the standard compound did not have an IC50 value close to the established average for that compound, the entire experiment was discarded and repeated again.","β1-adrenergic receptor binding was done on rat cortical membrane following a previously described procedure (Beer et al., Biochem.","Pharmacol.","37: 1145-1151, 1988).","In brief, male Sprague-Dawley rats weighing 250-350 g were decapitated and their brains quickly removed.","The cerebral cortices were dissected on ice, weighed and promptly transferred to a 50 ml test tube containing approximately 30 ml of 50 mM Tris-HCl, pH 7.8 (at room temperature).","The tissues were homogenized with a polytron and centrifuged at 20,000×g for 12 min at 4° C. The pellet was washed again in the same manner and resuspended at a concentration of 20 mg (original wet wt) per 1 ml in the assay buffer (20 mM Tris-HCl, 10 mM MgCl2, 1 mM EDTA, 0.1 mM ascorbic acid at pH 7.8).","To block the β2 sites present in the cortical membrane preparation, 30 nM ICI 118-551 was also added to the assay buffer.","To wells containing 100 μl of the test drug and 100 μl of [3H]CGP-12177 (1.4 nM final concentration), 0.8 ml of tissue homogenate was added.","After 2 hours at 25° C., the incubation was terminated by rapid filtration.","Nonspecific binding was determined by 10 μM propranolol.","HEK 293 cells stability transfected with cDNA encoding human β2-AR (provided by Dr. Brian Kobilka, Stanford Medical Center, Palo Alto, Calif.) were grown in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS), 0.05% penicillin-streptomycin, and 400 μg/ml G418 as previously described (Pauwels et al., Biochem.","Pharmacol.","42: 1683-1689, 1991).","The cells were scraped from the 150×25 mm plates and centrifuged at 500×g for 5 minutes.","The pellet was homogenized in 50 mM Tris-HCl, pH 7.7, with a Polytron, centrifuged at 27,000×g, and resuspended in the same buffer.","The latter process was repeated, and the pellet was resuspended in 25 mM Tris-HCl containing 120 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl2, 0.8 mM MgCl2, and 5 mM glucose, pH 7.4.The binding assays contained 0.3 nM [3H]CGP-12177 in a volume of 1.0 ml.","Nonspecific binding was determined by 1 μM propranolol.","According to the above-described methods, binding affinities, expressed as Ki values, were determined using membranes obtained from a HEK 293 cell line stably transfected with cDNA encoding human β2-AR (Pauwels et al., Biochem.","Pharmacol.","42: 1683-1689, 1991) with [3H]CGP-12177 as the marker ligand.","The resulting IC50 values and Hill coefficients were calculated for each test compound using GraphPad Prism® software and Ki values were calculated using the Cheng-Prusoff transformation (Biochem Pharmacol 22: 3099-3108, 1973): Ki=IC50/(1+L/Kd)+Eqn.","1.Where: L is the concentration of [3H]CGP-12177 and Kd is the binding affinity of the [3]CGP-12177.Each test compounds was assayed three times.","The relative binding affinities to the β2-AR for the stereoisomers of compounds 1-4 and 6 were R,R>R,S>S,R≈S,S (FIG.","5; Table 1, below).","This stereoselectivity is consistent with the previously reported potencies of the formoterol stereoisomers (Trofast et al., Chiralty 3: 443-450, 1991) and results from binding studies with the isoproterenol derivative PTFAM, compound 48, FIG.","6 (Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987).","With compound 5, no significant difference was found between the Ki values of the R,R and R,S isomers, thus the order was R,R=R,S>S,R>S,S.","The Ki value for (R)-7 was greater than that of (S)-7, which is consistent with the established enantioselective binding preference for β2-ARs with the R-configuration at the stereogenic center containing the β-OH moiety, c.f.","(Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987; Wieland et al., Proc.","Natl.","Acad.","Sci.","USA 93: 9276-9281, 1996; Kikkawa et al., Mol.","Pharmacol.","53: 128-134, 1998; and Zuurmond et al., Mol.","Pharmacol.","56: 909-916, 1999).","TABLE 1 The binding affinities to the β2-AR of the compounds synthesized in this study calculated as Ki ± SEM (nM), n = 3.Comparison of β1- and β2 adrenergic binding affinity of fenoterol isomers Compound Ki β1 Ki β2 Ki β1/Ki β2 (R,R)-1 14750 ± 2510 345 ± 34 43 (R,S)-1 18910 ± 2367 3695 ± 246 5 (S,R)-1 >100,000 10330 ± 1406 NC (S,S)-1 >100,000 27749 ± 6816 NC (R,R)-2 21992 ± 3096 474 ± 35 46 (R,S)-2 30747 ± 6499 1930 ± 135 16 (S,R)-2 33378 ± 9170 5269 ± 509 6 (S,S)-2 >100,000 15881 ± 2723 NC (R,R)-3 24956 ± 2100 2934 ± 168 9 (R,S)-3 31324 ± 3485 7937 ± 397 4 (S,R)-3 77491 ± 3583 23125 ± 2093 3 (S,S)-3 31440 ± 1681 28624 ± 906 1 (R,R)-4 17218 ± 1270 1864 ± 175 9 (R,S)-4 33047 ± 2779 6035 ± 434 4 (S,R)-4 >100,000 30773 ± 3259 NC (S,S)-4 >100,000 28749 ± 1811 NC (R,R)-5 3349 ± 125 241 ± 38 14 (R,S)-5 15791 ± 6269 341 ± 23 46 (S,R)-5 34715 ± 9092 1784 ± 148 19 (S,S)-5 >100,000 2535 ± 209 NC (R,R)-6 10185 ± 499 9275 ± 902 1 (R,S)-6 >100,000 31440 ± 1681 NC (S,R)-6 61295 ± 5821 >100,000 NC (S,S)-6 52609 ± 1434 56420 ± 5186 1 (R)-7 42466 ± 3466 10466 ± 1461 4 (S)-7 52178 ± 3006 20562 ± 3721 3 When just the R,R isomers were compared, (R,R)-5 had the highest relative affinity of the tested compounds, although the difference between (R,R)-5 and (R,R)-1 did not reach statistical significance, Table 1.The only other (R,R) stereoisomer with sub-micromolar affinity was (R,R)-2, which had a significantly lower binding affinity than (R,R)-5, p=0.0051, and (R,R)-1, p=0.0291, although the mean Ki value for (R,R)-2 is only 23% greater than that of (R,R)-1.The minimal effect of transforming the p-OH moiety into a methyl ether is consistent with previous data from Schirrmacher et al.","(Bioorg.","Med.","Chem.","Lett.","13: 2687-92, 2003).","In the previous study, rac-1 was converted into a [18F]-fluoroethoxy ether without significant loss of in vitro activity and it was concluded that, within the accuracy of the experimental measurements, the derivatization did not change the binding affinity of the rac-1 to the β2-AR.","Binding affinities, expressed as Ki values, for the β1-AR were determined using rat cortical membranes with [3H]-CGP-12177 as the marker ligand (Beer et al., Biochem.","Pharmacol.","37: 1145-1151, 1988.).","The calculated Ki for (R,R)-5 was 3,349 nM and the binding affinities for the all of the remaining test compounds were >10,000 nM, Table 1.Unlike the data from the β2-AR binding studies, there was no clear trend which could be associated with the stereochemistry of the compounds.","The relative selectivity of the compounds for the β2-AR and β1-AR was determined using the ratio Ki β1/Ki β2, Table 1.Of particular interest were the ratios for the four compounds with sub-micromolar affinity for the β2-AR, (R,R)-1, (R,R)-2, (R,R)-5 and (R,S)-5, which were 46, 43, 14 and 46, respectively.","The results for (R,R)-1 and (R,R)-2 are consistent with previously reported Ki βi/Ki β2 ratio of 53 for the β2-AR-selective agonist (R,R)-TA-2005, compound 49, FIG.","6.The observed loss of β2-AR selectivity for (R,R)-5 was unexpected as was the 3-fold increase in selectivity displayed by (R,S)-5 relative to (R,R)-5.Previous studies with the stereoisomers of 47 indicated that both the (R,R)- and (R,S)-isomers had a high degree of selectivity for the β2-AR, relative to the β1-AR, with the selectivity of the (R,R)-isomer greater than that of the (R,S)-isomer (Trofast et al., Chirality 3: 443-450, 1991).","This is the case for compounds 1 and 2, but reversed for 5.It is also interesting to note that (S,R)-5 had a similar selectivity (19-fold) and its affinity for the β2-AR was only 7-fold weaker than (R,R)-5, 1783 nM and 241 nM, respectively.","These studies demonstrate that (R,R)- or (R,S)-naphthyl fenoterol analogues have a higher binding affinity for β2-adrenergic receptors than any isoform of fenoterol.","The (R,R)-methyoxy fenoterol analogue has a similar Ki for the β2-adrenergic receptor as (R,R)-fenoterol.","Thus, such analogues are viable candidates for β2-adrenergic receptor agonists and can likely be used to treat disorders that are presently treated with commercially available (±)-fenoterol.","Example 7 Cardiomyocyte Contractility Studies with Fenoterol Analogues This example illustrates the pharmacological activities of the compounds with sub-micromolar affinity for the β2-AR and (R,S)-1 and (S,S)-1.In these studies, the contraction amplitude indexed by electrical pacing induced shortening of cell length was measured in single ventricular myocytes before and after exposure to a single dose of the test compounds.","Contractile response to the agonist was expressed as a percentage of the basal contractility and the specificity of the agonist towards β2-adrenergic receptor was determined by the inhibitory effect of ICI 118,551 (10−7 mol/L; Tocris Cookson Ltd., Bristol, U.K.), a selective β2-AR antagonist.","All of the compounds tested, except for (S,S)-1, produced a significant contractile response which was blocked by ICI 118,551, while (S,S)-1 had no observed pharmacological effect, FIG.","7.These results were consistent with the results from the previous study (Beigi et al., Chirality, 18: 822-827, 2006) and with the observations that for agonist activity at the β2-AR an R-configuration is preferred at the stereogenic center containing the β-OH moiety, c.f.","(Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987; Wieland et al., Proc.","Natl.","Acad.","Sci.","USA 93: 9276-9281, 1996; Kikkawa et al., Mol.","Pharmacol.","53: 128-134, 1998; and Zuurmond et al., Mol.","Pharmacol.","56: 909-916, 1999).","It is of interest to note that maximum effect was elicited with 0.1 μM (R,R)-5 and (R,S)-5 while the other active compounds required 0.5 μM concentrations.","In addition, while the equivalent activities of (R,R)-5 and (R,S)-5 were suggested by the binding data, the observed activity of (R,S)-1 was unexpected as previous studies of the stereoisomers of 47 (Trofast et al., Chiralty 3: 443-450, 1991) and 48 (Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987) indicated that the agonist activities of the (R,R)-isomers were significantly greater than the activities of the corresponding (R,S)-isomers.","Example 8 Comparative Molecular Field Analysis This example illustrates the use of Comparative Molecular Field Analysis (CoMFA) to analyze the disclosed compounds.","The disclosed compounds were analyzed using Comparative Molecular Field Analysis, a 3D QSAR technique applicable to the analysis of the relative activities of stereoisomers and/or enantiomers at a selected target.","CoMFA was performed as implemented in SYBYL 7.2.","(TRIMS Inc., St. Louis, Mo.).","Molecular models of all derivatives were prepared in HyperChem v. 6.03 (HyperCube Inc., Gainesville, Fla.) using ModelBuild procedure to ensure the same conformation of the scaffold.","Models were extracted to SYBYL and the partial atomic charges (Gasteiger—Huckel type) were calculated.","Ligand models were aligned using as a common substructure of the two asymmetric carbon atoms in the core of the fenoterol molecule (—C*—CH2—NH—C*—CH2—).","Two types of molecular fields (steric and electrostatic) were sampled on the grid (2 Å spacing) lattice surrounding each structure.","Distance-dependent dielectric constant was used in electrostatic calculations and energetic cutoffs of 30 kcal/mol for both the steric and the electrostatic energies were set.","The Partial Least Square correlation procedure applied for resultant database extracted four statistically significant components and the following validation parameters were obtained for the best solution: R2=0.920, F (4,21)=60.380, standard error of estimate=0.223, cross-validated (leave-one-out) R2=0.847.In general, electrostatic fields accounts for 48.1% of explained variance and steric fields accounts for 51.9%.","The resulting 3D QSAR model shows good statistical correlation with experimental data, R2=0.920 and F=60.380, and good prediction power as indicated by the cross-validated R2 value (Q2)=0.847 and the standard error of prediction (SEP)=0.309, Table 2.TABLE 2 The pKd predicted by the CoMFA model.","Derivative pKd Measured pKd Predicted (R,R)-1 6.46 5.84 (R,S)-1 5.43 5.48 (S,R)-1 4.99 5.02 (S,S)-1 4.56 4.66 (R,R)-2 6.32 6.17 (R,S)-2 5.71 5.80 (S,R)-2 5.28 5.34 (S,S)-2 4.80 4.99 (R,R)-3 5.53 5.57 (R,S)-3 5.10 5.21 (S,R)-3 4.64 4.75 (S,S)-3 4.54 4.39 (R,R)-4 5.73 5.58 (R,S)-4 5.22 5.25 (S,R)-4 4.51 4.75 (S,S)-4 4.54 4.43 (R,R)-5 6.62 6.72 (R,S)-5 6.47 6.36 (S,R)-5 5.75 5.90 (S,S)-5 5.60 5.54 (R,R)-6 5.03 5.01 (R,S)-6 4.50 4.66 (S,R)-6 4.00 4.19 (S,S)-6 4.25 3.84 (R)-7 4.98 5.33 (S)-7 4.69 4.51 In the first stage, the model was used to identify the regions responsible for the discrimination between the stereoisomers.","The CoMFA procedure produced several distinct asymmetric regions located in close proximity of each chiral center.","The first chiral center (carrying the β hydroxyl group) is surrounded by an electropositive region behind the molecule.","An electropositive region can be associated with hydrogen bond formation and indicates favorable donor properties or unfavorable acceptor properties of the pseudoreceptor.","In this case, the location of the electropositive field indicates that the orientation of the β-OH moiety behind the plane of the model (the S configuration at the chiral center) would hinder H bond formation with the receptor.","The electropositive region is closely associated with a steric unfavorable region behind the first chiral center.","This is an additional indication that the model demonstrates a preference for the β-hydroxyl group in the R configuration.","The preference for the R configuration at this center is consistent with previous models and experimental data, which demonstrated that the R configuration is favored for functional activity at β-AR receptors (c.f., Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987; Wieland et al., Proc.","Natl.","Acad.","Sci.","USA 93: 9276-9281, 1996; Kikkawa et al., Mol.","Pharmacol.","53: 128-134, 1998; and Zuurmond et al., Mol.","Pharmacol.","56: 909-916, 1999).","The CoMFA model also demonstrated the effect of the second chiral center.","The preferred configuration can be derived from the binding data, where for compounds 1-4 and 6 the (R,R)-isomers had the higher affinities relative to their respective (R,S)-isomers, while the Ki values for (R,R)-5 and (R,S)-5 were equivalent, Table 1.Thus, in this model, the more active isomers are those with the methyl moiety on the stereogenic center on the aminoalkyl portion of the molecules pointing out of the plane of the figure of the CoMFA model.","This is depicted by a steric disfavoring region behind the second chiral center of the molecule, and indicates a preference for the R configuration at this site.","In this study, only the aminoalkyl portion of the fenoterol molecule was altered and, therefore, the key CoMFA regions are associated with this aspect of the molecule.","In the resulting analysis, all four interacting regions were identified in the proximity of the aromatic moiety and all can be used to generate hypotheses concerning the mode of binding action of the studied derivatives.","In the model, the large electropositive region encompassing the area close to the —OH or OCH3 substituents represents H-bond donor properties of the pseudoreceptor to these moieties.","These interactions are responsible for the relatively higher binding affinities of the 0-derivatives, compounds 1 and 2, relative to compounds 3 and 4, in the latter compound the p-amino substituent should be positively charged under the experimental conditions.","A large electronegative region and another electropositive region, both located parallel on two sides of the aromatic system most likely represent π-π or π-hydrogen bond interactions between the β2-AR and electron-rich aromatic moieties, such as the naphthyl ring.","This is consistent with the increased affinity of compounds 1, 2 and 5 relative to the other compounds examined in this study.","The role of this interaction is suggested by the observation that the Ki values for (R,R)-5 and (R,S)-5 were equivalent to (R,R)-1 and (R,R)-2, Table 1.Two steric regions are located close to the electrostatic regions and one favors and the other disfavors bulkiness in the respective areas.","This indicates that the binding of the aminoalkyl portions of the molecules are also sterically restricted.","The binding of agonists and antagonists to the β2-AR has been studied using site-directed mutagenesis and molecular modeling techniques (Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987; Wieland et al., Proc.","Natl.","Acad.","Sci.","USA 93: 9276-9281, 1996; Kikkawa et al., Mol.","Pharmacol.","53: 128-134, 1998; Zuurmond et al., Mol.","Pharmacol.","56: 909-916, 1999; Kontoyianni et al., J. Med.","Chem.","39: 4406-4420, 1996; Furse et al., J. Med.","Chem.","46: 4450-4462, 2003; and Swaminath et al.","J. Biol.","Chem.","279: 686-691, 2004).","There is general agreement that the binding of the “catechol” portion of an agonist occurs within a binding area created by the transmembrane (TM) helices identified as TM3, TM5 and TM6.The binding process is a sequential event that produces conformational changes leading to G-protein activation (Furse et al., J. Med.","Chem.","46: 4450-4462, 2003).","A key aspect in this process is the interaction of the hydroxyl moiety on the chiral carbon of the agonist with the Asn-293 residue in TM6, and for this interaction an R-configuration is preferable at the chiral carbon (Eimerl et al., Biochem.","Pharmacol.","36: 3523-3527, 1987; Kikkawa et al., Mol.","Pharmacol.","53: 128-134, 1998; and Swaminath et al.","J. Biol.","Chem.","279: 686-691, 2004).","Since the “catechol” portion of the fenoterol molecule was not altered in this study, it follows that in the CoMFA model, an R-configuration at the first stereogenic center is preferred in most stable complexes.","The majority of the binding and functional studies of β2-AR agonists have been conducted with small N-alkyl substituents such as methyl, isopropyl and t-butyl, c.f.","(Kontoyianni et al., J. Med.","Chem.","39: 4406-4420, 1996).","However, while these compounds are active at the β2-AR, they are not subtype selective.","This is illustrated by the Ki β1/Ki β2 ratios determined for compounds 49, 50 and 51 (FIG.","6) which were 53, 1.7 and 1.3, respectively (Kikkawa, et al.","Mol.","Pharmacol.","53: 128-134, 1998)).","The removal of the p-methoxyphenyl moiety not only reduced the selectivity, but also the affinities as the respective β2Ki values were 12 nM, 170 nM and 6300 nM (Kikkawa, et al.","Mol.","Pharmacol.","53: 128-134, 1998).","The role that aminoalkyl substituents play in β2-AR selectivity has been investigated using site-directed mutagenesis and molecular modeling techniques (Kikkawa, et al.","Mol.","Pharmacol.","53: 128-134, 1998); Furse et al., J. Med.","Chem.","46: 4450-4462, 2003; and Swaminath et al.","J. Biol.","Chem.","279: 686-691, 2004).","Using (R,R)-49 as the model ligand, Kikkawa, et al.","determined that hydrogen bond formation between the p-methoxy oxygen on compound 49 and the hydroxyl group of tyrosine 308 (Y308) located in the extracellular end of TM7 was the source of the β2-AR selectivity (Mol.","Pharmacol.","53: 128-134, 1998).","Furse and Lybrand developed a de novo model of the β2-AR and investigated molecular complexes of several ligands (agonist and antagonist) with this subtype (J. Med.","Chem.","46: 4450-4462, 2003).","Among the structures investigated, (R,R)-49 has the same aminoalkyl substituent as the compound 2.Examination of the (R,R)-49/β2-AR complex revealed that the p-methoxy group oxygen of (R,R)-49 formed a hydrogen bond with the hydroxy group of Y308, which supports the model proposed by Kikkawa, et al.","(Mol.","Pharmacol.","53: 128-134, 1998).","The distance between the two oxygen atoms bonded in the model was 3.22 Å.","However, the methoxy moiety of the ligand was also located in close proximity to three other polar residues, histidine 296 (H296) in TM6, tryptophan 109 (W109) in TM3 and asparagine 312 (N312) in TM7, each of which can interact with an aromatic group on the aminoalkyl portion of (R,R)-49.In the Furse and Lybrand model, the distance between the oxygen atom of the ligand and the hydrogen atom of H296 was 5.88 Å and H296 was proposed as an alternative hydrogen bond donor for interaction with the methoxy group of (R,R)-49.Since Y308 and H296 are found only in β2-AR, the corresponding residues found in the β1-AR are F359 and K347, respectively, the interaction with H296 and Y308 has been proposed as the source of β1/β2 selectivity (Furse et al., J. Med.","Chem.","46: 4450-4462, 2003).","Since the previous studies of β1/β2 selectivity utilized (R,R)-49, the subtype selectivity of the (R,R)-stereoisomers of the compounds synthesized in our study were compared to the subtype selectivity of (R,R)-49.The data from this study suggest that hydrogen bond formation between Y308 and/or H296 and the oxygen atom on the p-substituent of the agonist is involved in β2-AR selectivity.","The interaction is possible with (R,R)-1 and (R,R)-2 and the Ki β1/Ki β2 ratios for these compounds are 43 and 46, respectively, which are comparable to the Ki β1/Ki β2 ratio of 53 determined for (R,R)-49.The Ki β1/Ki β2 ratios for compounds 3, 4, 6 and 7 were <10 and reflect the fact that they do not have the ability to form hydrogen bonds with Y308 or H296.The hydrogen bonding interactions were also suggested by the CoMFA model identifying a large electropositive region surrounding the area close to the —OH or —OCH3 substituents, representing hydrogen-bond donor properties of the pseudoreceptor.","The data from this study also suggest that an aromatic moiety on the aminoalkyl portion of the compound contributes to Ki and subtype selectivity, even if the aromatic moiety is unable to form a hydrogen bond with the receptor.","This is demonstrated by the comparison of the Kiβ2 values for the (R,R)-isomers of compounds 1-5 which were <3,000 nM with Kiβ2 value of (R,R)-6 which was 9,000 nM and the Kiβ1/Ki β2 ratios which were ≥9 for 1-5 while compound 6 displayed no subtype selectivity, Table 1.One possible mechanism to explain the data is π-hydrogen bond formation.","The cloud of π-electrons of aromatic rings can act as hydrogen bond acceptors, although it has been estimated that the interaction would be about half as strong as a normal hydrogen bond (Levitt and Perutz J. Mol.","Biol.","201: 751-754, 1998).","The higher affinity and subtype selectivity for (R,R)-5 relative to (R,R)-3 and (R,R)-4 or (R)-7 is consistent with the greater π electron distribution in the napthyl ring relative to the other aromatic rings.","The CoMFA model also identified a large electronegative region and another electropositive region, both located parallel to the aromatic system, which are most likely associated with π-π or π-hydrogen bond interactions between the β2-AR and electron-rich aromatic moieties, such as the naphthyl ring.","Using the model developed by Furse and Lybrand with (R,R)-49 as the interacting ligand, Y308, H296, W109 and N312 were identified as possible sources of π-π and/or π-hydrogen bond interactions.","In the β2-AR model, the estimated distances between the p-methoxy moiety on (R,R)-49 and W109 and N312 were 4.80 Å and 3.45 Å, respectively.","Since W109 and N312 are fully conserved in all β-AR subtypes, the interactions suggested by the CoMFA model may represent the source of the increase affinities for (R,R)-1, (R,R)-2 and (R,R)-5, relative to the other (R,R)-isomers, but not the observed β1/β2 selectivity.","The data from this study and the resulting CoMFA model indicate that the binding process of the tested compounds with the β2-AR includes the interaction of the chiral center on the aminoalkyl portion of the agonist with a sterically restricted site on the receptor.","The existence of a sterically restricted site has been previously suggested from the data obtained in the development of 3D models for agonist and antagonist complexes with the β2-AR (Kobilka, Mol.","Pharm.","65: 1060-1062, 2004).","For example, (R,R)-49 and similar compounds with substituents larger than a methyl group at the stereogenic center on the aminoalkyl portion were suggested to produce significant steric interactions that would unfavorably affect the ligand-receptor complexes.","The binding of an agonist to the β2-AR has been described as a multistep interrelated process, in which sequential interactions between the agonist and receptor produce corresponding conformational changes (Kobilka, Mol.","Pharm.","65: 1060-1062, 2004).","The CoMFA model reflects the final agonist/β2-AR complex and, in order to discern the effect of the steric restricted site, it is necessary to consider the effect that interaction with this site has on the outcome of the binding process.","A detailed description of the present CoMFA model is disclosed in Jozwiak et al.","(J. Med.","Chem., 50 (12): 2903-2915, 2007) which is hereby incorporated by reference in its entirety.","If one assumes that the interaction of the “catechol” portion of the agonist with the binding area created by TM3, TM5 and TM6 (the first binding area), then these interactions will fix the position of the aminoalkyl portion of the agonist relative to the steric restricted site, and perhaps even create this site.","In the CoMFA model, the steric restrictions at the site force the methyl moiety at the chiral center of the aminoalkyl portion to point out of the plane of the model.","Due to the free rotation about the N-atom, the configuration at the chiral center bearing the methyl moiety may likely not affect the ability of the molecule to minimize the interaction with the steric restricted site.","However, in the minimum energy conformation, e.g., with the methyl group pointing out of the plane of the CoMFA model, the orientation of the remaining segment of the aminoalkyl portion relative to the second binding area would be affected by the stereochemistry.","Indeed, R and S configurations would produce mirror image relationships to the second binding area.","This situation is illustrated in FIG.","5 where the catechol, first chiral center and the methyl moieties of (R,R)-5 and (R,S)-5 have been overlaid upon each other.","The studies elucidating the source of β2-AR selectivity have primarily utilized (R,R)-49 and one previous study of the effect of chirality on subtype selectivity reported that (R,R)-47 had a higher β2-AR selectivity than (R,S)-47 (Trofast et al., Chiralty 3: 443-450, 1991).","Thus, the observed equivalent affinities and functional activities of (R,R)-5 and (R,S)-5 at the β2-AR and the 3-fold increased β2-AR selectivity of (R,S)-5 was an unexpected result.","One possible explanation of these results is that the naphthyl moiety of (R,S)-5 does not interact with the site defined by Y308 and H296 and is directed towards and binds to another site on the β2-AR.","This interaction also conveys or participates in subtype selectivity as well as increased binding affinity and agonist activity.","Since the previous models of β2-AR selectivity only employed (R,R)-isomers, it is possible that this site has been overlooked.","Another explanation of the data is suggested by the “rocking tetrahedron” chiral recognition mechanism proposed by Sokolov and Zefirov (Doklady Akademii Nauk SSSR 319: 1382-1383, 1991).","In this approach to molecular chiral recognition, the enantiomeric ligands are secured to a chiral selector by two binding interactions.","The interactions must be non-equivalent and directional so that only one orientation is possible.","The tethered enantiomers still have conformational mobility and the remaining moieties on the chiral center will sweep out overlapping but not identical steric volumes.","Where and to what extent the chiral selector interacts with these steric volumes, determines the enantioselectivity of the process.","If the chirality of the chiral selector places the interaction perpendicular to the plane of the ligand, no enantioselectivity is observed.","As a deviation from the perpendicular increases, so does the enantioselectivity relative to the R or S configuration.","With (R,R)-5 and (R,S)-5, the interactions with the first binding area and the steric restricted site of the CoMFA model are two non-equivalent and directional interactions that place the remaining constituents on the second chiral center in the same, albeit mirror image, orientation relative to the second binding area.","As discussed above, the interactions of the 1-napthyl moieties of compound 5 with Y308 and H296 are believed to be the source of the observed β2-AR selectivity.","If the 1-naphthyl rings sweep out overlapping but not identical steric volumes, then the observed Kiβ2 values and subtype selectivity indicate the following: 1) the Kiβ2-AR values represent the sum total of the π-hydrogen bond and π-π interactions between the 1-naphthyl moieties and Y308 and H296, as well as additional non-β2-AR specific interactions with other residues such as W109 and N312; 2) the steric volume swept out by (R,S)-5 increases the probability of interactions of Y308 and H296 with the π cloud of the naphtyl moiety relative to the (R,R)-5; and 3) the steric volume swept out by (R,R)-5 increases the probability of interactions with non-β2-AR specific sites relative to (R,S)-5.The effect of the configuration at the second chiral center and conformational-based chiral selectivity is also illustrated by the affinities and subtype selectivities of (R,R)-3, (R,S)-3 and (R)-7, Table 1.The inversion of the chirality at the second chiral carbon from R to S, reduced the Kiβ2 value of the (R,S)-3/β2-AR complex relative to the (R,R)-3/β2-AR complex by ˜3-fold while there was no significant difference between their Kiβ1 values.","The increased subtype selectivity observed for (R,R)-3 relative to (R,S)-3, 9 versus 4, respectively, essentially reflects the differences in Kiβ2 values, which could be a reflection of increased conformational energy required to bring the aromatic portion of the aminoalkyl chain into contact with the electropositive and electronegative regions that comprise the second binding area or a decrease in the probability that this interaction would occur.","The removal of the methyl moiety on the second chiral center, and thereby the chirality at this site ((R)-7), had a similar effect as inverting the chirality at this site from R to S. The Kiβ2 values for (R)-7 was 32% higher than (R,S)-3 and there was no difference in the β2-AR selectivity, Table 1.These results suggest that for compound 3, the primary effect of the R configuration at the second chiral site was to direct the aminoalkyl chain towards the second binding area which increased the probability of interacting with this site and reduces the conformational energy required to achieve this interaction.","A difference between compounds 3 and 5 is the steric areas swept out by the aromatic substituents.","In the case of compound 3, the phenyl ring produces a smaller, more linear area, while with compound 5, the 1-naphthyl ring system produces a relatively larger and broader area.","These differences can be used to guide the synthesis of additional derivatives.","In an example, (R,R)-2 and (R,S)-5 are chosen as possible candidates for the development of a new selective β2-AR agonist.","These compounds may have increased and extended systemic exposures relative to the commercially available rac-1 due to changes in molecular hydrophobicity, metabolic profile and transporter interactions.","The present example provides a pharmacophore model which may be used as a structural guide for the design of new compounds with β2-AR selectivity which can be tested for use in the treatment of a desired condition, including congestive heart failure.","Example 9 Pharmacokinetic Studies of (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol This example demonstrates the plasma concentrations of (R,R)-Fenoterol, (R,R)-Methoxyfenoterol and (R,S)-Naphtylfenoterol administered as an intravenous (IV) bolus to male Sprague-Dawley rats.","(R,R)-Fenoterol, (R,R)-Methoxyfenoterol and (R,S)-Naphtylfenoterol were administered to jungular vein cannulated (JVC) rats at a single dosage of 5 mg/ml intravenously (see Table 3).","Dose calculations (mg/kg) were based on the individual body weight measured on the day of treatment.","Study duration for pharmacokinetic studies was 6 hours.","Plasma samples were collected over six hours at the following nine timepoints: prior to administration of the desired dose; 5.00-5.30 minutes after dose; 15.00-16.30 minutes after dose; 30.00-33.00 minutes after dose; 60-65 minutes after dose; 120-125 minutes after dose; 240-245 minutes after dose; 300-305 minutes after dose; and 360-365 minutes after dose.","Urine was collected for 0-6 hours and 6 to 24 hours from 3 rats in each treatment group.","TABLE 3 Study conditions for measuring plasma concentrations of (R,R)- fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol.","Dose Dose No.","of Rats level Concentration No.","of for plasma Compound: (mg/kg): (mg/ml): Rats: analysis: (R,R)- 5 2.5 6 5 fenoterol (R,R)- 5 2.5 6 5 methoxyfenoterol (R,S)- 5 2.5 6 2 naphtylfenoterol Pharmacokinetic parameters for (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol after intravenous administration to rats (5 mg/kg) were analyzed according to a two-compartment open model (see Table 4).","A drug that follows the pharmacokinetics of a two-compartment model does not equilibrate rapidly throughout the body, as is assumed for a one-compartment model.","In the two-compartment model, the drug distributes into two compartments, the central compartment and the tissue, or peripheral compartment.","The central compartment represents the blood, extracellular fluid, and highly perfused tissues.","The drug distributes rapidly and uniformly in the central compartment.","A second compartment, known as the tissue or peripheral compartment, contains tissues in which the drug equilibrates more slowly.","Drug transfer between the two compartments is assumed to take place by first-order processes.","The following abbreviations are utilized in Table 4 below: alpha—macro rate constant associated with the distribution phase; beta—macro rate constant associated with the elimination phase; A, B—zero time intercept associated with the alpha phase and beta phase, respectively; AUC—area under the curve; T1/2 (K10)—half-life associated with the rate constant K10; K10—elimination rate—rate at which the drug leaves the system from the central compartment; K12—rate at which drug enters tissue compartment from the central compartment; K21—rate at which drug enters central compartment from tissue compartment; V1—volume of distribution of the central compartment; V2—volume of distribution of the tissue compartment; Vss—volume of distribution at steady state; and Cl—clearance.","TABLE 4 Pharmacokinetic parameters for (R,R)-fenoterol, (R,R)- methoxyfenoterol and (R,S)-naphtylfenoterol after intravenous administration to rats (5 mg/kg).","(R,R)- (R,R)- (R,S)- fenoterol methoxyfenoterol naphtylfenoterol (n = 2) (n = 5) (n = 5) Weight Weight Weight Parameter Units 306 ± 11 296 ± 8 297 ± 10 Two-compartment open model A μg/ml 1.6300 4.6437 4.0365 Alpha 1/min 0.0710 0.1982 0.1764 B μg/ml 0.0577 0.3900 0.4372 Beta 1/min 0.0086 0.0054 0.0046 AUC min*μg/ml 29.6861 96.1011 116.88 T1/2 (K10) min 12.19 13.23 18.11 K10 1/min 0.0568 0.0524 0.0383 K12 1/min 0.0119 0.1309 0.1213 K21 1/min 0.0107 0.0203 0.0214 V1 ml 906.5 294.01 330.83 V2 ml 1005.20 1895.00 1872.92 Vss ml 1911.70 2189.02 2203.75 Cl ml/min 51.54 15.40 12.66 Tables 5-7 and FIG.","8 illustrate the individual plasma concentrations of (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol after IV administration to rats (5 mg/kg).","The average concentration of (R,R)-fenoterol in plasma was dramatically lower (1.34 μg/ml) five minutes after IV administration to rats (5 mg/kg) compared to either the average concentration of (R,R)-methoxyfenoterol (2.12 μg/ml) or (R,S)-naphtylfenoterol (2.11 μg/ml).","TABLE 5 Individual plasma concentrations of (R,R)-fenoterol after intravenous administration (5 mg/kg).","Concentration (ug/ml) Time (min) Rat# 01 Rat #02 Average 5 1.34 1.34 15 0.36 0.36 30 0.17 0.50 0.34 60 0.05 0.05 0.05 120 0.03 0.01 0.02 240 0.0003 0.02 0.01 300 0.005 0.005 360 0.08 0.03 0.06 TABLE 6 Individual plasma concentrations of (R,R)-methoxyfenoterol after intravenous administration (5 mg/kg).","Concentration (ug/ml) Rat# Rat# Rat# Rat# Rat# Time (min) 13 14 15 16 18 Average 5 1.94 2.14 2.51 1.89 2.12 15 0.48 0.54 0.62 0.67 0.56 0.58 30 0.31 0.40 0.46 0.48 0.38 0.41 60 0.23 0.25 0.24 0.33 0.25 0.26 120 0.14 0.16 0.18 0.21 0.14 0.17 240 0.09 0.12 0.17 0.14 0.08 0.12 300 0.06 0.07 0.07 0.09 0.07 0.07 360 0.05 0.06 0.05 0.08 0.04 0.06 TABLE 7 Individual plasma concentrations of (R,S)-naphtylfenoterol after intravenous administration (5 mg/kg).","Concentration (ug/ml) Rat# Rat# Rat# Rat# Rat# Time (min) 25 26 27 28 29 Average 5 2.52 2.16 1.64 2.10 2.11 15 0.85 0.78 0.50 0.60 0.68 30 0.49 0.54 0.34 0.33 0.43 60 0.36 0.42 0.37 0.29 0.24 0.34 120 0.25 0.29 0.26 0.22 0.18 0.24 240 0.11 0.11 0.13 0.13 0.11 0.12 300 0.10 0.11 0.12 0.11 0.10 0.11 360 0.08 0.08 0.11 0.10 0.09 0.09 The data demonstrate that the two derivatives, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol, have a significantly higher systemic exposure (AUC) and longer clearance compared to (R,R)-fenoterol which may produce a longer acting drug.","It is suggested that the longer clearance time may be the result of inhibiting glucuronidation.","Example 10 Treatment of Cardiac Disorders with (R,R)-Fenoterol or Fenoterol Analogues Based upon the teaching disclosed herein, a cardiac disorder such as congestive heart failure is treated by administering a therapeutic effective dose of (R,R)-fenoterol or one or more of the fenoterol analogues disclosed above (see Sections III and IV).","In an example, a subject who has been diagnosed with congestive heart failure is identified.","Following subject selection, a therapeutic effective dose of (R,R)-fenoterol or the respective fenoterol analogue is administered to the subject.","For example, a therapeutic effective dose of the (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative is administered to the subject.","In a further example, a therapeutic effective dose of the (R,S)-fenoterol analogue including a napthyl derivative is administered to the subject.","The fenoterol analogue is prepared and purified as described in Section III.B and Example 5.The amount of (R,R)-fenoterol or fenoterol analogue or a pharmaceutical composition thereof administered to reduce, inhibit, and/or treat congestive heart failure depends on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition (see Section V).","Ideally, a therapeutically effective amount of an agent is the amount sufficient to prevent, reduce, and/or inhibit, and/or treat the cardiac disorder (e.g., congestive heart failure) in a subject without causing a substantial cytotoxic effect in the subject.","In an example, (R,R)-fenoterol, a disclosed fenoterol analogue (such as an (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative or an (R,S)-fenoterol analogue including a napthyl derivative) or pharmaceutical composition is provided at a dosage range from about 0.001 to about 10 mg/kg body weight orally in single or divided doses.","In particular examples, the dosage range is from about 0.005 to about 5 mg/kg body weight orally in single or divided doses (assuming an average body weight of approximately 70 kg; values adjusted accordingly for persons weighing more or less than average).","In certain examples, a disclosed fenoterol compound or pharmaceutical composition is provided by oral administration in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.0 mg to about 10 mg, more particularly about 2.5 mg, about 5 mg, or about 10 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.","In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg active ingredient is administered two to four times a day.","For example, a tablet containing about 1 mg to about 10 mg active ingredient is administered two times a day.","Example 11 Treatment of Pulmonary Disorders with Fenoterol Analogues According to the teachings herein, a pulmonary disorder such as asthma or chronic obstructive pulmonary disease is treated by administering a therapeutic effective dose of the fenoterol analogues disclosed above (see Sections III-V).","In an example, a subject who has been diagnosed with or displays one of the symptoms associated with asthma or chronic obstructive pulmonary disease is identified.","Following subject selection, a therapeutic effective dose of the desired fenoterol analogue is administered to the subject.","For example, a therapeutic effective dose of the (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative is administered to the subject.","In a further example, a therapeutic effective dose of the (R,S)-fenoterol analogue including a napthyl derivative is administered to the subject.","The fenoterol analogue is prepared and purified as described in Section III.B and Example 5.The amount of the fenoterol analogue administered to prevent, reduce, inhibit, and/or treat the pulmonary disorder depends on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition.","Ideally, a therapeutically effective amount of an agent will be the amount sufficient to prevent, reduce, and/or inhibit, and/or treat the pulmonary disorder in a subject without causing a substantial cytotoxic effect in the subject.","In an example, (R,R)-fenoterol, a disclosed fenoterol analogue (such as an (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative or an (R,S)-fenoterol analogue including a napthyl derivative) or pharmaceutical composition is provided at a dosage range from about 0.001 to about 10 mg/kg body weight orally in single or divided doses.","In particular examples, the dosage range is from about 0.005 to about 5 mg/kg body weight orally in single or divided doses (assuming an average body weight of approximately 70 kg; values adjusted accordingly for persons weighing more or less than average).","In certain examples, a disclosed fenoterol compound or pharmaceutical composition is provided by oral administration in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.0 mg to about 10 mg, more particularly about 2.5 mg, about 5 mg, or about 10 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.","In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg active ingredient is administered two to four times a day.","For example, a tablet containing about 1 mg to about 10 mg active ingredient is administered two times a day.","In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention.","Rather, the scope of the invention is defined by the following claims.","We therefore claim as our invention all that comes within the scope and spirit of these claims."]],"string":"[\n [\n \"PREPARATION OF (R,R)-FENOTEROL AND (R,R)- OR (R,S)-FENOTEROL ANALOGUES AND THEIR USE IN TREATING CONGESTIVE HEART FAILURE\",\n \"This disclosure concerns the discovery of (R,R)- and (R,S)-fenoterol analogues which are highly effective at binding β2-adrenergic receptors.\",\n \"Exemplary chemical structures for these analogues are provided.\",\n \"Also provided are pharmaceutical compositions including the disclosed (R,R)-fenoterol and fenoterol analogues, and methods of using such compounds and compositions for the treatment of cardiac disorders such as congestive heart failure and pulmonary disorders such as asthma or chronic obstructive pulmonary disease.\"\n ],\n [\n \"1.A method for treating a pulmonary or cardiovascular disorder in a subject, comprising: administering to the subject with the pulmonary or cardiovascular disorder a therapeutically effective amount of a compound having the formula wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl or a combination thereof; R4 is H or lower alkyl; R5 is X is H, —OR6, or —NR7R8; R6 is lower alkyl; and R7 and R8 independently are H or lower alkyl, wherein the compound is optically active.\",\n \"2.The method of claim 1, wherein R5 is where X is H or —OR6 and R6 is lower alkyl.\",\n \"3.The method of claim 1, wherein R4 is lower alkyl.\",\n \"4.The method of claim 1, wherein the compound is a (R,R)- or (R,S)-compound.\",\n \"5.The method of claim 4, wherein R5 is where X is H or —OCH3.6.The method of claim 5, wherein R4 is methyl, ethyl, n-propyl, or isopropyl.\",\n \"7.The method of claim 5, wherein R4 is methyl.\",\n \"8.The method of claim 6, wherein R1-R3 are hydrogen.\",\n \"9.The method of claim 1, wherein the compound is 10.The method of claim 9, wherein the compound is a (R,R)- or (R,S)-compound.\",\n \"11.The method of claim 1, wherein the compound is 12.The method of claim 1, wherein the disorder is a cardiovascular disorder.\",\n \"13.The method of claim 12, wherein the cardiovascular disorder is congestive heart failure.\",\n \"14.The method of claim 1, wherein the disorder is a pulmonary disorder.\",\n \"15.The method of claim 14, wherein the pulmonary disorder is at least one of asthma or chronic pulmonary obstructive disease.\",\n \"16.The method of claim 1, wherein administering a therapeutically effective amount of the compound comprises administering a pharmaceutical composition comprising the therapeutically effective amount of the compound and at least one pharmaceutically acceptable carrier.\",\n \"17.A method of increasing cardiomyocyte contractility, comprising: contacting cardiomyocytes with a therapeutically effective amount of a compound having the formula wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl or a combination thereof; R4 is H or lower alkyl; R5 is X is H, —OR6, or —NR7R8; R6 is lower alkyl; and R7 and R8 independently are H or lower alkyl, wherein the compound is optically active.\",\n \"18.The method of claim 17, wherein: R4 is lower alkyl; and R5 is where X is H or —OR6 and R6 is lower alkyl.\",\n \"19.The method of claim 17, wherein the compound is 20.The method of claim 19, wherein the compound is a (R,R)- or (R,S)-compound.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Fenoterol, 5-[1-hydroxy-2[[2-(4-hydroxyphenyl)-1-methylethyl]-amino] ethyl]1,2-benzenediol, is a β2-adrenergic receptor agonist that has traditionally been used for the treatment of pulmonary disorders such as asthma.\",\n \"This drug has two chiral (asymmetric) carbons that can each be independently arranged in an R or S configuration, so that the drug exists in distinct (R,R), (R,S), (S,R) and (S,S) forms known as stereoisomers.\",\n \"Fenoterol is commercially available as a racemic mixture of the (R,R)- and (S,S)-compounds.\",\n \"Fenoterol is known to act as an agonist that binds to and activates the β2-adrenergic receptor.\",\n \"This activity has led to its clinical use in the treatment of asthma because this agonist's activity dilates constricted airways.\",\n \"Additional therapeutic uses for fenoterol remain to be thoroughly explored.\",\n \"Pharmacological studies of the class of drugs that includes fenoterol have shown that only one of the enantiomers is responsible for generating brochodilation.\",\n \"For example, studies have demonstrated that the primary bronchodilatory activity for racemic (±)-fenoterol resides in the (R,R)-isomer of fenoterol.\",\n \"Further, it has recently become apparent that the inactive enantiomer may be associated with adverse effects.\",\n \"For instance, the diastereomer (S,S)-fenoterol has been demonstrated to cause adverse side effects or development of tolerance often associated with β2-adrenergic receptor agonist treatment.\",\n \"It would therefore be advantageous to provide fenoterol compositions that were effective at treating disorders such as asthma, chronic obstructive pulmonary disease, or congestive heart failure, but had reduced side effects such as hypersensitivity and drug resistance (tolerance).\"\n ],\n [\n \"<SOH> SUMMARY <EOH>This disclosure concerns the discovery of fenoterol analogues that are highly effective at binding β2-adrenergic receptors.\",\n \"Exemplary chemical structures for these analogues are provided throughout the disclosure.\",\n \"By way of example, such compounds are represented by the following general formula: wherein R 1 -R 3 independently are hydrogen, acyl, alkoxy carbonyl, amino carbonyl (carbamoyl) or a combination thereof; R 4 is H or lower alkyl; R 5 is lower alkyl, wherein X, Y 1 , Y 2 and Y 3 independently are hydrogen, —OR 6 and —NR 7 R 8 ; R 6 is independently hydrogen, lower alkyl, acyl, alkoxy carbonyl or amino carbonyl; and R 7 and R 8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl.\",\n \"Pharmaceutical compositions containing, and methods of using (R,R)-fenoterol and fenoterol analogues are also provided.\",\n \"For example, the disclosed (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues (e.g., (R,R)-methoxyfenoterol, (R,R)-napthylfenoterol, and (R,S)-napthylfenoterol) are effective at treating cardiac disorders or pulmonary disorders.\",\n \"The foregoing and other features and advantages will become more apparent from the following detailed description of several embodiments, which proceeds with reference to the accompanying figures.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. patent application Ser.\",\n \"No.\",\n \"15/347,354, filed Nov. 9, 2016, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/199,208, filed Mar.\",\n \"6, 2014, now issued as U.S. Pat.\",\n \"No.\",\n \"9,522,871, which is a divisional of U.S. patent application Ser.\",\n \"No.\",\n \"13/333,866, filed Dec. 21, 2011, now issued as U.S. Pat.\",\n \"No.\",\n \"8,703,826, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"12/376,945, filed Feb. 9, 2009, now abandoned, which is a § 371 U.S. National Stage of International Application No.\",\n \"PCT/US2007/075731, filed Aug. 10, 2007, which in turn claims the benefit of U.S.\",\n \"Provisional Patent Application No.\",\n \"60/927,825, filed May 3, 2007, and U.S.\",\n \"Provisional Application No.\",\n \"60/837,161, filed Aug. 10, 2006, all of which are incorporated herein in their entirety by reference.\",\n \"FIELD The present disclosure relates to the field of pharmaceutical compositions and in particular, to the preparation of (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues and their use in treating congestive heart failure.\",\n \"BACKGROUND Fenoterol, 5-[1-hydroxy-2[[2-(4-hydroxyphenyl)-1-methylethyl]-amino] ethyl]1,2-benzenediol, is a β2-adrenergic receptor agonist that has traditionally been used for the treatment of pulmonary disorders such as asthma.\",\n \"This drug has two chiral (asymmetric) carbons that can each be independently arranged in an R or S configuration, so that the drug exists in distinct (R,R), (R,S), (S,R) and (S,S) forms known as stereoisomers.\",\n \"Fenoterol is commercially available as a racemic mixture of the (R,R)- and (S,S)-compounds.\",\n \"Fenoterol is known to act as an agonist that binds to and activates the β2-adrenergic receptor.\",\n \"This activity has led to its clinical use in the treatment of asthma because this agonist's activity dilates constricted airways.\",\n \"Additional therapeutic uses for fenoterol remain to be thoroughly explored.\",\n \"Pharmacological studies of the class of drugs that includes fenoterol have shown that only one of the enantiomers is responsible for generating brochodilation.\",\n \"For example, studies have demonstrated that the primary bronchodilatory activity for racemic (±)-fenoterol resides in the (R,R)-isomer of fenoterol.\",\n \"Further, it has recently become apparent that the inactive enantiomer may be associated with adverse effects.\",\n \"For instance, the diastereomer (S,S)-fenoterol has been demonstrated to cause adverse side effects or development of tolerance often associated with β2-adrenergic receptor agonist treatment.\",\n \"It would therefore be advantageous to provide fenoterol compositions that were effective at treating disorders such as asthma, chronic obstructive pulmonary disease, or congestive heart failure, but had reduced side effects such as hypersensitivity and drug resistance (tolerance).\",\n \"SUMMARY This disclosure concerns the discovery of fenoterol analogues that are highly effective at binding β2-adrenergic receptors.\",\n \"Exemplary chemical structures for these analogues are provided throughout the disclosure.\",\n \"By way of example, such compounds are represented by the following general formula: wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl, amino carbonyl (carbamoyl) or a combination thereof; R4 is H or lower alkyl; R5 is lower alkyl, wherein X, Y1, Y2 and Y3 independently are hydrogen, —OR6 and —NR7R8; R6 is independently hydrogen, lower alkyl, acyl, alkoxy carbonyl or amino carbonyl; and R7 and R8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl.\",\n \"Pharmaceutical compositions containing, and methods of using (R,R)-fenoterol and fenoterol analogues are also provided.\",\n \"For example, the disclosed (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues (e.g., (R,R)-methoxyfenoterol, (R,R)-napthylfenoterol, and (R,S)-napthylfenoterol) are effective at treating cardiac disorders or pulmonary disorders.\",\n \"The foregoing and other features and advantages will become more apparent from the following detailed description of several embodiments, which proceeds with reference to the accompanying figures.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 illustrates the chromatographic separation of (S,S)- and (R,R)-fenoterol.\",\n \"FIG.\",\n \"2A provides an ultraviolet spectra of (R,R)- and (S,S)-fenoterol.\",\n \"FIG.\",\n \"2B illustrates a circular dichroism spectra of (R,R)- and (S,S)-fenoterol.\",\n \"FIG.\",\n \"3 provides frontal chromatographic elution profiles of [+H]-(±)-fenoterol produced by the addition of (R,R)-fenoterol to the running buffer.\",\n \"FIG.\",\n \"4A is a graph including dose-response curves generated by treating freshly isolated rat ventricular myocytes with (±)-fenoterol, (R,R)-fenoterol or (S,S)-fenoterol.\",\n \"FIG.\",\n \"4B is a graph including dose-response curves of T50% relaxation in freshly isolated rat ventricular myocytes generated by treatment with (±)-fenoterol, (R,R)-fenoterol or (S,S)-fenoterol.\",\n \"FIG.\",\n \"5 illustrates the chemical structures of the stereoisomers of fenoterol and fenoterol analogs (compounds 2-7).\",\n \"FIG.\",\n \"6 illustrates the chemical structures of compounds 47-51.FIG.\",\n \"7 illustrates the effect of fenoterol and fenoterol analogs on cell contraction in single ventricular myocytes.\",\n \"FIG.\",\n \"8 is a graph illustrating time-dependent mean plasma concentration of (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-napthylfenoterol after administration (5 mg/mL).\",\n \"DETAILED DESCRIPTION OF SEVERAL EMBODIMENTS I.\",\n \"Introduction This disclosure provides fenoterol analogues that bind the β2-adrenergic receptor with comparable or greater activity than fenoterol.\",\n \"In one embodiment, the optically active fenoterol analogues are substantially purified from a racemic mixture.\",\n \"For example, an optically active fenoterol analogue is purified to represent greater than 90%, often greater than 95% of the composition.\",\n \"These analogues can be used to treat pulmonary disorders such as asthma and chronic obstructive pulmonary disease that have previously been treated with (±)-fenoterol.\",\n \"Use of the disclosed fenoterol analogues with an equal to higher efficacy than (±)-fenoterol can possibly reduce adverse effects previously observed with (±)-fenoterol.\",\n \"For example, use of a lower concentration of the fenoterol analogues to obtain a therapeutic effective response is expected to reduce side-effects such as hypersensitivity and drug resistance (tolerance) observed with the commercially available (±)-fenoterol.\",\n \"Also, purification of the analogues removes contaminants such as the inactive enantiomer which can be responsible for these adverse effects.\",\n \"The present disclosure also demonstrates that (R,R)-fenoterol is the active component of commercially available (±)-fenoterol.\",\n \"It is specifically contemplated that (R,R)-fenoterol as well as disclosed (R,R)- and (R,S)-fenoterol analogues can be used to treat cardiac disorders such as congestive heart failure.\",\n \"Use of substantially optically pure (R,R)-fenoterol or (R,R)- or (R,S)-fenoterol analogues to treat congestive heart failure is expected to reduce the incidence of side-effects caused by physiologically less active forms of the drug.\",\n \"II.\",\n \"Abbreviations and Terms AR: adrenergic receptor CD: circular dichroism CoMFA: comparative molecular field analysis HPLC: high performance liquid chromatography IAM-PC: immobilized artificial membrane chromatographic support ICYP: [125I]cyanopindolol UV: ultraviolet Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed subject matter belongs.\",\n \"Definitions of common terms in chemistry terms may be found in The McGraw-Hill Dictionary of Chemical Terms, 1985, and The Condensed Chemical Dictionary, 1981.As used herein, the singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise.\",\n \"Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise.\",\n \"Also, as used herein, the term “comprises” means “includes.” Hence “comprising A or B” means including A, B, or A and B.\",\n \"Except as otherwise noted, any quantitative values are approximate whether the word “about” or “approximately” or the like are stated or not.\",\n \"The materials, methods, and examples described herein are illustrative only and not intended to be limiting.\",\n \"Any molecular weight or molecular mass values are approximate and are provided only for description.\",\n \"Except as otherwise noted, the methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification.\",\n \"See, e.g., Loudon, Organic Chemistry, Fourth Edition, New York: Oxford University Press, 2002, pp.\",\n \"360-361, 1084-1085; Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fifth Edition, Wiley-Interscience, 2001; or Vogel, A Textbook of Practical Organic Chemistry, Including Qualitative Organic Analysis, Fourth Edition, New York: Longman, 1978.In order to facilitate review of the various embodiments disclosed herein, the following explanations of specific terms are provided: Acyl: A group of the formula RC(O)— wherein R is an organic group.\",\n \"Acyloxy: A group having the structure —OC(O)R, where R may be an optionally substituted alkyl or optionally substituted aryl.\",\n \"“Lower acyloxy” groups are those where R contains from 1 to 10 (such as from 1 to 6) carbon atoms.\",\n \"Alkoxy: A radical (or substituent) having the structure —O—R, where R is a substituted or unsubstituted alkyl.\",\n \"Methoxy (—OCH3) is an exemplary alkoxy group.\",\n \"In a substituted alkoxy, R is alkyl substituted with a non-interfering substituent.\",\n \"“Thioalkoxy” refers to —S—R, where R is substituted or unsubstituted alkyl.\",\n \"“Haloalkyloxy” means a radical —OR where R is a haloalkyl.\",\n \"Alkoxy carbonyl: A group of the formula —C(O)OR, where R may be an optionally substituted alkyl or optionally substituted aryl.\",\n \"“Lower alkoxy carbonyl” groups are those where R contains from 1 to 10 (such as from 1 to 6) carbon atoms.\",\n \"Alkyl: An acyclic, saturated, branched- or straight-chain hydrocarbon radical, which, unless expressly stated otherwise, contains from one to fifteen carbon atoms; for example, from one to ten, from one to six, or from one to four carbon atoms.\",\n \"This term includes, for example, groups such as methyl, ethyl, n-propyl, isopropyl, isobutyl, t-butyl, pentyl, heptyl, octyl, nonyl, decyl, or dodecyl.\",\n \"The term “lower alkyl” refers to an alkyl group containing from one to ten carbon atoms.\",\n \"Unless expressly referred to as an “unsubstituted alkyl,” alkyl groups can either be unsubstituted or substituted.\",\n \"An alkyl group can be substituted with one or more substituents (for example, up to two substituents for each methylene carbon in an alkyl chain).\",\n \"Exemplary alkyl substituents include, for instance, amino groups, amide, sulfonamide, halogen, cyano, carboxy, hydroxy, mercapto, trifluoromethyl, alkyl, alkoxy (such as methoxy), alkylthio, thioalkoxy, arylalkyl, heteroaryl, alkylamino, dialkylamino, alkylsulfano, keto, or other functionality.\",\n \"Amino carbonyl (carbamoyl): A group of the formula —OCN(R)R′—, wherein R and R′ are independently of each other hydrogen or a lower alkyl group.\",\n \"Asthma: Asthma is a disease of the respiratory system in which the airways constrict, become inflamed, and are lined with excessive amounts of mucus, often in response to one or more “triggers,” such as exposure to an environmental stimulant (or allergen), cold air, exercise, or emotional stress.\",\n \"This airway narrowing causes symptoms such as wheezing, shortness of breath, chest tightness, and coughing.\",\n \"The disorder is a chronic or recurring inflammatory condition in which the airways develop increased responsiveness to the various stimuli, characterized by bronchial hyper-responsiveness, inflammation, increased mucus production, and intermittent airway obstruction.\",\n \"Carbamate: A group of the formula —OC(O)N(R)—, wherein R is H, or an aliphatic group, such as a lower alkyl group or an aralkyl group Cardiac Disorder or Disease: In general, a cardiac disorder/disease is a class of disorders/diseases that involve the heart and/or blood vessels (arteries and veins).\",\n \"In a particular example, cardiac disorder/disease includes congestive heart failure.\",\n \"Chronic Obstructive Pulmonary Disease: A group of respiratory tract diseases including chronic bronchitis, emphysema and bronchiectasis that are characterized by airflow obstruction or limitation that is not fully reversible.\",\n \"The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.\",\n \"Congestive Heart Failure: Heart failure in which the heart is unable to maintain an adequate circulation of blood in the bodily tissues or to pump out the venous blood returned to it by the veins.\",\n \"Derivative: A chemical substance that differs from another chemical substance by one or more functional groups.\",\n \"Preferably, a derivative (such as a fenoterol analogue) retains a biological activity (such as β2-adrenergic receptor stimulation) of a molecule from which it was derived (such as a fenoterol).\",\n \"Isomers: Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”.\",\n \"Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”.\",\n \"Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers.” When a compound has an asymmetric center, for example, if a carbon atom is bonded to four different groups, a pair of enantiomers is possible.\",\n \"An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (−) isomers, respectively).\",\n \"A chiral compound can exist as either an individual enantiomer or as a mixture thereof.\",\n \"A mixture containing equal proportions of the enantiomers is called a “racemic mixture.” The compounds described herein may possess one or more asymmetric centers; such compounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof.\",\n \"Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof.\",\n \"The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see, e.g., March, Advanced Organic Chemistry, 4th edition, New York: John Wiley and Sons, 1992, Chapter 4).\",\n \"Optional: “Optional” or “optionally” means that the subsequently described event or circumstance can but need not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.\",\n \"Pharmaceutically Acceptable Carriers: The pharmaceutically acceptable carriers (vehicles) useful in this disclosure are conventional.\",\n \"Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 19th Edition (1995), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compounds or molecules, such as one or more nucleic acid molecules, proteins or antibodies that bind these proteins, and additional pharmaceutical agents.\",\n \"In general, the nature of the carrier will depend on the particular mode of administration being employed.\",\n \"For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle.\",\n \"For solid compositions (for example, powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate.\",\n \"In addition to biologically-neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.\",\n \"Phenyl: Phenyl groups may be unsubstituted or substituted with one, two or three substituents, with substituent(s) independently selected from alkyl, heteroalkyl, aliphatic, heteroaliphatic, thioalkoxy, halo, haloalkyl (such as —CF3), nitro, cyano, —OR (where R is hydrogen or alkyl), —N(R)R′ (where R and R′ are independently of each other hydrogen or alkyl), —COOR (where R is hydrogen or alkyl) or —C(O)N(R′)R″ (where R′ and R″ are independently selected from hydrogen or alkyl).\",\n \"Pulmonary Disorder or Disease: In general, pulmonary disorder/disease includes any disorder/disease pertaining to the lungs.\",\n \"In a particular example, pulmonary disorder/disease includes asthma and chronic obstructive pulmonary disease.\",\n \"Purified: The term “purified” does not require absolute purity; rather, it is intended as a relative term.\",\n \"Thus, for example, a purified preparation is one in which a desired component such as an (R,R)-enantiomer of fenoterol is more enriched than it was in a preceding environment such as in a (±)-fenoterol mixture.\",\n \"A desired component such as (R,R)-enantiomer of fenoterol is considered to be purified, for example, when at least about 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% of a sample by weight is composed of the desired component.\",\n \"Purity of a compound may be determined, for example, by high performance liquid chromatography (HPLC) or other conventional methods.\",\n \"In an example, the specific fenoterol analogue enantiomers are purified to represent greater than 90%, often greater than 95% of the other enantiomers present in a purified preparation.\",\n \"In other cases, the purified preparation may be essentially homogeneous, wherein other stereoisomers are less than 1%.\",\n \"Compounds described herein may be obtained in a purified form or purified by any of the means known in the art, including silica gel and/or alumina chromatography.\",\n \"See, e.g., Introduction to Modern Liquid Chromatography, 2nd Edition, ed.\",\n \"by Snyder and Kirkland, New York: John Wiley and Sons, 1979; and Thin Layer Chromatography, ed.\",\n \"by Stahl, New York: Springer Verlag, 1969.In an example, a compound includes purified fenoterol or fenoterol analogue with a purity of at least about 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% of a sample by weight relative to other contaminants.\",\n \"In a further example, a compound includes at least two purified stereoisomers each with a purity of at least about 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% of a sample by weight relative to other contaminants.\",\n \"For instance, a compound can include a substantially purified (R,R)-fenoterol analogue and a substantially purified (R,S)-fenoterol analogue.\",\n \"Subject: The term “subject” includes both human and veterinary subjects, for example, humans, non-human primates, dogs, cats, horses, rats, mice, and cows.\",\n \"Similarly, the term mammal includes both human and non-human mammals.\",\n \"Treating or treatment: With respect to disease, either term includes (1) preventing the disease, e.g., causing the clinical symptoms of the disease not to develop in a subject that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease, (2) inhibiting the disease, e.g., arresting the development of the disease or its clinical symptoms, or (3) relieving the disease, e.g., causing regression of the disease or its clinical symptoms.\",\n \"Therapeutically Effective Amount: A quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent.\",\n \"For example, this may be the amount of (R,R)-fenoterol or (R,R)- or (R,S)-fenoterol analogue useful in preventing, reducing, and/or inhibiting, and/or treating a cardiac disorder such as congestive heart failure.\",\n \"Ideally, a therapeutically effective amount of an agent is an amount sufficient to prevent, reduce, and/or inhibit, and/or treat the disorder in a subject without causing a substantial cytotoxic effect in the subject.\",\n \"The effective amount of an agent useful for preventing, reducing, and/or inhibiting, and/or treating a disorder in a subject will be dependent on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition.\",\n \"III.\",\n \"(R,R)-Fenoterol and Fenoterol Analogues A.\",\n \"Chemical Structure Some exemplary fenoterol analogues disclosed herein have the formula: wherein R1-R3 independently are hydrogen, acyl, alkoxy carbonyl, amino carbonyl or a combination thereof; R4 is H or lower alkyl; R5 is lower alkyl, wherein X and Y independently are selected from hydrogen, lower —OR6 and —NR7R8; R6 is lower alkyl or acyl; and R7 and R8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl.\",\n \"With continued reference to the general formula for fenoterol analogues above, Y may be —OH In one embodiment, R5 is a 1- or 2-napthyl derivative optionally having 1, 2 or 3 substituents.\",\n \"Examples of such R5 groups are represented by the formula wherein Y1, Y2 and Y3 independently are hydrogen, lower —OR6 and —NR7R8; R6 is independently for each occurrence selected from lower alkyl and acyl; and R7 and R8 independently are hydrogen, lower alkyl, alkoxy carbonyl, acyl or amino carbonyl (carbamoyl).\",\n \"In particular compounds at least one of Y1, Y2 and Y3 is —OCH3.Particular R5 groups include those represented by the formulas wherein R6 is lower alkyl, such as methyl, ethyl, propyl or isopropyl or acyl, such as acetyl.\",\n \"Exemplary R5 groups include In one example, R4 is lower alkyl and R5 is wherein X and Y independently are selected from H, lower alkyl —OR6 and —NR7R8; R6 is lower alkyl; and R7 and R8 independently are hydrogen or lower alkyl.\",\n \"In a further example, R4 is selected from ethyl, n-propyl, and isopropyl and R5 has the formula wherein X is H, —OR6 or —NR7R8.For example, R6 may be methyl or R7 and R8 are hydrogen.\",\n \"In an additional example, R5 has the formula In further embodiments, R4 is selected from methyl, ethyl, n-propyl and isopropyl and R5 represents Examples of suitable groups for R1-R3 that can be cleaved in vivo to provide a hydroxy group include, without limitation, acyl, acyloxy and alkoxy carbonyl groups.\",\n \"Compounds having such cleavable groups are referred to as “prodrugs.” The term “prodrug,” as used herein, means a compound which includes a substituent that is convertible in vivo (e.g., by hydrolysis) to a hydroxyl group.\",\n \"Various forms of prodrugs are known in the art, for example, as discussed in Bundgaard, (ed.\",\n \"), Design of Prodrugs, Elsevier (1985); Widder, et al.\",\n \"(ed.\",\n \"), Methods in Enzymology, Vol.\",\n \"4, Academic Press (1985); Krogsgaard-Larsen, et al., (ed), Design and Application of Prodrugs, Textbook of Drug Design and Development, Chapter 5, 113 191 (1991); Bundgaard, et al., Journal of Drug Delivery Reviews, 8:1 38 (1992); Bundgaard, Pharmaceutical Sciences, 77:285 et seq.\",\n \"(1988); and Higuchi and Stella (eds.)\",\n \"Prodrugs as Novel Drug Delivery Systems, American Chemical Society (1975).\",\n \"An exemplary (R,R)-compound has the chemical structure of: X and R1-R3 are as described above.\",\n \"An additional exemplary (R,R)-compound has the chemical structure: An exemplary (R,S)-compound has the chemical structure: wherein X and R1-R3 are as described above.\",\n \"An additional exemplary (R,S)-compound has the chemical structure: An exemplary (S,R)-compound has the chemical structure: wherein X and R1-R3 are as described above.\",\n \"An exemplary (S,S)-compound has the chemical structure: wherein X and R1-R3 are as described above.\",\n \"Examples of chemical structures illustrating the various stereoisomers of fenoterol are provided below.\",\n \"Particular method embodiments contemplate the use of solvates (such as hydrates), pharmaceutically acceptable salts and/or different physical forms of (R,R)-fenoterol or any of the fenoterol analogues herein described.\",\n \"1.Solvates, Salts and Physical Forms “Solvate” means a physical association of a compound with one or more solvent molecules.\",\n \"This physical association involves varying degrees of ionic and covalent bonding, including by way of example covalent adducts and hydrogen bonded solvates.\",\n \"In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid.\",\n \"“Solvate” encompasses both solution-phase and isolable solvates.\",\n \"Representative solvates include ethanol associated compound, methanol associated compounds, and the like.\",\n \"“Hydrate” is a solvate wherein the solvent molecule(s) is/are H2O.\",\n \"The disclosed compounds also encompass salts including, if several salt-forming groups are present, mixed salts and/or internal salts.\",\n \"The salts are generally pharmaceutically-acceptable salts that are non-toxic.\",\n \"Salts may be of any type (both organic and inorganic), such as fumarates, hydrobromides, hydrochlorides, sulfates and phosphates.\",\n \"In an example, salts include non-metals (e.g., halogens) that form group VII in the periodic table of elements.\",\n \"For example, compounds may be provided as a hydrobromide salt.\",\n \"Additional examples of salt-forming groups include, but are not limited to, a carboxyl group, a phosphonic acid group or a boronic acid group, that can form salts with suitable bases.\",\n \"These salts can include, for example, nontoxic metal cations which are derived from metals of groups IA, IB, IIA and IIB of the periodic table of the elements.\",\n \"In one embodiment, alkali metal cations such as lithium, sodium or potassium ions, or alkaline earth metal cations such as magnesium or calcium ions can be used.\",\n \"The salt can also be a zinc or an ammonium cation.\",\n \"The salt can also be formed with suitable organic amines, such as unsubstituted or hydroxyl-substituted mono-, di- or tri-alkylamines, in particular mono-, di- or tri-alkylamines, or with quaternary ammonium compounds, for example with N-methyl-N-ethylamine, diethylamine, triethylamine, mono-, bis- or tris-(2-hydroxy-lower alkyl)amines, such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine or tris(hydroxymethyl)methylamine, N,N-di-lower alkyl-N-(hydroxy-lower alkyl)amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine, or N-methyl-D-glucamine, or quaternary ammonium compounds such as tetrabutylammonium salts.\",\n \"Exemplary compounds disclosed herein possess at least one basic group that can form acid-base salts with inorganic acids.\",\n \"Examples of basic groups include, but are not limited to, an amino group or imino group.\",\n \"Examples of inorganic acids that can form salts with such basic groups include, but are not limited to, mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid.\",\n \"Basic groups also can form salts with organic carboxylic acids, sulfonic acids, sulfo acids or phospho acids or N-substituted sulfamic acid, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid, and, in addition, with amino acids, for example with α-amino acids, and also with methanesulfonic acid, ethanesulfonic acid, 2-hydroxymethanesulfonic acid, ethane-1,2-disulfonic acid, benzenedisulfonic acid, 4-methylbenzenesulfonic acid, naphthalene-2-sulfonic acid, 2- or 3-phosphoglycerate, glucose-6-phosphate or N-cyclohexylsulfamic acid (with formation of the cyclamates) or with other acidic organic compounds, such as ascorbic acid.\",\n \"In a currently preferred embodiment, fenoterol is provided as a hydrobromide salt and exemplary fenoterol analogues are provided as their fumarate salts.\",\n \"Additional counterions for forming pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, 19th Edition, Mack Publishing Company, Easton, Pa., 1995.In one aspect, employing a pharmaceutically acceptable salt may also serve to adjust the osmotic pressure of a composition.\",\n \"In certain embodiments the compounds used in the method are provided are polymorphous.\",\n \"As such, the compounds can be provided in two or more physical forms, such as different crystal forms, crystalline, liquid crystalline or non-crystalline (amorphous) forms.\",\n \"2.Use for the Manufacture of a Medicament Any of the above described compounds (e.g., (R,R)-fenoterol or fenoterol analogues or a hydrate or pharmaceutically acceptable salt thereof) or combinations thereof are intended for use in the manufacture of a medicament for β2-adrenergic receptor stimulation in a subject or for the treatment of pulmonary and cardiac disorders (e.g., asthma and congestive heart failure).\",\n \"Formulations suitable for such medicaments, subjects who may benefit from same and other related features are described elsewhere herein.\",\n \"B.\",\n \"Methods of Synthesis The disclosed fenoterol analogues can be synthesized by any method known in the art.\",\n \"Many general references providing commonly known chemical synthetic schemes and conditions useful for synthesizing the disclosed compounds are available (see, e.g., Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fifth Edition, Wiley-Interscience, 2001; or Vogel, A Textbook of Practical Organic Chemistry, Including Qualitative Organic Analysis, Fourth Edition, New York: Longman, 1978).\",\n \"Compounds as described herein may be purified by any of the means known in the art, including chromatographic means, such as HPLC, preparative thin layer chromatography, flash column chromatography and ion exchange chromatography.\",\n \"Any suitable stationary phase can be used, including normal and reversed phases as well as ionic resins.\",\n \"Most typically the disclosed compounds are purified via open column chromatography or prep chromatography.\",\n \"Suitable exemplary syntheses of fenoterol analogues are provided below: Scheme III describes an exemplary synthesis for the chiral building blocks used in Scheme II.\",\n \"The (R)- and (S)-3′,5′-dibenzyloxyphenyl-bromohydrin enantiomers were obtained by the enantiospecific reduction of 3,5-dibenzyloxy-α-bromoacetophenone using boron-methyl sulfide complex (BH3SCH3) and either (1R,2S)- or (1S,2R)-cis-1-amino-2-indanol.\",\n \"The required (R)- and (S)-2-benzylaminopropanes were prepared by enantioselective crystallization of the rac-2-benzylaminopropanes using either (R)- or (S)-mandelic acid as the counter ion.\",\n \"IV.\",\n \"Pharmaceutical Compositions The disclosed (R,R)-fenoterol and fenoterol analogues can be useful, at least, for the treatment of pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD) and cardiac disorders such as congestive heart failure.\",\n \"Accordingly, pharmaceutical compositions comprising at least one disclosed fenoterol compound or analogue are also described herein.\",\n \"Formulations for pharmaceutical compositions are well known in the art.\",\n \"For example, Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 19th Edition, 1995, describes exemplary formulations (and components thereof) suitable for pharmaceutical delivery of (R,R)-fenoterol and disclosed fenoterol analogues.\",\n \"Pharmaceutical compositions comprising at least one of these compounds can be formulated for use in human or veterinary medicine.\",\n \"Particular formulations of a disclosed pharmaceutical composition may depend, for example, on the mode of administration (e.g., oral or parenteral) and/or on the disorder to be treated (e.g., pulmonary disorder or cardiac disorder such as congestive heart failure).\",\n \"In some embodiments, formulations include a pharmaceutically acceptable carrier in addition to at least one active ingredient, such as a fenoterol compound.\",\n \"Pharmaceutically acceptable carriers useful for the disclosed methods and compositions are conventional in the art.\",\n \"The nature of a pharmaceutical carrier will depend on the particular mode of administration being employed.\",\n \"For example, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle.\",\n \"For solid compositions such as powder, pill, tablet, or capsule forms conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate.\",\n \"In addition to biologically neutral carriers, pharmaceutical compositions to be administered can optionally contain minor amounts of non-toxic auxiliary substances or excipients, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like; for example, sodium acetate or sorbitan monolaurate.\",\n \"Other non-limiting excipients include, nonionic solubilizers, such as cremophor, or proteins, such as human serum albumin or plasma preparations.\",\n \"The disclosed pharmaceutical compositions may be formulated as a pharmaceutically acceptable salt.\",\n \"Pharmaceutically acceptable salts are non-toxic salts of a free base form of a compound that possesses the desired pharmacological activity of the free base.\",\n \"These salts may be derived from inorganic or organic acids.\",\n \"Non-limiting examples of suitable inorganic acids are hydrochloric acid, nitric acid, hydrobromic acid, sulfuric acid, hydriodic acid, and phosphoric acid.\",\n \"Non-limiting examples of suitable organic acids are acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, methyl sulfonic acid, salicylic acid, formic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, asparagic acid, aspartic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, and the like.\",\n \"Lists of other suitable pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, 19th Edition, Mack Publishing Company, Easton, Pa., 1995.A pharmaceutically acceptable salt may also serve to adjust the osmotic pressure of the composition.\",\n \"The dosage form of a disclosed pharmaceutical composition will be determined by the mode of administration chosen.\",\n \"For example, in addition to injectable fluids, oral dosage forms may be employed.\",\n \"Oral formulations may be liquid such as syrups, solutions or suspensions or solid such as powders, pills, tablets, or capsules.\",\n \"Methods of preparing such dosage forms are known, or will be apparent, to those skilled in the art.\",\n \"Certain embodiments of the pharmaceutical compositions comprising a disclosed compound may be formulated in unit dosage form suitable for individual administration of precise dosages.\",\n \"The amount of active ingredient such as (R,R)-fenoterol administered will depend on the subject being treated, the severity of the disorder, and the manner of administration, and is known to those skilled in the art.\",\n \"Within these bounds, the formulation to be administered will contain a quantity of the extracts or compounds disclosed herein in an amount effective to achieve the desired effect in the subject being treated.\",\n \"In particular examples, for oral administration the compositions are provided in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.0 mg, about 2.5 mg, 5 mg, about 10 mg, or about 50 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.\",\n \"In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg (such as about 2 mg to about 10 mg) active ingredient is administered two to four times a day, such as two times, three times or four times.\",\n \"V. Methods of Use The present disclosure includes methods of treating disorders including pulmonary and cardiac disorders.\",\n \"In some examples, the pulmonary disorder is asthma or chronic obstructive pulmonary disease.\",\n \"In other examples, the cardiac disorder is congestive heart failure.\",\n \"Disclosed methods includes administering (R,R)-fenoterol or a disclosed fenoterol analogue (and, optionally, one or more other pharmaceutical agents) to a subject in a pharmaceutically acceptable carrier and in an amount effective to treat the pulmonary and/or cardiac disorder.\",\n \"Routes of administration useful in the disclosed methods include but are not limited to oral and parenteral routes, such as intravenous (iv), intraperitoneal (ip), rectal, topical, ophthalmic, nasal, and transdermal.\",\n \"Formulations for these dosage forms are described above.\",\n \"An effective amount of (R,R)-fenoterol or a disclosed fenoterol analogue will depend, at least, on the particular method of use, the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition.\",\n \"A “therapeutically effective amount” of a composition is a quantity of a specified compound sufficient to achieve a desired effect in a subject being treated.\",\n \"For example, this may be the amount of a (R,R)-fenoterol necessary to prevent, inhibit, reduce or relieve the pulmonary and/or cardiac disorder and/or one or more symptoms of disorder in a subject.\",\n \"Ideally, a therapeutically effective amount of (R,R)-fenoterol or a disclosed fenoterol analogue is an amount sufficient to prevent, inhibit, reduce or relieve the pulmonary and/or cardiac disorder and/or one or more symptoms of the disorder without causing a substantial cytotoxic effect on host cells.\",\n \"Therapeutically effective doses of a disclosed fenoterol compound or pharmaceutical composition can be determined by one of skill in the art, with a goal of achieving concentrations that are at least as high as the EC50 of the applicable compound disclosed in the examples herein.\",\n \"An example of a dosage range is from about 0.001 to about 10 mg/kg body weight orally in single or divided doses.\",\n \"In particular examples, a dosage range is from about 0.005 to about 5 mg/kg body weight orally in single or divided doses (assuming an average body weight of approximately 70 kg; values adjusted accordingly for persons weighing more or less than average).\",\n \"For oral administration, the compositions are, for example, provided in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.5 mg, about 5 mg, about 10 mg, or about 50 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.\",\n \"In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg active ingredient is administered two to four times a day, such as two times, three times or four times.\",\n \"The specific dose level and frequency of dosage for any particular subject may be varied and will depend upon a variety of factors, including the activity of the specific compound, the metabolic stability and length of action of that compound, the age, body weight, general health, sex and diet of the subject, mode and time of administration, rate of excretion, drug combination, and severity of the condition of the subject undergoing therapy.\",\n \"The subject matter of the present disclosure is further illustrated by the following non-limiting Examples.\",\n \"EXAMPLES Example 1 Materials and Methods Reagents.\",\n \"Phenylmethylsulfonyl fluoride (PMSF), benzamidine, leupeptin, pepstatin A, MgCl2, EDTA, Trizma-Hydrochloride (Tris-HCl), (±)-propranolol and minimal essential medium (MEM) were obtained from Sigma Aldrich (St. Louis, Mo.).\",\n \"Egg phosphatidylcholine lipids (PC) were obtained from Avanti Polar Lipids (Alabaster, Ala.).\",\n \"(±)-fenoterol was purchased from Sigma Aldrich and [3H]-(±)-fenoterol was acquired from Amersham Biosciences (Boston, Mass.).\",\n \"The organic solvents n-hexane, 2-propanol and triethylamine were obtained as ultra pure HPLC grade solvents from Carlo Erba (Milan, Italy).\",\n \"Fetal bovine serum and penicillin-streptomycin were purchased from Life Technologies (Gaithersburg, Md.\",\n \"), and [125I]-(±)-iodocyanopindolol (ICYP) was purchased from NEN Life Science Products, Inc. (Boston, Mass.).\",\n \"Preparation and Identification of (R,R)-Fenoterol and (S,S)-Fenoterol.\",\n \"(R,R)-fenoterol and (S,S)-fenoterol were prepared from (±)-fenoterol using chiral HPLC techniques employing an HPLC column (25 cm×0.46 cm i.d.)\",\n \"containing the amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase (CHIRALPAK® AD CSP, Chiral Technologies, West Chester, Pa.; CHIRALPAK is a registered trademark of Daicel Chemical Industries Ltd., Exton, Pa.).\",\n \"The chromatographic system consisted of a JASCO® PU-980 solvent delivery system, and a JASCO® MD-910 multi-wavelength detector set at λ=230 nm, connected to a computer workstation; JASCO is a registered trademark of JASCO, Inc., Tokyo, Japan).\",\n \"A Rheodyne model 7125 injector with 20 μl sample loop was used to inject 0.2-0.3 mg (±)-fenoterol onto the chromatographic system.\",\n \"The mobile phase was n-hexane/2-propanol (88/12 v/v) with 0.1% triethylamine, the flow rate was 1 mL/minute and the temperature of the system was maintained at 25° C. using a column heater/chiller (Model 7955, Jones Chromatography Ltd., UK).\",\n \"The separated (R,R)-fenoterol and (S,S)-fenoterol were collected in 10-mL fractions as the respective peaks eluted from the chromatographic column.\",\n \"A 2-mL intermediate fraction was collected and discarded to improve the enantiomeric purity of the collected isomers.\",\n \"The stereochemical configurations of the resolved (R,R)-fenoterol and (S,S)-fenoterol were established using circular dichroism (CD) measurements obtained with a JASCO® J-800 spectropolarimeter.\",\n \"The (R,R)-fenoterol and (S,S)-fenoterol were dissolved in 2-propanol and the measurements were obtained using 1 cm path length at room temperature.\",\n \"Immobilized β2-AR Frontal Chromatography.\",\n \"The liquid chromatography column containing the immobilized β2-AR was prepared using a previously described technique (Beigi et al., Anal.\",\n \"Chem., 76: 7187-7193, 2004).\",\n \"In brief, cellular membranes were obtained from a HEK 293 cell line that had been transfected with cDNA encoding human β2-AR.\",\n \"An aliquot of a cell pellet suspension corresponding to 5-7 mg total protein, as determined by the micro BCA method, was used to create the column.\",\n \"The membranes were prepared in 10 mL buffer composed of Tris-HCl [50 mM, pH 7.4] containing MgCl2 (2 mM), benzamidine (1 mM), leupeptin (0.03 mM) pepstatin A (0.005 mM) and EDTA (1 mM).\",\n \"A 180 mg aliquot of immobilized artificial membrane chromatographic support (IAM-PC, 12 micron particle size, 300 {acute over (Å)} pore size obtained from Regis Chemical Co., Morton Grove, Ill.) and 80 μM PC were added to the membrane preparation and the resulting mixture was stirred at room temperature for 3 hours, transferred into (5 cm length) nitrocellulose dialysis membrane (MW cutoff 10,000 Da, Pierce Chemical, Rockford, Ill.) and placed in 1 L of dialysis buffer composed of Tris-HCl [50 mM, pH 7.4] containing EDTA (1 mM), MgCl2 (2 mM), NaCl (300 mM) and PMSF (0.2 mM) at 4° C. for 24 hours.\",\n \"The dialysis step was repeated twice using fresh buffer.\",\n \"After dialysis, the mixture was centrifuged at 120×g for 3 minutes, the supernatant was discarded and the pellet of IAM support containing the immobilized receptor-bearing membranes was collected.\",\n \"The pellet was resuspended in 2 mL chromatographic running buffer, composed of Tris-HCl [10 mM, pH 7.4] containing EDTA (1 mM) and MgCl2 (2 mM) and the suspension was pumped through a HR 5/2 chromatographic glass column (Amersham Pharmacia Biotech, Uppsala, Sweden) at a flow rate of 0.3 mL/minutes using a peristaltic pump.\",\n \"The end adaptors were assembled producing a total gel-bed volume of 0.4 mL.\",\n \"The column was stored at 4° C. when not in use.\",\n \"The column containing the immobilized β2-AR stationary phase was placed in a chromatographic system composed of a HPLC pump (10-AD, Shimadzu Inc., Columbia, Md.\",\n \"), a manually controlled FPLC injector (Amersham Biotechnology, Uppsala, Sweden) with a 50 μL sample loop, the packed immobilized receptor column and an on-line radioactive flow detector (IN/US, Tampa, Fla.), all connected sequentially.\",\n \"In the frontal chromatographic studies, sample volumes of 5-7 mL were applied continuously until the elution profile showed a plateau region.\",\n \"The running buffer was composed of Tris-HCl [10 mM, pH 7.4] containing EDTA (1 mM) and MgCl2 (2 mM) and 0.05 nM [3H]-(±)-fenoterol, the marker ligand.\",\n \"(R,R)-fenoterol or (S,S)-fenoterol was added to the running buffer in sequential concentrations of 0.1, 80.0, 240, and 700 nM, and applied to the column.\",\n \"The immobilized receptor column was equilibrated with about 80 mL of running buffer, without the added (R,R)-fenoterol or (S,S)-fenoterol respectively, in between each sample injection.\",\n \"All chromatographic studies were carried out at room temperature at a flow rate of 0.2 mL/minutes.\",\n \"The data were analyzed to determine the number of binding sites and dissociation constant using the non-linear equation (1), [ M ] ( Vi - V min ) = P [ M ] Kd + [ M ] ( Eq .\",\n \" 1 ) where Vi is the solute elution volume, Vmin is the elution volume at the saturation point, P is the number of available binding sites, M is the concentration of the marker ligand and Kd is the dissociation constant of the ligand.\",\n \"Ligand-Displacement Binding.\",\n \"Twenty-four hours after adenoviral infection with human β2-AR, HEK293 cells were harvested in lysis buffer, Tris-HCl [5 mM, pH 7.4] containing EGTA [5 mM], and homogenized with 15 strokes on ice.\",\n \"Samples were centrifuged at 30,000×g for 15 minutes to pellet membranes.\",\n \"Membranes were resuspended in binding buffer, Tris-HCl [20 mM, pH 7.4] containing NaCl (120 mM), KCl (5.4 mM), CaCl2 (1.8 mM), MgCl2 (0.8 mM), and glucose (5 mM) and stored in aliquots at −80° C. Binding assays were performed on 5-10 μg of membrane protein using saturating amounts (1-300 pM) of the β-AR-specific ligand [125I]cyanopindolol (ICYP).\",\n \"For competition binding, the 5-10 μg of membrane protein were pretreated with 50 μM of GTPγs (non-hydrolyzable guanosine triphosphate) and then incubated with 125ICYP (50 pM) and different concentrations of fenoterol or its isomers in a total volume of 250 μL.\",\n \"Nonspecific binding was determined in the presence of 20 μM propranolol.\",\n \"Reactions were conducted in 250 μL of binding buffer at 37° C. for 1 hour.\",\n \"The binding reaction was terminated by addition of ice-cold Tris-HCl [10 mM, pH 7.4] to the membrane suspension, followed by rapid vacuum filtration through glass-fiber filters (Whatman GF/C).\",\n \"Each filter was washed three times with an additional 7 mL of ice-cold Tris-HCl [10 mM, pH 7.4].\",\n \"The radioactivity of the wet filters was determined in a gamma counter.\",\n \"All assays were performed in duplicate, and receptor density was normalized to milligrams of membrane protein.\",\n \"Kd and the maximal number of binding sites (Bmax) for ICYP were determined by Scatchard analysis of saturation binding isotherms.\",\n \"Data from competition studies were analyzed using 1- or 2-site competition binding curves with GRAPHPAD PRISM® Software (GRAPHPAD PRISM is a registered trademark of GraphPad Software, Inc., San Diego, Calif.).\",\n \"Example 2 Purification and Identification of (R,R)-Fenoterol and (S,S)-Fenoterol This example demonstrates the resolution of (R,R)-fenoterol and (S,S)-fenoterol from (±)-fenoterol to a high degree of enantiomeric purity.\",\n \"Using the chromatographic conditions described in Example 1, (±)-fenoterol was separated into its component enantiomers, (R,R)-fenoterol and (S,S)-fenoterol, on the AD-CSP.\",\n \"As illustrated in FIG.\",\n \"1, the two stereoisomers were resolved with enantioselectivity factor (α) of 1.21 and a resolution factor (RS) of 1.06.Because of the observed tailing of the chromatographic peaks, a 2-mL intermediate fraction was collected and discarded.\",\n \"The collected peaks were analyzed using the same chromatographic conditions and the data demonstrated that both enantiomers had been prepared with >97% stereochemical purity.\",\n \"The assignment of the absolute configuration of the isolated fractions was accomplished using their chiroptical properties.\",\n \"The ultraviolet (UV) spectra of both fractions contained identical maxima at about 280 and 230, indicating the same UV chromophores for the two enantiomers.\",\n \"The circular dichroism (CD) spectrum shows, for the less retained enantiomeric fraction, negative CD bands at about 280 and 215 nm, while the spectrum is positive at 230 and 200 nm.\",\n \"The sign of the CD bands is reversed for the most retained fenoterol fraction, this confirming the enantiomeric nature of the two fractions.\",\n \"The lowest energy UV and CD spectra of the two enantiomeric fractions are presented in FIGS.\",\n \"2A and 2B, respectively.\",\n \"The less retained chromatographic fraction showed a negative CD band at about 280 nm, while the CD spectrum of the most retained chromatographic fraction contained a positive CD band at the same wavelength (FIG.\",\n \"2B).\",\n \"These results indicate that each of the fractions contained one of the fenoterol enantiomers.\",\n \"The sign of the lowest energy CD band can be used to assign the absolute configuration to the separated fenoterol enantiomers, by applying the Brewster-Buta/Smith-Fontana sector rule for chiral benzylic derivatives (Brewster and Buta, J.\",\n \"Am.\",\n \"Chem.\",\n \"Soc., 88: 2233-2240, 1996).\",\n \"This sector rule is used to predict the sign of the CD band related to the 1Lb electronic transition of the benzylic compounds, with either hydroxyl or amine moieties and has been primarily applied to conformationally mobile aromatic compounds containing a single stereogenic center.\",\n \"In the case of fenoterol, there are two stereogenic centers.\",\n \"However, it is believed that the observed optical activity is mainly determined by the arylcarbinol moiety, because of the distance between the aromatic ring and the stereogenic center.\",\n \"The application of this rule permitted the assignment of the absolute configuration of (S,S) to the fenoterol enantiomer contained in the less retained fraction that showed a negative CD band at 280 nm, and the absolute configuration of (R,R) to the fenoterol enantiomer contained in the most retained fraction that showed a positive CD band at 280 nm.\",\n \"This assignment was confirmed by the independent synthesis of (S,S)-fenoterol and (R,R)-fenoterol.\",\n \"These studies indicate that (R,R)-fenoterol and (S,S)-fenoterol can be separated from (±)-fenoterol to a high degree of enantiomeric purity.\",\n \"Example 3 Chromatographic Determination of the Binding of (R,R)-Fenoterol and (S,S)-Fenoterol to the Immobilized β2-AR This example demonstrates that (R,R)-fenoterol is responsible for the β2-AR binding of the clinically used drug (±)-fenoterol.\",\n \"The preparation, characterization and application of a liquid chromatographic stationary phase containing immobilized membranes obtained from the β2-AR HEK-293 cell line have been previously reported (Beigi et al., Anal.\",\n \"Chem., 76: 7187-7193, 2004).\",\n \"For example, Beigi et al.\",\n \"(Anal.\",\n \"Chem., 76: 7187-7193, 2004) demonstrated that frontal displacement chromatography could be used to determine the dissociation constants (Kd) for the binding of two β2-AR antagonists, (S)-propranolol and CGP 12177A, to the immobilized β2-AR.\",\n \"Zonal displacement chromatography using CGP 12177A as the marker ligand demonstrated that the immobilized β2-AR had retained its enantioselectivity as the addition of (S)-propranolol to the mobile phase produced a greater displacement than the addition of (R)-propranolol (Id.).\",\n \"The addition of (±)-fenoterol to the mobile phase was also shown to produce a conformation change in the immobilized β2-AR (Id.).\",\n \"Agonist-induced conformational changes of the β2-AR, as well as most G-protein coupled receptors, from a resting to active state have been documented (Ghanoui et al., Proc.\",\n \"Natl.\",\n \"Acad.\",\n \"Sci.\",\n \"U.S.A., 98: 5997-6002, 2001).\",\n \"Presently, the immobilized β2-AR column was equilibrated with the running buffer containing the [3H]-fenoterol, the marker ligand, before the initiation of the displacement studies.\",\n \"It was assumed that the binding data calculated using frontal displacement chromatography reflects the binding of (R,R)-fenoterol and (S,S)-fenoterol to the active state of the receptor.\",\n \"In frontal chromatography, the initial flat portion of the chromatographic trace represents the binding of a marker ligand that is specific for the immobilized target, in this study the β2-AR, as well as non-specific binding to other sites on the immobilized membrane fragments.\",\n \"Saturation of specific binding sites produces a breakthrough front followed by a plateau representing the establishment of a new equilibrium.\",\n \"The addition of a second compound into the mobile phase will produce a shift of the chromatographic trace to the left if the compound competes with the marker for binding to the β2-AR.\",\n \"The relationship between the magnitude of this shift and the concentration of the marker ligand can be used to calculate the binding affinity of the displacer for the target and the number of active binding sites.\",\n \"This approach has been recently reviewed (Moaddel and Wainer, Anal.\",\n \"Chem.\",\n \"Acata, 546: 97-105, 2006).\",\n \"As shown in FIG.\",\n \"3 (curve 1), the addition of [3H]-fenoterol to the running buffer produced the expected frontal chromatography trace.\",\n \"Sequential addition of increasing concentrations of (R,R)-fenoterol to the running buffer produced a corresponding shift in the chromatographic traces towards smaller retention volumes (FIG.\",\n \"3, curves 2-4).\",\n \"The magnitude and the shift and the corresponding concentrations of (R,R)-fenoterol were analyzed using Eqn 1 and the calculated dissociation constant, Kd, was 472 nM and the amount of available binding sites [P] was 176 pmoles per column, r2=0.9999 (n=2).\",\n \"The sequential addition of increasing concentrations of (S,S)-fenoterol to the running buffer produced no corresponding shift in the chromatographic traces toward shorter retention times.\",\n \"Thus, (S,S)-fenoterol had no significant affinity for the immobilized β2-AR.\",\n \"In order to validate the chromatographic results, a standard membrane binding study was conducted using membranes obtained from the same HEK-293 cell line used to create the immobilized β2-AR column.\",\n \"The data reflected the presence of a single binding site with (mean±SD) Kd=457±55 nM (n=4) for (R,R)-fenoterol and 109,000±10,400 nM (n=4) for (S,S)-fenoterol.\",\n \"These data indicate that frontal affinity chromatography on immobilized cellular membrane columns can be used to determine the magnitude and enantioselectivity of ligand binding to the target receptor.\",\n \"Further, the results from the frontal affinity chromatography and ligand competition binding studies both demonstrate that (R,R)-fenoterol is responsible for the β2-AR binding of the clinically used drug (±)-fenoterol.\",\n \"Example 4 The Effect of (R,R)-Fenoterol and (S,S)-Fenoterol on Cardiomyocyte Contractility This example demonstrates that (R,R)-fenoterol and (S,S)-fenoterol differentially activate β2-adrenergic receptor/stimulatory heterotrimeric G protein (AR/Gs) signaling in regards to cell contractility.\",\n \"To determine if (R,R)-fenoterol and (S,S)-fenoterol differentially activate β2-AR/Gs signaling in the regulation of cell contractility, freshly isolated adult rat cardiomyocytes were perfused with various concentrations of either (R,R)-fenoterol or (S,S)-fenoterol.\",\n \"These studies were carried out using a previously described approach (Thou et al., Mol.\",\n \"Pharmacol., 200, 58: 887-894).\",\n \"In brief, single ventricular myocytes were isolated from 2-4 month old rat hearts by a standard enzymatic technique.\",\n \"The isolated cells were resuspended in HEPES buffer solution [20 mM, pH 7.4] containing, NaCl (137 mM), KCl (5.4 mM), MgCl2 (1.2 mM), NaH2PO4 (1.0 mM), CaCl2 (1.0 mM), and glucose (20 mM).\",\n \"All studies were performed within 8 hours of cell isolation.\",\n \"The cells were placed on the stage of an inverted microscope (Zeiss model IM-35, Zeiss, Thornwood, N.Y.), perfused with the HEPES-buffered solution at a flow rate of 1.8 mL/minutes, and electrically stimulated at 0.5 Hz at 23° C. Cell length was monitored by an optical edge-tracking method using a photodiode array (Model 1024 SAQ, Reticon, Boston, Mass.)\",\n \"with a 3 ms time resolution.\",\n \"Cell contraction was measured by the percent shortening of cell length following electrical stimulation.\",\n \"The addition of (R,R)-fenoterol (10−8 to 10−5 M) produced a markedly elevated positive inotropic effect and a significant upward shift of the dose-response curve compared to (±)-fenoterol (FIG.\",\n \"4A).\",\n \"This was demonstrated by an increase in the maximum contractile response from 265±11.6% to 306±11.8% resting cell length (p<0.05) and a reduction in EC50 from −7.0±0.2 to −7.1±0.2 log [M](p<0.05).\",\n \"In contrast, (S,S)-fenoterol had only a minor positive inotropic effect (FIG.\",\n \"4B).\",\n \"The cardiomyocyte contractility studies indicate that (R,R)-fenoterol is responsible for the observed β2-AR agonist activity in cardiomyocytes.\",\n \"Example 5 Synthesis General Procedures: All reactions were carried out using commercial grade reagents and solvents.\",\n \"Tetrahydrofuran (THF) was dried by refluxing over sodium and benzophenone.\",\n \"Dichloromethane was dried by refluxing over calcium hydride.\",\n \"Ultraviolet spectra were recorded on a Cary 50 Concentration spectrophotometer.\",\n \"Optical rotations were done on a Rudolph Research Autopol IV.\",\n \"NMR Spectra were recorded on a Varian Mercury VMX 300-MHz spectrophotometer using tetramethylsilane as the internal standard.\",\n \"NMR multiplicities were reported by using the following abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; p, pentet; m, multiplet; apt., apparent; and br, broad.\",\n \"Low resolution mass spectra were obtained on a Finnigan LCQDuo LC MS/MS atmospheric pressure chemical ionization (API) quadrupole ion trap MS system equipped with both electrospray (ESI) and atmospheric pressure chemical ionization (APCI) probes.\",\n \"Analytical HPLC data was obtained using a Waters 2690 Separations Module with PDA detection.\",\n \"Method (a): ThermoHypersil BDS 100×4.6 mm C18 column, H2O/CH3CN/TFA.\",\n \"Method (b): Brownlee Phenyl Spheri-5 100×4.6 mm, water/acetonitrile/TFA.\",\n \"Method (c): Vydac 150×4 mm C18 column, H2O/isopropanol/TFA.\",\n \"Method (d): CHIRALPAK® AD-H 250×10 mm, 95/5/0.05 CH3CN/isopropanol/diethylamine.\",\n \"Merck silica gel (230-400 mesh) was used for open column chromatography.\",\n \"3′,5′-Dibenzyloxy-α-bromoacetophenone (46).\",\n \"A solution of 2.4 mL (46 mmol) of Br2 in 45 mL of CHCl3 was added dropwise over 1 h to a chilled, stirring solution of 9.66 g (29 mmol) of 3′,5′-dibenzyloxyacetophenone (45) in 40 mL of CHCl3.The resulting solution was allowed to warm to room temperature over 1 hour with good stirring, then poured into 100 mL of cold H2O and transferred to a separatory funnel where the CHCl3 fraction was isolated, washed with brine solution, dried (Na2SO4), filtered, and concentrated to 10.8 g. This material was applied to 500 g of silica gel, eluting with CHCl3 to obtain 2.65 g (22%) of compound 46 as a white solid.\",\n \"1H NMR (CDCl3) δ 4.39 (s, 2H), 5.08 (s, 4H), 6.85 (t, 1H, J=2.1 Hz), 7.20 (d, 2H, J=2.4 Hz), 7.31-7.44 (m, 10H).\",\n \"General Procedure for the Enantioselective Reduction of Compound 46 to 3′,5′-Dibenzyloxyphenylbromohydrins [(R)-8, (S)-/3].\",\n \"Under argon atmosphere, 0.06 mL (0.316 mmol, 10 mol %) of 5.0 M boron-methyl sulfide complex (BH3SCH3) in diethyl ether was added in one portion to a solution of 25 mg (0.16 mmol, 5 mol %) of the appropriate cis-1-amino-2-indanol in 3 mL of dry THF.\",\n \"This material under argon was added over 30 minutes to a solution of 1.3 g (3.16 mmol) of 3′,5′-dibenzyloxy-α-bromoacetophenone in 20 mL of dry THF, while at the same time adding in ˜0.05 mL pulses, 0.45 mL of 5.0 M boron-methyl sulfide complex.\",\n \"The resulting solution was stirred under argon for 2 hours, and then quenched with 3 mL of methanol, controlling gas evolution.\",\n \"Solvents were removed in vacuo and the resulting residue taken up in 30 mL of CHCl3 and washed with 25 mL of 0.2 M sulfuric acid followed by 20 mL of brine, then dried (Na2SO4), filtered, and evaporated.\",\n \"(R)-(−)-3′,5′-Dibenzyloxyphenylbromohydrin [(R)-8].\",\n \"Prepared with (1R,2D)-(+)-cis-1-amino-2-indanol as the enantioselective reduction catalyst to give 1.02 g (78%) of (R)-8 as a fine white powder.\",\n \"1H NMR (CDCl3) δ 3.44 (dd, 1H, J=9.0, 10.5 Hz), 3.55 (dd, 1H, J=3.3, 10.5 Hz), 4.79 (dd, 1H, J=3.3, 8.7 Hz), 4.97 (s, 4H), 6.51 (t, 1H, J=2.4 Hz), 6.57 (d, 2H, J=1.8 Hz), 7.21-7.38 (m, 10H); [α]D=−12.1° (c=1.0 MeOH).\",\n \"(S)-(+)-3′,5′-Dibenzyloxyphenylbromohydrin [(S)-8].\",\n \"Prepared with (1S,2R)-(−)-cis-1-amino-2-indanol as the enantioselective reduction catalyst to give 1.07 g (82%) of (S)-8 as a fine white powder.\",\n \"1H NMR (CDCl3) δ 3.43 (dd, 1H, J=9.0, 10.5 Hz), 3.55 (dd, 1H, J=3.3, 10.5 Hz), 4.78 (dd, 1H, J=3.3, 8.7 Hz), 4.96 (s, 4H), 6.50 (t, 1H, J=2.4 Hz), 6.57 (d, 2H, J=1.8 Hz), 7.21-7.39 (m, 10H); [α]D=+11.8° (c=0.90 MeOH).\",\n \"4-Benzyloxyphenylacetone (34).\",\n \"To 10.0 g (41.3 mmol) of 4-benzyloxyphenylacetic acid (31) was added, 20 mL of acetic anhydride and 20 mL of pyridine, which was heated to reflux with stirring under argon atmosphere for 6 hours.\",\n \"Solvents were evaporated and residue dissolved in CHCl3 (50 mL) and washed with 1N NaOH (2×50 mL).\",\n \"Dried organic layer (MgSO4), filtered, and evaporated to 11.8 g of an amber oil.\",\n \"Vacuum distillation at 0.1 mm Hg in an oil-bath set to 170° C. followed by silica gel chromatography eluting with 8/2 CH2Cl2-hexanes gave 2.68 g (27%).\",\n \"1H NMR (CDCl3) δ 2.14 (s, 3H), 3.63 (s, 2H), 5.05 (s, 2H), 6.94 (d, 2H, J=8.7 Hz), 7.10 (d, 2H, J=8.7 Hz), 7.26-7.47 (m, 5H).\",\n \"Phenylacetone (35).\",\n \"A solution of 20.4 g (0.15 mol) of phenylacetic acid, acetic anhydride (70 mL) and pyridine (70 mL) was heated to reflux with stirring under argon atmosphere for 6 hours.\",\n \"Solvents were evaporated and residue dissolved in CHCl3 (100 mL), washed with 1N NaOH (2×100 mL) and dried the organic layer (MgSO4), filtered, and evaporated to give 20.4 g. Vacuum distillation at 0.1 mm Hg in an oil bath set to 160° C., followed by silica gel chromatography eluting with 1/1 hexanes/CH2Cl2 gave 5.5 g (27%).\",\n \"1H (CDCl3) δ 2.15 (s, 3H), 3.70 (s, 2H), 7.20-7.36 (m, 5H).\",\n \"1-Naphthalen-1-yl-propan-2-one (36).\",\n \"A solution of 37.2 g (20 mmol) of naphthoic acid (33), acetic anhydride (100 mL) and pyridine (100 mL) was heated to reflux with stirring under argon atmosphere for 6 hours.\",\n \"Evaporated solvents, dissolved residue in CHCl3 (200 mL) and washed with 1N NaOH (2×150 mL), dried organic layer (MgSO4), filtered, and evaporated to give 34.6 g. Distillation at 0.5 mm Hg in an oil bath set to 170° C., followed silica gel chromatography eluting with 1/1 hexanes/CH2Cl2 gave 9.7 g (26%).\",\n \"1H (CDCl3) δ 2.11 (s, 3H), 4.12 (s, 2H), 7.40-7.53 (m, 4H), 7.81 (d, 1H, J=8.4 Hz), 7.87-7.90 (m, 2H).\",\n \"General Procedure for Preparation of 2-benzylaminopropanes (37-39, 42, 43).\",\n \"To the appropriate ketone (1 eq) in CH2Cl2 (c=0.5 M), cooled to 0° C. was added glacial HOAc (1 eq), followed by benzylamine (1 eq) and NaBH(AcO)3 (1.4 eq).\",\n \"The reaction mixture was warmed to room temperature and stirred under argon for 20 hours.\",\n \"The reaction mixture was cooled (ice bath), 10% NaOH (5 eq) was added dropwise and then extracted into CH2Cl2, washed with brine.\",\n \"The product was then dried (Na2SO4), filtered and evaporated.\",\n \"1-(4-benzyloxy)-2-benzylaminopropane (37).\",\n \"Prepared from 4-benzyloxyphenylacetone (34; 2.0 g, 8.3 mmol) to afford 2.61 g (95%) as a tan solid.\",\n \"1H (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.50-2.58 (m, 1H).\",\n \"2.68-2.77 (m, 1H), 2.82-2.89 (m, 1H), 3.75 (dd, 2H, J=12 Hz, J=30 Hz), 5.05 (s, 2H), 6.90 (d, 2H, J=8.7 Hz), 7.04 (d, 2H, J=8.7 Hz), 7.17-7.42 (m, 10H); MS (APCI+) m/z (rel): 332 (100).\",\n \"1-Phenyl-2-benzylaminopropane (38).\",\n \"Prepared from phenylacetone (35; 5.5 g, 41 mmol) to afford 8.4 g (91%) as a tan solid.\",\n \"1H (CDCl3) δ 1.09 (d, 3H, J=6.3 Hz), 2.61-2.81 (m, 2H), 2.92 (m, 1H), 3.80 (dd, 2H), 7.14-7.30 (m, 10H); MS (APCI+) m/z (rel): 226 (100).\",\n \"1-(1′-Naphthyl)-2-benzylaminopropane (39).\",\n \"Prepared from 1-naphthalen-1-yl-propan-2-one (36; 5.0 g, 27.1 mmol) to afford 7.0 g (94%) as a tan solid.\",\n \"1H (CDCl3) δ 1.14 (d, 3H, J=6.0 Hz), 3.02-3.18 (m, 2H), 3.27 (m, 1H), 3.80 (dd, 2H, J=13.2, 43.8 Hz), 7.13-7.23 (m, 5H), 7.31-7.48 (m, 4H), 7.73 (d, 1H, J=7.8 Hz), 7.83-7.86 (m, 1H), 7.96-7.99 (m, 1H); MS (APCI+) m/z (rel): 276 (100).\",\n \"1-(4′-Methoxyphenyl)-2-benzylaminopropane (42).\",\n \"Prepared from 4-methoxyphenyl-acetone (40; 2.75 g, 13.1 mmol) to afford 2.31 g (97%).\",\n \"1H (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.56-2.75 (m, 2H), 2.90 (m, 1H), 3.79 (s, 1H), 3.79 (m, 2H, J=13.2 Hz), 6.82 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.7 Hz), 7.18-7.32 (m, 5H); MS (APCI+) m/z (rel): 256 (100).\",\n \"1-(4′-nitrophenyl)-2-benzylaminopropane (43).\",\n \"Prepared from 4-nitrophenyl-acetone (41; 4.95 g, 28 mmol) to afford 7.32 g (98%) as an amber oil.\",\n \"1H (CDCl3) δ 1.60 (d, 3H, J=6.3 Hz), 2.73-2.85 (m, 1H), 3.00-3.12 (m, 2H), 3.86 (dd, 2H, J=26 Hz, J=60 Hz), 7.23-7.40 (m, 5H), 7.30 (d, 2H, J=9.0 Hz), 8.14 (d, 2H, J=8.7 Hz).\",\n \"MS (APCI+) m/z (rel): 271 (100).\",\n \"General Procedure for Enantiomeric Separation of 2-benzylaminopropanes [(R)-10-14, (S)-10-14].\",\n \"The appropriate racemic 2-benzylaminopropane (1 eq) was combined with the appropriate optically active mandelic acid (1 eq) in methanol (c=0.5 M) and refluxed until the solution homogenized, then cooled to RT.\",\n \"The crystals were filtered, collected, and recrystallized twice from methanol (c=0.3 M) to afford the optically active 2-benzylaminopropane.mandelic acid salt.\",\n \"The salts were converted to the free amine for the purpose of collecting NMR and rotation data by partitioning the mandelic acid salt between 10% K2CO3 and CHCl3, drying organic extracts (Na2SO4) and evaporating.\",\n \"(R)-(−)-1-(4′-benzyloxy)-2-benzylaminopropane [(R)-10].\",\n \"A sample of 2.13 g (6.42 mmol) of 1-(4-benzyloxy)-2-benzylaminopropane (37) was reacted with 972 mg (6.42 mmol) of (R)-(−)-mandelic acid to give 295 mg (28% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.12 (d, 3H, J=6.3 Hz), 2.58-2.78 (m, 2H), 2.82-2.91 (m, 1H), 3.75 (dd, 2H, J=12 Hz, J=30 Hz)), 5.07 (s, 2H), 6.93 (d, 2H, J=8.7 Hz), 7.10 (d, 2H, J=8.7 Hz), 7.21-7.42 (m, 10H); MS (APCI+) m/z (rel): 332 (100); [α]D=−19.1° (c=1.4, MeOH).\",\n \"(S)-(+)-1-(4′-benzyloxy)-2-benzylaminopropane [(S)-10].\",\n \"The washes from the separation of (R)-10 were concentrated and partitioned between 50 mL of chloroform and 50 mL of 10% K2CO3 in water.\",\n \"Washed organics with brine, dried (Na2SO4), filtered and evaporated to 1.70 g (5.1 mmol).\",\n \"The organics were brought to reflux with 782 mg (5.1 mmol) of (S)-(+)-mandelic acid (as previously described) and crystallized 3 times to obtain 670 mg of the (S)-amine.\",\n \"(S)-mandelic acid salt.\",\n \"The (S)-amine.\",\n \"(S)-mandelic acid salt was triturated in ether then partitioned between 30 mL of chloroform and 20 mL of 10% K2CO3 in water.\",\n \"The organic partition was washed with brine, then dried (Na2SO4), filtered and evaporated to give 366 mg of the free amine (33% based on enantiomeric abundance).\",\n \"1H NMR (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.58-2.78 (m, 2H), 2.82-2.91 (m, 1H), 3.76 (dd, 2H, J=12, 30 Hz), 5.06 (s, 2H), 6.93 (d, 2H, J=8.7 Hz), 7.09 (d, 2H, J=8.7 Hz), 7.21-7.42 (m, 10H); MS (APCI+) m/z (rel): 332 (100); [α]D=+19.2° (c=1.5 MeOH).\",\n \"(R)-(−)-1-(4′-Methoxyphenyl)-2-benzylaminopropane [(R)-11].\",\n \"A sample of 3.02 g (11.8 mmol) of 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 1.8 g (11.8 mmol) (S)-(+)-mandelic acid to give 530 mg (35% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.10 (d, 3H, J=6.3 Hz), 2.57-2.76 (m, 2H), 2.88-2.94 (m, 1H), 3.79 (s, 3H), 3.72-3.88 (m, 2H), 6.82 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.15-7.31 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=−30.4° (c=1.25 MeOH).\",\n \"(S)-(+)-1-(4′-Methoxyphenyl)-2-benzylaminopropane [(S)-11].\",\n \"A sample of 3.36 g (13.2 mmol) of the racemate 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 2.0 g (13.2 mmol) of (R)-(−)-mandelic acid to give 740 mg (44% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR, (CDCl3) δ 1.10 (d, 3H, J=6.2 Hz), 2.55-2.76 (m, 2H), 2.88-2.95 (m, 1H), 3.73-3.88 (m, 2H), 3.79 (s, 3H), 6.80 (d, 2H, J=8.7 Hz), 7.08 (d, 2H, J=8.4 Hz), 7.15-7.30 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=+30.5° (c=1.1 MeOH).\",\n \"(R)-(−)-1-(4′-nitrophenyl)-2-benzylaminopropane [(R)-12].\",\n \"A sample of 2.0 g (7.3 mmol) of 1-(4′-nitrophenyl)-2-benzylaminopropane (43) was reacted with 1.13 g (7.3 mmol) of (S)-(+)-mandelic acid to give 486 mg (49% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.60 (d, 3H, J=6.3 Hz), 2.73-2.85 (m, 1H), 3.00-3.12 (m, 2H), 3.86 (dd, 2H, J=26 Hz, J=60 Hz), 7.23-7.40 (m, 5H), 7.30 (d, 2H, J=9.0 Hz), 8.14 (d, 2H, J=8.7 Hz); MS (APCI+) m/z (rel): 271 (100); [α]D=−9.3° (c=1.0 MeOH).\",\n \"(S)-(+)-1-(4′-nitrophenyl)-2-benzylaminopropane [(S)-12].\",\n \"A sample of 2.0 g (7.3 mmol) of 1-(4′-nitrophenyl)-2-benzylaminopropane (43) was reacted with 1.13 g (7.3 mmol) of (R)-(−)-mandelic acid to give 640 mg (65% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.60 (d, 3H, J=6.3 Hz), 2.73-2.85 (m, 1H), 3.00-3.12 (m, 2H), 3.86 (dd, 2H, J=26, 60 Hz), 7.23-7.40 (m, 5H), 7.30 (d, 2H, J=9.0 Hz), 8.14 (d, 2H, J=8.7 Hz); MS (APCI+) m/z (rel): 271 (100); [α]D=+8.2° (c=1.0 MeOH).\",\n \"(R)-(−)-1-Phenyl-2-benzylaminopropane [(R)-13].\",\n \"A sample of 2.62 g (11.6 mmol) of 1-phenyl-2-benzylaminopropane (38) was reacted with 1.77 g (11.6 mmol) of (S)-(+)-mandelic acid to give 747 mg (57% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.13 (d, 3H, J=6.0 Hz), 2.62-2.84 (m, 2H), 2.92-2.99 (m, 1H), 3.81 (dd, 2H, J=13.2, 34.5 Hz) 7.14-7.29 (m, 10H); MS (APCI+) m/z (rel): 226 (100); [α]D=−24.5° (c=1.10 MeOH).\",\n \"(S)-(+)-1-Phenyl-2-benzylaminopropane [(S)-13].\",\n \"A sample of 5.0 g (22.2 mmol) of racemic 1-phenyl-2-benzylaminopropane (38) was reacted with 3.4 g (22.2 mmol) of (R)-(−)-mandelic acid to give 2.15 g (86% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.11 (d, 3H, J=6.0 Hz), 2.62-2.84 (m, 2H), 2.92-2.99 (m, 1H), 3.81 (dd, 2H, J=13.2, 34.5 Hz), 7.14-7.29 (m, 5H); MS (APCI+) m/z (rel): 226 (100); [α]D=+18.2° (c=0.85 MeOH).\",\n \"(R)-(−)-1-(1′-Naphthyl)-2-benzylaminopropane [(R)-14].\",\n \"The washes recovered from the separation of (S)-14 were concentrated and partitioned between 40 mL of choroform and 40 mL of 10% K2CO3 in water.\",\n \"The organic partition was washed with 20 mL of brine then dried (Na2SO4) to afford 1.16 g (4.2 mmol) of the free amine, which was reacted with 640 mg (4.2 mmol) of (S)-(+)-mandelic acid.\",\n \"588 mg (46% based on enantiomeric abundance) of the free amine was obtained.\",\n \"1H NMR (CDCl3) δ 1.07 (d, 3H, J=6.0 Hz), 3.02-3.18 (m, 2H), 3.27 (m, 1H), 3.74 (dd, 2H, J=13.2, 30.9 Hz), 7.13-7.23 (m, 5H), 7.31-7.48 (m, 4H), 7.73 (d, 1H, J=7.8 Hz), 7.83-7.86 (m, 1H), 7.96-7.99 (m, 1H); MS (APCI+) m/z (rel): 276 (100); [α]D=−5.8° (c=1.0 MeOH).\",\n \"(S)-(+)-1-(1′-Naphthyl)-2-benzylaminopropane [(S)-14].\",\n \"A sample of 2.6 g (9.4 mmol) of 1-(1′-naphthyl)-2-benzylaminopropane (39) was reacted with 1.44 g (9.4 mmol) of (R)-(−)-mandelic acid to give 420 mg (21% based on enantiomeric abundance) of the free amine after workup.\",\n \"1H NMR (CDCl3) δ 1.07 (d, 3H, J=6.0 Hz), 3.02-3.18 (m, 2H), 3.27 (m, 1H), 3.74 (dd, 2H, J=13.2, 30.9 Hz), 7.13-7.23 (m, 5H), 7.31-7.48 (m, 4H), 7.73 (d, 1H, J=7.8 Hz), 7.83-7.86 (m, 1H), 7.96-7.99 (m, 1H); MS (APCI+) m/z (rel): 276 (100); [α]D=+6.3° (c=1.0 MeOH).\",\n \"(R)-(−)-2-Benzylaminoheptane [(R)-15].\",\n \"A sample of 0.65 mL (4.4 mmol) of (R)-(−)-2-aminoheptane (R-44) 0.44 mL (4.4 mmol) of benzaldehyde and 0.1 mL of HOAc were combined in 40 mL of CH2Cl2 and then cooled to 0° C. To the reaction mixture was added 2.75 mg (13 mmol) of sodium triacetoxyborohydride in one portion, which was stirred under argon at room temperature for 28 hours.\",\n \"The reaction mixture was diluted with 30 mL of CH2Cl2, cooled in an ice bath and 80 mL of 5% NaOH (in water) was added.\",\n \"Fractions were separated, organics (Na2SO4) dried and evaporated to 638 mg (71%) of (R)-15.1H NMR (CDCl3) δ 0.88 (m, 3H), 1.08 (d, 3H J=6.6 Hz), 1.20-1.39 (m, 6H), 1.41-1.67 (m, 2H), 3.62-3.77 (m, 1H), 3.75 (p, 2H, J=12 Hz), 7.17-7.41 (m, 5H); MS (APCI+) m/z (rel): 206 (100); [α]D=+6.9° (c=1.0, MeOH).\",\n \"(S)-(+)-2-Benzylaminoheptane [(S)-15].\",\n \"A sample of 0.15 mL (1 mmol) of (S)-(+)-2-aminoheptane ((S)-44) 0.1 mL (1 mmol) of benzaldehyde and 0.1 mL of HOAc were combined in 10 mL of CH2Cl2 and cooled to 0° C., then added 650 mg (3 mmol) of sodium triacetoxyborohydride in one portion.\",\n \"The reaction mixture was stirred under argon at room temperature for 28 hours.\",\n \"The mixture was diluted with 10 mL of dichloromethane, cooled in an ice bath and 20 mL of 5% NaOH (in water) was added.\",\n \"Fractions were separated, organics were dried (Na2SO4) and evaporated to 154 mg (70%).\",\n \"1H NMR (CDCl3) δ 0.88 (m, 3H), 1.08 (d, 3H J=6.6 Hz), 1.19-1.37 (m, 6H), 1.41-1.67 (m, 2H), 3.62-3.77 (m, 1H), 3.75 (p, 2H, J=12 Hz), 7.17-7.41 (m, 5H); MS (APCI+) m/z (rel): 206 (100); [α]D=+7.8° (c=1.0, MeOH).\",\n \"Preparation of Fenoterol Analogs, Procedure A.\",\n \"To form the epoxide, the appropriate 3′,5′-dibenzyloxyphenylbromohydrin ((R)-8) or (S)-8 (1 eq) was combined with K2CO3 (1.4 eq) in 1:1 THF/MeOH (c=0.3 M) and stirred for 2 hours under argon at room temperature.\",\n \"The solvent was removed and the residue partitioned between toluene and H2O.\",\n \"The toluene fraction was isolated, dried (Na2SO4), filtered, and evaporated.\",\n \"The residue was dissolved with the appropriate free benzylamine (R)- or (S)-10-15, 28 (0.95 eq) in a good amount of toluene and evaporated again under high vacuum to remove trace H2O.\",\n \"The resulting colorless residue was heated to 120° C. under argon for 20 hours, cooled and checked by 1H NMR and mass spectrometry to confirm coupling.\",\n \"The residue was dissolved in EtOH (c=0.07 M) with heat and transferred to a Parr flask, where it was hydrogenated at 50 psi of hydrogen over 10% (wt) Pd/C (10 mg cat/65 mg bromohydrin) for 24 hours.\",\n \"Complete debenzylation was confirmed by mass spectrometry.\",\n \"The mixture was filtered through Celite, the filter cake rinsed with isopropanol, and the filtrate concentrated.\",\n \"The residue was dissolved in 1:1 isopropanol/EtOH (c=0.2 M) and brought to reflux for 30 minutes with 0.5 eq of fumaric acid.\",\n \"The reaction was cooled and the solvent removed.\",\n \"The crude material was purified by open column chromatograph or preparative chromatograph.\",\n \"Column Separation of (R,R)-1 and (S,S)-1, Procedure B.\",\n \"A sample of 75 mg of fenoterol HBr was dissolved in 1.5 mL of 95/5/0.05 CH3CN/isopropanol/HNEt2 and applied in 100 μL injections to a CHIRALPAK® AD-H 10×250 mm 5 μm semi-preparative column using a waters 2690 Separations Module, PDA set to 280 nm.\",\n \"The eluting solvent was 95/5/0.05 CH3CN/isopropanol/HNEt2, 5 mL/min.\",\n \"Retention times for (S,S) and (R,R) isomers were 4.8 min and 7.8 min, respectively.\",\n \"(R,R)-(−)-Fenoterol [(R,R)-1].\",\n \"Obtained according to Procedure B to give 40 mg collected after evaporation.\",\n \"1H NMR (CD3OD) δ 1.05 (d, 3H, J=6.3 Hz), 2.49 (q, 1H, J=6.9 Hz), 2.62-2.74 (m, 2H), 2.80-2.91 (m, 2H), 4.55 (dd, 1H, J=5.1, J=3.3 Hz), 6.16 (t, 1H, J=2.4 Hz), 6.27 (d, 2H, J=2.1 Hz), 6.68 (d, 2H, J=8.4 Hz), 6.94 (d, 2H, J=8.4 Hz); 13C NMR (CD3CN) δ 20.3, 43.2, 55.1, 55.2, 72.4, 102.2, 105.4, 116.0, 131.3, 131.8, 147.4, 156.2, 159.0; UV (MeOH) λmax 279 nm (ε 2,760), 225 (12,900), 204 (32,600); MS (APCI+) m/z (rel): 304 (100, M+H); [α]D=−29.0° (conc=0.2% MeOH); HPLC: (a) 0.1% diethylamine in H2O, 0.50 mL/min, 254 nm, tR 2.90 min, 99% pure; (d) tR 7.8 min, >99% pure.\",\n \"(S,S)-(+)-Fenoterol [(S,S)-1].\",\n \"Obtained according to Procedure B to give 35 mg after evaporation.\",\n \"1H NMR (CD3OD) δ 1.05 (d, 3H, J=6.6 Hz), 2.49 (q, 1H, J=7.2 Hz), 2.62-2.76 (m, 2H), 2.80-2.94 (m, 2H), 4.55 (dd, 1H, J=4.8, J=3.3 Hz), 6.16 (t, 1H, J=2.1 Hz), 6.27 (d, 2H, J=2.4 Hz), 6.68 (d, 2H, J=8.4 Hz), 6.94 (d, 2H, J=8.4 Hz); 13C (CD3CN) δ 20.3, 43.2, 55.0, 55.2, 72.4, 102.2, 105.4, 116.0, 131.3, 131.8, 147.4, 156.2, 159.0; UV (MeOH) λmax 279 nm (ε 2,680), 224 (12,700), 204 (32,800); MS (APCI+) m/z (rel): 304 (100, M+H); [α]D=+28.5° (conc=0.20% MeOH); HPLC: (a) 0.1% diethylamine in H2O, 0.50 mL/min, 254 nm, tR 2.72 min, >99% pure; (d) tR 4.8 min, >99% pure.\",\n \"(R,S)-(−)-Fenoterol Fumarate [(R,S)-1].\",\n \"Prepared from (R)-8 and (S)-10 according to Procedure A to give 168 mg (64%).\",\n \"1H NMR (CD3OD) δ 1.22 (d, 3H, J=6.6 Hz), 2.64 (dd, 1H, J=9.9 Hz, J=13.2 Hz), 3.01-3.51 (m, 4H), 4.79 (dd, 1H, J=3.0 Hz, J=9.9 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.1 Hz), 6.75 (s, 1H), 6.76 (d, 2H, J=8.4 Hz), 7.05 (d, 2H, J=8.1 Hz); 13C NMR (CD3OD) δ 16.2, 39.1, 52.5, 57.4, 70.4, 103.4, 105.3, 116.7, 127.8, 131.4, 135.2, 144.6, 157.7, 160.0, 168.2; UV (MeOH) λmax 278 nm (ε 2,520), 205 (27,900); MS (ESI+) m/z (rel): 304 (100, M+H); [α]D=−7.5° (cone=0.75% MeOH); HPLC: (a) 70/30/0.05.1.00 mL/min, 282 nm, tR 1.35 min, >99% pure; (b) 50/50/0.05.1.0 ml, 0.50 mL/min, 254 nm, tR 2.72 min, >99% pure; (d) tR 4.8 min, 1.00 mL/min, 280 nm, tR 2.10 min, 97.5% pure.\",\n \"(S,R)-(+)-Fenoterol Fumarate [(S,R)-1].\",\n \"Prepared from (S)-8 and (R)-10 according to Procedure A to give 104 mg (39%).\",\n \"1H NMR (CD3OD) δ 1.22 (d, 3H, J=6.6 Hz), 2.64 (dd, 1H, J=9.9 Hz, J=13.5 Hz), 3.47-3.04 (m, 4H), 4.80 (dd, 1H, J=2.7, J=9.6 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.1 Hz), 6.75 (s, 1H), 6.76 (d, 2H, J=8.4 Hz), 7.05 (d, 2H, J=8.4 Hz); 13C NMR (CD3OD) δ 16.2, 39.1, 52.5, 57.4, 70.4, 103.4, 105.3, 116.7, 127.8, 131.4, 135.2, 144.6, 157.7, 159.9, 168.2; UV (MeOH) λmax 278 nm (ε 2,640), 202 (36,600); MS (ESI+) m/z (rel): 304 (100, M+H), 413 (10); [α]D=+6.4° (conc=0.50% MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 282 nm, tR 1.35 min, 95.9% pure; (b) 50/50/0.05, 1.0 mL/min, 280 nm, tR 2.06 min, 99% pure.\",\n \"(R,R)-(−)-1-p-Methoxyphenyl-2-(β-3′,5′-dihydroxy-phenyl-β-oxy)ethylamino-propane Fumarate [(R,R)-2].\",\n \"Prepared from (R)-8 and (R)-11 according to Procedure A to give 172 mg (38%).\",\n \"1H NMR (CD3OD) δ 1.08 (d, 3H, J=6.3 Hz), 3.05-2.56 (m, 5H), 4.57 (dd.\",\n \"1H, J=8.4, 5.4 Hz), 6.16 (m, 1H), 6.26 (d, 2H, J=2.7 Hz), 6.81 (d, 2H, J=8.7 Hz), 7.03 (d, 2H J=8.7 Hz); 13C NMR (CD3OD) δ 18.8, 42.3, 54.5, 55.6, 56.0, 72.6, 103.0, 105.4, 115.0, 131.1, 131.2, 131.3, 146.2, 159.8, 159.9; UV (MeOH) λmax 277 nm (ε 3,590), 224 (17,700), 207 (29,500); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=−24.9° (c=0.8 MeOH); HPLC: (a) 70/30/0.05, 1.0 mL/min, 282 nm, tR 1.54 min, 96.5% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.51 min, 95.9% pure.\",\n \"(S,S)-(+)-1-p-Methoxyphenyl-2-(β-3′,5′-dihydroxy-phenyl-(β-oxy)ethylamino-propane Fumarate [(S,S)-2].\",\n \"Prepared from (S)-8 and (S)-11 according to Procedure A to give 318 mg (53%).\",\n \"1H NMR (CD3OD) δ 1.15 (d, 3H, J=6.0 Hz), 2.58-3.22 (m, 5H), 3.77 (s, 3H), 4.68 (dd, 1H, J=4.8, 8.4 Hz), 6.18 (t, 1H, J=2.1 Hz), 6.31 (d, 2H, J=2.1 Hz), 2.23 (s, 0.5 H, fumarate), 6.84 (d, 2H, J=8.7 Hz), 7.10 (d, 2H, J=9.0 Hz); 13C NMR (CD3OD) δ 16.1, 39.9, 52.4, 54.5, 55.3, 70.4, 101.9, 104.2, 114.0, 129.2, 130.1, 144.4, 158.7, 158.9; UV (MeOH) λmax 277 nm (ε 2,100), 224 (11,00), 205 (22,700); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=+28.6° (c=0.95 MeOH); HPLC: (a) 70/30/0.05, 1.0 mL/min, 282 nm, tR 1.67 min, 96.0% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.51 min, 97.1% pure.\",\n \"(R,S)-(+1p-Methoxyphenyl-2-(β-3′,5′-dihydroxy-phenyl-(β-oxy)ethylaminopropane Fumarate [(R,S)-2].\",\n \"Prepared from (R)-8 and (S)-11 according to Procedure A to give 160 mg (38%).\",\n \"1H NMR (CD3OD) δ 1.20 (d, 3H, J=6.6 Hz), 2.62-2.71 (m, 1H), 2.98-3.20 (m, 3H), 3.30-3.42 (m, 2H), 4.73-4.81 (m, 1H), 6.21 (m, 2H), 3.35 (m, 2H), 6.71 (s, 0.5H, fumarate), 6.56-6.89 (m, 2H), 7.11-7.19 (m, 2H); 13C NMR (CD3OD) δ 15.6, 38.5, 51.8, 54.5, 55.9, 69.7, 102.1, 104.1, 114.1, 128.5, 130.2, 136.0, 143.8, 158.8, 159.1; UV (MeOH) λmax 277 nm (ε 4,100), 224 (21,400), 203 (50,600); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=−7.2° (c=1.5 MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 282 nm, tR 1.40 min, 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.51 min, 96.1% pure.\",\n \"(S,R)-(+)-1-p-Methoxyphenyl-2-(β-3′,5′-dihydroxyphenyl-β-oxy)ethylaminopropane Fumarate [(S,R)-2].\",\n \"Prepared from (S)-8 and (R)-11 according to Procedure A to give 200 mg (51%).\",\n \"1H NMR (CD3OD) δ 1.12 (d, 3H, J=6.0 Hz), 2.58-3.13 (m, 5H), 3.77 (s, 3H), 4.62 (dd, 1H, J=3.6, 9.0 Hz), 6.15 (m, 1H), 6.30 (d, 2H, J=1.8 Hz), 6.85 (d, 2H, J=8.7 Hz), 7.11 (d, 2H, J=8.7 Hz); 13C NMR (CD3OD) δ 18.2, 41.4, 54.1, 55.7, 56.5, 64.7, 103.0, 105.3, 115.1, 130.7, 131.3, 145.9, 159.8, 160.0; UV (MeOH) λmax 277 nm (ε 3,150), 224 (3,310), 205 (30,600); MS (ESI+) m/z (rel): 318 (100, M+H); [α]D=+14.1° (c=0.95 MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 282 nm, tR 1.42 min, 97.7% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.52 min, 97.8% pure.\",\n \"(R,R)-(+5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(R,R)-3].\",\n \"Prepared from (R)-8 and (R)-12 according to Procedure A to give 88 mg (42%).\",\n \"1H NMR (CD3OD) δ 1.23 (m, 3H), 2.70-3.24 (m, 4H), 3.54 (m, 1H), 4.84 (dd, 1H, J=3.3, 9.6 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.38 (d, 2H, J=2.1 Hz), 6.75 (s, 2H, fumarate), 7.35 (dd, 4H, J=8.1, 21.0 Hz); 13C (CD3OD) δ 15.5, 39.6, 52.7, 56.6, 70.3, 103.4, 105.3, 123.8, 132.0, 132.1, 135.2, 137.5, 144.7, 160.0, 168.1; UV (MeOH) λmax 284 nm (ε 1,520), 206 (21,700); MS (ESI+) m/z (rel): 303 (100, M+H); [α]D=−6.8° (conc=1.0% MeOH); HPLC: (a) 80/20/0.05, 0.70 mL/min, 276 nm, tR 2.07 min, 95.5% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.60, 97.16% pure.\",\n \"(S,S)-(+)-5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(S,S)-3].\",\n \"Prepared from (S)-8 and (S)-12 according to Procedure A to give 56 mg (25%).\",\n \"1H NMR (CD3OD) δ 1.23 (m, 3H), 2.62-3.27 (m, 4H), 3.55 (m, 1H), 4.74-4.88 (m, 1H), 6.22 (t, 1H, J=1.8 Hz), 6.37 (d, 2H, J=2.4 Hz), 6.75 (s, 2H, fumarate), 7.32 (dd, 4H, J=8.7, 25.8 Hz); 13C NMR (CD3OD) δ 15.5, 39.6, 52.5, 56.7, 70.7, 103.4, 105.3, 123.3, 131.8, 132.0, 135.2, 136.9, 144.7, 160.0, 168.1; UV (MeOH) λmax 284 nm (ε 1,720), 207 (28,400); MS (ESI+) m/z (rel): 303 (100, M+H), 329 (20); [α]D=+11.1° (conc=0.50% MeOH); HPLC: (a) 80/20/0.05, 0.7 mL/min, 276 nm, tR 2.01 min, <99% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.50 min, 99.4% pure.\",\n \"(R,S)-(+5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(R,S)-3].\",\n \"Prepared from (R)-8 and (S)-12 according to Procedure A to give 72 mg (35%).\",\n \"1H NMR (CD3OD) δ 1.23 (m, 3H), 2.73-3.24 (m, 4H), 3.51 (m, 1H), 4.80 (dd, 1H, J=2.7, 9.6 Hz), 6.22 (t, 1H, J=2.1 Hz), 6.36 (d, 2H, J=2.4 Hz), 6.75 (s, 2H, fumarate), 7.32 (dd, 4H, J=8.4, 25.2 Hz); 13C NMR (CD3OD) δ 16.1, 39.12, 5.16, 56.9, 70.4, 103.4, 105.3, 123.4, 132.0, 132.0, 135.2, 136.8, 144.6, 160, 168.10; UV (MeOH) λmax 284 nm (ε 1,620), 205 (27,200); MS (ESI+) m/z (rel): 303 (100, M+H), 134 (14); [α]D=−7.5° (conc=0.50% MeOH); HPLC: (a) 80/20/0.05, 0.7 mL/min, 276 nm, tR 2.08 min, 95.0% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.51 min, 97.4% pure.\",\n \"(S,R)-(+)-5-{2-[2-(4-Aminophenyl)-1-methylethylamino]-1-hydroxyethyl}-1,3-benzenediol Fumarate [(S,R)-3].\",\n \"Prepared from (S)-8 and (R)-12 according to Procedure A to give 93 mg (42%).\",\n \"1H NMR (CD3OD) δ 1.23 (d, 3H, J=6.3 Hz), 2.70-3.78 (m, 4H), 3.42-3.62 (m, 1H), 4.80 (dd, 1H, J=3.0, 9.9 Hz), 6.22 (t, 1H, J=2.1 Hz), 6.37 (d, 2H, J=2.1 Hz), 6.75 (s, 2H, fumarate), 7.33 (dd, 4H, J=8.4, 26.7 Hz); 13C NMR (CD3OD) δ 16.2, 39.1, 52.6, 56.9, 70.5, 103.4, 105.3, 123.5, 132.1, 133.7, 135.2, 137.1, 144.7, 160.0, 168.1 UV (MeOH) λmax 284 nm (ε 8,230), 207 (100,000); MS (ESI+) m/z (rel): 303 (100, M+H), 134 (18); [α]D=+11.4° (conc=0.50% MeOH); HPLC: (a) 70/30/0.05, 1.00 mL/min, 280 nm, tR 1.45 min, 99% pure; (b) 50/50/0.05, 1.0 mL/min, 282 nm, tR 2.63 min, 95.33% pure.\",\n \"(R,R)-(+5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(R,R)-4].\",\n \"Prepared from (R)-8 and (R)-13 according to Procedure A to give 92 mg (26%).\",\n \"1H NMR (CD3OD) δ 1.22 (m, 3H), 2.68-3.28 (m, 2H), 3.10-3.28 (m, 2H), 3.53 (br-m, 1H), 4.75-4.80 (m, 1H), 6.24 (t, 1H, J=2.4 Hz), 6.38 (d, 2H, J=2.1 Hz), 6.75 (s, 1H, fumarate), 7.22-7.33 (m, 5H); 13C NMR (CD3OD) δ 15.5, 40.3, 56.9, 70.2, 103.4, 105.3, 128.3, 129.9, 130.3, 135.2, 137.3, 144.6, 144.6, 159.9, 168.1; UV (MeOH) λmax 277 nm (ε 926), 204 (18,700); MS (APCI+) m/z 288 (100, M+H); [α]D=−21.2° (conc=0.85% MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm; tR 1.73 min; 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.46 min, 97.5% pure.\",\n \"(S,S)-(+)-5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(S,S)-4].\",\n \"Prepared from (S)-8 and (S)-13 according to Procedure A to give 184 mg (51%).\",\n \"1H NMR (CD3OD) δ 1.21 (m, 3H), 2.70-3.13 (m, 2H), 3.15-3.23 (m, 2H), 3.54 (br-m, 1H), 4.79-4.86 (m, 1H), 6.24 (t, 1H, J=2.1 Hz), 6.39 (t, 2H, J=2.7 Hz), 6.76 (s, 1H, fumarate), 7.22-7.32 (m, 5H); 13C NMR (CD3OD) δ 15.5, 40.3, 56.9, 70.2, 103.4, 105.3, 128.3, 129.9, 130.3, 135.1, 137.3, 144.6, 144.6, 159.9, 168.1 UV (MeOH) λmax 278 nm (ε 1,510), 207 (26,600); MS (APCI+) m/z 288 (100, M+H); [α]D=+19.3° (conc=0.90% MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm, tR 1.49 min; 98.4% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.35 min, 99% pure.\",\n \"(R,S)-(+5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(R,S)-4].\",\n \"Prepared from (R)-8 and (S)-13 according to Procedure A to give 170 mg (45%).\",\n \"1H NMR (CD3OD) δ 1.22 (m, 3H), 2.68-3.28 (m, 2H), 3.13-3.28 (m, 2H), 3.53 (br-m, 1H), 4.76-4.80 (m, 1H), 6.23 (t, 1H, J=2.1 Hz), 6.37 (t, 2H, J=3.0 Hz), 6.75 (s, 1H, fumarate), 7.24-7.37 (m, 5H); 13C NMR (CD3OD) δ 16.3, 24.2, 39.8, 57.2, 70.5, 103.4, 105.3, 128.4, 130.0, 130.4, 135.2, 137.4, 144.6, 160.1 UV (MeOH) λmax 278 nm (ε 1,110), 205 (31,000); MS (APCI+) m/z (rel): 288 (100, M+H); [α]D=−6.9° (conc=0.85% MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm, tR 1.53 min, 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.46 min, 98.5% pure.\",\n \"(S,R)-(+)-5-[1-Hydroxy-2-(1-methyl-2-phenylethylamino)ethyl]-1,3-benzenediol fumarate [(S,R)-4].\",\n \"Prepared from (S)-8 and (R)-13 according to Procedure A to give 212 mg (59%).\",\n \"1H NMR (CD3OD) δ 1.22 (m, 3H), 2.72 (dd, 1H J=10.2, 13.2 Hz), 3.11 (dd, 1H, J=10.2, 12.6 Hz), 3.18-3.27 (m, 2H), 3.48-3.61 (m, 1H), 4.83 (dd, 1H, J=3.3, 9.9 Hz), 6.22 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.4 Hz), 6.75 (s, 1H, fumarate), 7.24-7.37 (m, 5H); 13C NMR (CD3OD) δ 16.3, 24.2, 39.8, 57.2, 70.5, 103.4, 105.3, 128.4, 130.0, 130.4, 135.2, 137.4, 144.6, 160.1; UV (MeOH) λmax 278 nm (ε 1,680), 206 (35,500); MS (APCI+) m/z (rel): 288 (100, M+H), 270 (19, M-OH); [α]D=+9.1° (conc=1.1%, MeOH); HPLC: (a) 50/50/0.05, 1.00 mL/min, 282 nm, tR 1.51 min, 99% pure; (b) 50/50/0.05, 2.0 mL/min, 276 nm, tR 1.43 min, 99% pure.\",\n \"(R,R)-(+5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(R,R)-5].\",\n \"Prepared from (R)-8 and (R)-14 according to Procedure A to give 135 mg (46%).\",\n \"1H NMR (CD3OD) δ 1.18-1.23 (m, 3H), 3.16-3.34 (m, 1H, 2H), 3.69-3.74 (m, 2H), 4.78-4.80 (m, 1H), 6.23 (t, 1H, J=2.4 Hz), 6.38 (m, 2H), 7.41-7.61 (m, 4H), 7.83 (d, 1H, J=7.5 Hz), 7.90 (d, 1H, J=7.8 Hz), 8.10 (m, 1H); 13C NMR (CD3OD) δ 16.2, 37.2, 54.5, 56.1, 70.3, 103.4, 105.3, 124.3, 126.5, 127.0, 127.7, 129.3, 130.1, 133.2, 135.2, 135.6, 144.7, 160.1, 168.2; UV (MeOH) λmax 282 nm (ε 5,860), 224 (50,900), 208 (35,500); MS (APCI+) m/z (rel): 338 (100, M+H), 169 (15, fragment); [α]D=−20.4 (conc=0.50% MeOH); HPLC: (a) 60/40/0.05, 1.00 mL/min, 282 nm, tR 2.08 min, 95.7% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.20 min, 99% pure.\",\n \"(S,S)-(+)-5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(S,S)-5].\",\n \"Prepared from (S)-8 and (S)-14 according to Procedure A to give 118 mg (40%)1H NMR (CD3OD) δ 1.13-1.17 (m, 3H), 3.14-3.26 (m, 1H, 2H), 3.61-3.76 (m, 2H), 4.44-4.75 (m, 1H), 6.18 (t, 1H, J=2.4 Hz), 6.33 (m, 2H), 7.36-7.52 (m, 4H), 7.77 (dd, 1H, J=1.8, 7.5 Hz), 7.84 (d, 1H, J=8.1 Hz), 8.04 (t, 1H, J=8.4 Hz); 13C NMR (CD3OD) δ 16.1, 37.1, 54.4, 56.0, 70.3, 103.3, 105.3, 124.3, 126.5, 127.0, 127.7, 129.2, 130.0, 133.2, 135.2, 135.7, 144.5, 160.0, 168.1; UV (MeOH) λmax 282 nm (ε 6,210), 223 (56,400), 208 (42,700); MS (APCI+) m/z (rel): 338 (100, M+H), 169 (8, fragment); [α]D=+20.0° (conc=1.1% MeOH); HPLC: (a) 60/40/0.05, 1.00 mL/min, 282 nm, tR 2.35 min, 98.9% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.26 min, 97.2% pure.\",\n \"(R,S)-(+5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(R,S)-5].\",\n \"Prepared from (R)-8 and (S)-14 according to Procedure A to give 114 mg (39%).\",\n \"1H NMR (CD3OD) δ 1.08-1.11 (m, 3H), 3.02-3.24 (m, 1H, 2H), 3.54-3.68 (m, 2H), 4.45-4.75 (m, 1H), 6.11 (t, 1H, J=1.8 Hz), 6.26 (m, 2H), 6.63 (s, 2H fumarate), 7.28-7.48 (m, 4H), 7.70 (d, 1H, J=7.5 Hz), 7.77 (d, 1H, J=7.8 Hz), 7.97 (t, 1H, J=7.8 Hz); 13C NMR (CD3OD) δ 16.0, 37.1, 52.5, 56.0, 70.4, 103.4, 105.3, 124.4, 126.5, 127.0, 127.6, 129.2, 130.1, 133.1, 135.2, 135.5, 144.7, 159.9, 168.2; UV (MeOH) λmax 281 nm (ε 12,600), 224 (61,900), 204 (47,200); MS (APCI+) m/z (rel): 338 (100, M+H), 190 (15, fragment); [α]D=−11.3° (conc=0.85% MeOH); HPLC: (a) 60/40/0.05, 1.00 mL/min, 282 nm, tr 2.30 min, 98.6% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.36 min, 99% pure.\",\n \"(S,R)-(+)-5-{1-hydroxy-2-[1-methyl-2-(1-naphthyl)ethylamino]ethyl}-1,3-benzenediol fumarate [(S,R)-5].\",\n \"Prepared from (S)-8 and (R)-14 according to Procedure A to give 123 mg (42%).\",\n \"1H NMR (CD3OD) δ 1.18-1.22 (m, 3H), 3.10-3.28 (m, 1H, 2H), 3.69-3.78 (m, 2H), 4.45-4.75 (m, 1H), 6.23 (t, 1H, J=2.1 Hz), 6.39 (m, 2H), 6.73 (s, 2H fumarate), 7.39-7.59 (m, 4H), 7.80 (d, 1H, J=7.5 Hz), 7.88 (d, 1H, J=7.8 Hz), 8.01 (t, 1H, J=9.0 Hz); 13C NMR (CD3OD) δ 16.4, 37.4, 52.5, 56.2, 70.6, 103.4, 105.3, 124.4, 126.5, 127.0, 129.3, 130.1, 133.1, 133.4, 135.6, 136.3, 144.8, 160.0, 171.4; UV (MeOH) λmax 282 nm (ε 7,740), 224 (70,900), 206 (55,800); MS (ESI+) m/z (rel): 338 (100, M+H); [α]D=+15.5 (conc=1.0% MeOH) HPLC: (a) 60/40/0.05, 1.0 mL/min, 282 nm, tR 1.95, 95.7% pure; (b) 50/50/0.05, 1.5 mL/min, 282 nm, tR 2.29 min, 95.7% pure.\",\n \"(R,R)-(+5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(R,R)-6].\",\n \"Prepared from (R)-8 and (R)-15 according to Procedure A to give 45 mg (29%).\",\n \"1H NMR (CD3OD) δ 0.920 (t, 3H, J=6.9 Hz), 1.30 (d, 3H, J=6.9 Hz), 1.29-1.64 (m, 8H), 3.01-3.18 (m, 2H), 3.14-3.30 (m, 1H), 4.80 (dd, 1H, J=3.3, 9.6 Hz), 6.22 (t, 1H, J=2.1 Hz), 6.36 (d, 2H, J=2.4 Hz), 6.75 (s, 1H, fumarate); 13C NMR (CD3OD) δ 14.3, 16.0, 23.5, 26.2, 32.6, 34.2, 52.1, 55.7, 70.2, 103.3, 105.3, 135.2, 144.7, 160.0, 168.0; UV (MeOH) λmax 278 nm (ε 931), 203 nm (20,100); MS (ESI+) m/z (rel): 268 (100, M+H); [α]D=−8.8° (conc=1.1% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.18 min, 96.6% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.06 min, 98.9% pure.\",\n \"(S,S)-(+)-5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(S,S)-6].\",\n \"Prepared from (S)-8 and (S)-15 according to Procedure A to give 96 mg (43%).\",\n \"1H NMR (CD3OD) δ 0.923 (t, 3H, J=6.6 Hz); 1.31 (d, 3H, J=6.6 Hz), 1.26-1.84 (m, 8H), 2.01-3.18 (m, 2H), 3.14-3.30 (m, 1H), 4.81 (dd, 1H, J=3.3, 9.6 Hz), 6.23 (t, 1H, J=2.4 Hz), 6.39 (d, 2H, J=2.1 Hz), 6.76 (s, 1H, fumarate): 13C NMR (CD3OD) δ 14.2, 16.0, 23.4, 26.3, 32.6, 34.1, 52.1, 55.8, 70.2, 103.4, 105.3, 135.2, 144.7, 159.9, 168.2; UV (MeOH) λmax 278 nm (ε 1,340), 203 (28,800); MS (APCI+) m/z (rel): 268 (100, M+H); [α]D=+10.8° (conc=0.50% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.16 min, 97.0% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.11 min, 99% pure.\",\n \"(R,S)-(+5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(R,S)-6].\",\n \"Prepared from (R)-8 and (S)-15 according to Procedure A to give 83 mg (38%).\",\n \"1H NMR (CD3OD) δ 0.924 (m, 3H); 1.32 (d, 3H, J=6.6 Hz), 1.26-1.84 (m, 8H), 2.98-3.20 (m, 2H), 3.32-3.22 (m, 1H), 4.78 (dd, 1H, J=3.0, 9.9 Hz), 6.23 (t, 1H, J=2.1 Hz), 6.37 (d, 2H, J=1.8 Hz), 6.76 (s, 1H, fumarate); 13C NMR (CD3OD) δ 14.2, 16.4, 23.4, 26.2, 32.6, 33.5, 52.2, 56.0, 70.4, 103.4, 105.3, 135.2, 144.7, 160.0, 168.1; UV (MeOH) λmax 276 nm (ε 2,770), 203 (35,900); MS (APCI+) m/z (rel): 268 (100, M+H); [α]D=−15.9° (conc=0.70% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.16 min, 97.0% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.07 min, 96.2% pure.\",\n \"(S,R)-(+)-5-[1-Hydroxy-2-(1-methylhexylamino)ethyl]-1,3-benzenediol Fumarate [(S,R)-6].\",\n \"Prepared from (S)-8 and (R)-15 according to Procedure A to give 81 mg (38%).\",\n \"1H NMR (CD3OD) δ 0.920 (t, 3H, J=6.3 Hz), 1.32 (d, 3H, J=6.9 Hz), 1.30-1.77 (m, 8H), 2.99-3.17 (m, 2H), 3.23-3.26 (m, 1H), 4.76 (dd, 1H, J=3.0, 9.6 Hz), 6.22 (t, 1H, J=2.4 Hz), 6.36 (d, 2H, J=2.1 Hz), 6.75 (s, 1H, fumarate); 13C NMR (CD3OD) δ 14.2, 16.5, 23.5, 26.2, 32.6, 39.5, 52.2, 56.0, 70.4, 103.4, 105.3, 135.2, 144.7, 160.0, 168.0; UV (MeOH) λmax 278 nm (ε 1,440), 204 (29,900); MS (APCI+) m/z (rel): 268 (100, M+H); [α]D=+12.7° (conc=1.0% MeOH); HPLC: (c) 70/30/0.1, 1.0 mL/min, 276 nm, tR 2.16 min, 99% pure; (b) 50/50/0.05, 1.0 mL/min, 279 nm, tR 2.02 min, 95.7% pure.\",\n \"(R)-(+5-(1-Hydroxy-2-phenethylaminoethyl)-1,3-benzenediol fumarate [(R)-7].\",\n \"Prepared from (R)-8 and 28 to give 37 mg (15%).\",\n \"1H NMR (CD3OD) δ 2.94-3.23 (m, 6H), 4.73 (dd, 1H, J=3.3, 9.9 Hz), 6.15 (t, 1H, J=2.4 Hz), 6.29 (d, 2H, J=1.8 Hz), 7.19-7.28 (m, 5H), 6.69 (s, 1H); UV (MeOH) λmax 278 nm (ε 1,360), 205 (32,600); MS (APCI+) m/z (rel): 274 (100, M+H); [α]D=−13.0° (conc=1.0% MeOH); HPLC: (a) 80/20/0.05, 1.00 mL/min, 282 nm, tR 1.47 min, 96.7% pure; (b) 50/50/0.05, 1.0 mL/min, 272 nm, tR 2.78 min, 95.1% pure.\",\n \"(S)-(+)-5-(1-hydroxy-2-phenethylaminoethyl)-1,3-benzenediol fumarate [(S)-7].\",\n \"Prepared from (S)-8 and 28 to give 51 mg (17%).\",\n \"1H NMR (CD3OD) δ 2.87-3.21 (m, 6H), 4.68 (dd, 1H, J=3.6, 9.9 Hz), 6.10 (t, 1H, J=2.4 Hz), 6.24 (d, 2H, J=2.1 Hz), 6.63 (s, 1H), 7.12-7.21 (m, 5H); UV (MeOH) λmax 278 nm (ε 1,280), 204 (33,700); MS (APCI+) m/z (rel): 274 (100, M+H); [α]D=+14.64° (conc=1.1% MeOH); HPLC: (a) 80/20/0.05, 1.00 mL/min, 282 nm, tR 1.47 min, 98.6% pure; (b) 50/50/0.05, 1.0 mL/min, 272 nm, tR 2.74 min, 98.8% pure.\",\n \"(R,R)-(−)-ethylfenoterol.\",\n \"1H NMR: (300 MHz, CD3OD): δ 0.950 (t, 3H, J=7.5 Hz), 1.67 (m, 2H), 2.83-3.18 (m, 4H), 3.33-3.40 (m, 1H), 3.37 (s, 4H), 4.82 (m, 1H), 6.24 (d, 1H, J=2.1 Hz), 6.37 (d, 2H, J=1.8 Hz), 6.73 (s, 2H, fum), 6.76 (d, 2H, J=8.4 Hz), 7.05 (d, 2H, J=8.7 Hz) ppm.\",\n \"CMR: 13C (75 MHz, CD3OD): δ 9.43, 23.28, 36.56, 52.29, 62.16, 70.02, 103.4, 105.3, 116.7, 127.8, 131.3, 136.5, 144.6, 157.6, 159.9, 172.3 ppm.\",\n \"UV: (Methanol), λmax (ε): 206 nm (22,500), 223 (12,300), 278 (2,460).\",\n \"MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 318 (100, M+H).\",\n \"HPLC 1: Column: Varian Sunfire C18 100×4.6; 70/30/0.1 water/acetonitrile/TFA; 1.0 mL/min; Det: 278 nm; 2.76 min (fumarate, 6.99%), 3.57 min (90.11%); Purity: 97.1%.\",\n \"HPLC 2: Column: Chiralpak IA 250×10; 90/10/0.05 acetonitrile/methanol/TFA; 2.0 mL/min; Det: 278 nm; 5.26 (RR isomer, 92.37%), 7.11 min (fumarate, 5.02%); Purity 97.5%.\",\n \"Specific Rotation: [α]D=−15.6 (free amine, 0.5% MeOH).\",\n \"(R,S)-(−)-ethylfenoterol.\",\n \"1H NMR: (300 MHz, CD3OD): δ 0.972 (t, 3H, J=7.5 Hz), 1.70 (p, 2H, J=6.9 Hz)), 2.86-3.22 (m, 4H), 3.32-3.37 (m, 1H), 3.34 (s, 4H), 4.82 (m, 1H), 6.25 (t, 1H, J=2.1 Hz), 6.36 (d, 2H, J=1.8 Hz), 6.74 (s, 2H, fum), 6.77 (d, 2H, J=8.4 Hz), 7.08 (d, 2H, J=8.7 Hz) ppm.\",\n \"CMR: 13C (75 MHz, CD3OD): δ 9.820, 24.16, 36.48, 52.30, 62.32, 69.92, 103.3, 105.3, 116.8, 127.7, 131.3, 136.1, 144.4, 157.6, 159.8, 171.3 ppm.\",\n \"UV: (Methanol), λmax (c): 204 nm (26,900), 224 (11,500), 278 (2,320).\",\n \"MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 318 (100, M+H).\",\n \"HPLC 1: Column: Varian Sunfire C18 100×4.6; 70/30/0.1 water/acetonitrile/TFA; 1.0 mL/min; Det: 278 nm; 2.79 min (fumarate, 3.34%), 3.56 min (96.11%); Purity: 99.5% HPLC 2: Column: Chiralpak IA 250×10; 90/10/0.05 acetonitrile/methanol/TFA; 2.0 mL/min; Det: 278 nm; 5.88 (RS isomer, 97.08%), 7.12 min (fumarate, 2.92%); Purity >99%.\",\n \"Specific Rotation: [α]D=−7.2 (free amine, 0.5% MeOH).\",\n \"C22H25NO4.0.5C4H4O4 1H NMR: (300 MHz, CD3OD): δ 1.22 (t, 3H, J=6.6 Hz), 3.09-3.21 (m, 3H), 3.59-3.69 (m, 2H), 3.99 (s, 3H), 4.74-4.83 (m, 1H), 6.23 (t, 1H, J=2.4 Hz), 6.37 (dd, 2H, J=2.4, 5.7 Hz), 6.74 (s, 1H), 6.86 (d, 1H, J=7.8 Hz), 7.32 (d, 1H, J=7.8 Hz), 7.48 (t, 1H, J=6.9 Hz), 7.56 (t, 1H, J=6.9 Hz), 8.02 (dd, 1H, J=8.4, 12.0 Hz), 8.27 (d, 1H, J=8.7 Hz) ppm.\",\n \"CMR: 13C (75 MHz, CD3OD): δ 15.78, 36.66, 52.39, 55.96, 70.20, 103.4, 104.5, 105.3, 123.8, 124.3, 124.9, 126.2, 127.4, 128.1, 129.5, 133.8, 135.2, 144.6, 156.6, 160.0, 168.3 ppm.\",\n \"UV: (Methanol), λmax (c): 298 nm (4,970), 286 (9,920), 234 (22,600), 210 (42,500).\",\n \"MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 368 (100, M+H).\",\n \"Specific Rotation: [α]D=−28.8 (Free Amine; 0.5% MeOH).\",\n \"C22H25NO4.0.5C4H4O4 1H NMR: (300 MHz, CD3OD): δ 1.20 (t, 3H, J=6.6 Hz), 3.07-3.21 (m, 3H), 3.52-3.75 (m, 2H), 3.97 (s, 3H), 4.69-4.83 (m, 1H), 6.24 (t, 1H, J=2.1 Hz), 6.39 (dd, 2H, J=2.4, 5.4 Hz), 6.74 (s, 1H), 6.84 (d, 1H, J=7.8 Hz), 7.31 (d, 1H, J=8.1 Hz), 7.48 (t, 1H, J=6.9 Hz), 7.56 (t, 1H, J=6.9 Hz), 8.01 (dd, 1H, J=8.4, 13.5 Hz), 8.27 (d, 1H, J=7.8 Hz) ppm.\",\n \"CMR: 13C (75 MHz, CD3OD): δ 15.77, 36.64, 52.37, 55.94, 70.46, 103.4, 104.5, 105.3, 123.8, 124.3, 124.9, 126.2, 127.4, 128.1, 129.4, 133.8, 135.5, 144.7, 156.6, 160.0, 169.0 ppm.\",\n \"UV: (Methanol), λmax (c): 298 nm (5,430), 286 (5,710), 233 (25,100), 210 (43,200).\",\n \"MS: (LCQ DUO ESI positive ion mass spectrum) M/z (rel): 368 (100, M+H).\",\n \"Specific Rotation: [α]D=−15.8 (Free Amine; 0.5% MeOH).\",\n \"A step in the synthesis of the 4 stereoisomers of 1-6 was the coupling of the epoxide formed from either (R)- or (S)-3′,5′-dibenzyloxyphenylbromohydrin with the (R)- or (S)-enantiomer of the appropriate benzyl-protected 2-amino-3-benzylpropane (1-5) or the (R)- or (S)-enantiomer of N-benzyl-2-aminoheptane (6), Scheme I.\",\n \"The synthesis of (R)-7 and (S)-7 was accomplished using 2-phenethylamine, Scheme II.\",\n \"This approach was similar to the one developed by Trofast et al.\",\n \"(Chirality 3: 443-450, 1991) for the synthesis of the stereoisomers of formoterol, compound 47, FIG.\",\n \"6.The resulting compounds were then deprotected by hydrogenation over Pd/C and purified as the fumarate salts.\",\n \"The chiral building blocks used in the syntheses were produced using Scheme III.\",\n \"The (R)- and (S)-3′,5′-dibenzyloxyphenyl-bromohydrin enantiomers were obtained by the enantiospecific reduction of 3,5-dibenzyloxya-bromoacetophenone using boron-methyl sulfide complex (BH3SCH3) and either (1R,2S)- or (1S,2R)-cis-1-amino-2-indanol.\",\n \"The required (R)- and (S)-2-benzylaminopropanes were prepared by enantioselective crystallization of the rac-2-benzylaminopropanes using either (R)- or (S)-mandelic acid as the counter ion.\",\n \"Example 6 Binding Affinities of Exemplary Fenoterol Analogues for β1 and β2 Adrenergic Receptors This example demonstrates that fenoterol analogues have an equivalent if not greater binding affinity for β2-adrenergic receptors than fenoterol.\",\n \"Compounds were tested up to three times each to determine their binding affinities at the β□- and β2-adrenergic receptors.\",\n \"Competition curves with standard and unknown compounds included at least six concentrations (in triplicate).\",\n \"For each compound, graphs were prepared containing individual competition curves obtained for that test compound.\",\n \"IC50 values and Hill coefficients were calculated using GraphPad Prism® software.\",\n \"Ki values were calculated using the Cheng-Prusoff transformation (Biochem Pharmacol 22: 3099-3108, 1973).\",\n \"In each experiment, a standard compound was simultaneously run on the 96-well plate.\",\n \"If the standard compound did not have an IC50 value close to the established average for that compound, the entire experiment was discarded and repeated again.\",\n \"β1-adrenergic receptor binding was done on rat cortical membrane following a previously described procedure (Beer et al., Biochem.\",\n \"Pharmacol.\",\n \"37: 1145-1151, 1988).\",\n \"In brief, male Sprague-Dawley rats weighing 250-350 g were decapitated and their brains quickly removed.\",\n \"The cerebral cortices were dissected on ice, weighed and promptly transferred to a 50 ml test tube containing approximately 30 ml of 50 mM Tris-HCl, pH 7.8 (at room temperature).\",\n \"The tissues were homogenized with a polytron and centrifuged at 20,000×g for 12 min at 4° C. The pellet was washed again in the same manner and resuspended at a concentration of 20 mg (original wet wt) per 1 ml in the assay buffer (20 mM Tris-HCl, 10 mM MgCl2, 1 mM EDTA, 0.1 mM ascorbic acid at pH 7.8).\",\n \"To block the β2 sites present in the cortical membrane preparation, 30 nM ICI 118-551 was also added to the assay buffer.\",\n \"To wells containing 100 μl of the test drug and 100 μl of [3H]CGP-12177 (1.4 nM final concentration), 0.8 ml of tissue homogenate was added.\",\n \"After 2 hours at 25° C., the incubation was terminated by rapid filtration.\",\n \"Nonspecific binding was determined by 10 μM propranolol.\",\n \"HEK 293 cells stability transfected with cDNA encoding human β2-AR (provided by Dr. Brian Kobilka, Stanford Medical Center, Palo Alto, Calif.) were grown in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS), 0.05% penicillin-streptomycin, and 400 μg/ml G418 as previously described (Pauwels et al., Biochem.\",\n \"Pharmacol.\",\n \"42: 1683-1689, 1991).\",\n \"The cells were scraped from the 150×25 mm plates and centrifuged at 500×g for 5 minutes.\",\n \"The pellet was homogenized in 50 mM Tris-HCl, pH 7.7, with a Polytron, centrifuged at 27,000×g, and resuspended in the same buffer.\",\n \"The latter process was repeated, and the pellet was resuspended in 25 mM Tris-HCl containing 120 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl2, 0.8 mM MgCl2, and 5 mM glucose, pH 7.4.The binding assays contained 0.3 nM [3H]CGP-12177 in a volume of 1.0 ml.\",\n \"Nonspecific binding was determined by 1 μM propranolol.\",\n \"According to the above-described methods, binding affinities, expressed as Ki values, were determined using membranes obtained from a HEK 293 cell line stably transfected with cDNA encoding human β2-AR (Pauwels et al., Biochem.\",\n \"Pharmacol.\",\n \"42: 1683-1689, 1991) with [3H]CGP-12177 as the marker ligand.\",\n \"The resulting IC50 values and Hill coefficients were calculated for each test compound using GraphPad Prism® software and Ki values were calculated using the Cheng-Prusoff transformation (Biochem Pharmacol 22: 3099-3108, 1973): Ki=IC50/(1+L/Kd)+Eqn.\",\n \"1.Where: L is the concentration of [3H]CGP-12177 and Kd is the binding affinity of the [3]CGP-12177.Each test compounds was assayed three times.\",\n \"The relative binding affinities to the β2-AR for the stereoisomers of compounds 1-4 and 6 were R,R>R,S>S,R≈S,S (FIG.\",\n \"5; Table 1, below).\",\n \"This stereoselectivity is consistent with the previously reported potencies of the formoterol stereoisomers (Trofast et al., Chiralty 3: 443-450, 1991) and results from binding studies with the isoproterenol derivative PTFAM, compound 48, FIG.\",\n \"6 (Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987).\",\n \"With compound 5, no significant difference was found between the Ki values of the R,R and R,S isomers, thus the order was R,R=R,S>S,R>S,S.\",\n \"The Ki value for (R)-7 was greater than that of (S)-7, which is consistent with the established enantioselective binding preference for β2-ARs with the R-configuration at the stereogenic center containing the β-OH moiety, c.f.\",\n \"(Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987; Wieland et al., Proc.\",\n \"Natl.\",\n \"Acad.\",\n \"Sci.\",\n \"USA 93: 9276-9281, 1996; Kikkawa et al., Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998; and Zuurmond et al., Mol.\",\n \"Pharmacol.\",\n \"56: 909-916, 1999).\",\n \"TABLE 1 The binding affinities to the β2-AR of the compounds synthesized in this study calculated as Ki ± SEM (nM), n = 3.Comparison of β1- and β2 adrenergic binding affinity of fenoterol isomers Compound Ki β1 Ki β2 Ki β1/Ki β2 (R,R)-1 14750 ± 2510 345 ± 34 43 (R,S)-1 18910 ± 2367 3695 ± 246 5 (S,R)-1 >100,000 10330 ± 1406 NC (S,S)-1 >100,000 27749 ± 6816 NC (R,R)-2 21992 ± 3096 474 ± 35 46 (R,S)-2 30747 ± 6499 1930 ± 135 16 (S,R)-2 33378 ± 9170 5269 ± 509 6 (S,S)-2 >100,000 15881 ± 2723 NC (R,R)-3 24956 ± 2100 2934 ± 168 9 (R,S)-3 31324 ± 3485 7937 ± 397 4 (S,R)-3 77491 ± 3583 23125 ± 2093 3 (S,S)-3 31440 ± 1681 28624 ± 906 1 (R,R)-4 17218 ± 1270 1864 ± 175 9 (R,S)-4 33047 ± 2779 6035 ± 434 4 (S,R)-4 >100,000 30773 ± 3259 NC (S,S)-4 >100,000 28749 ± 1811 NC (R,R)-5 3349 ± 125 241 ± 38 14 (R,S)-5 15791 ± 6269 341 ± 23 46 (S,R)-5 34715 ± 9092 1784 ± 148 19 (S,S)-5 >100,000 2535 ± 209 NC (R,R)-6 10185 ± 499 9275 ± 902 1 (R,S)-6 >100,000 31440 ± 1681 NC (S,R)-6 61295 ± 5821 >100,000 NC (S,S)-6 52609 ± 1434 56420 ± 5186 1 (R)-7 42466 ± 3466 10466 ± 1461 4 (S)-7 52178 ± 3006 20562 ± 3721 3 When just the R,R isomers were compared, (R,R)-5 had the highest relative affinity of the tested compounds, although the difference between (R,R)-5 and (R,R)-1 did not reach statistical significance, Table 1.The only other (R,R) stereoisomer with sub-micromolar affinity was (R,R)-2, which had a significantly lower binding affinity than (R,R)-5, p=0.0051, and (R,R)-1, p=0.0291, although the mean Ki value for (R,R)-2 is only 23% greater than that of (R,R)-1.The minimal effect of transforming the p-OH moiety into a methyl ether is consistent with previous data from Schirrmacher et al.\",\n \"(Bioorg.\",\n \"Med.\",\n \"Chem.\",\n \"Lett.\",\n \"13: 2687-92, 2003).\",\n \"In the previous study, rac-1 was converted into a [18F]-fluoroethoxy ether without significant loss of in vitro activity and it was concluded that, within the accuracy of the experimental measurements, the derivatization did not change the binding affinity of the rac-1 to the β2-AR.\",\n \"Binding affinities, expressed as Ki values, for the β1-AR were determined using rat cortical membranes with [3H]-CGP-12177 as the marker ligand (Beer et al., Biochem.\",\n \"Pharmacol.\",\n \"37: 1145-1151, 1988.).\",\n \"The calculated Ki for (R,R)-5 was 3,349 nM and the binding affinities for the all of the remaining test compounds were >10,000 nM, Table 1.Unlike the data from the β2-AR binding studies, there was no clear trend which could be associated with the stereochemistry of the compounds.\",\n \"The relative selectivity of the compounds for the β2-AR and β1-AR was determined using the ratio Ki β1/Ki β2, Table 1.Of particular interest were the ratios for the four compounds with sub-micromolar affinity for the β2-AR, (R,R)-1, (R,R)-2, (R,R)-5 and (R,S)-5, which were 46, 43, 14 and 46, respectively.\",\n \"The results for (R,R)-1 and (R,R)-2 are consistent with previously reported Ki βi/Ki β2 ratio of 53 for the β2-AR-selective agonist (R,R)-TA-2005, compound 49, FIG.\",\n \"6.The observed loss of β2-AR selectivity for (R,R)-5 was unexpected as was the 3-fold increase in selectivity displayed by (R,S)-5 relative to (R,R)-5.Previous studies with the stereoisomers of 47 indicated that both the (R,R)- and (R,S)-isomers had a high degree of selectivity for the β2-AR, relative to the β1-AR, with the selectivity of the (R,R)-isomer greater than that of the (R,S)-isomer (Trofast et al., Chirality 3: 443-450, 1991).\",\n \"This is the case for compounds 1 and 2, but reversed for 5.It is also interesting to note that (S,R)-5 had a similar selectivity (19-fold) and its affinity for the β2-AR was only 7-fold weaker than (R,R)-5, 1783 nM and 241 nM, respectively.\",\n \"These studies demonstrate that (R,R)- or (R,S)-naphthyl fenoterol analogues have a higher binding affinity for β2-adrenergic receptors than any isoform of fenoterol.\",\n \"The (R,R)-methyoxy fenoterol analogue has a similar Ki for the β2-adrenergic receptor as (R,R)-fenoterol.\",\n \"Thus, such analogues are viable candidates for β2-adrenergic receptor agonists and can likely be used to treat disorders that are presently treated with commercially available (±)-fenoterol.\",\n \"Example 7 Cardiomyocyte Contractility Studies with Fenoterol Analogues This example illustrates the pharmacological activities of the compounds with sub-micromolar affinity for the β2-AR and (R,S)-1 and (S,S)-1.In these studies, the contraction amplitude indexed by electrical pacing induced shortening of cell length was measured in single ventricular myocytes before and after exposure to a single dose of the test compounds.\",\n \"Contractile response to the agonist was expressed as a percentage of the basal contractility and the specificity of the agonist towards β2-adrenergic receptor was determined by the inhibitory effect of ICI 118,551 (10−7 mol/L; Tocris Cookson Ltd., Bristol, U.K.), a selective β2-AR antagonist.\",\n \"All of the compounds tested, except for (S,S)-1, produced a significant contractile response which was blocked by ICI 118,551, while (S,S)-1 had no observed pharmacological effect, FIG.\",\n \"7.These results were consistent with the results from the previous study (Beigi et al., Chirality, 18: 822-827, 2006) and with the observations that for agonist activity at the β2-AR an R-configuration is preferred at the stereogenic center containing the β-OH moiety, c.f.\",\n \"(Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987; Wieland et al., Proc.\",\n \"Natl.\",\n \"Acad.\",\n \"Sci.\",\n \"USA 93: 9276-9281, 1996; Kikkawa et al., Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998; and Zuurmond et al., Mol.\",\n \"Pharmacol.\",\n \"56: 909-916, 1999).\",\n \"It is of interest to note that maximum effect was elicited with 0.1 μM (R,R)-5 and (R,S)-5 while the other active compounds required 0.5 μM concentrations.\",\n \"In addition, while the equivalent activities of (R,R)-5 and (R,S)-5 were suggested by the binding data, the observed activity of (R,S)-1 was unexpected as previous studies of the stereoisomers of 47 (Trofast et al., Chiralty 3: 443-450, 1991) and 48 (Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987) indicated that the agonist activities of the (R,R)-isomers were significantly greater than the activities of the corresponding (R,S)-isomers.\",\n \"Example 8 Comparative Molecular Field Analysis This example illustrates the use of Comparative Molecular Field Analysis (CoMFA) to analyze the disclosed compounds.\",\n \"The disclosed compounds were analyzed using Comparative Molecular Field Analysis, a 3D QSAR technique applicable to the analysis of the relative activities of stereoisomers and/or enantiomers at a selected target.\",\n \"CoMFA was performed as implemented in SYBYL 7.2.\",\n \"(TRIMS Inc., St. Louis, Mo.).\",\n \"Molecular models of all derivatives were prepared in HyperChem v. 6.03 (HyperCube Inc., Gainesville, Fla.) using ModelBuild procedure to ensure the same conformation of the scaffold.\",\n \"Models were extracted to SYBYL and the partial atomic charges (Gasteiger—Huckel type) were calculated.\",\n \"Ligand models were aligned using as a common substructure of the two asymmetric carbon atoms in the core of the fenoterol molecule (—C*—CH2—NH—C*—CH2—).\",\n \"Two types of molecular fields (steric and electrostatic) were sampled on the grid (2 Å spacing) lattice surrounding each structure.\",\n \"Distance-dependent dielectric constant was used in electrostatic calculations and energetic cutoffs of 30 kcal/mol for both the steric and the electrostatic energies were set.\",\n \"The Partial Least Square correlation procedure applied for resultant database extracted four statistically significant components and the following validation parameters were obtained for the best solution: R2=0.920, F (4,21)=60.380, standard error of estimate=0.223, cross-validated (leave-one-out) R2=0.847.In general, electrostatic fields accounts for 48.1% of explained variance and steric fields accounts for 51.9%.\",\n \"The resulting 3D QSAR model shows good statistical correlation with experimental data, R2=0.920 and F=60.380, and good prediction power as indicated by the cross-validated R2 value (Q2)=0.847 and the standard error of prediction (SEP)=0.309, Table 2.TABLE 2 The pKd predicted by the CoMFA model.\",\n \"Derivative pKd Measured pKd Predicted (R,R)-1 6.46 5.84 (R,S)-1 5.43 5.48 (S,R)-1 4.99 5.02 (S,S)-1 4.56 4.66 (R,R)-2 6.32 6.17 (R,S)-2 5.71 5.80 (S,R)-2 5.28 5.34 (S,S)-2 4.80 4.99 (R,R)-3 5.53 5.57 (R,S)-3 5.10 5.21 (S,R)-3 4.64 4.75 (S,S)-3 4.54 4.39 (R,R)-4 5.73 5.58 (R,S)-4 5.22 5.25 (S,R)-4 4.51 4.75 (S,S)-4 4.54 4.43 (R,R)-5 6.62 6.72 (R,S)-5 6.47 6.36 (S,R)-5 5.75 5.90 (S,S)-5 5.60 5.54 (R,R)-6 5.03 5.01 (R,S)-6 4.50 4.66 (S,R)-6 4.00 4.19 (S,S)-6 4.25 3.84 (R)-7 4.98 5.33 (S)-7 4.69 4.51 In the first stage, the model was used to identify the regions responsible for the discrimination between the stereoisomers.\",\n \"The CoMFA procedure produced several distinct asymmetric regions located in close proximity of each chiral center.\",\n \"The first chiral center (carrying the β hydroxyl group) is surrounded by an electropositive region behind the molecule.\",\n \"An electropositive region can be associated with hydrogen bond formation and indicates favorable donor properties or unfavorable acceptor properties of the pseudoreceptor.\",\n \"In this case, the location of the electropositive field indicates that the orientation of the β-OH moiety behind the plane of the model (the S configuration at the chiral center) would hinder H bond formation with the receptor.\",\n \"The electropositive region is closely associated with a steric unfavorable region behind the first chiral center.\",\n \"This is an additional indication that the model demonstrates a preference for the β-hydroxyl group in the R configuration.\",\n \"The preference for the R configuration at this center is consistent with previous models and experimental data, which demonstrated that the R configuration is favored for functional activity at β-AR receptors (c.f., Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987; Wieland et al., Proc.\",\n \"Natl.\",\n \"Acad.\",\n \"Sci.\",\n \"USA 93: 9276-9281, 1996; Kikkawa et al., Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998; and Zuurmond et al., Mol.\",\n \"Pharmacol.\",\n \"56: 909-916, 1999).\",\n \"The CoMFA model also demonstrated the effect of the second chiral center.\",\n \"The preferred configuration can be derived from the binding data, where for compounds 1-4 and 6 the (R,R)-isomers had the higher affinities relative to their respective (R,S)-isomers, while the Ki values for (R,R)-5 and (R,S)-5 were equivalent, Table 1.Thus, in this model, the more active isomers are those with the methyl moiety on the stereogenic center on the aminoalkyl portion of the molecules pointing out of the plane of the figure of the CoMFA model.\",\n \"This is depicted by a steric disfavoring region behind the second chiral center of the molecule, and indicates a preference for the R configuration at this site.\",\n \"In this study, only the aminoalkyl portion of the fenoterol molecule was altered and, therefore, the key CoMFA regions are associated with this aspect of the molecule.\",\n \"In the resulting analysis, all four interacting regions were identified in the proximity of the aromatic moiety and all can be used to generate hypotheses concerning the mode of binding action of the studied derivatives.\",\n \"In the model, the large electropositive region encompassing the area close to the —OH or OCH3 substituents represents H-bond donor properties of the pseudoreceptor to these moieties.\",\n \"These interactions are responsible for the relatively higher binding affinities of the 0-derivatives, compounds 1 and 2, relative to compounds 3 and 4, in the latter compound the p-amino substituent should be positively charged under the experimental conditions.\",\n \"A large electronegative region and another electropositive region, both located parallel on two sides of the aromatic system most likely represent π-π or π-hydrogen bond interactions between the β2-AR and electron-rich aromatic moieties, such as the naphthyl ring.\",\n \"This is consistent with the increased affinity of compounds 1, 2 and 5 relative to the other compounds examined in this study.\",\n \"The role of this interaction is suggested by the observation that the Ki values for (R,R)-5 and (R,S)-5 were equivalent to (R,R)-1 and (R,R)-2, Table 1.Two steric regions are located close to the electrostatic regions and one favors and the other disfavors bulkiness in the respective areas.\",\n \"This indicates that the binding of the aminoalkyl portions of the molecules are also sterically restricted.\",\n \"The binding of agonists and antagonists to the β2-AR has been studied using site-directed mutagenesis and molecular modeling techniques (Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987; Wieland et al., Proc.\",\n \"Natl.\",\n \"Acad.\",\n \"Sci.\",\n \"USA 93: 9276-9281, 1996; Kikkawa et al., Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998; Zuurmond et al., Mol.\",\n \"Pharmacol.\",\n \"56: 909-916, 1999; Kontoyianni et al., J. Med.\",\n \"Chem.\",\n \"39: 4406-4420, 1996; Furse et al., J. Med.\",\n \"Chem.\",\n \"46: 4450-4462, 2003; and Swaminath et al.\",\n \"J. Biol.\",\n \"Chem.\",\n \"279: 686-691, 2004).\",\n \"There is general agreement that the binding of the “catechol” portion of an agonist occurs within a binding area created by the transmembrane (TM) helices identified as TM3, TM5 and TM6.The binding process is a sequential event that produces conformational changes leading to G-protein activation (Furse et al., J. Med.\",\n \"Chem.\",\n \"46: 4450-4462, 2003).\",\n \"A key aspect in this process is the interaction of the hydroxyl moiety on the chiral carbon of the agonist with the Asn-293 residue in TM6, and for this interaction an R-configuration is preferable at the chiral carbon (Eimerl et al., Biochem.\",\n \"Pharmacol.\",\n \"36: 3523-3527, 1987; Kikkawa et al., Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998; and Swaminath et al.\",\n \"J. Biol.\",\n \"Chem.\",\n \"279: 686-691, 2004).\",\n \"Since the “catechol” portion of the fenoterol molecule was not altered in this study, it follows that in the CoMFA model, an R-configuration at the first stereogenic center is preferred in most stable complexes.\",\n \"The majority of the binding and functional studies of β2-AR agonists have been conducted with small N-alkyl substituents such as methyl, isopropyl and t-butyl, c.f.\",\n \"(Kontoyianni et al., J. Med.\",\n \"Chem.\",\n \"39: 4406-4420, 1996).\",\n \"However, while these compounds are active at the β2-AR, they are not subtype selective.\",\n \"This is illustrated by the Ki β1/Ki β2 ratios determined for compounds 49, 50 and 51 (FIG.\",\n \"6) which were 53, 1.7 and 1.3, respectively (Kikkawa, et al.\",\n \"Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998)).\",\n \"The removal of the p-methoxyphenyl moiety not only reduced the selectivity, but also the affinities as the respective β2Ki values were 12 nM, 170 nM and 6300 nM (Kikkawa, et al.\",\n \"Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998).\",\n \"The role that aminoalkyl substituents play in β2-AR selectivity has been investigated using site-directed mutagenesis and molecular modeling techniques (Kikkawa, et al.\",\n \"Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998); Furse et al., J. Med.\",\n \"Chem.\",\n \"46: 4450-4462, 2003; and Swaminath et al.\",\n \"J. Biol.\",\n \"Chem.\",\n \"279: 686-691, 2004).\",\n \"Using (R,R)-49 as the model ligand, Kikkawa, et al.\",\n \"determined that hydrogen bond formation between the p-methoxy oxygen on compound 49 and the hydroxyl group of tyrosine 308 (Y308) located in the extracellular end of TM7 was the source of the β2-AR selectivity (Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998).\",\n \"Furse and Lybrand developed a de novo model of the β2-AR and investigated molecular complexes of several ligands (agonist and antagonist) with this subtype (J. Med.\",\n \"Chem.\",\n \"46: 4450-4462, 2003).\",\n \"Among the structures investigated, (R,R)-49 has the same aminoalkyl substituent as the compound 2.Examination of the (R,R)-49/β2-AR complex revealed that the p-methoxy group oxygen of (R,R)-49 formed a hydrogen bond with the hydroxy group of Y308, which supports the model proposed by Kikkawa, et al.\",\n \"(Mol.\",\n \"Pharmacol.\",\n \"53: 128-134, 1998).\",\n \"The distance between the two oxygen atoms bonded in the model was 3.22 Å.\",\n \"However, the methoxy moiety of the ligand was also located in close proximity to three other polar residues, histidine 296 (H296) in TM6, tryptophan 109 (W109) in TM3 and asparagine 312 (N312) in TM7, each of which can interact with an aromatic group on the aminoalkyl portion of (R,R)-49.In the Furse and Lybrand model, the distance between the oxygen atom of the ligand and the hydrogen atom of H296 was 5.88 Å and H296 was proposed as an alternative hydrogen bond donor for interaction with the methoxy group of (R,R)-49.Since Y308 and H296 are found only in β2-AR, the corresponding residues found in the β1-AR are F359 and K347, respectively, the interaction with H296 and Y308 has been proposed as the source of β1/β2 selectivity (Furse et al., J. Med.\",\n \"Chem.\",\n \"46: 4450-4462, 2003).\",\n \"Since the previous studies of β1/β2 selectivity utilized (R,R)-49, the subtype selectivity of the (R,R)-stereoisomers of the compounds synthesized in our study were compared to the subtype selectivity of (R,R)-49.The data from this study suggest that hydrogen bond formation between Y308 and/or H296 and the oxygen atom on the p-substituent of the agonist is involved in β2-AR selectivity.\",\n \"The interaction is possible with (R,R)-1 and (R,R)-2 and the Ki β1/Ki β2 ratios for these compounds are 43 and 46, respectively, which are comparable to the Ki β1/Ki β2 ratio of 53 determined for (R,R)-49.The Ki β1/Ki β2 ratios for compounds 3, 4, 6 and 7 were <10 and reflect the fact that they do not have the ability to form hydrogen bonds with Y308 or H296.The hydrogen bonding interactions were also suggested by the CoMFA model identifying a large electropositive region surrounding the area close to the —OH or —OCH3 substituents, representing hydrogen-bond donor properties of the pseudoreceptor.\",\n \"The data from this study also suggest that an aromatic moiety on the aminoalkyl portion of the compound contributes to Ki and subtype selectivity, even if the aromatic moiety is unable to form a hydrogen bond with the receptor.\",\n \"This is demonstrated by the comparison of the Kiβ2 values for the (R,R)-isomers of compounds 1-5 which were <3,000 nM with Kiβ2 value of (R,R)-6 which was 9,000 nM and the Kiβ1/Ki β2 ratios which were ≥9 for 1-5 while compound 6 displayed no subtype selectivity, Table 1.One possible mechanism to explain the data is π-hydrogen bond formation.\",\n \"The cloud of π-electrons of aromatic rings can act as hydrogen bond acceptors, although it has been estimated that the interaction would be about half as strong as a normal hydrogen bond (Levitt and Perutz J. Mol.\",\n \"Biol.\",\n \"201: 751-754, 1998).\",\n \"The higher affinity and subtype selectivity for (R,R)-5 relative to (R,R)-3 and (R,R)-4 or (R)-7 is consistent with the greater π electron distribution in the napthyl ring relative to the other aromatic rings.\",\n \"The CoMFA model also identified a large electronegative region and another electropositive region, both located parallel to the aromatic system, which are most likely associated with π-π or π-hydrogen bond interactions between the β2-AR and electron-rich aromatic moieties, such as the naphthyl ring.\",\n \"Using the model developed by Furse and Lybrand with (R,R)-49 as the interacting ligand, Y308, H296, W109 and N312 were identified as possible sources of π-π and/or π-hydrogen bond interactions.\",\n \"In the β2-AR model, the estimated distances between the p-methoxy moiety on (R,R)-49 and W109 and N312 were 4.80 Å and 3.45 Å, respectively.\",\n \"Since W109 and N312 are fully conserved in all β-AR subtypes, the interactions suggested by the CoMFA model may represent the source of the increase affinities for (R,R)-1, (R,R)-2 and (R,R)-5, relative to the other (R,R)-isomers, but not the observed β1/β2 selectivity.\",\n \"The data from this study and the resulting CoMFA model indicate that the binding process of the tested compounds with the β2-AR includes the interaction of the chiral center on the aminoalkyl portion of the agonist with a sterically restricted site on the receptor.\",\n \"The existence of a sterically restricted site has been previously suggested from the data obtained in the development of 3D models for agonist and antagonist complexes with the β2-AR (Kobilka, Mol.\",\n \"Pharm.\",\n \"65: 1060-1062, 2004).\",\n \"For example, (R,R)-49 and similar compounds with substituents larger than a methyl group at the stereogenic center on the aminoalkyl portion were suggested to produce significant steric interactions that would unfavorably affect the ligand-receptor complexes.\",\n \"The binding of an agonist to the β2-AR has been described as a multistep interrelated process, in which sequential interactions between the agonist and receptor produce corresponding conformational changes (Kobilka, Mol.\",\n \"Pharm.\",\n \"65: 1060-1062, 2004).\",\n \"The CoMFA model reflects the final agonist/β2-AR complex and, in order to discern the effect of the steric restricted site, it is necessary to consider the effect that interaction with this site has on the outcome of the binding process.\",\n \"A detailed description of the present CoMFA model is disclosed in Jozwiak et al.\",\n \"(J. Med.\",\n \"Chem., 50 (12): 2903-2915, 2007) which is hereby incorporated by reference in its entirety.\",\n \"If one assumes that the interaction of the “catechol” portion of the agonist with the binding area created by TM3, TM5 and TM6 (the first binding area), then these interactions will fix the position of the aminoalkyl portion of the agonist relative to the steric restricted site, and perhaps even create this site.\",\n \"In the CoMFA model, the steric restrictions at the site force the methyl moiety at the chiral center of the aminoalkyl portion to point out of the plane of the model.\",\n \"Due to the free rotation about the N-atom, the configuration at the chiral center bearing the methyl moiety may likely not affect the ability of the molecule to minimize the interaction with the steric restricted site.\",\n \"However, in the minimum energy conformation, e.g., with the methyl group pointing out of the plane of the CoMFA model, the orientation of the remaining segment of the aminoalkyl portion relative to the second binding area would be affected by the stereochemistry.\",\n \"Indeed, R and S configurations would produce mirror image relationships to the second binding area.\",\n \"This situation is illustrated in FIG.\",\n \"5 where the catechol, first chiral center and the methyl moieties of (R,R)-5 and (R,S)-5 have been overlaid upon each other.\",\n \"The studies elucidating the source of β2-AR selectivity have primarily utilized (R,R)-49 and one previous study of the effect of chirality on subtype selectivity reported that (R,R)-47 had a higher β2-AR selectivity than (R,S)-47 (Trofast et al., Chiralty 3: 443-450, 1991).\",\n \"Thus, the observed equivalent affinities and functional activities of (R,R)-5 and (R,S)-5 at the β2-AR and the 3-fold increased β2-AR selectivity of (R,S)-5 was an unexpected result.\",\n \"One possible explanation of these results is that the naphthyl moiety of (R,S)-5 does not interact with the site defined by Y308 and H296 and is directed towards and binds to another site on the β2-AR.\",\n \"This interaction also conveys or participates in subtype selectivity as well as increased binding affinity and agonist activity.\",\n \"Since the previous models of β2-AR selectivity only employed (R,R)-isomers, it is possible that this site has been overlooked.\",\n \"Another explanation of the data is suggested by the “rocking tetrahedron” chiral recognition mechanism proposed by Sokolov and Zefirov (Doklady Akademii Nauk SSSR 319: 1382-1383, 1991).\",\n \"In this approach to molecular chiral recognition, the enantiomeric ligands are secured to a chiral selector by two binding interactions.\",\n \"The interactions must be non-equivalent and directional so that only one orientation is possible.\",\n \"The tethered enantiomers still have conformational mobility and the remaining moieties on the chiral center will sweep out overlapping but not identical steric volumes.\",\n \"Where and to what extent the chiral selector interacts with these steric volumes, determines the enantioselectivity of the process.\",\n \"If the chirality of the chiral selector places the interaction perpendicular to the plane of the ligand, no enantioselectivity is observed.\",\n \"As a deviation from the perpendicular increases, so does the enantioselectivity relative to the R or S configuration.\",\n \"With (R,R)-5 and (R,S)-5, the interactions with the first binding area and the steric restricted site of the CoMFA model are two non-equivalent and directional interactions that place the remaining constituents on the second chiral center in the same, albeit mirror image, orientation relative to the second binding area.\",\n \"As discussed above, the interactions of the 1-napthyl moieties of compound 5 with Y308 and H296 are believed to be the source of the observed β2-AR selectivity.\",\n \"If the 1-naphthyl rings sweep out overlapping but not identical steric volumes, then the observed Kiβ2 values and subtype selectivity indicate the following: 1) the Kiβ2-AR values represent the sum total of the π-hydrogen bond and π-π interactions between the 1-naphthyl moieties and Y308 and H296, as well as additional non-β2-AR specific interactions with other residues such as W109 and N312; 2) the steric volume swept out by (R,S)-5 increases the probability of interactions of Y308 and H296 with the π cloud of the naphtyl moiety relative to the (R,R)-5; and 3) the steric volume swept out by (R,R)-5 increases the probability of interactions with non-β2-AR specific sites relative to (R,S)-5.The effect of the configuration at the second chiral center and conformational-based chiral selectivity is also illustrated by the affinities and subtype selectivities of (R,R)-3, (R,S)-3 and (R)-7, Table 1.The inversion of the chirality at the second chiral carbon from R to S, reduced the Kiβ2 value of the (R,S)-3/β2-AR complex relative to the (R,R)-3/β2-AR complex by ˜3-fold while there was no significant difference between their Kiβ1 values.\",\n \"The increased subtype selectivity observed for (R,R)-3 relative to (R,S)-3, 9 versus 4, respectively, essentially reflects the differences in Kiβ2 values, which could be a reflection of increased conformational energy required to bring the aromatic portion of the aminoalkyl chain into contact with the electropositive and electronegative regions that comprise the second binding area or a decrease in the probability that this interaction would occur.\",\n \"The removal of the methyl moiety on the second chiral center, and thereby the chirality at this site ((R)-7), had a similar effect as inverting the chirality at this site from R to S. The Kiβ2 values for (R)-7 was 32% higher than (R,S)-3 and there was no difference in the β2-AR selectivity, Table 1.These results suggest that for compound 3, the primary effect of the R configuration at the second chiral site was to direct the aminoalkyl chain towards the second binding area which increased the probability of interacting with this site and reduces the conformational energy required to achieve this interaction.\",\n \"A difference between compounds 3 and 5 is the steric areas swept out by the aromatic substituents.\",\n \"In the case of compound 3, the phenyl ring produces a smaller, more linear area, while with compound 5, the 1-naphthyl ring system produces a relatively larger and broader area.\",\n \"These differences can be used to guide the synthesis of additional derivatives.\",\n \"In an example, (R,R)-2 and (R,S)-5 are chosen as possible candidates for the development of a new selective β2-AR agonist.\",\n \"These compounds may have increased and extended systemic exposures relative to the commercially available rac-1 due to changes in molecular hydrophobicity, metabolic profile and transporter interactions.\",\n \"The present example provides a pharmacophore model which may be used as a structural guide for the design of new compounds with β2-AR selectivity which can be tested for use in the treatment of a desired condition, including congestive heart failure.\",\n \"Example 9 Pharmacokinetic Studies of (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol This example demonstrates the plasma concentrations of (R,R)-Fenoterol, (R,R)-Methoxyfenoterol and (R,S)-Naphtylfenoterol administered as an intravenous (IV) bolus to male Sprague-Dawley rats.\",\n \"(R,R)-Fenoterol, (R,R)-Methoxyfenoterol and (R,S)-Naphtylfenoterol were administered to jungular vein cannulated (JVC) rats at a single dosage of 5 mg/ml intravenously (see Table 3).\",\n \"Dose calculations (mg/kg) were based on the individual body weight measured on the day of treatment.\",\n \"Study duration for pharmacokinetic studies was 6 hours.\",\n \"Plasma samples were collected over six hours at the following nine timepoints: prior to administration of the desired dose; 5.00-5.30 minutes after dose; 15.00-16.30 minutes after dose; 30.00-33.00 minutes after dose; 60-65 minutes after dose; 120-125 minutes after dose; 240-245 minutes after dose; 300-305 minutes after dose; and 360-365 minutes after dose.\",\n \"Urine was collected for 0-6 hours and 6 to 24 hours from 3 rats in each treatment group.\",\n \"TABLE 3 Study conditions for measuring plasma concentrations of (R,R)- fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol.\",\n \"Dose Dose No.\",\n \"of Rats level Concentration No.\",\n \"of for plasma Compound: (mg/kg): (mg/ml): Rats: analysis: (R,R)- 5 2.5 6 5 fenoterol (R,R)- 5 2.5 6 5 methoxyfenoterol (R,S)- 5 2.5 6 2 naphtylfenoterol Pharmacokinetic parameters for (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol after intravenous administration to rats (5 mg/kg) were analyzed according to a two-compartment open model (see Table 4).\",\n \"A drug that follows the pharmacokinetics of a two-compartment model does not equilibrate rapidly throughout the body, as is assumed for a one-compartment model.\",\n \"In the two-compartment model, the drug distributes into two compartments, the central compartment and the tissue, or peripheral compartment.\",\n \"The central compartment represents the blood, extracellular fluid, and highly perfused tissues.\",\n \"The drug distributes rapidly and uniformly in the central compartment.\",\n \"A second compartment, known as the tissue or peripheral compartment, contains tissues in which the drug equilibrates more slowly.\",\n \"Drug transfer between the two compartments is assumed to take place by first-order processes.\",\n \"The following abbreviations are utilized in Table 4 below: alpha—macro rate constant associated with the distribution phase; beta—macro rate constant associated with the elimination phase; A, B—zero time intercept associated with the alpha phase and beta phase, respectively; AUC—area under the curve; T1/2 (K10)—half-life associated with the rate constant K10; K10—elimination rate—rate at which the drug leaves the system from the central compartment; K12—rate at which drug enters tissue compartment from the central compartment; K21—rate at which drug enters central compartment from tissue compartment; V1—volume of distribution of the central compartment; V2—volume of distribution of the tissue compartment; Vss—volume of distribution at steady state; and Cl—clearance.\",\n \"TABLE 4 Pharmacokinetic parameters for (R,R)-fenoterol, (R,R)- methoxyfenoterol and (R,S)-naphtylfenoterol after intravenous administration to rats (5 mg/kg).\",\n \"(R,R)- (R,R)- (R,S)- fenoterol methoxyfenoterol naphtylfenoterol (n = 2) (n = 5) (n = 5) Weight Weight Weight Parameter Units 306 ± 11 296 ± 8 297 ± 10 Two-compartment open model A μg/ml 1.6300 4.6437 4.0365 Alpha 1/min 0.0710 0.1982 0.1764 B μg/ml 0.0577 0.3900 0.4372 Beta 1/min 0.0086 0.0054 0.0046 AUC min*μg/ml 29.6861 96.1011 116.88 T1/2 (K10) min 12.19 13.23 18.11 K10 1/min 0.0568 0.0524 0.0383 K12 1/min 0.0119 0.1309 0.1213 K21 1/min 0.0107 0.0203 0.0214 V1 ml 906.5 294.01 330.83 V2 ml 1005.20 1895.00 1872.92 Vss ml 1911.70 2189.02 2203.75 Cl ml/min 51.54 15.40 12.66 Tables 5-7 and FIG.\",\n \"8 illustrate the individual plasma concentrations of (R,R)-fenoterol, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol after IV administration to rats (5 mg/kg).\",\n \"The average concentration of (R,R)-fenoterol in plasma was dramatically lower (1.34 μg/ml) five minutes after IV administration to rats (5 mg/kg) compared to either the average concentration of (R,R)-methoxyfenoterol (2.12 μg/ml) or (R,S)-naphtylfenoterol (2.11 μg/ml).\",\n \"TABLE 5 Individual plasma concentrations of (R,R)-fenoterol after intravenous administration (5 mg/kg).\",\n \"Concentration (ug/ml) Time (min) Rat# 01 Rat #02 Average 5 1.34 1.34 15 0.36 0.36 30 0.17 0.50 0.34 60 0.05 0.05 0.05 120 0.03 0.01 0.02 240 0.0003 0.02 0.01 300 0.005 0.005 360 0.08 0.03 0.06 TABLE 6 Individual plasma concentrations of (R,R)-methoxyfenoterol after intravenous administration (5 mg/kg).\",\n \"Concentration (ug/ml) Rat# Rat# Rat# Rat# Rat# Time (min) 13 14 15 16 18 Average 5 1.94 2.14 2.51 1.89 2.12 15 0.48 0.54 0.62 0.67 0.56 0.58 30 0.31 0.40 0.46 0.48 0.38 0.41 60 0.23 0.25 0.24 0.33 0.25 0.26 120 0.14 0.16 0.18 0.21 0.14 0.17 240 0.09 0.12 0.17 0.14 0.08 0.12 300 0.06 0.07 0.07 0.09 0.07 0.07 360 0.05 0.06 0.05 0.08 0.04 0.06 TABLE 7 Individual plasma concentrations of (R,S)-naphtylfenoterol after intravenous administration (5 mg/kg).\",\n \"Concentration (ug/ml) Rat# Rat# Rat# Rat# Rat# Time (min) 25 26 27 28 29 Average 5 2.52 2.16 1.64 2.10 2.11 15 0.85 0.78 0.50 0.60 0.68 30 0.49 0.54 0.34 0.33 0.43 60 0.36 0.42 0.37 0.29 0.24 0.34 120 0.25 0.29 0.26 0.22 0.18 0.24 240 0.11 0.11 0.13 0.13 0.11 0.12 300 0.10 0.11 0.12 0.11 0.10 0.11 360 0.08 0.08 0.11 0.10 0.09 0.09 The data demonstrate that the two derivatives, (R,R)-methoxyfenoterol and (R,S)-naphtylfenoterol, have a significantly higher systemic exposure (AUC) and longer clearance compared to (R,R)-fenoterol which may produce a longer acting drug.\",\n \"It is suggested that the longer clearance time may be the result of inhibiting glucuronidation.\",\n \"Example 10 Treatment of Cardiac Disorders with (R,R)-Fenoterol or Fenoterol Analogues Based upon the teaching disclosed herein, a cardiac disorder such as congestive heart failure is treated by administering a therapeutic effective dose of (R,R)-fenoterol or one or more of the fenoterol analogues disclosed above (see Sections III and IV).\",\n \"In an example, a subject who has been diagnosed with congestive heart failure is identified.\",\n \"Following subject selection, a therapeutic effective dose of (R,R)-fenoterol or the respective fenoterol analogue is administered to the subject.\",\n \"For example, a therapeutic effective dose of the (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative is administered to the subject.\",\n \"In a further example, a therapeutic effective dose of the (R,S)-fenoterol analogue including a napthyl derivative is administered to the subject.\",\n \"The fenoterol analogue is prepared and purified as described in Section III.B and Example 5.The amount of (R,R)-fenoterol or fenoterol analogue or a pharmaceutical composition thereof administered to reduce, inhibit, and/or treat congestive heart failure depends on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition (see Section V).\",\n \"Ideally, a therapeutically effective amount of an agent is the amount sufficient to prevent, reduce, and/or inhibit, and/or treat the cardiac disorder (e.g., congestive heart failure) in a subject without causing a substantial cytotoxic effect in the subject.\",\n \"In an example, (R,R)-fenoterol, a disclosed fenoterol analogue (such as an (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative or an (R,S)-fenoterol analogue including a napthyl derivative) or pharmaceutical composition is provided at a dosage range from about 0.001 to about 10 mg/kg body weight orally in single or divided doses.\",\n \"In particular examples, the dosage range is from about 0.005 to about 5 mg/kg body weight orally in single or divided doses (assuming an average body weight of approximately 70 kg; values adjusted accordingly for persons weighing more or less than average).\",\n \"In certain examples, a disclosed fenoterol compound or pharmaceutical composition is provided by oral administration in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.0 mg to about 10 mg, more particularly about 2.5 mg, about 5 mg, or about 10 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.\",\n \"In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg active ingredient is administered two to four times a day.\",\n \"For example, a tablet containing about 1 mg to about 10 mg active ingredient is administered two times a day.\",\n \"Example 11 Treatment of Pulmonary Disorders with Fenoterol Analogues According to the teachings herein, a pulmonary disorder such as asthma or chronic obstructive pulmonary disease is treated by administering a therapeutic effective dose of the fenoterol analogues disclosed above (see Sections III-V).\",\n \"In an example, a subject who has been diagnosed with or displays one of the symptoms associated with asthma or chronic obstructive pulmonary disease is identified.\",\n \"Following subject selection, a therapeutic effective dose of the desired fenoterol analogue is administered to the subject.\",\n \"For example, a therapeutic effective dose of the (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative is administered to the subject.\",\n \"In a further example, a therapeutic effective dose of the (R,S)-fenoterol analogue including a napthyl derivative is administered to the subject.\",\n \"The fenoterol analogue is prepared and purified as described in Section III.B and Example 5.The amount of the fenoterol analogue administered to prevent, reduce, inhibit, and/or treat the pulmonary disorder depends on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition.\",\n \"Ideally, a therapeutically effective amount of an agent will be the amount sufficient to prevent, reduce, and/or inhibit, and/or treat the pulmonary disorder in a subject without causing a substantial cytotoxic effect in the subject.\",\n \"In an example, (R,R)-fenoterol, a disclosed fenoterol analogue (such as an (R,R)-fenoterol analogue including a OCH3 group or a naphthyl derivative or an (R,S)-fenoterol analogue including a napthyl derivative) or pharmaceutical composition is provided at a dosage range from about 0.001 to about 10 mg/kg body weight orally in single or divided doses.\",\n \"In particular examples, the dosage range is from about 0.005 to about 5 mg/kg body weight orally in single or divided doses (assuming an average body weight of approximately 70 kg; values adjusted accordingly for persons weighing more or less than average).\",\n \"In certain examples, a disclosed fenoterol compound or pharmaceutical composition is provided by oral administration in the form of a tablet containing from about 1.0 to about 50 mg of the active ingredient, particularly about 2.0 mg to about 10 mg, more particularly about 2.5 mg, about 5 mg, or about 10 mg of the active ingredient for the symptomatic adjustment of the dosage to the subject being treated.\",\n \"In one exemplary oral dosage regimen, a tablet containing from about 1 mg to about 50 mg active ingredient is administered two to four times a day.\",\n \"For example, a tablet containing about 1 mg to about 10 mg active ingredient is administered two times a day.\",\n \"In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention.\",\n \"Rather, the scope of the invention is defined by the following claims.\",\n \"We therefore claim as our invention all that comes within the scope and spirit of these claims.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874747"}}},{"rowIdx":4494685,"cells":{"text":{"kind":"list like","value":[["AUTONOMOUS FLUID INSTILLATION SYSTEM AND METHOD WITH TISSUE SITE PRESSURE MONITORING","A system and method for providing fluid to a tissue site is described.","The method fluidly couples an instillation therapy system to the tissue site and monitors a pressure supplied to the tissue site by a reduced-pressure source with the instillation therapy system for a time period.","The method provides fluid to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.","The system includes a pressure sensor fluidly coupled to the tissue site to measure a pressure proximate the tissue site.","A valve and a flow meter are fluidly between a fluid reservoir and the tissue site.","A controller is communicatively coupled to the pressure sensor and the valve and configured to monitor the pressure at the tissue site and a volume of fluid flow to the tissue and, in response, operate the valve."],["1.A method for providing fluid to a tissue site, the method comprising: fluidly coupling an instillation therapy system to the tissue site; monitoring a pressure supplied to the tissue site by a reduced-pressure source with the instillation therapy system for a time period; and providing fluid to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.","2.The method of claim 1, wherein providing fluid to the tissue site comprises opening a valve fluidly coupled between the tissue site and a fluid reservoir.","3.The method of claim 2, further comprising operating a pump fluidly coupled between the valve and the fluid reservoir.","4.The method of claim 1, wherein providing fluid to the tissue site comprises operating a pump fluidly coupled between the tissue site and a fluid reservoir.","5.The method of claim 1, wherein monitoring a pressure at the tissue site for a time period comprises: operating the reduced-pressure source fluidly coupled to the tissue site in an intermittent mode; monitoring the pressure at the tissue site to determine a pressure profile; and determining one or more operating parameters of a reduced-pressure treatment from the pressure profile.","6.The method of claim 5, wherein the one or more operating parameters comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on period and an off period for the reduced-pressure source.","7.The method of claim 5, wherein providing fluid to the tissue site comprises opening a valve fluidly coupled between the tissue site and a fluid reservoir in response to the one or more operating parameters.","8.The method of claim 7, wherein opening the valve in response to the one or more operating parameters comprises opening the valve when the pressure at the tissue site reaches a trigger pressure.","9.The method of claim 7, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during an off period of the reduced-pressure source.","10.The method of claim 7, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during an on period of the reduced-pressure source.","11.The method of claim 1, further comprising: monitoring a reduced-pressure ramp-down period while providing fluids; and reporting that a fluid reservoir is empty in response to a deviation of the reduced-pressure ramp-down period from an expected reduced-pressure ramp-down period.","12.A method for providing fluid to a tissue site, the method comprising: fluidly coupling an instillation therapy system to the tissue site; operating a reduced-pressure treatment system fluidly coupled to the tissue site to provide reduced-pressure therapy in an intermittent mode; monitoring a pressure at the tissue site; determining a pressure profile of the reduced-pressure therapy at the tissue site; and opening a valve fluidly coupled between the tissue site and a fluid reservoir in response to the pressure profile.","13.The method of claim 12, further comprising operating a pump fluidly coupled between the valve and the fluid reservoir.","14.The method of claim 12, further comprising determining one or more operating parameters of the reduced-pressure therapy from the pressure profile.","15.The method of claim 14, wherein the one or more operating parameters comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on period and an off period for a reduced-pressure source of the reduced-pressure treatment system.","16.The method of claim 15, wherein opening a valve fluidly coupled between the tissue site and a fluid reservoir comprises opening the valve in response to the one or more operating parameters.","17.The method of claim 16, wherein opening the valve in response to the one or more operating parameters comprises opening the valve when the pressure at the tissue site reaches the trigger pressure.","18.The method of claim 16, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during the off period of the reduced-pressure source.","19.The method of claim 16, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during the on period of the reduced-pressure source.","20.The method of claim 12, further comprising: determining an expected reduced-pressure ramp-down period from the pressure profile; monitoring the reduced-pressure ramp-down period when the valve is open; and reporting that a fluid reservoir is empty in response to a deviation of the reduced-pressure ramp-down period from the expected reduced-pressure ramp-down period.","21.A system for providing instillation therapy to a tissue site, the system comprising: a fluid interface configured to be fluidly coupled to the tissue site; a pressure sensor fluidly coupled to the fluid interface and configured to measure a pressure proximate the tissue site; a valve fluidly coupled to the fluid interface and having an open position configured to permit fluid communication through the valve and a closed position configured to prevent fluid communication through the valve; a flow meter configured to be fluidly coupled between the valve and the fluid interface; a fluid reservoir fluidly coupled to the valve; and a controller communicatively coupled to the pressure sensor and the valve, the controller configured to monitor the pressure measured by the pressure sensor and a volume of fluid flow through the flow meter and, in response, operate the valve.","22.The system of claim 21, wherein the controller is configured to operate the valve in response to one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, an on-state and an off-state of a reduced-pressure therapy system, and a duration of fluid delivery and an interval of fluid delivery.","23.The system of claim 21, wherein the controller is configured to determine a pressure profile in response to the pressure measured by the pressure sensor.","24.The system of claim 23, wherein the controller is configured to determine one or more operating parameters in response to the pressure profile.","25.The system of claim 24, wherein the one or more operating parameters comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on-state and an off-state of a reduced-pressure therapy system.","26.The system of claim 21, further comprising a user interface operationally coupled to the controller and configured to present one or more operating parameters of the system.","27.The system of claim 26, wherein the one or more operating parameters comprise one more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on-state and an off-state of a reduced-pressure therapy system.","28.The system of claim 26, wherein the user interface is further configured to receive operational input and communicate the operational input to the controller.","29.The system of claim 28, wherein the operational input may comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, a duration of fluid delivery, and an interval of fluid delivery.","30.The system of claim 21, further comprising a pump fluidly coupled between the fluid reservoir and the valve, the pump being operationally coupled to the controller.","31.The system of claim 21, further comprising a disposable connector fluidly coupled between the pressure sensor and the fluid interface.","32.The system of claim 21, further comprising at least one sensor fluidly coupled to a tube fluidly coupling the valve to the fluid interface and further operationally coupled to the controller, the at least one sensor configured to detect blockages in the tube.","33.-39.","(canceled)"],["<SOH> BACKGROUND <EOH>Clinical studies and practice have shown that reducing pressure in proximity to a tissue site can augment and accelerate growth of new tissue at the tissue site.","The applications of this phenomenon are numerous, but it has proven particularly advantageous for treating wounds.","Regardless of the etiology of a wound, whether trauma, surgery, or another cause, proper care of the wound is important to the outcome.","Treatment of wounds with reduced pressure may be commonly referred to as “reduced-pressure therapy,” but is also known by other names, including “negative-pressure therapy,” “negative-pressure wound therapy,” “reduced-pressure wound therapy,” “vacuum therapy,” and “vacuum-assisted closure,” for example.","Reduced-pressure therapy may provide a number of benefits, including migration of epithelial and subcutaneous tissues, improved blood flow, and micro-deformation of tissue at a tissue site.","Together, these benefits can increase development of granulation tissue and reduce healing times.","In addition, the delivery of therapeutic fluids (e.g.","saline or antibiotic fluids) to the tissue site can also provide benefits to healing of a tissue site.","Treatment of tissue sites with the delivery of therapeutic fluids may also be referred to as “instillation therapy.” Instillation therapy may assist in cleaning the tissue site by aiding in the removal of infectious agents or necrotic tissue.","The therapeutic fluids used in instillation therapy may also provide medicinal fluids, such as antibiotics, anti-fungals, antiseptics, analgesics, or other similar substances, to aid in the treatment of a tissue site.","While the clinical benefits of reduced-pressure therapy and instillation therapy are widely known, the cost and complexity of reduced-pressure therapy and instillation therapy can be a limiting factor in its application, and the development and operation of reduced-pressure systems, components, and processes continues to present significant challenges to manufacturers, healthcare providers, and patients."],["<SOH> BRIEF SUMMARY <EOH>In one example embodiment, a method for providing fluid to a tissue site may be described.","An instillation therapy system may be fluidly coupled to the tissue site, and a pressure supplied to the tissue site by a reduced-pressure source may be monitored with the instillation therapy system for a time period.","Fluid may be provided to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.","In another example embodiment, a method for providing fluid to a tissue site may be described.","An instillation therapy system may be fluidly coupled to the tissue site.","A reduced-pressure treatment system fluidly coupled to the tissue site may be operated to provide reduced-pressure therapy in an intermittent mode, and the instillation therapy system may monitor a pressure at the tissue site.","A pressure profile of the reduced-pressure therapy at the tissue site may be determined.","A valve fluidly coupled between the tissue site and a fluid reservoir may be opened in response to the pressure profile.","In still another embodiment, a system for providing instillation therapy to a tissue site may be described.","The system may include a fluid interface configured to be fluidly coupled to the tissue site and a pressure sensor fluidly coupled to the fluid interface and configured to measure a pressure proximate the tissue site.","The system may also include a valve fluidly coupled to the fluid interface.","The valve may have an open position configured to permit fluid communication through the valve and a closed position configured to prevent fluid communication through the valve.","The system may have a flow meter configured to be fluidly coupled between the valve and the fluid interface and a fluid reservoir fluidly coupled to the valve.","The system may include a controller communicatively coupled to the pressure sensor and the valve.","The controller may be configured to monitor the pressure measured by the pressure sensor and a volume of fluid flow through the flow meter and, in response, operate the valve.","In yet another example embodiment, a method for providing fluid to a tissue site may be described.","An instillation therapy system may be fluidly coupled to the tissue site and operated in a training mode.","A pressure profile of a reduced pressure source fluidly coupled to the tissue site may be determined in response to the training mode.","In response to the pressure profile, the instillation therapy system may deliver fluid to the tissue site.","In yet still another example embodiment, a method for delivering fluid to a tissue site may be described.","An instillation therapy system may be coupled to the tissue site, and the instillation therapy system may monitor a pressure at the tissue site.","Fluids may be delivered to the tissue site if the pressure at the tissue site is about a trigger pressure, and the instillation therapy system may continue to monitor the pressure at the tissue site if the pressure at the tissue site is not about the trigger pressure.","A fluid flow to the tissue site may be monitored in response to delivering fluids to the tissue site, and the instillation therapy system may determine if the fluid flow is about a dosage of fluids.","If the fluid flow is about the dosage of fluids, the fluid flow may be stopped.","And if the fluid flow is not about the dosage of fluids, the instillation therapy system may determine if a reduced-pressure source fluidly coupled to the tissue site is about to start an on period.","If the reduced-pressure source is not about to start the on period, fluids may continue to be delivered.","If the reduced-pressure source is about to enter the on period, fluid may stop being delivered, and the trigger pressure may be incremented if the reduced-pressure source is about to start the on period.","Other objects, features, and advantages of the embodiments described herein will become apparent with reference to the drawings and detailed description that follow."],["RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","14/561,718, filed Dec. 5, 2014, which claims the benefit, under 35 USC § 119(e), of the filing of U.S.","Provisional Patent Application No.","61/917,773, entitled “Autonomous Fluid Instillation System and Method with Tissue Site Pressure Monitoring,” filed Dec. 18, 2013, which is incorporated herein by reference for all purposes.","TECHNICAL FIELD The present invention relates generally to tissue treatment systems and more particularly, but without limitation, to a system and method for providing instillation therapy to a tissue site.","BACKGROUND Clinical studies and practice have shown that reducing pressure in proximity to a tissue site can augment and accelerate growth of new tissue at the tissue site.","The applications of this phenomenon are numerous, but it has proven particularly advantageous for treating wounds.","Regardless of the etiology of a wound, whether trauma, surgery, or another cause, proper care of the wound is important to the outcome.","Treatment of wounds with reduced pressure may be commonly referred to as “reduced-pressure therapy,” but is also known by other names, including “negative-pressure therapy,” “negative-pressure wound therapy,” “reduced-pressure wound therapy,” “vacuum therapy,” and “vacuum-assisted closure,” for example.","Reduced-pressure therapy may provide a number of benefits, including migration of epithelial and subcutaneous tissues, improved blood flow, and micro-deformation of tissue at a tissue site.","Together, these benefits can increase development of granulation tissue and reduce healing times.","In addition, the delivery of therapeutic fluids (e.g.","saline or antibiotic fluids) to the tissue site can also provide benefits to healing of a tissue site.","Treatment of tissue sites with the delivery of therapeutic fluids may also be referred to as “instillation therapy.” Instillation therapy may assist in cleaning the tissue site by aiding in the removal of infectious agents or necrotic tissue.","The therapeutic fluids used in instillation therapy may also provide medicinal fluids, such as antibiotics, anti-fungals, antiseptics, analgesics, or other similar substances, to aid in the treatment of a tissue site.","While the clinical benefits of reduced-pressure therapy and instillation therapy are widely known, the cost and complexity of reduced-pressure therapy and instillation therapy can be a limiting factor in its application, and the development and operation of reduced-pressure systems, components, and processes continues to present significant challenges to manufacturers, healthcare providers, and patients.","BRIEF SUMMARY In one example embodiment, a method for providing fluid to a tissue site may be described.","An instillation therapy system may be fluidly coupled to the tissue site, and a pressure supplied to the tissue site by a reduced-pressure source may be monitored with the instillation therapy system for a time period.","Fluid may be provided to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.","In another example embodiment, a method for providing fluid to a tissue site may be described.","An instillation therapy system may be fluidly coupled to the tissue site.","A reduced-pressure treatment system fluidly coupled to the tissue site may be operated to provide reduced-pressure therapy in an intermittent mode, and the instillation therapy system may monitor a pressure at the tissue site.","A pressure profile of the reduced-pressure therapy at the tissue site may be determined.","A valve fluidly coupled between the tissue site and a fluid reservoir may be opened in response to the pressure profile.","In still another embodiment, a system for providing instillation therapy to a tissue site may be described.","The system may include a fluid interface configured to be fluidly coupled to the tissue site and a pressure sensor fluidly coupled to the fluid interface and configured to measure a pressure proximate the tissue site.","The system may also include a valve fluidly coupled to the fluid interface.","The valve may have an open position configured to permit fluid communication through the valve and a closed position configured to prevent fluid communication through the valve.","The system may have a flow meter configured to be fluidly coupled between the valve and the fluid interface and a fluid reservoir fluidly coupled to the valve.","The system may include a controller communicatively coupled to the pressure sensor and the valve.","The controller may be configured to monitor the pressure measured by the pressure sensor and a volume of fluid flow through the flow meter and, in response, operate the valve.","In yet another example embodiment, a method for providing fluid to a tissue site may be described.","An instillation therapy system may be fluidly coupled to the tissue site and operated in a training mode.","A pressure profile of a reduced pressure source fluidly coupled to the tissue site may be determined in response to the training mode.","In response to the pressure profile, the instillation therapy system may deliver fluid to the tissue site.","In yet still another example embodiment, a method for delivering fluid to a tissue site may be described.","An instillation therapy system may be coupled to the tissue site, and the instillation therapy system may monitor a pressure at the tissue site.","Fluids may be delivered to the tissue site if the pressure at the tissue site is about a trigger pressure, and the instillation therapy system may continue to monitor the pressure at the tissue site if the pressure at the tissue site is not about the trigger pressure.","A fluid flow to the tissue site may be monitored in response to delivering fluids to the tissue site, and the instillation therapy system may determine if the fluid flow is about a dosage of fluids.","If the fluid flow is about the dosage of fluids, the fluid flow may be stopped.","And if the fluid flow is not about the dosage of fluids, the instillation therapy system may determine if a reduced-pressure source fluidly coupled to the tissue site is about to start an on period.","If the reduced-pressure source is not about to start the on period, fluids may continue to be delivered.","If the reduced-pressure source is about to enter the on period, fluid may stop being delivered, and the trigger pressure may be incremented if the reduced-pressure source is about to start the on period.","Other objects, features, and advantages of the embodiments described herein will become apparent with reference to the drawings and detailed description that follow.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a partial sectional view of a reduced-pressure therapy system and an instillation therapy system for treating a tissue site in accordance with this specification; FIG.","2 is a partial sectional view of another embodiment of the reduced-pressure therapy system and the instillation therapy system for treating a tissue site in accordance with an illustrative embodiment; FIG.","3 is a sectional view of a tube for fluidly coupling a reduced-pressure source to a reduced-pressure interface in accordance with an illustrative embodiment; FIG.","4 is a schematic diagram of the reduced-pressure therapy system and the instillation therapy system in accordance with an illustrative embodiment; FIG.","5 is a graphical depiction of the operation of the reduced-pressure therapy system of FIG.","4 in accordance with an illustrative embodiment; FIG.","6A is a graphical depiction of a pressure profile of reduced-pressure provided to the tissue site by the reduced-pressure therapy system of FIG.","4 in accordance with an illustrative embodiment; FIG.","6B is a graphical depiction of the pressure profile of FIG.","6A illustrating a training mode of the instillation therapy system of FIG.","4; FIG.","7 is a graphical depiction of the operation of a valve of the fluid source of FIG.","4 in accordance with an illustrative embodiment; FIG.","8 is a graphical depiction of the operation of the valve of the fluid source of FIG.","4 in accordance with another illustrative embodiment; FIG.","9 is a block diagram illustrating operative steps of the fluid source of FIG.","4; FIG.","10 is a block diagram illustrating operative steps of an intermittent mode of operation of the fluid source of FIG.","4; FIG.","11 is a block diagram illustrating operative steps of a training mode of operation of the fluid source of FIG.","4; FIG.","12 is a block diagram illustrating operative steps of a dynamic mode of operation of the fluid source of FIG.","4; and FIG.","13 is a block diagram illustrating additional operative steps of the dynamic mode of operation of the fluid source of FIG.","4.DESCRIPTION OF EXAMPLE EMBODIMENTS New and useful systems and methods for providing instillation therapy in a reduced-pressure therapy environment are set forth in the appended claims.","Objectives, advantages, and a preferred mode of making and using the systems and methods may be understood best by reference to the following detailed description in conjunction with the accompanying drawings.","The description provides information that enables a person skilled in the art to make and use the claimed subject matter, but may omit certain details already well-known in the art.","Moreover, descriptions of various alternatives using terms such as “or” do not necessarily require mutual exclusivity unless clearly required by the context.","The claimed subject matter may also encompass alternative embodiments not specifically described in detail.","The following detailed description is, therefore, to be taken as illustrative and not limiting.","The example embodiments may also be described herein with reference to spatial relationships between various elements or to the spatial orientations of various elements depicted in the attached drawings.","In general, such relationships or orientation assume a frame of reference consistent with or relative to a patient in a position to receive treatment.","However, as should be recognized by those skilled in the art, this frame of reference is merely a descriptive expedient rather than a strict prescription.","FIG.","1 is a partial sectional view of a therapy system 100 that may include a reduced-pressure therapy system 101 and an instillation therapy system 116 fluidly coupled to a tissue site 114 in accordance with some embodiments.","In an illustrative embodiment, the therapy system 100 may also include a dressing 102 coupled to a tissue site 114.The dressing 102 may include a drape, such as a drape 108, and a tissue interface, such as a manifold 110.The reduced-pressure therapy system 101 may include a reduced-pressure source 104 fluidly coupled to the dressing 102.The reduced-pressure therapy system 101 may also include a fluid container, such as a container 112, fluidly coupled to the dressing 102 and the reduced-pressure source 104 by a reduced-pressure interface 105, a tube 107, and a tube 109.The instillation therapy system 116 may include a fluid source 118 and a fluid interface 120.The fluid source 118 may be fluidly coupled to the fluid interface 120 with a fluid connector 122 and one or more tubes, such as a tube 123 and a tube 124.A tissue interface, such as the manifold 110, may be placed within, over, on, or otherwise proximate a tissue site, such as the tissue site 114.For example, the manifold 110 may be placed against the tissue site 114, and the drape 108 may be placed over the manifold 110 and sealed to tissue proximate the tissue site 114.Tissue proximate a tissue site is often undamaged epidermis peripheral to the tissue site.","Thus, the dressing 102 can provide a sealed therapeutic environment 103 proximate a tissue site.","The sealed therapeutic environment 103 may be substantially isolated from the external environment, and the reduced-pressure source 104 can reduce the pressure in the sealed therapeutic environment 103.Reduced pressure applied uniformly through a tissue interface in the sealed therapeutic environment 103 can induce macrostrain and microstrain in a tissue site, as well as remove exudates and other fluids from the tissue site.","The removed exudates and other fluids can be collected in the container 112 and disposed of properly.","A “tissue site,” such as the tissue site 114, may refer to a wound or defect located on or within tissue including, but not limited to, bone tissue, adipose tissue, muscle tissue, neural tissue, dermal tissue, vascular tissue, connective tissue, cartilage, tendons, or ligaments.","A wound may include chronic, acute, traumatic, subacute, and dehisced wounds, partial-thickness burns, ulcers (such as diabetic, pressure, or venous insufficiency ulcers), flaps, and grafts, for example.","The term “tissue site” may also refer to areas of any tissue that are not necessarily wounded or defective, but are instead areas in which it may be desirable to add or promote the growth of additional tissue.","For example, reduced pressure may be used in certain tissue areas to grow additional tissue that may be harvested and transplanted to another tissue location.","“Reduced pressure” generally refers to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to the sealed therapeutic environment 103 provided by the dressing 102.In many cases, the local ambient pressure may also be the atmospheric pressure at which a patient is located.","Alternatively, the pressure may be less than a hydrostatic pressure associated with tissue at a tissue site.","Unless otherwise indicated, values of pressure stated herein are gauge pressures.","Similarly, references to increases in reduced pressure typically refer to a decrease in absolute pressure, while decreases in reduced pressure typically refer to an increase in absolute pressure.","The fluid mechanics of using a reduced-pressure source to reduce pressure in another component or location, such as within the sealed therapeutic environment 103, can be mathematically complex.","However, the basic principles of fluid mechanics applicable to reduced-pressure therapy are generally well-known to those skilled in the art, and the process of reducing pressure may be described illustratively herein as “delivering,” “distributing,” or “generating” reduced pressure, for example.","In general, exudates and other fluids flow toward lower pressure along a fluid path.","Thus, the term “downstream” typically implies a position in a fluid path relatively closer to a reduced-pressure source, and conversely, the term “upstream” implies a position relatively further away from a reduced-pressure source.","Similarly, it may be convenient to describe certain features in terms of fluid “inlet” or “outlet” in such a frame of reference.","This orientation is generally presumed for purposes of describing various features and components of reduced-pressure therapy systems herein.","However, the fluid path may also be reversed in some applications (such as by substituting a positive-pressure source for a reduced-pressure source) and this descriptive convention should not be construed as a limiting convention.","A tissue interface, such as the manifold 110, can generally be adapted to contact a tissue site or other layers of a dressing, such as the dressing 102.A tissue interface may be partially or fully in contact with a tissue site.","If a tissue site is a wound, for example, a tissue interface may partially or completely fill the wound, or may be placed over the wound.","A tissue interface may take many forms, and may have many sizes, shapes, or thicknesses depending on a variety of factors, such as the type of treatment being implemented or the nature and size of a tissue site.","For example, the size and shape of a tissue interface may be adapted to the contours of deep and irregular shaped tissue sites.","Generally, a manifold, such as the manifold 110, for example, is a substance or structure adapted to distribute or remove fluids from a tissue site.","A manifold may include flow channels or pathways that can distribute fluids provided to and removed from a tissue site.","In one illustrative embodiment, the flow channels or pathways may be interconnected to improve distribution of fluids provided to or removed from a tissue site.","For example, a manifold may be an open-cell, porous tissue collection, or other porous material such as gauze or felted mat that generally includes structural elements arranged to form flow channels.","Liquids, gels, and other foams may also include or be cured to include flow channels.","In one illustrative embodiment, the manifold 110 may be a porous foam pad having interconnected cells adapted to distribute reduced pressure across a tissue site.","The foam material may be either hydrophobic or hydrophilic.","In one non-limiting example, the manifold 110 may be reticulated polyurethane foam, such as GranuFoam® dressing available from Kinetic Concepts, Inc. of San Antonio, Tex.","In some embodiments, the manifold 110 may be made from a hydrophilic material, and the manifold 110 may also wick fluid away from a tissue site, while continuing to distribute reduced pressure to the tissue site.","The wicking properties of the manifold 110 may draw fluid away from a tissue site by capillary flow or other wicking mechanisms.","An example of a hydrophilic foam is a polyvinyl alcohol, open-cell foam such as V.A.C.","WhiteFoam® dressing available from Kinetic Concepts, Inc. of San Antonio, Tex.","Other hydrophilic foams may include those made from polyether.","Other foams that may exhibit hydrophilic characteristics include hydrophobic foams that have been treated or coated to provide hydrophilicity.","A tissue interface may further promote granulation at a tissue site if pressure within a sealed therapeutic environment is reduced.","For example, any or all of the surfaces of the manifold 110 may have an uneven, coarse, or jagged profile that can induce microstrains and stresses at the tissue site 114 if reduced pressure is applied to the sealed therapeutic environment 103 through the manifold 110.In some example embodiments, a tissue interface may be constructed from bioresorbable materials.","Suitable bioresorbable materials may include, without limitation, a polymeric blend of polylactic acid (PLA) and polyglycolic acid (PGA).","The polymeric blend may also include without limitation polycarbonates, polyfumarates, and capralactones.","A tissue interface may further serve as a scaffold for new cell-growth, or a scaffold material may be used in conjunction with the tissue interface to promote cell-growth.","In general, a scaffold material may be a biocompatible or biodegradable substance or structure used to enhance or promote the growth of cells or formation of tissue, such as a three-dimensional porous structure that provides a template for cell growth.","Illustrative examples of scaffold materials include calcium phosphate, collagen, PLA/PGA, coral hydroxy apatites, carbonates, or processed allograft materials.","The drape 108 is an example of a sealing member.","A sealing member may be constructed from a material that can provide a fluid seal between two components or two environments, such as between a therapeutic environment and a local external environment.","A sealing member may be, for example, an impermeable or semi-permeable, elastomeric material that can provide a seal adequate to maintain a reduced pressure at a tissue site for a given reduced-pressure source.","For semi-permeable materials, the permeability generally should be low enough that a desired reduced pressure may be maintained.","An attachment device may be used to attach a sealing member to an attachment surface, such as undamaged epidermis, a gasket, or another sealing member.","An attachment device may take many forms.","For example, an attachment device may be a medically-acceptable, pressure-sensitive adhesive that extends about a periphery, a portion, or an entire sealing member.","Other example embodiments of an attachment device may include a double-sided tape, paste, hydrocolloid, hydrogel, silicone gel, organogel, or an acrylic adhesive.","In general, components of the reduced-pressure therapy system 101 may be coupled directly or indirectly to each other.","For example, the reduced-pressure source 104 may be directly coupled to the container 112 by the tube 107 and indirectly coupled to the dressing 102 through the container 112 and the tube 109.Components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components.","In some embodiments, components may be fluidly coupled with a tube, such as the tube 107 or the tube 109, for example.","A “tube,” as used herein, broadly refers to a tube, pipe, hose, conduit, or other structure with one or more lumina adapted to convey fluids between two ends.","Typically, a tube is an elongated, cylindrical structure with some flexibility, but the geometry and rigidity may vary.","In some embodiments, components may additionally or alternatively be coupled by virtue of physical proximity, being integral to a single structure, or being formed from the same piece of material.","Coupling may also include mechanical, thermal, electrical, or chemical coupling (such as a chemical bond) in some contexts.","A reduced-pressure interface, such as the reduced-pressure interface 105 may be a device or component operable to fluidly couple the reduced-pressure source 104 to the dressing 102.In one illustrative embodiment, the reduced-pressure interface 105 may be a T.R.A.C.® Pad or Sensa T.R.A.C.® Pad available from KCI of San Antonio, Tex., modified as described in more detail below.","The reduced-pressure interface 105 may fluidly couple the reduced pressure provided by the reduced-pressure source 104 to the manifold 110 through the drape 108.The manifold 110 may distribute the fluid to the sealed therapeutic environment 103.Thus, the reduced-pressure interface 105 allows reduced pressure to be delivered to the sealed therapeutic environment 103.The reduced-pressure interface 105 may be made of a semi-rigid material.","In some embodiments, the reduced-pressure interface 105 may be made from a plasticized polyvinyl chloride (PVC), polyurethane, cyclic olefin copolymer elastomer, thermoplastic elastomer, poly acrylic, silicone polymer, or polyether block amide copolymer.","A reduced-pressure source, such as the reduced-pressure source 104, may be a reservoir of air at a reduced pressure, or may be a manual or electrically-powered device that can reduce the pressure in a sealed volume, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example.","The reduced-pressure source may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate reduced-pressure therapy.","While the amount and nature of reduced pressure applied to a tissue site may vary according to therapeutic requirements, the pressure typically ranges between about −5 mm Hg (−667 Pa) and about −500 mm Hg (−66.7 kPa).","Common therapeutic ranges are between about −75 mm Hg (−9.9 kPa) and about −300 mm Hg (−39.9 kPa).","A “container,” such as the container 112, may broadly include a canister, pouch, bottle, vial, or other fluid collection apparatus.","A container can be used to manage exudates and other fluids withdrawn from a tissue site.","In many environments, a rigid container may be preferred or required for collecting, storing, and disposing of fluids.","In other environments, fluids may be properly disposed of without rigid container storage, and a re-usable container could reduce waste and costs associated with reduced-pressure therapy.","A fluid source, such as the fluid source 118, may be a reservoir of fluid at an atmospheric or greater pressure, or may be a manual or electrically-powered device, such as a pump, that can convey fluid to a sealed volume, such as the sealed therapeutic environment 103, for example.","A fluid source may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate instillation therapy.","The amount and nature of the fluid applied to a tissue site may vary according to therapeutic requirements, which may include the size of the sealed therapeutic environment, the type of fluid, and any additives to the fluid.","In some embodiments, the fluid may include: hypochlorite based solutions, such as hypochlorous acid and sodium hypochlorite; silver nitrate; sulfur based solutions, such as sulfonamides; biguanides, such as polyhexanide; cationic solutions, such as octenidine and benzalkonium chloride; and isotonic solutions.","A fluid interface, such as the fluid interface 120 may be a device or component operable to fluidly couple the fluid source 118 to the dressing 102.The fluid interface 120 may fluidly couple the fluid provided by the fluid source 118 to the manifold 110 through the drape 108.The manifold 110 may distribute the fluid to the sealed therapeutic environment 103.Thus, the fluid interface 120 allows fluid to be delivered to the sealed therapeutic environment 103.In some embodiments, the fluid interface 120 may also fluidly couple the fluid source 118 to the manifold 110 to determine a pressure at the tissue site 114.In some embodiments, the fluid interface 120 may couple two tubes, such as the tube 124 and the tube 123 to the manifold 110.The fluid interface 120 may be made of a semi-rigid material.","In some embodiments, the fluid interface 120 may be made from a plasticized polyvinyl chloride (PVC), polyurethane, cyclic olefin copolymer elastomer, thermoplastic elastomer, poly acrylic, silicone polymer, or polyether block amide copolymer.","A fluid connector, such as the fluid connector 122, may be a device or component configured to couple the tube 124 and the tube 123 to the fluid source 118.A fluid connector may fluidly couple one or more tubes to one or more components of a fluid source.","In some embodiments, a fluid connector may fluidly couple a multi-lumen tube to one or more components of a fluid source.","In some embodiments, a fluid connector may also be releasably coupled to a fluid source so that the fluid connector may be discarded after use of the fluid connector 122.In some embodiments, a fluid connector may be a device permanently attached to a fluid source.","In general, components of the instillation therapy system 116 may be coupled directly or indirectly to each other.","For example, the fluid source 118 may be directly coupled to the fluid interface 120 and indirectly coupled to the dressing 102 through the fluid interface 120.Components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components.","In some embodiments, components may be fluidly coupled with a tube, for example the tube 123 or the tube 124.In some embodiments, the tube 123 and the tube 124 may be single-lumen conduits having a central flow passage extending through each tube.","In operation, the reduced-pressure therapy system 101 may provide reduced pressure to the sealed therapeutic environment 103 through the reduced-pressure interface 105.Fluid, including exudates and other liquids, may be drawn from the tissue site 114 through the manifold 110 and into the reduced-pressure interface 105.Similarly, the instillation therapy system 116 may provide fluids to the sealed therapeutic environment 103 through the fluid interface 120.Fluid, including therapeutic liquids, may flow from the fluid source 118, through the tube 124 and into the sealed therapeutic environment 103 through the fluid interface 120.The fluids may be distributed to the tissue site 114 by the manifold 110.In some embodiments, the reduced-pressure therapy system 101 and the instillation therapy system 116 may operate concurrently.","If the reduced-pressure therapy system 101 and the instillation therapy system 116 operate concurrently, the fluid interface 120 and the reduced-pressure interface 105 may be positioned to maximize the distance between them.","For example, if the tissue site 114 is elongated and includes two opposing ends, the fluid interface 120 and the reduced-pressure interface 105 may be positioned proximate the opposing ends.","If the tissue site 114 is generally circular, the fluid interface 120 and the reduced-pressure interface 105 may be placed proximate opposing ends of a diameter of the tissue site 114.Fluid may flow from the fluid interface 120 through the sealed therapeutic environment 103 to the reduced-pressure interface 105.In some embodiments, the reduced pressure supplied through the reduced-pressure interface 105 may aid in the distribution of fluids provided through the fluid interface 120.In some embodiments, the reduced-pressure therapy system 101 and the instillation therapy system 116 may not operate concurrently.","In these embodiments, the instillation therapy system 116 may provide fluid to the sealed therapeutic environment 103 while the reduced-pressure therapy system 101 is not providing reduced pressure.","The fluid source 118 may include a pump that may move the fluid to the manifold 110 for distribution to the tissue site 114.The fluid may remain in the sealed therapeutic environment 103 until the operation of the reduced-pressure therapy system 101.If the reduced-pressure therapy system 101 provides reduced pressure, the reduced-pressure therapy system 101 may draw the fluid from the sealed therapeutic environment 103 into the container 112.FIG.","2 is a partial sectional view of the reduced-pressure therapy system 101 and the instillation therapy system 116 illustrating additional details that may be associated with some embodiments.","In some embodiments, the fluid interface 120 and the reduced-pressure interface 105 may be combined into a dressing interface 121.As shown in FIG.","2, the dressing interface 121 maybe coupled to the dressing in a manner similar to the fluid interface 120 and the reduced-pressure interface 105.The dressing interface 121 may be configured to receive the tube 123, the tube 124, and the tube 109 and provide a fluid coupling through the drape 108 to the tissue site 114 and the sealed therapeutic environment 103.In some embodiments, the dressing interface 121 may be similar to and operate as described in U.S. patent application Ser.","No.","13/009,220, by Locke, et al., entitled “Wound-Connection Pads for Fluid Instillation and Negative Pressure Wound Therapy, and Systems and Methods,” filed Jan. 19, 2011, which is incorporated by reference herein for all purposes.","The dressing interface 121 may fluidly couple the fluid provided by the fluid source 118 and the reduced pressure provided by the reduced-pressure source 104 to the manifold 110 through the drape 108.The dressing interface 121 may be made of a semi-rigid material.","In some embodiments, the dressing interface 121 may be made from a plasticized polyvinyl chloride (PVC), polyurethane, cyclic olefin copolymer elastomer, thermoplastic elastomer, poly acrylic, silicone polymer, or polyether block amide copolymer.","In the embodiment of FIG.","2, operation of the instillation therapy system 116 and the reduced-pressure therapy system 101 may alternate.","The instillation therapy system 116 may provide fluid through the dressing interface 121 while the reduced-pressure therapy system 101 is not operating, and the reduced-pressure therapy system 101 may provide reduced-pressure through the dressing interface 121 while the instillation therapy system 116 is not operating.","FIG.","3 is a sectional view of the tube 109 illustrating additional details that may be associated with some embodiments of the reduced-pressure therapy system 101.As shown, the tube 109 may be a multi-lumen tube.","In the illustrative embodiment, the tube 109 may include at least one primary lumen 126 and one or more secondary lumens 128.In some embodiments, the tube 109 includes four secondary lumens 128.The tube 109 may have different shapes and include more or fewer primary lumens 126 and secondary lumens 128.The primary lumen 126 may provide a path between the reduced-pressure source 104 and the reduced-pressure interface 105 for delivery of reduced pressure.","The secondary lumens 128 may function as sensing lumens.","In some embodiments, the secondary lumens 128 may fluidly communicate pressure at a terminal end of the tube 109 within the reduced-pressure interface 105 to the reduced-pressure source 104.The secondary lumens 128 may be fluidly isolated from the primary lumen 126 so as not to interfere with the process of sensing the pressure.","The pressure communicated by the secondary lumens 128 may be representative of the pressure at the tissue site 114.Referring back to FIG.","1 and FIG.","2, the tube 123 and the tube 124 may be combined into a multi-lumen tube, similar to the tube 109, each having at least one primary lumen, similar to the primary lumens 126 of the tube 109, and one or more secondary lumens, similar to the secondary lumens 128 of the tube 109.If the tube 123 and the tube 124 are combined into a multi-lumen tube, the secondary lumens may be fluidly coupled between the tissue site 114 and the fluid source 118 to sense pressure at the tissue site 114.The primary lumens would deliver instillation fluid to the tissue site 114.Referring more specifically to FIG.","2, the pressure being sensed by the tube 123 may be replaced by the secondary lumens 128 if the tube 124 is a multi-lumen tube.","Reduced-pressure therapy has been shown to improve healing of tissue sites.","Similarly, instillation therapy has been shown to improve the healing of tissue sites.","Furthermore, tissue sites treated with both reduced-pressure therapy and instillation therapy have been shown to have improved healing over the use of reduced-pressure therapy or instillation therapy alone.","Current systems providing both reduced-pressure therapy and instillation therapy are complex and difficult to properly administer to a tissue site.","In addition, the systems may be quite expensive, which may pose problems for the use of such systems in some locations, in particular, in locations where health care services may not be readily available.","Some systems provide both reduced-pressure therapy and instillation therapy without the complexity and cost involved in combined systems; however, these systems may be labor intensive and require significant clinician involvement for the proper administration of therapy.","For example, in some systems providing both reduced-pressure therapy and instillation therapy, the reduced-pressure therapy system may be coupled to the tissue site, and a clinician may use a syringe to administer fluids to the tissue site through the dressing.","Administering fluids with a syringe requires the clinician to actively monitor the dressing and the fluid application to prevent inadvertent over application of fluids.","As it may be difficult to see the tissue site through the sealing member, a clinician may find it difficult to accurately determine the appropriate initiation and termination of instillation therapy.","As disclosed herein, the instillation therapy system 116 can overcome these shortcomings and others by providing an instillation therapy system that may monitor the delivery of reduced pressure to a tissue site by a reduced-pressure system, and in response, the instillation therapy system may provide fluids in response to the reduced-pressure therapy.","For example, in some embodiments of the instillation therapy system 116, the instillation therapy system 116 may monitor a pressure in the sealed therapeutic environment 103 and, in response, administer fluids in accordance with the administration of reduced pressure by the reduced-pressure therapy system 101.FIG.","4 is a schematic diagram of the therapy system 100 illustrating additional details that may be associated with some embodiments of the instillation therapy system 116.In some embodiments, the fluid source 118 may include a controller 202, a user interface 204, and a sensor 206.The user interface 204 and the sensor 206 may each be communicatively coupled to the controller 202.As used herein, communicative coupling may refer to a coupling between components that permits the transmission of signals between the components.","In some embodiments, the signals may be discrete or continuous signals.","A discrete signal may be a signal representing a value at a particular instance in a time period.","A plurality of discrete signals may be used to represent a changing value over a time period.","A continuous signal may be a signal that provides a value for each instance in a time period.","The signals may also be analog signals or digital signals.","An analog signal may be a continuous signal that includes a time varying feature that represents another time varying quantity.","A digital signal may be a signal composed of a sequence of discrete values.","In some embodiments, the communicative coupling between the controller 202, the user interface 204, and the sensor 206 may be one-way communication.","In one-way communication, signals may only be sent in one direction.","For example, the sensor 206 may generate a signal that may be communicated to the controller 202, but the controller 202 may not be capable of sending a signal to the sensor 206.In some embodiments, the communicative coupling between the controller 202, the user interface 204, and the sensor 206 may be two-way communication.","In two-way communication, signals may be sent in both directions.","For example, the controller 202 and the user interface 204 may be communicatively coupled so that the controller 202 may send and receive signals from the user interface 204.Similarly, the user interface 204 may send and receive signals from the controller 202.In some embodiments, signal transmission between the controller 202 and another device, such as the user interface 204, may be referred to as the controller 202 operating the device.","The controller 202 may be a computing device or system, such as a programmable logic controller, a data processing system, or the like.","In other embodiments, the controller 202 may be configured to receive input from the sensor 206.In some embodiments, the controller 202 is configured to receive input from both the user interface 204 and the sensor 206.In some embodiments, the controller 202 may receive input, such as an electrical signal, from an alternative source, such as through an electrical port, for example.","In some embodiments, the controller 202 may be a data processing system.","A data processing system suitable for storing and/or executing program code may include at least one processor coupled directly or indirectly to memory elements through a system bus.","The memory elements can include local memory employed during actual execution of the program code, bulk storage, and cache memories which provide temporary storage of at least some program code in order to reduce the number of times code is retrieved from bulk storage during execution.","In some embodiments, the controller 202 may be a programmable logic controller (“PLC”).","A PLC may be a digital computer configured to receive one or more inputs and send one or more outputs in response to the one or more inputs.","A PLC may include a non-volatile memory configured to store programs or operational instructions.","In some embodiments, the non-volatile memory may be operationally coupled to a battery-back up so that the non-volatile memory retains the programs or operational instructions if the PLC otherwise loses power.","In some embodiments, a PLC may be configured to receive discrete signals and continuous signals and produce discrete and continuous signals in response.","A user interface, such as the user interface 204, may be a device configured to allow communication between the controller 202 and an environment external (external environment) to the fluid source 118.In some embodiments, an external environment may include an operator or a computer system configured to interface with the fluid source 118, for example.","In some embodiments, a user interface may receive a signal from a controller and present the signal in a manner that may be understood by an external environment.","In some embodiments, a user interface may receive signals from an external environment and, in response, send signals to a controller.","A controller may process the signals received from a user interface and take further action.","In some embodiments, a user interface may be a graphical user interface, a touchscreen, or one or more motion tracking devices.","A user interface may also include one or more display screens, such as a liquid crystal display (“LCD”), lighting devices, such as light emitting diodes (“LED”) of various colors, and audible indicators, such as a whistle, configured to emit a sound that may be heard by an operator.","A user interface may further include one or more devices, such as knobs, buttons, keyboards, remotes, touchscreens, ports that may be configured to receive a discrete or continuous signal from another device, or other similar devices; these devices may be configured to permit the external environment to interact with the user interface 204.A pressure sensor, such as the sensor 206, may be a piezoresistive strain gauge, a capacitive sensor, an electromagnetic sensor, a piezoelectric sensor, an optical sensor, or a potentiometric sensor, for example.","In some embodiments, a pressure sensor can measure a strain caused by an applied pressure.","A pressure sensor may be calibrated by relating a known amount of strain to a known pressure applied.","The known relationship may be used to determine an unknown applied pressure based on a measured amount of strain.","In some embodiments, a pressure sensor may include a receptacle configured to receive an applied pressure.","In an illustrative embodiment, the sensor 206 may be fluidly coupled to the fluid interface 120 by the tube 123 to receive a pressure from the tube 123.The fluid source 118 may also include a valve 208, a flow meter 209, and a fluid reservoir 210.In some embodiments, the valve 208 may be communicatively coupled to the controller 202, and the valve 208 may be further fluidly coupled between the fluid reservoir 210 and the fluid interface 120.A valve, such as the valve 208, may be a device configured to selectively permit fluid flow through the valve.","A valve may be a ball valve, a gate valve, a butterfly valve, or other valve type that may be operated to prevent or permit fluid flow through the valve.","Generally, a valve may include a valve body having a flow passage, a valve member disposed in the flow passage and operable to selectively block the flow passage, and an actuator configured to operate the valve member.","An actuator may be configured to position the valve member in a closed position, preventing fluid flow through the flow passage of the valve, an open position, permitting fluid flow through the fluid passage of the valve, or a metering position, permitting fluid flow through the flow passage of the valve at a selected flow rate.","In some embodiments, the actuator may be a mechanical actuator configured to be operated by an operator.","In some embodiments, the actuator may be an electromechanical actuator configured to be operated in response to the receipt of a signal input.","For example, the actuator may include an electrical motor configured to receive a signal from a controller, such as the controller 202.In response to the signal, the electrical motor of the actuator may move the valve member of the valve.","In some embodiments, the valve 208 may be configured to selectively permit fluid communication between the fluid reservoir 210 and the fluid interface 120 in response to a signal from the controller 202.In this context, the controller 202 may be referred to as: operating the valve; placing the valve 208 in an open position, a closed position, or a metering position; and opening the valve 208, closing the valve 208, or metering the valve 208.In some embodiments, the flow meter 209 may be communicatively coupled to the controller 202, and the flow meter 209 may be further fluidly coupled between the valve 208 and the fluid interface 120.A flow meter, such as the flow meter 209, may be a device configured to determine a fluid flow rate.","A flow meter may include a mechanical flow meter, a pressure based flow meter, an optical flow meter, an open channel flow meter, a thermal mass flow meter, a vortex flow meter, electromagnetic, ultrasonic and coriolis flow meters, and laser doppler flow meters.","The flow meter 209 may determine a rate of fluid flow through the valve 208 and transmit a signal to the controller 202 corresponding to the determined flow rate.","The controller 202 may receive the determined flow rate and determine a total volume of fluid delivered in response.","A fluid reservoir, such as the fluid reservoir 210, may be a container for storing or holding fluid.","A fluid reservoir may broadly include a canister, pouch, bottle, vial, or other fluid storage apparatus.","A fluid reservoir can be used to manage fluid to be delivered to a tissue site.","In many environments, a rigid fluid reservoir may be preferred or required for storing and delivering of fluids.","In other environments, fluids may be properly stored and delivered without a rigid fluid reservoir.","In some embodiments, a fluid reservoir may be a device that is integrated into a fluid source.","For example, the fluid reservoir 210 may be an integral component of the fluid source 118.In other embodiments, a fluid reservoir may be a removable component of a fluid source.","For example, the fluid reservoir 210 may be removable from the fluid source 118.In still other embodiments, a fluid reservoir may be a separate component from a fluid source that may be fluidly coupled to the fluid source.","For example, the fluid reservoir 210 may be a separate device that may be fluidly coupled by a tube to the fluid source 118.In some embodiments, the valve 208 may be fluidly coupled to the fluid interface 120 through the tube 124.Operation of the valve 208 may permit fluid to flow from the fluid reservoir 210 through the tube 124 into the fluid interface 120, where the fluid may be distributed by the manifold 110.In some embodiments, the sensor 206 may be fluidly coupled to the fluid interface 120 through the tube 123.In some embodiments, the tube 123 may fluidly communicate a pressure at the fluid interface 120 to the sensor 206.In some embodiments, the pressure at the fluid interface 120 may be representative of a pressure in the sealed therapeutic environment 103.In some embodiments, the sensor 206 may be an electronic strain gauge sensor that is incorporated into the fluid interface 120.The strain gauge may have a thin piezoresistive film on the drape of the pad which deforms under pressure.","The deformation may indicate the pressure in the sealed therapeutic environment 103.In some embodiments, the fluid interface 120 may be communicatively coupled to the controller 202 so that the controller 202 may receive a signal from the strain gauge.","In some embodiments, the fluid source 118 may include an instillation pump 212.The instillation pump 212 may be fluidly coupled between the valve 208 and the fluid interface 120 and communicatively coupled to the controller 202.The instillation pump 212 may be operated by the controller 202 in a manner similar to the operation of the valve 208 to provide fluid to the fluid interface 120 and the sealed therapeutic environment 103.In other embodiments, the instillation pump 212 may replace the valve 208.In some embodiments, the instillation pump 212 may be configured to pre-charge a dosage of fluid for delivery to the tissue site 114.For example, the instillation pump 212 may be configured to pressurize a dosage of fluid prior to delivery of fluids so that the fluids may be delivered to the tissue site 114.A dosage of fluid may be the volume of fluid prescribed by a caregiver to treat the tissue site 114 during a cycle of instillation therapy.","In some embodiments, the fluid source 118 may also include an instillation sensor 214.The instillation sensor 214 may be fluidly coupled to the tube 124 and communicatively coupled to the controller 202.In some embodiments, the controller 202 may monitor pressure in the tube 124 with the instillation sensor 214.In the event that the instillation sensor 214 sends a signal that deviates from the signal received from the sensor 206, the controller 202 may operate the user interface 204 to indicate a blockage or a leak condition.","In operation, the sensor 206 may determine the pressure in the fluid interface 120.As previously described, the pressure in the fluid interface 120 may be representative of the pressure in the sealed therapeutic environment 103.The controller 202 may receive the signal sent by the sensor 206, and in response, the controller 202 may operate the valve 208 and the user interface 204.In some embodiments, the controller 202 may determine that the valve 208 should be in the open position in response to the signal received from the sensor 206.The controller 202 may transmit a signal to the valve 208 to cause the valve 208 to actuate and move from the metering or the closed position to the open position.","If the valve 208 is positioned in the open position, fluid may flow from the fluid reservoir 210 into the sealed therapeutic environment through the valve 208, the tube 124, and the fluid interface 120.In some embodiments, the controller 202 may also generate and send a signal to the user interface 204 in response to the signal from the sensor 206.For example, the controller 202 may receive a signal from the sensor 206 corresponding to a particular pressure in the fluid interface 120.In response, the controller 202 may generate and send a signal to the user interface 204.The user interface 204 may receive the signal and, in response, provide a visual or auditory output that may be understood by the external environment.","For example, in some embodiments, the user interface 204 may be an LCD.","The user interface 204 may receive a signal corresponding to a particular pressure in the fluid interface 120 from the controller 202.The user interface 204 may display the signal on the LCD as a numerical representation of the particular pressure at the fluid interface 120.In some embodiments, the controller 202 may include operational instructions permitting the controller 202 to operate the valve 208 to provide instillation therapy.","In some embodiments, the controller 202 may operate the valve 208 in a constant mode.","In the constant mode, the fluid source 118 may deliver fluids to the fluid interface 120 without adjustment in response to conditions external to the fluid source 118.For example, the controller 202 may receive a signal from the user interface 204 that corresponds to a selection of the constant mode.","In response, the controller 202 may send a signal to the valve 208, placing the valve 208 in the open position.","Fluid may flow freely from the fluid reservoir 210 to the fluid interface 120.In some embodiments, the controller 202 may receive a signal from the user interface 204 that corresponds to a selection of the constant mode at a selected flow rate.","In response, the controller 202 may send a signal to the valve 208 instructing the valve 208 to move to a metering position corresponding to the selected flow rate.","Fluid may flow from the fluid reservoir 210 to the fluid interface 120 at the selected flow rate.","In some embodiments, the controller 202 may operate the valve 208 in an intermittent mode.","In the intermittent mode, the fluid source 118 may deliver fluid to the tissue site 114 in discrete time periods independent of conditions external to the fluid source 118.For example, the fluid source 118 may provide fluids for a period of one minute followed by a period of one minute where the fluid source 118 provides no fluids.","In some embodiments, the controller 202 may receive a signal from the user interface 204 corresponding to a selection of the intermittent mode.","In some embodiments, the controller 202 may include pre-determined time periods for a duration of fluid delivery and an interval between fluid delivery for the intermittent mode.","In some embodiments, the signal from the user interface 204 may also provide a duration of fluid delivery and a duration of no delivery.","In response, the controller 202 may send a signal to the valve 208 to move the valve 208 to the open position, providing fluids and initiating the duration of fluid delivery.","When the duration of fluid delivery ends, the controller 202 may send a signal to the valve 208 to move the valve 208 to the closed position, blocking fluid flow and initiating the interval between fluid delivery.","When the interval between fluid delivery ends, the controller 202 may send a signal to the valve 208 to move the valve 208 to the open position, providing fluid and initiating the duration of fluid delivery.","Opening and closing of the valve 208 may repeat until the instillation therapy concludes.","In some embodiments, the controller 202 may receive a signal from the user interface 204 corresponding to a selection of the intermittent mode and a selected flow rate.","In response, the controller 202 may send a signal to the valve 208 to move the valve to a metering position corresponding to the selected flow rate during the duration of fluid delivery.","In other embodiments, the controller 202 may operate the instillation pump 212 to control the delivery of fluids during the duration of fluid delivery and the interval between fluid delivery.","In some embodiments of the intermittent mode, the controller 202 may monitor the flow rate through the valve 208 with the flow meter 209.The controller 202 may operate the valve 208 in response to a total volume of fluid flow through the valve 208.For example, the controller 202 may operate the valve 208, placing the valve 208 in an open position.","The controller 202 my monitor the flow rate with the flow meter 209, determining the total volume of fluid delivered while the valve 208 is in the open position.","If the total volume of fluid delivered reaches a predetermined total volume of fluid to be delivered, also referred to as a dosage of fluid, the controller 202 may operate the valve 208, moving the valve 208 to the closed position.","In some embodiments, the controller 202 may operate the valve 208 in a dynamic mode.","During the dynamic mode, the controller 202 may coordinate the delivery of instillation fluid with the delivery of reduced pressure by a reduced-pressure source.","For example, the controller 202 may open the valve 208 when reduced pressure is still present in the sealed therapeutic environment 103, which draws fluid from the fluid reservoir 210, through the valve 208 and into the sealed therapeutic environment 103.Using the reduced pressure in a sealed therapeutic environment to draw fluid from the fluid reservoir 210 may simultaneously decrease the reduced pressure in the sealed therapeutic environment 103.As the reduced pressure decreases in the sealed therapeutic environment 103, the rate of fluid flow from the fluid reservoir 210 may also slow down.","If the pressure in the sealed therapeutic environment 103 and the ambient pressure proximate the fluid reservoir 210 are approximately the same, fluid flow from the fluid reservoir 210 may stop, thereby avoiding over-pressurizing the sealed therapeutic environment 103 with the instillation fluids.","In some embodiments, the controller 202 may monitor the volume of fluid flow through the valve 208 with the flow meter 209.If a predetermined dosage of fluid has been delivered prior to the sealed therapeutic environment 103 reaching ambient pressure, the controller 202 may close the valve 208.In the dynamic mode, the fluid source 118 may provide fluids to the fluid interface 120 in response to operation of the reduced-pressure therapy source 104.In some embodiments, the controller 202 may be programmed to open the valve 208 in response to a particular pressure that may be detected by the sensor 206.In some embodiments, the particular pressure may also be referred to as a trigger pressure (Pt).","Generally, if the signal from the sensor 206 corresponds with a pressure that is about equal to the trigger pressure (Pt) following a period of generally static or steady-state reduced pressure, the controller 202 may open the valve 208 in response.","If the trigger pressure (Pt) is less than an ambient pressure proximate the fluid reservoir 210, (that is, the trigger pressure (Pt) is a greater reduced-pressure than the ambient pressure), that reduced pressure draws instillation fluid from the fluid reservoir 210 through the valve 208 to the fluid interface 120.In some embodiments, the controller 202 may position the valve 208 in a metering position in response to the trigger pressure (Pt), permitting fluid flow at predefined flow rates.","Further detailed operation of the dynamic mode may be described with respect to FIG.","4, FIG.","5, FIG.","6A, FIG.","7, and FIG.","8.FIG.","5 is a graphical representation of the operation of the reduced-pressure therapy system 101 that may be associated with some embodiments.","In FIG.","5, the y-axis represents the operating state of the reduced-pressure therapy system 101, which may be either in an “on-state” or an “off-state,” and the x-axis represents time.","FIG.","6A is a graphical representation of a pressure profile 301 (Ps) of the sealed therapeutic environment 103 as measured at the sensor 206 that may be associated with some embodiments.","In FIG.","6A, the y-axis represents the absolute value of the reduced pressure measured by the sensor 206 at the fluid interface 120, and the x-axis represents time.","As previously described, the reduced pressure measured at the fluid interface 120 may be representative of the reduced pressure in the sealed therapeutic environment 103 formed by the tissue site 114 and the drape 108.FIG.","7 is a graphical representation of the operation of the valve 208 that may be associated with some embodiments.","In FIG.","7, the y-axis represents the position of a valve member of the valve 208, which may be in an open position or a closed position in response to the pressure profile 301 (Ps), and the x-axis represents time.","FIG.","8 is a graphical representation of the operation of the valve 208 that may be associated with other embodiments.","In FIG.","8, the y-axis represents the position of a valve member of the valve 208, which may be in an open position or a closed position in response to the pressure profile 301 (Ps), and the x-axis represents time.","Some or all of FIGS.","5, 6A, 7, and 8 include a reference line 302, a reference line 304, a reference line 306, a reference line 308, a reference line 310, a reference line 312, and a reference line 314.The reference lines 302-314 are positioned at the same location of the x-axis in each figure in which the reference lines appear.","Thus, the reference lines 302, 304, 306, 308, 310, 312, and 314 align FIG.","5, FIG.","6A, FIG.","7, and FIG.","8 to relate the operation of the reduced-pressure source 104 and the fluid source 118 based on the conditions in the sealed therapeutic environment 103.In some embodiments, the reduced-pressure therapy system 101 may be operating in an intermittent mode so that reduced-pressure may be supplied to the sealed therapeutic environment 103 in discrete time increments.","As shown in FIG.","5, in the intermittent mode of operation, the reduced-pressure source 104 may have a time period in which the reduced-pressure source 104 is operating to provide reduced pressure, such as during “on-state.” The reduced-pressure source 104 may also have a time period in which the reduced-pressure source 104 is not providing reduced pressure, such as during an “off-state.” As described with respect to FIG.","5, the on-state represents operation of a pump or other device in the reduced-pressure source 104 to provide reduced pressure to the sealed therapeutic environment 103.The off-state represents a time period in which the reduced-pressure source 104 may be powered on, but it is not providing reduced-pressure to the sealed therapeutic environment 103.As shown in FIG.","5, the reduced-pressure source 104 may be turned on at the reference line 302.The reduced-pressure source 104 may be turned off at the reference line 304.Thus, the reduced-pressure source 104 is in an “on-state” 320 between the reference line 302 and the reference line 304 and in an “off-state” 322 between the reference line 304 and the reference line 312.The reduced-pressure source 104 may be turned on at the reference line 312.The reduced-pressure source 104 may be turned off at the reference line 314.Thus, the reduced-pressure source 104 is in an “on-state” 324 between the reference line 312 and the reference line 314 and in an “off-state” 326 after the reference line 314.In FIG.","5, the graph representing operation of the reduced-pressure source 104 forms a square wave having a duty cycle represented as the ratio between the off-state 322 and the on-state 320.In some embodiments, the off-state 322 may be twice as long as the on-state 320, that is, a duty cycle or ratio of the off-state 322 to the on-state 320 is 2/1.In other embodiments, the duty cycle may be 1/1, 3/1, 4/1, or other similar ratios.","FIG.","6A may illustrate the pressure profile 301 (Ps) associated with the pressure at the fluid interface 120.In an illustrative embodiment, the absolute value of the pressure may range from about 0 mm Hg to about 120 mm Hg gauge pressure.","As described herein, pressure at about 0 mm Hg may be referred to as an atmospheric pressure or minimum pressure (Pmin), as shown by the dashed line 329.Reduced-pressure at about 120 mm Hg may be referred to as a therapy pressure.","The therapy pressure may be set by a caregiver for a maximum pressure (Pmax), as shown by the dashed line 327.At reference line 302, when the reduced-pressure source 104 begins the on-state 320, the pressure profile 301 (Ps) may be about 0 mm Hg.","The pressure profile 301 (Ps) increases to a value of about 120 mm Hg during the on-state 320.A slope of the pressure profile 301 (Ps) between the reference line 302 and the reference line 304 as the pressure profile 301 (Ps) increases from about 0 mm Hg to about 120 mm Hg may be referred to as a reduced-pressure ramp-up period 328.The reduced-pressure ramp-up period 328 corresponds to a time interval during which the pressure profile 301 (Ps) increases within the sealed therapeutic environment 103 from an ambient pressure (Pmin) at an inflection point 303 to the maximum pressure (Pmax) at an inflection point 305.The inflection point 303 is located at the intersection of the reference line 302, the dashed line 329, and pressure profile 301 (Ps).","The inflection point 305 is located at the intersection of the pressure profile 301 (Ps) and the dashed line 327 between the reference line 302 and the reference line 304.When the sealed therapeutic environment 103 reaches the therapy pressure (Pmax), the reduced-pressure therapy system 101 may be programmed to maintain the therapy pressure (Pmax) for a predetermined period of time.","While the reduced-pressure therapy system 101 maintains the therapy pressure (Pmax), the pressure profile 301 (Ps) may have a substantially flat slope for a reduced-pressure therapy period 330.The reduced-pressure therapy period 330 may continue until the reduced-pressure source 104 switches to the off-state 322 at the reference line 304.The reduced-pressure therapy period 330 may be a time interval of steady-state reduced pressure in the sealed therapeutic environment 103.As shown, the reduced-pressure therapy period 330 may extend from the inflection point 305 to the inflection point 307.The inflection point 307 is located at the intersection of the reference line 304, the dashed line 327, and the pressure profile 301 (Ps).","In the reduced-pressure therapy period 330, the reduced-pressure source 104 may be operating to maintain the reduced-pressure at about the therapy pressure (Pmax), for example, at about 120 mm Hg.","When the reduced-pressure source 104 switches from the on-state 320 to the off-state 322, as shown at the reference line 304 in FIG.","5, the pressure profile 301 (Ps) may enter a reduced-pressure ramp-down period 332, as shown in FIG.","6A.","The reduced-pressure ramp-down period 332 corresponds to a time interval during which the pressure profile 301 (Ps) decreases within the sealed therapeutic environment 103 from the maximum pressure (Pmax) to the minimum pressure (Pmin).","As shown in FIG.","6A, the reduced-pressure ramp-down period 332 is a portion of the pressure profile 301 (Ps) beginning at the inflection point 307 and ending at an inflection point 309.The inflection point 309 is located at the intersection of the pressure profile 301 (Ps) and the dashed line 329.As the reduced pressure profile 301 (Ps) decreases during the reduced-pressure ramp-down period 332, the pressure profile 301 (Ps) may reach the trigger pressure (Pt).","The trigger pressure (Pt) represented by the dashed line 334.If the pressure profile 301 (Ps) reaches the trigger pressure (Pt), instillation of fluids may commence as shown by the reference line 306.In some embodiments, the trigger pressure (Pt) may be set during the manufacturing process.","When the pressure profile 301 (Ps) reaches about 0 mm Hg, the slope of the pressure profile 301 (Ps) may remain substantially flat in a soak period 336.The soak period 336 may correspond with a time interval during which there is no reduced-pressure therapy.","The soak period 336 extends from the inflection point 309 to an inflection point 311.The inflection point 311 is located at the intersection of the reference line 312, the dashed line 329 and the pressure profile 301 (Ps).","Eventually, the reduced-pressure therapy may resume at the inflection point 311 when the reduced-pressure source 104 returns to the on-state 324.Instillation of fluids, which commenced at the reference line 306 may continue to the reference line 308 as described below with respect to FIG.","7.Continued operation of the reduced-pressure source 104 may cause the pressure profile 301 (Ps) illustrated in FIG.","6A to cyclically repeat.","A second cycle may commence with the on-state 324 of the reduced-pressure source 104 initiating a reduced-pressure ramp-up period 341 and a reduced-pressure therapy period 343.The second cycle may have an off-state 326, initiating a reduced-pressure ramp-down period 345 and concluding at the end of a soak period 349.As further illustrated, the pressure profile 301 (Ps) of FIG.","6A appears to lag relative to the operation of the reduce-pressure source 104 illustrated in FIG.","5.The lag may occur due to a period of time required for the pressure in the sealed therapeutic environment 103 to respond to the operation of the reduced-pressure source 104.In other embodiments, the pressure profile 301 (Ps) of FIG.","6A may not lag the operation of the reduced-pressure source 104.As described with respect to FIG.","6A and FIG.","7, the dynamic mode of the instillation therapy system 116 and the fluid source 118 may be configured to operate in coordination with the operation of the reduced-pressure therapy system 101 and the reduced-pressure source 104.In the dynamic mode, the controller 202 may know the pressure profile 301 (Ps) and the trigger pressure (Pt) as illustrated in FIG.","6A.","In some embodiments, the controller 202 may determine the pressure profile 301 (Ps) and the trigger pressure (Pt) in a training mode.","In some embodiments, a caregiver may provide the pressure profile 301 (Ps) and the trigger pressure (Pt) through the user interface 204.In an illustrative embodiment, the controller 202 may monitor the pressure profile 301 (Ps) through the sensor 206 to provide instillation therapy.","In some embodiments, the controller 202 may close the valve 208 until the pressure profile 301 (Ps) reaches the trigger pressure (Pt) following the reduced-pressure therapy period 330.When the pressure profile 301 (Ps) reaches the trigger pressure (Pt) the controller 202 may open the valve 208, as shown by reference line 306.The controller 202 may then monitor the fluid flow through the valve 208 with the flow meter 209.When the dosage has passed through the valve 208, the controller 202 may close the valve 208 as shown at the reference line 308.The dosage of fluid may remain within the sealed therapeutic environment 103 until the reduced-pressure ramp-up period 341 begins at the inflection point 309.As the on-state 324 of the reduced-pressure source 104 causes the pressure profile 301 (Ps) to increase, the fluid delivered during the instillation of fluids may be removed through the tube 109 to the container 112.In some embodiments, the flow rate through the valve 208 may not be sufficient to deliver the dosage of fluid prior to the repetition of the duty cycle of the reduced-pressure source 104.In response, the controller 202 may close the valve 208 prior to the repetition of the duty cycle of the reduced-pressure source 104.For example, if the valve 208 is still open, the controller 202 may close the valve 208 at the reference line 312.If the dosage of fluid is not fully delivered based on the initial trigger pressure (Pt), the controller 202 may adjust the trigger pressure (Pt) to increase the time for fluid flow.","For example, if the initial trigger pressure (Pt) is about 75 mm Hg reduced pressure and the controller 202 determines that the full dosage of fluid could not be delivered prior to the inflection point 311, the controller 202 may reset the trigger pressure (Pt) to 80 mm Hg reduced pressure as indicated by the dashed line 334a.","The pressure profile 301 (Ps) reaches the trigger pressure (Pt) 334a sooner than the trigger pressure (Pt) 334.In response, the controller 202 may open the valve 208 sooner as indicated by the reference line 310, increasing the dosage period.","In this manner, the controller 202 may adjust instillation to provide a complete dosage of fluid to the sealed therapeutic environment 103.FIG.","6B is a graphical representation of the pressure profile 301 (Ps) of the sealed therapeutic environment 103 that may be associated with some embodiments.","In FIG.","6B, the y-axis represents the absolute value of the reduced pressure measured by the sensor 206 at the fluid interface 120, and the x-axis represents time.","In some embodiments, the controller 202 may operate in a training mode to determine the pressure profile 301 (Ps) and the duty cycle of the reduced-pressure source 104.In the training mode, the controller 202 may send a signal to the valve 208 to move the valve 208 to the closed position.","The controller 202 may monitor a signal received from the sensor 206.In some embodiments, the sensor 206 may send a continuing signal that corresponds to an instantaneous pressure in the sealed therapeutic environment 103.An instantaneous pressure may refer to a pressure at the moment at which the pressure is measured.","In some embodiments, the signal sent by the sensor 206 may reflect the pressure profile 301 (Ps) displayed graphically in FIG.","6B.","The controller 202 may monitor the signal from the sensor 206 for at least one duty cycle of the reduced-pressure source 104.The controller 202 may store the signal received from the sensor 206 at the initiation of the dynamic mode.","The controller 202 may monitor the signal from the sensor 206 and compare pressures to determine the pressure profile 301 (Ps).","For example, the controller 202 may record a reduced pressure received from the sensor 206 at a first instant in time, such as a time 402.The controller 202 may then record a reduced pressure received from the sensor 206 at a second instant in time, such as a time 404.The controller 202 may compare the reduced pressure at the time 402 and the time 404.If the reduced pressure at the time 404 is greater than the reduced pressure at the time 402, the controller 202 may store the reduced pressure at time 404 as the maximum reduced pressure (Pmax).","The reduced pressure at the time 404, may then be compared to a reduced pressure at a third instant in time, for example, a time 406.The process may repeat until a reduced pressure at a later instant in time is not greater than the reduced pressure at the previous instant in time.","If a subsequent reduced pressure is greater than an immediately prior reduced pressure, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure ramp-up period 328 of FIG.","6B.","In some embodiments, comparisons between pressures may occur at multiple instances between each time shown.","If the reduced pressure at the second instant in time is about the same as the reduced pressure at the first instant in time, such as at the time 406 and a time 408, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure therapy period 330 or the soak period 336.The reduced pressure at the time 406 and the time 408 may then be compared to the maximum reduced pressure (Pmax), and if the reduced pressure at the time 406 and the time 408 is about the same as the maximum reduced pressure (Pmax), the controller 202 may determine that the reduced pressure profile 301 (Ps) is in the reduced-pressure therapy period 330.If the reduced pressure at the second instant in time is less than the reduced pressure at the first instant in time, such as at the time 408 and a time 410, the controller 202 may store the reduced pressure at the time 410 as the minimum reduced pressure (Pmin).","The reduced pressure at the time 410 may then be compared to a reduced pressure at a third instant in time, repeating the process until a reduced pressure at a later instant in time is not less than the reduced pressure at the previous instant in time.","If a subsequent reduced pressure is less than an immediately prior reduced pressure, such as at the time 410 and a time 412, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure ramp-down period 332 of FIG.","6B.","If the reduced pressure at the second instant in time is about the same as the reduced pressure at the first instant in time, such as at a time 414 and a time 416, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure therapy period 330 or the soak period 336.The reduced pressure at the time 414 and the time 416 may then be compared to the minimum reduced pressure (Pmin), and if the reduced pressure at the time 414 and the time 416 is about the same as the minimum reduced pressure (Pmin), the controller 202 may determine that the pressure profile 301 (Ps) is in the soak period 336 of FIG.","6B.","The controller 202 may continue to monitor the signal from the sensor 206, following the process previously described.","If the controller 202 determines that the pressure profile 301 (Ps) is repeating, for example, the controller 202 repeatedly identifies the same maximum reduced pressure (Pmax) and minimum reduced pressure (Pmin) at about the same time intervals, the controller 202 may exit the training mode.","During the time in which the controller 202 monitors the signal from the sensor 206, the controller 202 may store the pressure profile 301 (Ps) in a memory of the controller 202.The controller 202 may also store time intervals between the maximum reduced pressure (Pmax) and minimum reduced pressure (Pmin) to determine the on-state 320, the on-state 324, the off state 322, and the off-state 326 of the reduced-pressure source 104.The controller 202 may then determine one or more parameters of the reduced-pressure therapy as described above.","In some embodiments, the parameters may include the maximum pressure (Pmax) in the sealed therapeutic environment 103 and the minimum pressure (Pmin) in the sealed therapeutic environment 103.In some embodiments, the controller 202 may calculate an expected trigger pressure (Pt) based on the measured time intervals between the on-states 320/324 of the reduced-pressure source 104 and an expected flow rate through the valve 208.In some embodiments, the controller 202 may provide a signal to the user interface 204 so that the parameters may be displayed on the user interface 204.In some embodiments, the external environment may interact with the user interface 204 to override and replace the parameters determined from the training mode.","In some embodiments, the controller 202 may store an expected reduced-pressure ramp-down period 332.For example, the controller 202 may determine an expected slope of the pressure profile 301 (Ps) during the reduced-pressure ramp-down period 332 when fluid is being supplied to the sealed therapeutic environment 103.The controller 202 may monitor the signal from the sensor 206 during the reduced-pressure ramp-down period 332.During instillation therapy, the actual reduced-pressure ramp-down period 332 may deviate from the expected reduced-pressure ramp-down period 332 while providing a dosage of fluid.","A deviation of the reduced-pressure ramp-down period 332 may indicate that the fluid flow through the fluid interface 120 consists of an unexpected fluid, for example a gas rather than an instillation fluid.","If a gas is flowing through the fluid interface 120, the fluid reservoir 210 may be empty.","If the actual reduced-pressure ramp-down period 332 deviates from the expected reduced-pressure ramp-down period 332, the controller 202 may signal the user interface 204 to display an alarm indicating that the fluid reservoir 210 may be empty.","FIG.","9 illustrates a flow chart 900 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.","1, which may be implemented in accordance with an embodiment.","The system receives a signal from a user interface at block 902.For example, the controller 202 may receive a signal from the user interface 204.Next, at block 904, the system may determine whether the signal represents a selection of a constant mode.","Illustratively, the controller 202 may determine if the signal represents a selection of the constant mode.","If the system determines that the signal represents a selection of the constant mode at block 904 (YES), the system operates in the constant mode to deliver fluids for a predetermined period of time at block 906.For example, the controller 202 may open the valve 208, permitting fluid flow from the fluid reservoir 210 to the sealed therapeutic environment 103.If the system determines that the signal does not represent a selection of the constant mode at block 904 (NO), the system determines if the signal represents a selection of the intermittent mode.","For example, the controller 202 determines if the signal represents a selection of the intermittent mode.","If the system determines that the signal represents a selection of the intermittent mode at block 908 (YES), the system operates in the intermittent mode such that a predetermined number of dosages may be delivered to the sealed therapeutic environment 103 over a predetermined period of time at block 909.If the system determines that the signal does not represent a selection of the intermittent mode at block 908 (NO), the system determines if the signal represents a selection of the dynamic mode at block 910.If the system determines the signal represents a selection of the dynamic mode at block 910 (YES), the system operates in the training mode at block 912 after which the system operates in the dynamic mode to deliver fluids at block 914 for a predetermined period of time.","For example, the controller 202 may operate in the training mode and then the controller 202 may deliver fluids in accordance with the pressure profile 301 (Ps) determined in the training mode of block 912.FIG.","10 illustrates a flow chart 1000 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.","1 during the intermittent mode, which may be implemented in accordance with an embodiment.","In an illustrative embodiment, the system determines if the system received a selection of a duration of fluid delivery at block 1002.For example, the controller 202 may determine if the user interface 204 received a selection of a duration of fluid delivery.","If the system determines that no duration of fluid delivery was selected at block 1002, the system delivers fluids for a pre-determined duration of fluid delivery at block 1004.For example, the controller 202 may open the valve 208 for a predetermined duration of fluid delivery, such as one minute.","The system stops delivering fluids for a predetermined interval between fluid delivery at block 1006.For example, the controller 202 may close the valve 208 for a predetermined interval between fluid delivery, such as 1 minute.","The system then determines whether a predetermined number of on-off cycles has occurred at block 1007.If a predetermined number of on-off cycles has not occurred at block 1007 (NO), the system repeats beginning at block 1004.If a predetermined number of on-off cycles has occurred at block 1007 (YES), the intermittent mode ends.","If the system determines that a duration of fluid delivery was selected at block 1002 (YES), the system determines if an interval between fluid delivery was selected at block 1008.If the system determines that an interval between fluid delivery was selected at block 1008 (YES), the system delivers fluids for the selected duration of fluid delivery at block 1010 and stops delivering fluids for the interval between fluid delivery at block 1012.For example, the controller 202 may open the valve 208 for a selected duration of fluid delivery received through the user interface 204, such as two minutes and the controller 202 may close the valve 208 for a selected interval between fluid delivery, such as three minutes.","The system then determines whether a predetermined number of on-off cycles has occurred at block 1014.If a predetermined number of on-off cycles has not occurred at block 1014 (NO), the system repeats beginning at block 1010.If a predetermined number of on-off cycles has occurred at block 1014 (YES), the intermittent mode ends.","If the system determines that no interval between fluid delivery was selected at block 1008 (NO), the system delivers fluids for the selected duration of fluid delivery at block 1016 and stops delivering fluids for a predetermined interval between fluid delivery at block 1018.For example, the controller 202 may open the valve 208 for a selected duration of fluid delivery received through the user interface 204, such as two minutes, and the controller 202 may close the valve 208 for a predetermined interval between fluid delivery, such as two minutes.","The system then determines whether a predetermined number of on-off cycles has occurred at block 1020.If a predetermined number of on-off cycles has not occurred at block 1020 (NO), the system repeats beginning at block 1016.If a predetermined number of on-off cycles has occurred at block 1020 (YES), the intermittent mode ends.","FIG.","11 illustrates a flow chart 1100 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.","1 during the training mode, which may be implemented in accordance with an embodiment.","The system closes a valve at block 1102.For example, the controller 202 may close the valve 208.The system monitors the pressure at the tissue site at block 1104.For example, the controller 202 monitors the signal representing the pressure from the sensor 206.The system determines a cyclical pressure profile at the tissue site at block 1106.For example, the controller 202 may determine the pressure profile 301.The system may determine a maximum pressure, a minimum pressure, and the time intervals for the on period and the off period of the duty cycle of the reduced-pressure source at block 1108.For example, the controller 202 may determine a maximum pressure (Pmax), a minimum pressure (Pmin), and the time interval of the on-states 320/324 and the off-states 322/326 of the reduced-pressure source 104.FIG.","12 illustrates a flow chart 1200 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.","1 during fluid delivery in the dynamic mode, which may be implemented in accordance with an embodiment.","The system monitors the pressure at the tissue site at block 1202.For example, the controller 202 monitors the signal from the sensor 206 representing the pressure in the sealed therapeutic environment 103.The system determines if the trigger pressure has been reached at block 1204.For example, the controller 202 may determine if the trigger pressure 334 (Pt) has been reached by the pressure profile 301 (Ps).","If the system determines that the trigger pressure has not been reached at block 1204 (NO), the system continues to monitor the pressure at the tissue site.","If the system determines that the trigger pressure has been reached at block 1204 (YES), the system delivers fluids at block 1206.For example, the controller 202 opens the valve 208 to permit fluid flow to the sealed therapeutic environment 103.The system monitors fluid flow at block 1208.For example, the controller 202 monitors the signal from the flow meter 209 representing the fluid flow through the valve 208.The system determines if a full fluid dosage has been delivered at block 1209.For example, the controller 202 determines if the full dosage of fluid has passed through the valve 208.If the system determines that the full fluid dosage has not been delivered at block 1209 (NO), the system determines whether the reduced-pressure source is entering an on period at block 1210.For example, the controller 202 may monitor how long the reduced-pressure source 104 has been in the off-state 322 to determine if the reduced-pressure source 104 is about to enter the on-state 324.If the system determines that the reduced-pressure source is not entering an on-state at block 1210 (NO), the system continues delivering fluids at block 1206.If the system determines that the reduced-pressure source is entering an on-state at block 1210 (YES), the system increments the trigger pressure at block 1211, and the system stops delivering fluids at block 1212.For example, the controller 202 may adjust the trigger pressure to begin fluid delivery at a higher reduced pressure and close the valve 208.If the system determines that the full dosage of fluid has been delivered at block 1209 (YES), the system stops delivering fluids at block 1212.For example, the controller 202 may close the valve 208, stopping fluid delivery.","The system determines whether a predetermined number of on-off cycles of fluid delivery has been completed at block 1214.If the system determines that a predetermined number of on-off cycles of fluid delivery has been completed at block 1214 (YES), the process ends.","If the system determines that a predetermined number of on-off cycles of fluid delivery has not been completed at block 1214 (NO), the system repeats beginning at block 1202.FIG.","13 illustrates a flow chart 1300 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.","1 during fluid delivery, which may be implemented in accordance with an embodiment.","In the illustrated flow chart, the instillation therapy system 116 may determine if the fluid reservoir 210 is empty.","The system monitors the pressure at the tissue site at block 1302.For example, the controller 202 monitors the signal from the sensor 206 representing the pressure in the sealed therapeutic environment 103.The system determines if a reduced-pressure ramp-down period is the expected reduced-pressure ramp-down period at block 1304.For example, the controller 202 may determine if a reduced-pressure ramp-down period is the expected reduced-pressure ramp-down period 332.If the system determines that the reduced-pressure ramp-down period is the expected reduced-pressure ramp-down period at block 1304 (YES), the system repeats at block 1302.If the system determines that the reduced-pressure ramp-down period is not the expected reduced-pressure ramp-down period 332, the system indicates an empty fluid reservoir at block 1306 and ends.","For example, the controller 202 may activate an alarm on the user interface 204 indicating an empty fluid reservoir 210.The systems and methods described herein may provide significant advantages, some of which have already been mentioned.","For example, the instillation therapy system may provide a combined reduced-pressure therapy and instillation therapy system that may be simple to set-up.","The instillation therapy system may also provide an instillation system that may be used with an independent reduced-pressure system that may be capable of intermittent therapy.","The instillation therapy system may also use the reduced-pressure source as the mechanism to draw the fluid to the sealed therapeutic environment, allowing the instillation therapy system to use simpler components.","The instillation therapy system may also overcome a head pressure differential.","The instillation therapy system may provide feedback on critical parameters related to the performance of a reduced-pressure source regarding the level of reduced-pressure delivered to a sealed therapeutic environment.","The instillation therapy system may be configured manually, or through a training mode.","The instillation therapy system can also deliver fluid in sync with an intermittent reduced-pressure cycle or in a continuous manner or variations in between.","It should be apparent from the foregoing that an invention having significant advantages has been provided.","While shown in only a few forms, the systems and methods illustrated are susceptible to various changes and modifications without departing from the spirit thereof."]],"string":"[\n [\n \"AUTONOMOUS FLUID INSTILLATION SYSTEM AND METHOD WITH TISSUE SITE PRESSURE MONITORING\",\n \"A system and method for providing fluid to a tissue site is described.\",\n \"The method fluidly couples an instillation therapy system to the tissue site and monitors a pressure supplied to the tissue site by a reduced-pressure source with the instillation therapy system for a time period.\",\n \"The method provides fluid to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.\",\n \"The system includes a pressure sensor fluidly coupled to the tissue site to measure a pressure proximate the tissue site.\",\n \"A valve and a flow meter are fluidly between a fluid reservoir and the tissue site.\",\n \"A controller is communicatively coupled to the pressure sensor and the valve and configured to monitor the pressure at the tissue site and a volume of fluid flow to the tissue and, in response, operate the valve.\"\n ],\n [\n \"1.A method for providing fluid to a tissue site, the method comprising: fluidly coupling an instillation therapy system to the tissue site; monitoring a pressure supplied to the tissue site by a reduced-pressure source with the instillation therapy system for a time period; and providing fluid to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.\",\n \"2.The method of claim 1, wherein providing fluid to the tissue site comprises opening a valve fluidly coupled between the tissue site and a fluid reservoir.\",\n \"3.The method of claim 2, further comprising operating a pump fluidly coupled between the valve and the fluid reservoir.\",\n \"4.The method of claim 1, wherein providing fluid to the tissue site comprises operating a pump fluidly coupled between the tissue site and a fluid reservoir.\",\n \"5.The method of claim 1, wherein monitoring a pressure at the tissue site for a time period comprises: operating the reduced-pressure source fluidly coupled to the tissue site in an intermittent mode; monitoring the pressure at the tissue site to determine a pressure profile; and determining one or more operating parameters of a reduced-pressure treatment from the pressure profile.\",\n \"6.The method of claim 5, wherein the one or more operating parameters comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on period and an off period for the reduced-pressure source.\",\n \"7.The method of claim 5, wherein providing fluid to the tissue site comprises opening a valve fluidly coupled between the tissue site and a fluid reservoir in response to the one or more operating parameters.\",\n \"8.The method of claim 7, wherein opening the valve in response to the one or more operating parameters comprises opening the valve when the pressure at the tissue site reaches a trigger pressure.\",\n \"9.The method of claim 7, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during an off period of the reduced-pressure source.\",\n \"10.The method of claim 7, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during an on period of the reduced-pressure source.\",\n \"11.The method of claim 1, further comprising: monitoring a reduced-pressure ramp-down period while providing fluids; and reporting that a fluid reservoir is empty in response to a deviation of the reduced-pressure ramp-down period from an expected reduced-pressure ramp-down period.\",\n \"12.A method for providing fluid to a tissue site, the method comprising: fluidly coupling an instillation therapy system to the tissue site; operating a reduced-pressure treatment system fluidly coupled to the tissue site to provide reduced-pressure therapy in an intermittent mode; monitoring a pressure at the tissue site; determining a pressure profile of the reduced-pressure therapy at the tissue site; and opening a valve fluidly coupled between the tissue site and a fluid reservoir in response to the pressure profile.\",\n \"13.The method of claim 12, further comprising operating a pump fluidly coupled between the valve and the fluid reservoir.\",\n \"14.The method of claim 12, further comprising determining one or more operating parameters of the reduced-pressure therapy from the pressure profile.\",\n \"15.The method of claim 14, wherein the one or more operating parameters comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on period and an off period for a reduced-pressure source of the reduced-pressure treatment system.\",\n \"16.The method of claim 15, wherein opening a valve fluidly coupled between the tissue site and a fluid reservoir comprises opening the valve in response to the one or more operating parameters.\",\n \"17.The method of claim 16, wherein opening the valve in response to the one or more operating parameters comprises opening the valve when the pressure at the tissue site reaches the trigger pressure.\",\n \"18.The method of claim 16, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during the off period of the reduced-pressure source.\",\n \"19.The method of claim 16, wherein opening the valve in response to the one or more operating parameters comprises opening the valve during the on period of the reduced-pressure source.\",\n \"20.The method of claim 12, further comprising: determining an expected reduced-pressure ramp-down period from the pressure profile; monitoring the reduced-pressure ramp-down period when the valve is open; and reporting that a fluid reservoir is empty in response to a deviation of the reduced-pressure ramp-down period from the expected reduced-pressure ramp-down period.\",\n \"21.A system for providing instillation therapy to a tissue site, the system comprising: a fluid interface configured to be fluidly coupled to the tissue site; a pressure sensor fluidly coupled to the fluid interface and configured to measure a pressure proximate the tissue site; a valve fluidly coupled to the fluid interface and having an open position configured to permit fluid communication through the valve and a closed position configured to prevent fluid communication through the valve; a flow meter configured to be fluidly coupled between the valve and the fluid interface; a fluid reservoir fluidly coupled to the valve; and a controller communicatively coupled to the pressure sensor and the valve, the controller configured to monitor the pressure measured by the pressure sensor and a volume of fluid flow through the flow meter and, in response, operate the valve.\",\n \"22.The system of claim 21, wherein the controller is configured to operate the valve in response to one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, an on-state and an off-state of a reduced-pressure therapy system, and a duration of fluid delivery and an interval of fluid delivery.\",\n \"23.The system of claim 21, wherein the controller is configured to determine a pressure profile in response to the pressure measured by the pressure sensor.\",\n \"24.The system of claim 23, wherein the controller is configured to determine one or more operating parameters in response to the pressure profile.\",\n \"25.The system of claim 24, wherein the one or more operating parameters comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on-state and an off-state of a reduced-pressure therapy system.\",\n \"26.The system of claim 21, further comprising a user interface operationally coupled to the controller and configured to present one or more operating parameters of the system.\",\n \"27.The system of claim 26, wherein the one or more operating parameters comprise one more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, and an on-state and an off-state of a reduced-pressure therapy system.\",\n \"28.The system of claim 26, wherein the user interface is further configured to receive operational input and communicate the operational input to the controller.\",\n \"29.The system of claim 28, wherein the operational input may comprise one or more of a maximum reduced pressure, a minimum reduced pressure, a trigger pressure, a duration of fluid delivery, and an interval of fluid delivery.\",\n \"30.The system of claim 21, further comprising a pump fluidly coupled between the fluid reservoir and the valve, the pump being operationally coupled to the controller.\",\n \"31.The system of claim 21, further comprising a disposable connector fluidly coupled between the pressure sensor and the fluid interface.\",\n \"32.The system of claim 21, further comprising at least one sensor fluidly coupled to a tube fluidly coupling the valve to the fluid interface and further operationally coupled to the controller, the at least one sensor configured to detect blockages in the tube.\",\n \"33.-39.\",\n \"(canceled)\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Clinical studies and practice have shown that reducing pressure in proximity to a tissue site can augment and accelerate growth of new tissue at the tissue site.\",\n \"The applications of this phenomenon are numerous, but it has proven particularly advantageous for treating wounds.\",\n \"Regardless of the etiology of a wound, whether trauma, surgery, or another cause, proper care of the wound is important to the outcome.\",\n \"Treatment of wounds with reduced pressure may be commonly referred to as “reduced-pressure therapy,” but is also known by other names, including “negative-pressure therapy,” “negative-pressure wound therapy,” “reduced-pressure wound therapy,” “vacuum therapy,” and “vacuum-assisted closure,” for example.\",\n \"Reduced-pressure therapy may provide a number of benefits, including migration of epithelial and subcutaneous tissues, improved blood flow, and micro-deformation of tissue at a tissue site.\",\n \"Together, these benefits can increase development of granulation tissue and reduce healing times.\",\n \"In addition, the delivery of therapeutic fluids (e.g.\",\n \"saline or antibiotic fluids) to the tissue site can also provide benefits to healing of a tissue site.\",\n \"Treatment of tissue sites with the delivery of therapeutic fluids may also be referred to as “instillation therapy.” Instillation therapy may assist in cleaning the tissue site by aiding in the removal of infectious agents or necrotic tissue.\",\n \"The therapeutic fluids used in instillation therapy may also provide medicinal fluids, such as antibiotics, anti-fungals, antiseptics, analgesics, or other similar substances, to aid in the treatment of a tissue site.\",\n \"While the clinical benefits of reduced-pressure therapy and instillation therapy are widely known, the cost and complexity of reduced-pressure therapy and instillation therapy can be a limiting factor in its application, and the development and operation of reduced-pressure systems, components, and processes continues to present significant challenges to manufacturers, healthcare providers, and patients.\"\n ],\n [\n \"<SOH> BRIEF SUMMARY <EOH>In one example embodiment, a method for providing fluid to a tissue site may be described.\",\n \"An instillation therapy system may be fluidly coupled to the tissue site, and a pressure supplied to the tissue site by a reduced-pressure source may be monitored with the instillation therapy system for a time period.\",\n \"Fluid may be provided to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.\",\n \"In another example embodiment, a method for providing fluid to a tissue site may be described.\",\n \"An instillation therapy system may be fluidly coupled to the tissue site.\",\n \"A reduced-pressure treatment system fluidly coupled to the tissue site may be operated to provide reduced-pressure therapy in an intermittent mode, and the instillation therapy system may monitor a pressure at the tissue site.\",\n \"A pressure profile of the reduced-pressure therapy at the tissue site may be determined.\",\n \"A valve fluidly coupled between the tissue site and a fluid reservoir may be opened in response to the pressure profile.\",\n \"In still another embodiment, a system for providing instillation therapy to a tissue site may be described.\",\n \"The system may include a fluid interface configured to be fluidly coupled to the tissue site and a pressure sensor fluidly coupled to the fluid interface and configured to measure a pressure proximate the tissue site.\",\n \"The system may also include a valve fluidly coupled to the fluid interface.\",\n \"The valve may have an open position configured to permit fluid communication through the valve and a closed position configured to prevent fluid communication through the valve.\",\n \"The system may have a flow meter configured to be fluidly coupled between the valve and the fluid interface and a fluid reservoir fluidly coupled to the valve.\",\n \"The system may include a controller communicatively coupled to the pressure sensor and the valve.\",\n \"The controller may be configured to monitor the pressure measured by the pressure sensor and a volume of fluid flow through the flow meter and, in response, operate the valve.\",\n \"In yet another example embodiment, a method for providing fluid to a tissue site may be described.\",\n \"An instillation therapy system may be fluidly coupled to the tissue site and operated in a training mode.\",\n \"A pressure profile of a reduced pressure source fluidly coupled to the tissue site may be determined in response to the training mode.\",\n \"In response to the pressure profile, the instillation therapy system may deliver fluid to the tissue site.\",\n \"In yet still another example embodiment, a method for delivering fluid to a tissue site may be described.\",\n \"An instillation therapy system may be coupled to the tissue site, and the instillation therapy system may monitor a pressure at the tissue site.\",\n \"Fluids may be delivered to the tissue site if the pressure at the tissue site is about a trigger pressure, and the instillation therapy system may continue to monitor the pressure at the tissue site if the pressure at the tissue site is not about the trigger pressure.\",\n \"A fluid flow to the tissue site may be monitored in response to delivering fluids to the tissue site, and the instillation therapy system may determine if the fluid flow is about a dosage of fluids.\",\n \"If the fluid flow is about the dosage of fluids, the fluid flow may be stopped.\",\n \"And if the fluid flow is not about the dosage of fluids, the instillation therapy system may determine if a reduced-pressure source fluidly coupled to the tissue site is about to start an on period.\",\n \"If the reduced-pressure source is not about to start the on period, fluids may continue to be delivered.\",\n \"If the reduced-pressure source is about to enter the on period, fluid may stop being delivered, and the trigger pressure may be incremented if the reduced-pressure source is about to start the on period.\",\n \"Other objects, features, and advantages of the embodiments described herein will become apparent with reference to the drawings and detailed description that follow.\"\n ],\n [\n \"RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/561,718, filed Dec. 5, 2014, which claims the benefit, under 35 USC § 119(e), of the filing of U.S.\",\n \"Provisional Patent Application No.\",\n \"61/917,773, entitled “Autonomous Fluid Instillation System and Method with Tissue Site Pressure Monitoring,” filed Dec. 18, 2013, which is incorporated herein by reference for all purposes.\",\n \"TECHNICAL FIELD The present invention relates generally to tissue treatment systems and more particularly, but without limitation, to a system and method for providing instillation therapy to a tissue site.\",\n \"BACKGROUND Clinical studies and practice have shown that reducing pressure in proximity to a tissue site can augment and accelerate growth of new tissue at the tissue site.\",\n \"The applications of this phenomenon are numerous, but it has proven particularly advantageous for treating wounds.\",\n \"Regardless of the etiology of a wound, whether trauma, surgery, or another cause, proper care of the wound is important to the outcome.\",\n \"Treatment of wounds with reduced pressure may be commonly referred to as “reduced-pressure therapy,” but is also known by other names, including “negative-pressure therapy,” “negative-pressure wound therapy,” “reduced-pressure wound therapy,” “vacuum therapy,” and “vacuum-assisted closure,” for example.\",\n \"Reduced-pressure therapy may provide a number of benefits, including migration of epithelial and subcutaneous tissues, improved blood flow, and micro-deformation of tissue at a tissue site.\",\n \"Together, these benefits can increase development of granulation tissue and reduce healing times.\",\n \"In addition, the delivery of therapeutic fluids (e.g.\",\n \"saline or antibiotic fluids) to the tissue site can also provide benefits to healing of a tissue site.\",\n \"Treatment of tissue sites with the delivery of therapeutic fluids may also be referred to as “instillation therapy.” Instillation therapy may assist in cleaning the tissue site by aiding in the removal of infectious agents or necrotic tissue.\",\n \"The therapeutic fluids used in instillation therapy may also provide medicinal fluids, such as antibiotics, anti-fungals, antiseptics, analgesics, or other similar substances, to aid in the treatment of a tissue site.\",\n \"While the clinical benefits of reduced-pressure therapy and instillation therapy are widely known, the cost and complexity of reduced-pressure therapy and instillation therapy can be a limiting factor in its application, and the development and operation of reduced-pressure systems, components, and processes continues to present significant challenges to manufacturers, healthcare providers, and patients.\",\n \"BRIEF SUMMARY In one example embodiment, a method for providing fluid to a tissue site may be described.\",\n \"An instillation therapy system may be fluidly coupled to the tissue site, and a pressure supplied to the tissue site by a reduced-pressure source may be monitored with the instillation therapy system for a time period.\",\n \"Fluid may be provided to the tissue site with the instillation therapy system in response to the pressure at the tissue site during the time period.\",\n \"In another example embodiment, a method for providing fluid to a tissue site may be described.\",\n \"An instillation therapy system may be fluidly coupled to the tissue site.\",\n \"A reduced-pressure treatment system fluidly coupled to the tissue site may be operated to provide reduced-pressure therapy in an intermittent mode, and the instillation therapy system may monitor a pressure at the tissue site.\",\n \"A pressure profile of the reduced-pressure therapy at the tissue site may be determined.\",\n \"A valve fluidly coupled between the tissue site and a fluid reservoir may be opened in response to the pressure profile.\",\n \"In still another embodiment, a system for providing instillation therapy to a tissue site may be described.\",\n \"The system may include a fluid interface configured to be fluidly coupled to the tissue site and a pressure sensor fluidly coupled to the fluid interface and configured to measure a pressure proximate the tissue site.\",\n \"The system may also include a valve fluidly coupled to the fluid interface.\",\n \"The valve may have an open position configured to permit fluid communication through the valve and a closed position configured to prevent fluid communication through the valve.\",\n \"The system may have a flow meter configured to be fluidly coupled between the valve and the fluid interface and a fluid reservoir fluidly coupled to the valve.\",\n \"The system may include a controller communicatively coupled to the pressure sensor and the valve.\",\n \"The controller may be configured to monitor the pressure measured by the pressure sensor and a volume of fluid flow through the flow meter and, in response, operate the valve.\",\n \"In yet another example embodiment, a method for providing fluid to a tissue site may be described.\",\n \"An instillation therapy system may be fluidly coupled to the tissue site and operated in a training mode.\",\n \"A pressure profile of a reduced pressure source fluidly coupled to the tissue site may be determined in response to the training mode.\",\n \"In response to the pressure profile, the instillation therapy system may deliver fluid to the tissue site.\",\n \"In yet still another example embodiment, a method for delivering fluid to a tissue site may be described.\",\n \"An instillation therapy system may be coupled to the tissue site, and the instillation therapy system may monitor a pressure at the tissue site.\",\n \"Fluids may be delivered to the tissue site if the pressure at the tissue site is about a trigger pressure, and the instillation therapy system may continue to monitor the pressure at the tissue site if the pressure at the tissue site is not about the trigger pressure.\",\n \"A fluid flow to the tissue site may be monitored in response to delivering fluids to the tissue site, and the instillation therapy system may determine if the fluid flow is about a dosage of fluids.\",\n \"If the fluid flow is about the dosage of fluids, the fluid flow may be stopped.\",\n \"And if the fluid flow is not about the dosage of fluids, the instillation therapy system may determine if a reduced-pressure source fluidly coupled to the tissue site is about to start an on period.\",\n \"If the reduced-pressure source is not about to start the on period, fluids may continue to be delivered.\",\n \"If the reduced-pressure source is about to enter the on period, fluid may stop being delivered, and the trigger pressure may be incremented if the reduced-pressure source is about to start the on period.\",\n \"Other objects, features, and advantages of the embodiments described herein will become apparent with reference to the drawings and detailed description that follow.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a partial sectional view of a reduced-pressure therapy system and an instillation therapy system for treating a tissue site in accordance with this specification; FIG.\",\n \"2 is a partial sectional view of another embodiment of the reduced-pressure therapy system and the instillation therapy system for treating a tissue site in accordance with an illustrative embodiment; FIG.\",\n \"3 is a sectional view of a tube for fluidly coupling a reduced-pressure source to a reduced-pressure interface in accordance with an illustrative embodiment; FIG.\",\n \"4 is a schematic diagram of the reduced-pressure therapy system and the instillation therapy system in accordance with an illustrative embodiment; FIG.\",\n \"5 is a graphical depiction of the operation of the reduced-pressure therapy system of FIG.\",\n \"4 in accordance with an illustrative embodiment; FIG.\",\n \"6A is a graphical depiction of a pressure profile of reduced-pressure provided to the tissue site by the reduced-pressure therapy system of FIG.\",\n \"4 in accordance with an illustrative embodiment; FIG.\",\n \"6B is a graphical depiction of the pressure profile of FIG.\",\n \"6A illustrating a training mode of the instillation therapy system of FIG.\",\n \"4; FIG.\",\n \"7 is a graphical depiction of the operation of a valve of the fluid source of FIG.\",\n \"4 in accordance with an illustrative embodiment; FIG.\",\n \"8 is a graphical depiction of the operation of the valve of the fluid source of FIG.\",\n \"4 in accordance with another illustrative embodiment; FIG.\",\n \"9 is a block diagram illustrating operative steps of the fluid source of FIG.\",\n \"4; FIG.\",\n \"10 is a block diagram illustrating operative steps of an intermittent mode of operation of the fluid source of FIG.\",\n \"4; FIG.\",\n \"11 is a block diagram illustrating operative steps of a training mode of operation of the fluid source of FIG.\",\n \"4; FIG.\",\n \"12 is a block diagram illustrating operative steps of a dynamic mode of operation of the fluid source of FIG.\",\n \"4; and FIG.\",\n \"13 is a block diagram illustrating additional operative steps of the dynamic mode of operation of the fluid source of FIG.\",\n \"4.DESCRIPTION OF EXAMPLE EMBODIMENTS New and useful systems and methods for providing instillation therapy in a reduced-pressure therapy environment are set forth in the appended claims.\",\n \"Objectives, advantages, and a preferred mode of making and using the systems and methods may be understood best by reference to the following detailed description in conjunction with the accompanying drawings.\",\n \"The description provides information that enables a person skilled in the art to make and use the claimed subject matter, but may omit certain details already well-known in the art.\",\n \"Moreover, descriptions of various alternatives using terms such as “or” do not necessarily require mutual exclusivity unless clearly required by the context.\",\n \"The claimed subject matter may also encompass alternative embodiments not specifically described in detail.\",\n \"The following detailed description is, therefore, to be taken as illustrative and not limiting.\",\n \"The example embodiments may also be described herein with reference to spatial relationships between various elements or to the spatial orientations of various elements depicted in the attached drawings.\",\n \"In general, such relationships or orientation assume a frame of reference consistent with or relative to a patient in a position to receive treatment.\",\n \"However, as should be recognized by those skilled in the art, this frame of reference is merely a descriptive expedient rather than a strict prescription.\",\n \"FIG.\",\n \"1 is a partial sectional view of a therapy system 100 that may include a reduced-pressure therapy system 101 and an instillation therapy system 116 fluidly coupled to a tissue site 114 in accordance with some embodiments.\",\n \"In an illustrative embodiment, the therapy system 100 may also include a dressing 102 coupled to a tissue site 114.The dressing 102 may include a drape, such as a drape 108, and a tissue interface, such as a manifold 110.The reduced-pressure therapy system 101 may include a reduced-pressure source 104 fluidly coupled to the dressing 102.The reduced-pressure therapy system 101 may also include a fluid container, such as a container 112, fluidly coupled to the dressing 102 and the reduced-pressure source 104 by a reduced-pressure interface 105, a tube 107, and a tube 109.The instillation therapy system 116 may include a fluid source 118 and a fluid interface 120.The fluid source 118 may be fluidly coupled to the fluid interface 120 with a fluid connector 122 and one or more tubes, such as a tube 123 and a tube 124.A tissue interface, such as the manifold 110, may be placed within, over, on, or otherwise proximate a tissue site, such as the tissue site 114.For example, the manifold 110 may be placed against the tissue site 114, and the drape 108 may be placed over the manifold 110 and sealed to tissue proximate the tissue site 114.Tissue proximate a tissue site is often undamaged epidermis peripheral to the tissue site.\",\n \"Thus, the dressing 102 can provide a sealed therapeutic environment 103 proximate a tissue site.\",\n \"The sealed therapeutic environment 103 may be substantially isolated from the external environment, and the reduced-pressure source 104 can reduce the pressure in the sealed therapeutic environment 103.Reduced pressure applied uniformly through a tissue interface in the sealed therapeutic environment 103 can induce macrostrain and microstrain in a tissue site, as well as remove exudates and other fluids from the tissue site.\",\n \"The removed exudates and other fluids can be collected in the container 112 and disposed of properly.\",\n \"A “tissue site,” such as the tissue site 114, may refer to a wound or defect located on or within tissue including, but not limited to, bone tissue, adipose tissue, muscle tissue, neural tissue, dermal tissue, vascular tissue, connective tissue, cartilage, tendons, or ligaments.\",\n \"A wound may include chronic, acute, traumatic, subacute, and dehisced wounds, partial-thickness burns, ulcers (such as diabetic, pressure, or venous insufficiency ulcers), flaps, and grafts, for example.\",\n \"The term “tissue site” may also refer to areas of any tissue that are not necessarily wounded or defective, but are instead areas in which it may be desirable to add or promote the growth of additional tissue.\",\n \"For example, reduced pressure may be used in certain tissue areas to grow additional tissue that may be harvested and transplanted to another tissue location.\",\n \"“Reduced pressure” generally refers to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to the sealed therapeutic environment 103 provided by the dressing 102.In many cases, the local ambient pressure may also be the atmospheric pressure at which a patient is located.\",\n \"Alternatively, the pressure may be less than a hydrostatic pressure associated with tissue at a tissue site.\",\n \"Unless otherwise indicated, values of pressure stated herein are gauge pressures.\",\n \"Similarly, references to increases in reduced pressure typically refer to a decrease in absolute pressure, while decreases in reduced pressure typically refer to an increase in absolute pressure.\",\n \"The fluid mechanics of using a reduced-pressure source to reduce pressure in another component or location, such as within the sealed therapeutic environment 103, can be mathematically complex.\",\n \"However, the basic principles of fluid mechanics applicable to reduced-pressure therapy are generally well-known to those skilled in the art, and the process of reducing pressure may be described illustratively herein as “delivering,” “distributing,” or “generating” reduced pressure, for example.\",\n \"In general, exudates and other fluids flow toward lower pressure along a fluid path.\",\n \"Thus, the term “downstream” typically implies a position in a fluid path relatively closer to a reduced-pressure source, and conversely, the term “upstream” implies a position relatively further away from a reduced-pressure source.\",\n \"Similarly, it may be convenient to describe certain features in terms of fluid “inlet” or “outlet” in such a frame of reference.\",\n \"This orientation is generally presumed for purposes of describing various features and components of reduced-pressure therapy systems herein.\",\n \"However, the fluid path may also be reversed in some applications (such as by substituting a positive-pressure source for a reduced-pressure source) and this descriptive convention should not be construed as a limiting convention.\",\n \"A tissue interface, such as the manifold 110, can generally be adapted to contact a tissue site or other layers of a dressing, such as the dressing 102.A tissue interface may be partially or fully in contact with a tissue site.\",\n \"If a tissue site is a wound, for example, a tissue interface may partially or completely fill the wound, or may be placed over the wound.\",\n \"A tissue interface may take many forms, and may have many sizes, shapes, or thicknesses depending on a variety of factors, such as the type of treatment being implemented or the nature and size of a tissue site.\",\n \"For example, the size and shape of a tissue interface may be adapted to the contours of deep and irregular shaped tissue sites.\",\n \"Generally, a manifold, such as the manifold 110, for example, is a substance or structure adapted to distribute or remove fluids from a tissue site.\",\n \"A manifold may include flow channels or pathways that can distribute fluids provided to and removed from a tissue site.\",\n \"In one illustrative embodiment, the flow channels or pathways may be interconnected to improve distribution of fluids provided to or removed from a tissue site.\",\n \"For example, a manifold may be an open-cell, porous tissue collection, or other porous material such as gauze or felted mat that generally includes structural elements arranged to form flow channels.\",\n \"Liquids, gels, and other foams may also include or be cured to include flow channels.\",\n \"In one illustrative embodiment, the manifold 110 may be a porous foam pad having interconnected cells adapted to distribute reduced pressure across a tissue site.\",\n \"The foam material may be either hydrophobic or hydrophilic.\",\n \"In one non-limiting example, the manifold 110 may be reticulated polyurethane foam, such as GranuFoam® dressing available from Kinetic Concepts, Inc. of San Antonio, Tex.\",\n \"In some embodiments, the manifold 110 may be made from a hydrophilic material, and the manifold 110 may also wick fluid away from a tissue site, while continuing to distribute reduced pressure to the tissue site.\",\n \"The wicking properties of the manifold 110 may draw fluid away from a tissue site by capillary flow or other wicking mechanisms.\",\n \"An example of a hydrophilic foam is a polyvinyl alcohol, open-cell foam such as V.A.C.\",\n \"WhiteFoam® dressing available from Kinetic Concepts, Inc. of San Antonio, Tex.\",\n \"Other hydrophilic foams may include those made from polyether.\",\n \"Other foams that may exhibit hydrophilic characteristics include hydrophobic foams that have been treated or coated to provide hydrophilicity.\",\n \"A tissue interface may further promote granulation at a tissue site if pressure within a sealed therapeutic environment is reduced.\",\n \"For example, any or all of the surfaces of the manifold 110 may have an uneven, coarse, or jagged profile that can induce microstrains and stresses at the tissue site 114 if reduced pressure is applied to the sealed therapeutic environment 103 through the manifold 110.In some example embodiments, a tissue interface may be constructed from bioresorbable materials.\",\n \"Suitable bioresorbable materials may include, without limitation, a polymeric blend of polylactic acid (PLA) and polyglycolic acid (PGA).\",\n \"The polymeric blend may also include without limitation polycarbonates, polyfumarates, and capralactones.\",\n \"A tissue interface may further serve as a scaffold for new cell-growth, or a scaffold material may be used in conjunction with the tissue interface to promote cell-growth.\",\n \"In general, a scaffold material may be a biocompatible or biodegradable substance or structure used to enhance or promote the growth of cells or formation of tissue, such as a three-dimensional porous structure that provides a template for cell growth.\",\n \"Illustrative examples of scaffold materials include calcium phosphate, collagen, PLA/PGA, coral hydroxy apatites, carbonates, or processed allograft materials.\",\n \"The drape 108 is an example of a sealing member.\",\n \"A sealing member may be constructed from a material that can provide a fluid seal between two components or two environments, such as between a therapeutic environment and a local external environment.\",\n \"A sealing member may be, for example, an impermeable or semi-permeable, elastomeric material that can provide a seal adequate to maintain a reduced pressure at a tissue site for a given reduced-pressure source.\",\n \"For semi-permeable materials, the permeability generally should be low enough that a desired reduced pressure may be maintained.\",\n \"An attachment device may be used to attach a sealing member to an attachment surface, such as undamaged epidermis, a gasket, or another sealing member.\",\n \"An attachment device may take many forms.\",\n \"For example, an attachment device may be a medically-acceptable, pressure-sensitive adhesive that extends about a periphery, a portion, or an entire sealing member.\",\n \"Other example embodiments of an attachment device may include a double-sided tape, paste, hydrocolloid, hydrogel, silicone gel, organogel, or an acrylic adhesive.\",\n \"In general, components of the reduced-pressure therapy system 101 may be coupled directly or indirectly to each other.\",\n \"For example, the reduced-pressure source 104 may be directly coupled to the container 112 by the tube 107 and indirectly coupled to the dressing 102 through the container 112 and the tube 109.Components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components.\",\n \"In some embodiments, components may be fluidly coupled with a tube, such as the tube 107 or the tube 109, for example.\",\n \"A “tube,” as used herein, broadly refers to a tube, pipe, hose, conduit, or other structure with one or more lumina adapted to convey fluids between two ends.\",\n \"Typically, a tube is an elongated, cylindrical structure with some flexibility, but the geometry and rigidity may vary.\",\n \"In some embodiments, components may additionally or alternatively be coupled by virtue of physical proximity, being integral to a single structure, or being formed from the same piece of material.\",\n \"Coupling may also include mechanical, thermal, electrical, or chemical coupling (such as a chemical bond) in some contexts.\",\n \"A reduced-pressure interface, such as the reduced-pressure interface 105 may be a device or component operable to fluidly couple the reduced-pressure source 104 to the dressing 102.In one illustrative embodiment, the reduced-pressure interface 105 may be a T.R.A.C.® Pad or Sensa T.R.A.C.® Pad available from KCI of San Antonio, Tex., modified as described in more detail below.\",\n \"The reduced-pressure interface 105 may fluidly couple the reduced pressure provided by the reduced-pressure source 104 to the manifold 110 through the drape 108.The manifold 110 may distribute the fluid to the sealed therapeutic environment 103.Thus, the reduced-pressure interface 105 allows reduced pressure to be delivered to the sealed therapeutic environment 103.The reduced-pressure interface 105 may be made of a semi-rigid material.\",\n \"In some embodiments, the reduced-pressure interface 105 may be made from a plasticized polyvinyl chloride (PVC), polyurethane, cyclic olefin copolymer elastomer, thermoplastic elastomer, poly acrylic, silicone polymer, or polyether block amide copolymer.\",\n \"A reduced-pressure source, such as the reduced-pressure source 104, may be a reservoir of air at a reduced pressure, or may be a manual or electrically-powered device that can reduce the pressure in a sealed volume, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example.\",\n \"The reduced-pressure source may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate reduced-pressure therapy.\",\n \"While the amount and nature of reduced pressure applied to a tissue site may vary according to therapeutic requirements, the pressure typically ranges between about −5 mm Hg (−667 Pa) and about −500 mm Hg (−66.7 kPa).\",\n \"Common therapeutic ranges are between about −75 mm Hg (−9.9 kPa) and about −300 mm Hg (−39.9 kPa).\",\n \"A “container,” such as the container 112, may broadly include a canister, pouch, bottle, vial, or other fluid collection apparatus.\",\n \"A container can be used to manage exudates and other fluids withdrawn from a tissue site.\",\n \"In many environments, a rigid container may be preferred or required for collecting, storing, and disposing of fluids.\",\n \"In other environments, fluids may be properly disposed of without rigid container storage, and a re-usable container could reduce waste and costs associated with reduced-pressure therapy.\",\n \"A fluid source, such as the fluid source 118, may be a reservoir of fluid at an atmospheric or greater pressure, or may be a manual or electrically-powered device, such as a pump, that can convey fluid to a sealed volume, such as the sealed therapeutic environment 103, for example.\",\n \"A fluid source may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate instillation therapy.\",\n \"The amount and nature of the fluid applied to a tissue site may vary according to therapeutic requirements, which may include the size of the sealed therapeutic environment, the type of fluid, and any additives to the fluid.\",\n \"In some embodiments, the fluid may include: hypochlorite based solutions, such as hypochlorous acid and sodium hypochlorite; silver nitrate; sulfur based solutions, such as sulfonamides; biguanides, such as polyhexanide; cationic solutions, such as octenidine and benzalkonium chloride; and isotonic solutions.\",\n \"A fluid interface, such as the fluid interface 120 may be a device or component operable to fluidly couple the fluid source 118 to the dressing 102.The fluid interface 120 may fluidly couple the fluid provided by the fluid source 118 to the manifold 110 through the drape 108.The manifold 110 may distribute the fluid to the sealed therapeutic environment 103.Thus, the fluid interface 120 allows fluid to be delivered to the sealed therapeutic environment 103.In some embodiments, the fluid interface 120 may also fluidly couple the fluid source 118 to the manifold 110 to determine a pressure at the tissue site 114.In some embodiments, the fluid interface 120 may couple two tubes, such as the tube 124 and the tube 123 to the manifold 110.The fluid interface 120 may be made of a semi-rigid material.\",\n \"In some embodiments, the fluid interface 120 may be made from a plasticized polyvinyl chloride (PVC), polyurethane, cyclic olefin copolymer elastomer, thermoplastic elastomer, poly acrylic, silicone polymer, or polyether block amide copolymer.\",\n \"A fluid connector, such as the fluid connector 122, may be a device or component configured to couple the tube 124 and the tube 123 to the fluid source 118.A fluid connector may fluidly couple one or more tubes to one or more components of a fluid source.\",\n \"In some embodiments, a fluid connector may fluidly couple a multi-lumen tube to one or more components of a fluid source.\",\n \"In some embodiments, a fluid connector may also be releasably coupled to a fluid source so that the fluid connector may be discarded after use of the fluid connector 122.In some embodiments, a fluid connector may be a device permanently attached to a fluid source.\",\n \"In general, components of the instillation therapy system 116 may be coupled directly or indirectly to each other.\",\n \"For example, the fluid source 118 may be directly coupled to the fluid interface 120 and indirectly coupled to the dressing 102 through the fluid interface 120.Components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components.\",\n \"In some embodiments, components may be fluidly coupled with a tube, for example the tube 123 or the tube 124.In some embodiments, the tube 123 and the tube 124 may be single-lumen conduits having a central flow passage extending through each tube.\",\n \"In operation, the reduced-pressure therapy system 101 may provide reduced pressure to the sealed therapeutic environment 103 through the reduced-pressure interface 105.Fluid, including exudates and other liquids, may be drawn from the tissue site 114 through the manifold 110 and into the reduced-pressure interface 105.Similarly, the instillation therapy system 116 may provide fluids to the sealed therapeutic environment 103 through the fluid interface 120.Fluid, including therapeutic liquids, may flow from the fluid source 118, through the tube 124 and into the sealed therapeutic environment 103 through the fluid interface 120.The fluids may be distributed to the tissue site 114 by the manifold 110.In some embodiments, the reduced-pressure therapy system 101 and the instillation therapy system 116 may operate concurrently.\",\n \"If the reduced-pressure therapy system 101 and the instillation therapy system 116 operate concurrently, the fluid interface 120 and the reduced-pressure interface 105 may be positioned to maximize the distance between them.\",\n \"For example, if the tissue site 114 is elongated and includes two opposing ends, the fluid interface 120 and the reduced-pressure interface 105 may be positioned proximate the opposing ends.\",\n \"If the tissue site 114 is generally circular, the fluid interface 120 and the reduced-pressure interface 105 may be placed proximate opposing ends of a diameter of the tissue site 114.Fluid may flow from the fluid interface 120 through the sealed therapeutic environment 103 to the reduced-pressure interface 105.In some embodiments, the reduced pressure supplied through the reduced-pressure interface 105 may aid in the distribution of fluids provided through the fluid interface 120.In some embodiments, the reduced-pressure therapy system 101 and the instillation therapy system 116 may not operate concurrently.\",\n \"In these embodiments, the instillation therapy system 116 may provide fluid to the sealed therapeutic environment 103 while the reduced-pressure therapy system 101 is not providing reduced pressure.\",\n \"The fluid source 118 may include a pump that may move the fluid to the manifold 110 for distribution to the tissue site 114.The fluid may remain in the sealed therapeutic environment 103 until the operation of the reduced-pressure therapy system 101.If the reduced-pressure therapy system 101 provides reduced pressure, the reduced-pressure therapy system 101 may draw the fluid from the sealed therapeutic environment 103 into the container 112.FIG.\",\n \"2 is a partial sectional view of the reduced-pressure therapy system 101 and the instillation therapy system 116 illustrating additional details that may be associated with some embodiments.\",\n \"In some embodiments, the fluid interface 120 and the reduced-pressure interface 105 may be combined into a dressing interface 121.As shown in FIG.\",\n \"2, the dressing interface 121 maybe coupled to the dressing in a manner similar to the fluid interface 120 and the reduced-pressure interface 105.The dressing interface 121 may be configured to receive the tube 123, the tube 124, and the tube 109 and provide a fluid coupling through the drape 108 to the tissue site 114 and the sealed therapeutic environment 103.In some embodiments, the dressing interface 121 may be similar to and operate as described in U.S. patent application Ser.\",\n \"No.\",\n \"13/009,220, by Locke, et al., entitled “Wound-Connection Pads for Fluid Instillation and Negative Pressure Wound Therapy, and Systems and Methods,” filed Jan. 19, 2011, which is incorporated by reference herein for all purposes.\",\n \"The dressing interface 121 may fluidly couple the fluid provided by the fluid source 118 and the reduced pressure provided by the reduced-pressure source 104 to the manifold 110 through the drape 108.The dressing interface 121 may be made of a semi-rigid material.\",\n \"In some embodiments, the dressing interface 121 may be made from a plasticized polyvinyl chloride (PVC), polyurethane, cyclic olefin copolymer elastomer, thermoplastic elastomer, poly acrylic, silicone polymer, or polyether block amide copolymer.\",\n \"In the embodiment of FIG.\",\n \"2, operation of the instillation therapy system 116 and the reduced-pressure therapy system 101 may alternate.\",\n \"The instillation therapy system 116 may provide fluid through the dressing interface 121 while the reduced-pressure therapy system 101 is not operating, and the reduced-pressure therapy system 101 may provide reduced-pressure through the dressing interface 121 while the instillation therapy system 116 is not operating.\",\n \"FIG.\",\n \"3 is a sectional view of the tube 109 illustrating additional details that may be associated with some embodiments of the reduced-pressure therapy system 101.As shown, the tube 109 may be a multi-lumen tube.\",\n \"In the illustrative embodiment, the tube 109 may include at least one primary lumen 126 and one or more secondary lumens 128.In some embodiments, the tube 109 includes four secondary lumens 128.The tube 109 may have different shapes and include more or fewer primary lumens 126 and secondary lumens 128.The primary lumen 126 may provide a path between the reduced-pressure source 104 and the reduced-pressure interface 105 for delivery of reduced pressure.\",\n \"The secondary lumens 128 may function as sensing lumens.\",\n \"In some embodiments, the secondary lumens 128 may fluidly communicate pressure at a terminal end of the tube 109 within the reduced-pressure interface 105 to the reduced-pressure source 104.The secondary lumens 128 may be fluidly isolated from the primary lumen 126 so as not to interfere with the process of sensing the pressure.\",\n \"The pressure communicated by the secondary lumens 128 may be representative of the pressure at the tissue site 114.Referring back to FIG.\",\n \"1 and FIG.\",\n \"2, the tube 123 and the tube 124 may be combined into a multi-lumen tube, similar to the tube 109, each having at least one primary lumen, similar to the primary lumens 126 of the tube 109, and one or more secondary lumens, similar to the secondary lumens 128 of the tube 109.If the tube 123 and the tube 124 are combined into a multi-lumen tube, the secondary lumens may be fluidly coupled between the tissue site 114 and the fluid source 118 to sense pressure at the tissue site 114.The primary lumens would deliver instillation fluid to the tissue site 114.Referring more specifically to FIG.\",\n \"2, the pressure being sensed by the tube 123 may be replaced by the secondary lumens 128 if the tube 124 is a multi-lumen tube.\",\n \"Reduced-pressure therapy has been shown to improve healing of tissue sites.\",\n \"Similarly, instillation therapy has been shown to improve the healing of tissue sites.\",\n \"Furthermore, tissue sites treated with both reduced-pressure therapy and instillation therapy have been shown to have improved healing over the use of reduced-pressure therapy or instillation therapy alone.\",\n \"Current systems providing both reduced-pressure therapy and instillation therapy are complex and difficult to properly administer to a tissue site.\",\n \"In addition, the systems may be quite expensive, which may pose problems for the use of such systems in some locations, in particular, in locations where health care services may not be readily available.\",\n \"Some systems provide both reduced-pressure therapy and instillation therapy without the complexity and cost involved in combined systems; however, these systems may be labor intensive and require significant clinician involvement for the proper administration of therapy.\",\n \"For example, in some systems providing both reduced-pressure therapy and instillation therapy, the reduced-pressure therapy system may be coupled to the tissue site, and a clinician may use a syringe to administer fluids to the tissue site through the dressing.\",\n \"Administering fluids with a syringe requires the clinician to actively monitor the dressing and the fluid application to prevent inadvertent over application of fluids.\",\n \"As it may be difficult to see the tissue site through the sealing member, a clinician may find it difficult to accurately determine the appropriate initiation and termination of instillation therapy.\",\n \"As disclosed herein, the instillation therapy system 116 can overcome these shortcomings and others by providing an instillation therapy system that may monitor the delivery of reduced pressure to a tissue site by a reduced-pressure system, and in response, the instillation therapy system may provide fluids in response to the reduced-pressure therapy.\",\n \"For example, in some embodiments of the instillation therapy system 116, the instillation therapy system 116 may monitor a pressure in the sealed therapeutic environment 103 and, in response, administer fluids in accordance with the administration of reduced pressure by the reduced-pressure therapy system 101.FIG.\",\n \"4 is a schematic diagram of the therapy system 100 illustrating additional details that may be associated with some embodiments of the instillation therapy system 116.In some embodiments, the fluid source 118 may include a controller 202, a user interface 204, and a sensor 206.The user interface 204 and the sensor 206 may each be communicatively coupled to the controller 202.As used herein, communicative coupling may refer to a coupling between components that permits the transmission of signals between the components.\",\n \"In some embodiments, the signals may be discrete or continuous signals.\",\n \"A discrete signal may be a signal representing a value at a particular instance in a time period.\",\n \"A plurality of discrete signals may be used to represent a changing value over a time period.\",\n \"A continuous signal may be a signal that provides a value for each instance in a time period.\",\n \"The signals may also be analog signals or digital signals.\",\n \"An analog signal may be a continuous signal that includes a time varying feature that represents another time varying quantity.\",\n \"A digital signal may be a signal composed of a sequence of discrete values.\",\n \"In some embodiments, the communicative coupling between the controller 202, the user interface 204, and the sensor 206 may be one-way communication.\",\n \"In one-way communication, signals may only be sent in one direction.\",\n \"For example, the sensor 206 may generate a signal that may be communicated to the controller 202, but the controller 202 may not be capable of sending a signal to the sensor 206.In some embodiments, the communicative coupling between the controller 202, the user interface 204, and the sensor 206 may be two-way communication.\",\n \"In two-way communication, signals may be sent in both directions.\",\n \"For example, the controller 202 and the user interface 204 may be communicatively coupled so that the controller 202 may send and receive signals from the user interface 204.Similarly, the user interface 204 may send and receive signals from the controller 202.In some embodiments, signal transmission between the controller 202 and another device, such as the user interface 204, may be referred to as the controller 202 operating the device.\",\n \"The controller 202 may be a computing device or system, such as a programmable logic controller, a data processing system, or the like.\",\n \"In other embodiments, the controller 202 may be configured to receive input from the sensor 206.In some embodiments, the controller 202 is configured to receive input from both the user interface 204 and the sensor 206.In some embodiments, the controller 202 may receive input, such as an electrical signal, from an alternative source, such as through an electrical port, for example.\",\n \"In some embodiments, the controller 202 may be a data processing system.\",\n \"A data processing system suitable for storing and/or executing program code may include at least one processor coupled directly or indirectly to memory elements through a system bus.\",\n \"The memory elements can include local memory employed during actual execution of the program code, bulk storage, and cache memories which provide temporary storage of at least some program code in order to reduce the number of times code is retrieved from bulk storage during execution.\",\n \"In some embodiments, the controller 202 may be a programmable logic controller (“PLC”).\",\n \"A PLC may be a digital computer configured to receive one or more inputs and send one or more outputs in response to the one or more inputs.\",\n \"A PLC may include a non-volatile memory configured to store programs or operational instructions.\",\n \"In some embodiments, the non-volatile memory may be operationally coupled to a battery-back up so that the non-volatile memory retains the programs or operational instructions if the PLC otherwise loses power.\",\n \"In some embodiments, a PLC may be configured to receive discrete signals and continuous signals and produce discrete and continuous signals in response.\",\n \"A user interface, such as the user interface 204, may be a device configured to allow communication between the controller 202 and an environment external (external environment) to the fluid source 118.In some embodiments, an external environment may include an operator or a computer system configured to interface with the fluid source 118, for example.\",\n \"In some embodiments, a user interface may receive a signal from a controller and present the signal in a manner that may be understood by an external environment.\",\n \"In some embodiments, a user interface may receive signals from an external environment and, in response, send signals to a controller.\",\n \"A controller may process the signals received from a user interface and take further action.\",\n \"In some embodiments, a user interface may be a graphical user interface, a touchscreen, or one or more motion tracking devices.\",\n \"A user interface may also include one or more display screens, such as a liquid crystal display (“LCD”), lighting devices, such as light emitting diodes (“LED”) of various colors, and audible indicators, such as a whistle, configured to emit a sound that may be heard by an operator.\",\n \"A user interface may further include one or more devices, such as knobs, buttons, keyboards, remotes, touchscreens, ports that may be configured to receive a discrete or continuous signal from another device, or other similar devices; these devices may be configured to permit the external environment to interact with the user interface 204.A pressure sensor, such as the sensor 206, may be a piezoresistive strain gauge, a capacitive sensor, an electromagnetic sensor, a piezoelectric sensor, an optical sensor, or a potentiometric sensor, for example.\",\n \"In some embodiments, a pressure sensor can measure a strain caused by an applied pressure.\",\n \"A pressure sensor may be calibrated by relating a known amount of strain to a known pressure applied.\",\n \"The known relationship may be used to determine an unknown applied pressure based on a measured amount of strain.\",\n \"In some embodiments, a pressure sensor may include a receptacle configured to receive an applied pressure.\",\n \"In an illustrative embodiment, the sensor 206 may be fluidly coupled to the fluid interface 120 by the tube 123 to receive a pressure from the tube 123.The fluid source 118 may also include a valve 208, a flow meter 209, and a fluid reservoir 210.In some embodiments, the valve 208 may be communicatively coupled to the controller 202, and the valve 208 may be further fluidly coupled between the fluid reservoir 210 and the fluid interface 120.A valve, such as the valve 208, may be a device configured to selectively permit fluid flow through the valve.\",\n \"A valve may be a ball valve, a gate valve, a butterfly valve, or other valve type that may be operated to prevent or permit fluid flow through the valve.\",\n \"Generally, a valve may include a valve body having a flow passage, a valve member disposed in the flow passage and operable to selectively block the flow passage, and an actuator configured to operate the valve member.\",\n \"An actuator may be configured to position the valve member in a closed position, preventing fluid flow through the flow passage of the valve, an open position, permitting fluid flow through the fluid passage of the valve, or a metering position, permitting fluid flow through the flow passage of the valve at a selected flow rate.\",\n \"In some embodiments, the actuator may be a mechanical actuator configured to be operated by an operator.\",\n \"In some embodiments, the actuator may be an electromechanical actuator configured to be operated in response to the receipt of a signal input.\",\n \"For example, the actuator may include an electrical motor configured to receive a signal from a controller, such as the controller 202.In response to the signal, the electrical motor of the actuator may move the valve member of the valve.\",\n \"In some embodiments, the valve 208 may be configured to selectively permit fluid communication between the fluid reservoir 210 and the fluid interface 120 in response to a signal from the controller 202.In this context, the controller 202 may be referred to as: operating the valve; placing the valve 208 in an open position, a closed position, or a metering position; and opening the valve 208, closing the valve 208, or metering the valve 208.In some embodiments, the flow meter 209 may be communicatively coupled to the controller 202, and the flow meter 209 may be further fluidly coupled between the valve 208 and the fluid interface 120.A flow meter, such as the flow meter 209, may be a device configured to determine a fluid flow rate.\",\n \"A flow meter may include a mechanical flow meter, a pressure based flow meter, an optical flow meter, an open channel flow meter, a thermal mass flow meter, a vortex flow meter, electromagnetic, ultrasonic and coriolis flow meters, and laser doppler flow meters.\",\n \"The flow meter 209 may determine a rate of fluid flow through the valve 208 and transmit a signal to the controller 202 corresponding to the determined flow rate.\",\n \"The controller 202 may receive the determined flow rate and determine a total volume of fluid delivered in response.\",\n \"A fluid reservoir, such as the fluid reservoir 210, may be a container for storing or holding fluid.\",\n \"A fluid reservoir may broadly include a canister, pouch, bottle, vial, or other fluid storage apparatus.\",\n \"A fluid reservoir can be used to manage fluid to be delivered to a tissue site.\",\n \"In many environments, a rigid fluid reservoir may be preferred or required for storing and delivering of fluids.\",\n \"In other environments, fluids may be properly stored and delivered without a rigid fluid reservoir.\",\n \"In some embodiments, a fluid reservoir may be a device that is integrated into a fluid source.\",\n \"For example, the fluid reservoir 210 may be an integral component of the fluid source 118.In other embodiments, a fluid reservoir may be a removable component of a fluid source.\",\n \"For example, the fluid reservoir 210 may be removable from the fluid source 118.In still other embodiments, a fluid reservoir may be a separate component from a fluid source that may be fluidly coupled to the fluid source.\",\n \"For example, the fluid reservoir 210 may be a separate device that may be fluidly coupled by a tube to the fluid source 118.In some embodiments, the valve 208 may be fluidly coupled to the fluid interface 120 through the tube 124.Operation of the valve 208 may permit fluid to flow from the fluid reservoir 210 through the tube 124 into the fluid interface 120, where the fluid may be distributed by the manifold 110.In some embodiments, the sensor 206 may be fluidly coupled to the fluid interface 120 through the tube 123.In some embodiments, the tube 123 may fluidly communicate a pressure at the fluid interface 120 to the sensor 206.In some embodiments, the pressure at the fluid interface 120 may be representative of a pressure in the sealed therapeutic environment 103.In some embodiments, the sensor 206 may be an electronic strain gauge sensor that is incorporated into the fluid interface 120.The strain gauge may have a thin piezoresistive film on the drape of the pad which deforms under pressure.\",\n \"The deformation may indicate the pressure in the sealed therapeutic environment 103.In some embodiments, the fluid interface 120 may be communicatively coupled to the controller 202 so that the controller 202 may receive a signal from the strain gauge.\",\n \"In some embodiments, the fluid source 118 may include an instillation pump 212.The instillation pump 212 may be fluidly coupled between the valve 208 and the fluid interface 120 and communicatively coupled to the controller 202.The instillation pump 212 may be operated by the controller 202 in a manner similar to the operation of the valve 208 to provide fluid to the fluid interface 120 and the sealed therapeutic environment 103.In other embodiments, the instillation pump 212 may replace the valve 208.In some embodiments, the instillation pump 212 may be configured to pre-charge a dosage of fluid for delivery to the tissue site 114.For example, the instillation pump 212 may be configured to pressurize a dosage of fluid prior to delivery of fluids so that the fluids may be delivered to the tissue site 114.A dosage of fluid may be the volume of fluid prescribed by a caregiver to treat the tissue site 114 during a cycle of instillation therapy.\",\n \"In some embodiments, the fluid source 118 may also include an instillation sensor 214.The instillation sensor 214 may be fluidly coupled to the tube 124 and communicatively coupled to the controller 202.In some embodiments, the controller 202 may monitor pressure in the tube 124 with the instillation sensor 214.In the event that the instillation sensor 214 sends a signal that deviates from the signal received from the sensor 206, the controller 202 may operate the user interface 204 to indicate a blockage or a leak condition.\",\n \"In operation, the sensor 206 may determine the pressure in the fluid interface 120.As previously described, the pressure in the fluid interface 120 may be representative of the pressure in the sealed therapeutic environment 103.The controller 202 may receive the signal sent by the sensor 206, and in response, the controller 202 may operate the valve 208 and the user interface 204.In some embodiments, the controller 202 may determine that the valve 208 should be in the open position in response to the signal received from the sensor 206.The controller 202 may transmit a signal to the valve 208 to cause the valve 208 to actuate and move from the metering or the closed position to the open position.\",\n \"If the valve 208 is positioned in the open position, fluid may flow from the fluid reservoir 210 into the sealed therapeutic environment through the valve 208, the tube 124, and the fluid interface 120.In some embodiments, the controller 202 may also generate and send a signal to the user interface 204 in response to the signal from the sensor 206.For example, the controller 202 may receive a signal from the sensor 206 corresponding to a particular pressure in the fluid interface 120.In response, the controller 202 may generate and send a signal to the user interface 204.The user interface 204 may receive the signal and, in response, provide a visual or auditory output that may be understood by the external environment.\",\n \"For example, in some embodiments, the user interface 204 may be an LCD.\",\n \"The user interface 204 may receive a signal corresponding to a particular pressure in the fluid interface 120 from the controller 202.The user interface 204 may display the signal on the LCD as a numerical representation of the particular pressure at the fluid interface 120.In some embodiments, the controller 202 may include operational instructions permitting the controller 202 to operate the valve 208 to provide instillation therapy.\",\n \"In some embodiments, the controller 202 may operate the valve 208 in a constant mode.\",\n \"In the constant mode, the fluid source 118 may deliver fluids to the fluid interface 120 without adjustment in response to conditions external to the fluid source 118.For example, the controller 202 may receive a signal from the user interface 204 that corresponds to a selection of the constant mode.\",\n \"In response, the controller 202 may send a signal to the valve 208, placing the valve 208 in the open position.\",\n \"Fluid may flow freely from the fluid reservoir 210 to the fluid interface 120.In some embodiments, the controller 202 may receive a signal from the user interface 204 that corresponds to a selection of the constant mode at a selected flow rate.\",\n \"In response, the controller 202 may send a signal to the valve 208 instructing the valve 208 to move to a metering position corresponding to the selected flow rate.\",\n \"Fluid may flow from the fluid reservoir 210 to the fluid interface 120 at the selected flow rate.\",\n \"In some embodiments, the controller 202 may operate the valve 208 in an intermittent mode.\",\n \"In the intermittent mode, the fluid source 118 may deliver fluid to the tissue site 114 in discrete time periods independent of conditions external to the fluid source 118.For example, the fluid source 118 may provide fluids for a period of one minute followed by a period of one minute where the fluid source 118 provides no fluids.\",\n \"In some embodiments, the controller 202 may receive a signal from the user interface 204 corresponding to a selection of the intermittent mode.\",\n \"In some embodiments, the controller 202 may include pre-determined time periods for a duration of fluid delivery and an interval between fluid delivery for the intermittent mode.\",\n \"In some embodiments, the signal from the user interface 204 may also provide a duration of fluid delivery and a duration of no delivery.\",\n \"In response, the controller 202 may send a signal to the valve 208 to move the valve 208 to the open position, providing fluids and initiating the duration of fluid delivery.\",\n \"When the duration of fluid delivery ends, the controller 202 may send a signal to the valve 208 to move the valve 208 to the closed position, blocking fluid flow and initiating the interval between fluid delivery.\",\n \"When the interval between fluid delivery ends, the controller 202 may send a signal to the valve 208 to move the valve 208 to the open position, providing fluid and initiating the duration of fluid delivery.\",\n \"Opening and closing of the valve 208 may repeat until the instillation therapy concludes.\",\n \"In some embodiments, the controller 202 may receive a signal from the user interface 204 corresponding to a selection of the intermittent mode and a selected flow rate.\",\n \"In response, the controller 202 may send a signal to the valve 208 to move the valve to a metering position corresponding to the selected flow rate during the duration of fluid delivery.\",\n \"In other embodiments, the controller 202 may operate the instillation pump 212 to control the delivery of fluids during the duration of fluid delivery and the interval between fluid delivery.\",\n \"In some embodiments of the intermittent mode, the controller 202 may monitor the flow rate through the valve 208 with the flow meter 209.The controller 202 may operate the valve 208 in response to a total volume of fluid flow through the valve 208.For example, the controller 202 may operate the valve 208, placing the valve 208 in an open position.\",\n \"The controller 202 my monitor the flow rate with the flow meter 209, determining the total volume of fluid delivered while the valve 208 is in the open position.\",\n \"If the total volume of fluid delivered reaches a predetermined total volume of fluid to be delivered, also referred to as a dosage of fluid, the controller 202 may operate the valve 208, moving the valve 208 to the closed position.\",\n \"In some embodiments, the controller 202 may operate the valve 208 in a dynamic mode.\",\n \"During the dynamic mode, the controller 202 may coordinate the delivery of instillation fluid with the delivery of reduced pressure by a reduced-pressure source.\",\n \"For example, the controller 202 may open the valve 208 when reduced pressure is still present in the sealed therapeutic environment 103, which draws fluid from the fluid reservoir 210, through the valve 208 and into the sealed therapeutic environment 103.Using the reduced pressure in a sealed therapeutic environment to draw fluid from the fluid reservoir 210 may simultaneously decrease the reduced pressure in the sealed therapeutic environment 103.As the reduced pressure decreases in the sealed therapeutic environment 103, the rate of fluid flow from the fluid reservoir 210 may also slow down.\",\n \"If the pressure in the sealed therapeutic environment 103 and the ambient pressure proximate the fluid reservoir 210 are approximately the same, fluid flow from the fluid reservoir 210 may stop, thereby avoiding over-pressurizing the sealed therapeutic environment 103 with the instillation fluids.\",\n \"In some embodiments, the controller 202 may monitor the volume of fluid flow through the valve 208 with the flow meter 209.If a predetermined dosage of fluid has been delivered prior to the sealed therapeutic environment 103 reaching ambient pressure, the controller 202 may close the valve 208.In the dynamic mode, the fluid source 118 may provide fluids to the fluid interface 120 in response to operation of the reduced-pressure therapy source 104.In some embodiments, the controller 202 may be programmed to open the valve 208 in response to a particular pressure that may be detected by the sensor 206.In some embodiments, the particular pressure may also be referred to as a trigger pressure (Pt).\",\n \"Generally, if the signal from the sensor 206 corresponds with a pressure that is about equal to the trigger pressure (Pt) following a period of generally static or steady-state reduced pressure, the controller 202 may open the valve 208 in response.\",\n \"If the trigger pressure (Pt) is less than an ambient pressure proximate the fluid reservoir 210, (that is, the trigger pressure (Pt) is a greater reduced-pressure than the ambient pressure), that reduced pressure draws instillation fluid from the fluid reservoir 210 through the valve 208 to the fluid interface 120.In some embodiments, the controller 202 may position the valve 208 in a metering position in response to the trigger pressure (Pt), permitting fluid flow at predefined flow rates.\",\n \"Further detailed operation of the dynamic mode may be described with respect to FIG.\",\n \"4, FIG.\",\n \"5, FIG.\",\n \"6A, FIG.\",\n \"7, and FIG.\",\n \"8.FIG.\",\n \"5 is a graphical representation of the operation of the reduced-pressure therapy system 101 that may be associated with some embodiments.\",\n \"In FIG.\",\n \"5, the y-axis represents the operating state of the reduced-pressure therapy system 101, which may be either in an “on-state” or an “off-state,” and the x-axis represents time.\",\n \"FIG.\",\n \"6A is a graphical representation of a pressure profile 301 (Ps) of the sealed therapeutic environment 103 as measured at the sensor 206 that may be associated with some embodiments.\",\n \"In FIG.\",\n \"6A, the y-axis represents the absolute value of the reduced pressure measured by the sensor 206 at the fluid interface 120, and the x-axis represents time.\",\n \"As previously described, the reduced pressure measured at the fluid interface 120 may be representative of the reduced pressure in the sealed therapeutic environment 103 formed by the tissue site 114 and the drape 108.FIG.\",\n \"7 is a graphical representation of the operation of the valve 208 that may be associated with some embodiments.\",\n \"In FIG.\",\n \"7, the y-axis represents the position of a valve member of the valve 208, which may be in an open position or a closed position in response to the pressure profile 301 (Ps), and the x-axis represents time.\",\n \"FIG.\",\n \"8 is a graphical representation of the operation of the valve 208 that may be associated with other embodiments.\",\n \"In FIG.\",\n \"8, the y-axis represents the position of a valve member of the valve 208, which may be in an open position or a closed position in response to the pressure profile 301 (Ps), and the x-axis represents time.\",\n \"Some or all of FIGS.\",\n \"5, 6A, 7, and 8 include a reference line 302, a reference line 304, a reference line 306, a reference line 308, a reference line 310, a reference line 312, and a reference line 314.The reference lines 302-314 are positioned at the same location of the x-axis in each figure in which the reference lines appear.\",\n \"Thus, the reference lines 302, 304, 306, 308, 310, 312, and 314 align FIG.\",\n \"5, FIG.\",\n \"6A, FIG.\",\n \"7, and FIG.\",\n \"8 to relate the operation of the reduced-pressure source 104 and the fluid source 118 based on the conditions in the sealed therapeutic environment 103.In some embodiments, the reduced-pressure therapy system 101 may be operating in an intermittent mode so that reduced-pressure may be supplied to the sealed therapeutic environment 103 in discrete time increments.\",\n \"As shown in FIG.\",\n \"5, in the intermittent mode of operation, the reduced-pressure source 104 may have a time period in which the reduced-pressure source 104 is operating to provide reduced pressure, such as during “on-state.” The reduced-pressure source 104 may also have a time period in which the reduced-pressure source 104 is not providing reduced pressure, such as during an “off-state.” As described with respect to FIG.\",\n \"5, the on-state represents operation of a pump or other device in the reduced-pressure source 104 to provide reduced pressure to the sealed therapeutic environment 103.The off-state represents a time period in which the reduced-pressure source 104 may be powered on, but it is not providing reduced-pressure to the sealed therapeutic environment 103.As shown in FIG.\",\n \"5, the reduced-pressure source 104 may be turned on at the reference line 302.The reduced-pressure source 104 may be turned off at the reference line 304.Thus, the reduced-pressure source 104 is in an “on-state” 320 between the reference line 302 and the reference line 304 and in an “off-state” 322 between the reference line 304 and the reference line 312.The reduced-pressure source 104 may be turned on at the reference line 312.The reduced-pressure source 104 may be turned off at the reference line 314.Thus, the reduced-pressure source 104 is in an “on-state” 324 between the reference line 312 and the reference line 314 and in an “off-state” 326 after the reference line 314.In FIG.\",\n \"5, the graph representing operation of the reduced-pressure source 104 forms a square wave having a duty cycle represented as the ratio between the off-state 322 and the on-state 320.In some embodiments, the off-state 322 may be twice as long as the on-state 320, that is, a duty cycle or ratio of the off-state 322 to the on-state 320 is 2/1.In other embodiments, the duty cycle may be 1/1, 3/1, 4/1, or other similar ratios.\",\n \"FIG.\",\n \"6A may illustrate the pressure profile 301 (Ps) associated with the pressure at the fluid interface 120.In an illustrative embodiment, the absolute value of the pressure may range from about 0 mm Hg to about 120 mm Hg gauge pressure.\",\n \"As described herein, pressure at about 0 mm Hg may be referred to as an atmospheric pressure or minimum pressure (Pmin), as shown by the dashed line 329.Reduced-pressure at about 120 mm Hg may be referred to as a therapy pressure.\",\n \"The therapy pressure may be set by a caregiver for a maximum pressure (Pmax), as shown by the dashed line 327.At reference line 302, when the reduced-pressure source 104 begins the on-state 320, the pressure profile 301 (Ps) may be about 0 mm Hg.\",\n \"The pressure profile 301 (Ps) increases to a value of about 120 mm Hg during the on-state 320.A slope of the pressure profile 301 (Ps) between the reference line 302 and the reference line 304 as the pressure profile 301 (Ps) increases from about 0 mm Hg to about 120 mm Hg may be referred to as a reduced-pressure ramp-up period 328.The reduced-pressure ramp-up period 328 corresponds to a time interval during which the pressure profile 301 (Ps) increases within the sealed therapeutic environment 103 from an ambient pressure (Pmin) at an inflection point 303 to the maximum pressure (Pmax) at an inflection point 305.The inflection point 303 is located at the intersection of the reference line 302, the dashed line 329, and pressure profile 301 (Ps).\",\n \"The inflection point 305 is located at the intersection of the pressure profile 301 (Ps) and the dashed line 327 between the reference line 302 and the reference line 304.When the sealed therapeutic environment 103 reaches the therapy pressure (Pmax), the reduced-pressure therapy system 101 may be programmed to maintain the therapy pressure (Pmax) for a predetermined period of time.\",\n \"While the reduced-pressure therapy system 101 maintains the therapy pressure (Pmax), the pressure profile 301 (Ps) may have a substantially flat slope for a reduced-pressure therapy period 330.The reduced-pressure therapy period 330 may continue until the reduced-pressure source 104 switches to the off-state 322 at the reference line 304.The reduced-pressure therapy period 330 may be a time interval of steady-state reduced pressure in the sealed therapeutic environment 103.As shown, the reduced-pressure therapy period 330 may extend from the inflection point 305 to the inflection point 307.The inflection point 307 is located at the intersection of the reference line 304, the dashed line 327, and the pressure profile 301 (Ps).\",\n \"In the reduced-pressure therapy period 330, the reduced-pressure source 104 may be operating to maintain the reduced-pressure at about the therapy pressure (Pmax), for example, at about 120 mm Hg.\",\n \"When the reduced-pressure source 104 switches from the on-state 320 to the off-state 322, as shown at the reference line 304 in FIG.\",\n \"5, the pressure profile 301 (Ps) may enter a reduced-pressure ramp-down period 332, as shown in FIG.\",\n \"6A.\",\n \"The reduced-pressure ramp-down period 332 corresponds to a time interval during which the pressure profile 301 (Ps) decreases within the sealed therapeutic environment 103 from the maximum pressure (Pmax) to the minimum pressure (Pmin).\",\n \"As shown in FIG.\",\n \"6A, the reduced-pressure ramp-down period 332 is a portion of the pressure profile 301 (Ps) beginning at the inflection point 307 and ending at an inflection point 309.The inflection point 309 is located at the intersection of the pressure profile 301 (Ps) and the dashed line 329.As the reduced pressure profile 301 (Ps) decreases during the reduced-pressure ramp-down period 332, the pressure profile 301 (Ps) may reach the trigger pressure (Pt).\",\n \"The trigger pressure (Pt) represented by the dashed line 334.If the pressure profile 301 (Ps) reaches the trigger pressure (Pt), instillation of fluids may commence as shown by the reference line 306.In some embodiments, the trigger pressure (Pt) may be set during the manufacturing process.\",\n \"When the pressure profile 301 (Ps) reaches about 0 mm Hg, the slope of the pressure profile 301 (Ps) may remain substantially flat in a soak period 336.The soak period 336 may correspond with a time interval during which there is no reduced-pressure therapy.\",\n \"The soak period 336 extends from the inflection point 309 to an inflection point 311.The inflection point 311 is located at the intersection of the reference line 312, the dashed line 329 and the pressure profile 301 (Ps).\",\n \"Eventually, the reduced-pressure therapy may resume at the inflection point 311 when the reduced-pressure source 104 returns to the on-state 324.Instillation of fluids, which commenced at the reference line 306 may continue to the reference line 308 as described below with respect to FIG.\",\n \"7.Continued operation of the reduced-pressure source 104 may cause the pressure profile 301 (Ps) illustrated in FIG.\",\n \"6A to cyclically repeat.\",\n \"A second cycle may commence with the on-state 324 of the reduced-pressure source 104 initiating a reduced-pressure ramp-up period 341 and a reduced-pressure therapy period 343.The second cycle may have an off-state 326, initiating a reduced-pressure ramp-down period 345 and concluding at the end of a soak period 349.As further illustrated, the pressure profile 301 (Ps) of FIG.\",\n \"6A appears to lag relative to the operation of the reduce-pressure source 104 illustrated in FIG.\",\n \"5.The lag may occur due to a period of time required for the pressure in the sealed therapeutic environment 103 to respond to the operation of the reduced-pressure source 104.In other embodiments, the pressure profile 301 (Ps) of FIG.\",\n \"6A may not lag the operation of the reduced-pressure source 104.As described with respect to FIG.\",\n \"6A and FIG.\",\n \"7, the dynamic mode of the instillation therapy system 116 and the fluid source 118 may be configured to operate in coordination with the operation of the reduced-pressure therapy system 101 and the reduced-pressure source 104.In the dynamic mode, the controller 202 may know the pressure profile 301 (Ps) and the trigger pressure (Pt) as illustrated in FIG.\",\n \"6A.\",\n \"In some embodiments, the controller 202 may determine the pressure profile 301 (Ps) and the trigger pressure (Pt) in a training mode.\",\n \"In some embodiments, a caregiver may provide the pressure profile 301 (Ps) and the trigger pressure (Pt) through the user interface 204.In an illustrative embodiment, the controller 202 may monitor the pressure profile 301 (Ps) through the sensor 206 to provide instillation therapy.\",\n \"In some embodiments, the controller 202 may close the valve 208 until the pressure profile 301 (Ps) reaches the trigger pressure (Pt) following the reduced-pressure therapy period 330.When the pressure profile 301 (Ps) reaches the trigger pressure (Pt) the controller 202 may open the valve 208, as shown by reference line 306.The controller 202 may then monitor the fluid flow through the valve 208 with the flow meter 209.When the dosage has passed through the valve 208, the controller 202 may close the valve 208 as shown at the reference line 308.The dosage of fluid may remain within the sealed therapeutic environment 103 until the reduced-pressure ramp-up period 341 begins at the inflection point 309.As the on-state 324 of the reduced-pressure source 104 causes the pressure profile 301 (Ps) to increase, the fluid delivered during the instillation of fluids may be removed through the tube 109 to the container 112.In some embodiments, the flow rate through the valve 208 may not be sufficient to deliver the dosage of fluid prior to the repetition of the duty cycle of the reduced-pressure source 104.In response, the controller 202 may close the valve 208 prior to the repetition of the duty cycle of the reduced-pressure source 104.For example, if the valve 208 is still open, the controller 202 may close the valve 208 at the reference line 312.If the dosage of fluid is not fully delivered based on the initial trigger pressure (Pt), the controller 202 may adjust the trigger pressure (Pt) to increase the time for fluid flow.\",\n \"For example, if the initial trigger pressure (Pt) is about 75 mm Hg reduced pressure and the controller 202 determines that the full dosage of fluid could not be delivered prior to the inflection point 311, the controller 202 may reset the trigger pressure (Pt) to 80 mm Hg reduced pressure as indicated by the dashed line 334a.\",\n \"The pressure profile 301 (Ps) reaches the trigger pressure (Pt) 334a sooner than the trigger pressure (Pt) 334.In response, the controller 202 may open the valve 208 sooner as indicated by the reference line 310, increasing the dosage period.\",\n \"In this manner, the controller 202 may adjust instillation to provide a complete dosage of fluid to the sealed therapeutic environment 103.FIG.\",\n \"6B is a graphical representation of the pressure profile 301 (Ps) of the sealed therapeutic environment 103 that may be associated with some embodiments.\",\n \"In FIG.\",\n \"6B, the y-axis represents the absolute value of the reduced pressure measured by the sensor 206 at the fluid interface 120, and the x-axis represents time.\",\n \"In some embodiments, the controller 202 may operate in a training mode to determine the pressure profile 301 (Ps) and the duty cycle of the reduced-pressure source 104.In the training mode, the controller 202 may send a signal to the valve 208 to move the valve 208 to the closed position.\",\n \"The controller 202 may monitor a signal received from the sensor 206.In some embodiments, the sensor 206 may send a continuing signal that corresponds to an instantaneous pressure in the sealed therapeutic environment 103.An instantaneous pressure may refer to a pressure at the moment at which the pressure is measured.\",\n \"In some embodiments, the signal sent by the sensor 206 may reflect the pressure profile 301 (Ps) displayed graphically in FIG.\",\n \"6B.\",\n \"The controller 202 may monitor the signal from the sensor 206 for at least one duty cycle of the reduced-pressure source 104.The controller 202 may store the signal received from the sensor 206 at the initiation of the dynamic mode.\",\n \"The controller 202 may monitor the signal from the sensor 206 and compare pressures to determine the pressure profile 301 (Ps).\",\n \"For example, the controller 202 may record a reduced pressure received from the sensor 206 at a first instant in time, such as a time 402.The controller 202 may then record a reduced pressure received from the sensor 206 at a second instant in time, such as a time 404.The controller 202 may compare the reduced pressure at the time 402 and the time 404.If the reduced pressure at the time 404 is greater than the reduced pressure at the time 402, the controller 202 may store the reduced pressure at time 404 as the maximum reduced pressure (Pmax).\",\n \"The reduced pressure at the time 404, may then be compared to a reduced pressure at a third instant in time, for example, a time 406.The process may repeat until a reduced pressure at a later instant in time is not greater than the reduced pressure at the previous instant in time.\",\n \"If a subsequent reduced pressure is greater than an immediately prior reduced pressure, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure ramp-up period 328 of FIG.\",\n \"6B.\",\n \"In some embodiments, comparisons between pressures may occur at multiple instances between each time shown.\",\n \"If the reduced pressure at the second instant in time is about the same as the reduced pressure at the first instant in time, such as at the time 406 and a time 408, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure therapy period 330 or the soak period 336.The reduced pressure at the time 406 and the time 408 may then be compared to the maximum reduced pressure (Pmax), and if the reduced pressure at the time 406 and the time 408 is about the same as the maximum reduced pressure (Pmax), the controller 202 may determine that the reduced pressure profile 301 (Ps) is in the reduced-pressure therapy period 330.If the reduced pressure at the second instant in time is less than the reduced pressure at the first instant in time, such as at the time 408 and a time 410, the controller 202 may store the reduced pressure at the time 410 as the minimum reduced pressure (Pmin).\",\n \"The reduced pressure at the time 410 may then be compared to a reduced pressure at a third instant in time, repeating the process until a reduced pressure at a later instant in time is not less than the reduced pressure at the previous instant in time.\",\n \"If a subsequent reduced pressure is less than an immediately prior reduced pressure, such as at the time 410 and a time 412, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure ramp-down period 332 of FIG.\",\n \"6B.\",\n \"If the reduced pressure at the second instant in time is about the same as the reduced pressure at the first instant in time, such as at a time 414 and a time 416, the controller 202 may determine that the pressure profile 301 (Ps) is in the reduced-pressure therapy period 330 or the soak period 336.The reduced pressure at the time 414 and the time 416 may then be compared to the minimum reduced pressure (Pmin), and if the reduced pressure at the time 414 and the time 416 is about the same as the minimum reduced pressure (Pmin), the controller 202 may determine that the pressure profile 301 (Ps) is in the soak period 336 of FIG.\",\n \"6B.\",\n \"The controller 202 may continue to monitor the signal from the sensor 206, following the process previously described.\",\n \"If the controller 202 determines that the pressure profile 301 (Ps) is repeating, for example, the controller 202 repeatedly identifies the same maximum reduced pressure (Pmax) and minimum reduced pressure (Pmin) at about the same time intervals, the controller 202 may exit the training mode.\",\n \"During the time in which the controller 202 monitors the signal from the sensor 206, the controller 202 may store the pressure profile 301 (Ps) in a memory of the controller 202.The controller 202 may also store time intervals between the maximum reduced pressure (Pmax) and minimum reduced pressure (Pmin) to determine the on-state 320, the on-state 324, the off state 322, and the off-state 326 of the reduced-pressure source 104.The controller 202 may then determine one or more parameters of the reduced-pressure therapy as described above.\",\n \"In some embodiments, the parameters may include the maximum pressure (Pmax) in the sealed therapeutic environment 103 and the minimum pressure (Pmin) in the sealed therapeutic environment 103.In some embodiments, the controller 202 may calculate an expected trigger pressure (Pt) based on the measured time intervals between the on-states 320/324 of the reduced-pressure source 104 and an expected flow rate through the valve 208.In some embodiments, the controller 202 may provide a signal to the user interface 204 so that the parameters may be displayed on the user interface 204.In some embodiments, the external environment may interact with the user interface 204 to override and replace the parameters determined from the training mode.\",\n \"In some embodiments, the controller 202 may store an expected reduced-pressure ramp-down period 332.For example, the controller 202 may determine an expected slope of the pressure profile 301 (Ps) during the reduced-pressure ramp-down period 332 when fluid is being supplied to the sealed therapeutic environment 103.The controller 202 may monitor the signal from the sensor 206 during the reduced-pressure ramp-down period 332.During instillation therapy, the actual reduced-pressure ramp-down period 332 may deviate from the expected reduced-pressure ramp-down period 332 while providing a dosage of fluid.\",\n \"A deviation of the reduced-pressure ramp-down period 332 may indicate that the fluid flow through the fluid interface 120 consists of an unexpected fluid, for example a gas rather than an instillation fluid.\",\n \"If a gas is flowing through the fluid interface 120, the fluid reservoir 210 may be empty.\",\n \"If the actual reduced-pressure ramp-down period 332 deviates from the expected reduced-pressure ramp-down period 332, the controller 202 may signal the user interface 204 to display an alarm indicating that the fluid reservoir 210 may be empty.\",\n \"FIG.\",\n \"9 illustrates a flow chart 900 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.\",\n \"1, which may be implemented in accordance with an embodiment.\",\n \"The system receives a signal from a user interface at block 902.For example, the controller 202 may receive a signal from the user interface 204.Next, at block 904, the system may determine whether the signal represents a selection of a constant mode.\",\n \"Illustratively, the controller 202 may determine if the signal represents a selection of the constant mode.\",\n \"If the system determines that the signal represents a selection of the constant mode at block 904 (YES), the system operates in the constant mode to deliver fluids for a predetermined period of time at block 906.For example, the controller 202 may open the valve 208, permitting fluid flow from the fluid reservoir 210 to the sealed therapeutic environment 103.If the system determines that the signal does not represent a selection of the constant mode at block 904 (NO), the system determines if the signal represents a selection of the intermittent mode.\",\n \"For example, the controller 202 determines if the signal represents a selection of the intermittent mode.\",\n \"If the system determines that the signal represents a selection of the intermittent mode at block 908 (YES), the system operates in the intermittent mode such that a predetermined number of dosages may be delivered to the sealed therapeutic environment 103 over a predetermined period of time at block 909.If the system determines that the signal does not represent a selection of the intermittent mode at block 908 (NO), the system determines if the signal represents a selection of the dynamic mode at block 910.If the system determines the signal represents a selection of the dynamic mode at block 910 (YES), the system operates in the training mode at block 912 after which the system operates in the dynamic mode to deliver fluids at block 914 for a predetermined period of time.\",\n \"For example, the controller 202 may operate in the training mode and then the controller 202 may deliver fluids in accordance with the pressure profile 301 (Ps) determined in the training mode of block 912.FIG.\",\n \"10 illustrates a flow chart 1000 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.\",\n \"1 during the intermittent mode, which may be implemented in accordance with an embodiment.\",\n \"In an illustrative embodiment, the system determines if the system received a selection of a duration of fluid delivery at block 1002.For example, the controller 202 may determine if the user interface 204 received a selection of a duration of fluid delivery.\",\n \"If the system determines that no duration of fluid delivery was selected at block 1002, the system delivers fluids for a pre-determined duration of fluid delivery at block 1004.For example, the controller 202 may open the valve 208 for a predetermined duration of fluid delivery, such as one minute.\",\n \"The system stops delivering fluids for a predetermined interval between fluid delivery at block 1006.For example, the controller 202 may close the valve 208 for a predetermined interval between fluid delivery, such as 1 minute.\",\n \"The system then determines whether a predetermined number of on-off cycles has occurred at block 1007.If a predetermined number of on-off cycles has not occurred at block 1007 (NO), the system repeats beginning at block 1004.If a predetermined number of on-off cycles has occurred at block 1007 (YES), the intermittent mode ends.\",\n \"If the system determines that a duration of fluid delivery was selected at block 1002 (YES), the system determines if an interval between fluid delivery was selected at block 1008.If the system determines that an interval between fluid delivery was selected at block 1008 (YES), the system delivers fluids for the selected duration of fluid delivery at block 1010 and stops delivering fluids for the interval between fluid delivery at block 1012.For example, the controller 202 may open the valve 208 for a selected duration of fluid delivery received through the user interface 204, such as two minutes and the controller 202 may close the valve 208 for a selected interval between fluid delivery, such as three minutes.\",\n \"The system then determines whether a predetermined number of on-off cycles has occurred at block 1014.If a predetermined number of on-off cycles has not occurred at block 1014 (NO), the system repeats beginning at block 1010.If a predetermined number of on-off cycles has occurred at block 1014 (YES), the intermittent mode ends.\",\n \"If the system determines that no interval between fluid delivery was selected at block 1008 (NO), the system delivers fluids for the selected duration of fluid delivery at block 1016 and stops delivering fluids for a predetermined interval between fluid delivery at block 1018.For example, the controller 202 may open the valve 208 for a selected duration of fluid delivery received through the user interface 204, such as two minutes, and the controller 202 may close the valve 208 for a predetermined interval between fluid delivery, such as two minutes.\",\n \"The system then determines whether a predetermined number of on-off cycles has occurred at block 1020.If a predetermined number of on-off cycles has not occurred at block 1020 (NO), the system repeats beginning at block 1016.If a predetermined number of on-off cycles has occurred at block 1020 (YES), the intermittent mode ends.\",\n \"FIG.\",\n \"11 illustrates a flow chart 1100 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.\",\n \"1 during the training mode, which may be implemented in accordance with an embodiment.\",\n \"The system closes a valve at block 1102.For example, the controller 202 may close the valve 208.The system monitors the pressure at the tissue site at block 1104.For example, the controller 202 monitors the signal representing the pressure from the sensor 206.The system determines a cyclical pressure profile at the tissue site at block 1106.For example, the controller 202 may determine the pressure profile 301.The system may determine a maximum pressure, a minimum pressure, and the time intervals for the on period and the off period of the duty cycle of the reduced-pressure source at block 1108.For example, the controller 202 may determine a maximum pressure (Pmax), a minimum pressure (Pmin), and the time interval of the on-states 320/324 and the off-states 322/326 of the reduced-pressure source 104.FIG.\",\n \"12 illustrates a flow chart 1200 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.\",\n \"1 during fluid delivery in the dynamic mode, which may be implemented in accordance with an embodiment.\",\n \"The system monitors the pressure at the tissue site at block 1202.For example, the controller 202 monitors the signal from the sensor 206 representing the pressure in the sealed therapeutic environment 103.The system determines if the trigger pressure has been reached at block 1204.For example, the controller 202 may determine if the trigger pressure 334 (Pt) has been reached by the pressure profile 301 (Ps).\",\n \"If the system determines that the trigger pressure has not been reached at block 1204 (NO), the system continues to monitor the pressure at the tissue site.\",\n \"If the system determines that the trigger pressure has been reached at block 1204 (YES), the system delivers fluids at block 1206.For example, the controller 202 opens the valve 208 to permit fluid flow to the sealed therapeutic environment 103.The system monitors fluid flow at block 1208.For example, the controller 202 monitors the signal from the flow meter 209 representing the fluid flow through the valve 208.The system determines if a full fluid dosage has been delivered at block 1209.For example, the controller 202 determines if the full dosage of fluid has passed through the valve 208.If the system determines that the full fluid dosage has not been delivered at block 1209 (NO), the system determines whether the reduced-pressure source is entering an on period at block 1210.For example, the controller 202 may monitor how long the reduced-pressure source 104 has been in the off-state 322 to determine if the reduced-pressure source 104 is about to enter the on-state 324.If the system determines that the reduced-pressure source is not entering an on-state at block 1210 (NO), the system continues delivering fluids at block 1206.If the system determines that the reduced-pressure source is entering an on-state at block 1210 (YES), the system increments the trigger pressure at block 1211, and the system stops delivering fluids at block 1212.For example, the controller 202 may adjust the trigger pressure to begin fluid delivery at a higher reduced pressure and close the valve 208.If the system determines that the full dosage of fluid has been delivered at block 1209 (YES), the system stops delivering fluids at block 1212.For example, the controller 202 may close the valve 208, stopping fluid delivery.\",\n \"The system determines whether a predetermined number of on-off cycles of fluid delivery has been completed at block 1214.If the system determines that a predetermined number of on-off cycles of fluid delivery has been completed at block 1214 (YES), the process ends.\",\n \"If the system determines that a predetermined number of on-off cycles of fluid delivery has not been completed at block 1214 (NO), the system repeats beginning at block 1202.FIG.\",\n \"13 illustrates a flow chart 1300 that depicts logical operational steps performed by, for example, the instillation therapy system 116 of FIG.\",\n \"1 during fluid delivery, which may be implemented in accordance with an embodiment.\",\n \"In the illustrated flow chart, the instillation therapy system 116 may determine if the fluid reservoir 210 is empty.\",\n \"The system monitors the pressure at the tissue site at block 1302.For example, the controller 202 monitors the signal from the sensor 206 representing the pressure in the sealed therapeutic environment 103.The system determines if a reduced-pressure ramp-down period is the expected reduced-pressure ramp-down period at block 1304.For example, the controller 202 may determine if a reduced-pressure ramp-down period is the expected reduced-pressure ramp-down period 332.If the system determines that the reduced-pressure ramp-down period is the expected reduced-pressure ramp-down period at block 1304 (YES), the system repeats at block 1302.If the system determines that the reduced-pressure ramp-down period is not the expected reduced-pressure ramp-down period 332, the system indicates an empty fluid reservoir at block 1306 and ends.\",\n \"For example, the controller 202 may activate an alarm on the user interface 204 indicating an empty fluid reservoir 210.The systems and methods described herein may provide significant advantages, some of which have already been mentioned.\",\n \"For example, the instillation therapy system may provide a combined reduced-pressure therapy and instillation therapy system that may be simple to set-up.\",\n \"The instillation therapy system may also provide an instillation system that may be used with an independent reduced-pressure system that may be capable of intermittent therapy.\",\n \"The instillation therapy system may also use the reduced-pressure source as the mechanism to draw the fluid to the sealed therapeutic environment, allowing the instillation therapy system to use simpler components.\",\n \"The instillation therapy system may also overcome a head pressure differential.\",\n \"The instillation therapy system may provide feedback on critical parameters related to the performance of a reduced-pressure source regarding the level of reduced-pressure delivered to a sealed therapeutic environment.\",\n \"The instillation therapy system may be configured manually, or through a training mode.\",\n \"The instillation therapy system can also deliver fluid in sync with an intermittent reduced-pressure cycle or in a continuous manner or variations in between.\",\n \"It should be apparent from the foregoing that an invention having significant advantages has been provided.\",\n \"While shown in only a few forms, the systems and methods illustrated are susceptible to various changes and modifications without departing from the spirit thereof.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874749"}}},{"rowIdx":4494686,"cells":{"text":{"kind":"list like","value":[["Linear Solid-State Lighting With Low Voltage Control Free Of Electric Shock And Fire Hazard","A linear light-emitting diode (LED) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, and at least two pairs of electrical contacts controlled by the at least two proximity sensors, is used to replace a fluorescent tube or a conventional LED tube lamp.","The at least two proximity sensors and the at least two pairs of electrical contacts configured to respectively perform proximity sensing between the two lamp bases and two sockets in an existing lamp fixture are operated by using a low DC voltage.","When both two lamp bases are inserted in the two sockets, the at least two pairs of electrical contacts are driven to make an electrical coupling between the full-wave rectifier and the LED driving circuit."],["1.A linear light-emitting diode (LED) tube lamp, comprising: a housing having two ends; at least one LED printed circuit board (LED PCB) disposed between the two ends of the housing, the at least one LED PCB comprising one or more LED arrays disposed thereon; two lamp bases respectively connected to the two ends of the housing, each lamp base comprising a magnetic proximity sensor pair and at least one electrical conductor configured to connect to a lamp fixture socket that is wired to connect to either alternate current (AC) mains or ballasts; a controller comprising a first full-wave rectifier configured to convert an input AC voltage into a direct current (DC) voltage, a set of voltage dividers and regulators configured to convert the DC voltage into a low DC voltage, a switch control unit coupled to receive signals from the magnetic proximity sensor pair in each lamp base, and at least one switch controlled by the switch control unit; and an LED driving circuit configured to receive the DC voltage and to return an electric current via the at least one switch enabled by the controller so as to drive and to light up the one or more LED arrays; wherein: the low DC voltage is configured to operate the magnetic proximity sensor pair in each lamp base; when either one of the two lamp bases is out of the lamp fixture socket, the at least one switch disables an electric current flow from the LED driving circuit, thereby disconnecting an electric shock current returned from the one or more LED arrays to reach the at least one full-wave rectifier; and when the at least one electrical conductor in each lamp base is inserted into the respective lamp fixture socket, the controller enables the LED driving circuit to deliver electrical power to the one or more LED arrays.","2.The linear LED tube lamp of claim 1, wherein the LED driving circuit comprises a second full-wave rectifier configured to receive the DC voltage from the first full-wave rectifier and to operate the one or more LED arrays.","3.The linear LED tube lamp of claim 1, wherein the controller further comprises a diode configured to block an electric current backward flowing to the first full-wave rectifier.","4.The linear LED tube lamp of claim 1, wherein the at least one switch comprises a metal-oxide-semiconductor field-effect transistor (MOSFET), a transistor, a back-to-back thyristor, a silicon-controlled rectifier (SCR), a relay, or a combination thereof.","5.The linear LED tube lamp of claim 1, wherein the low DC voltage meets voltage requirements of a Class 2 circuit.","6.The linear LED tube lamp of claim 1, wherein the switch control unit comprises a transistor configured to control the at least one switch turning on and off.","7.The linear LED tube lamp of claim 1, wherein the switch control unit comprises a logic circuit configured to receive signals from the magnetic proximity sensor pair in each lamp base and to control the at least one switch turning on and off.","8.The linear LED tube lamp of claim 7, wherein the logic circuit comprises one or more logic gates.","9.The linear LED tube lamp of claim 8, wherein the one or more logic gates are implemented by one or more transistors.","10.The linear LED tube lamp of claim 1, wherein the magnetic proximity sensor pair in each lamp base comprises a magnet and a Hall effect sensor.","11.The linear LED tube lamp of claim 10, wherein the magnetic proximity sensor pair in each lamp base operates when the respective magnet is in close proximity to the respective Hall effect sensor.","12.A linear light-emitting diode (LED) tube lamp, comprising: a housing having two ends; two lamp bases respectively connected to the two ends of the housing, each lamp base comprising a displacement sensor, at least one pair of electrical contacts controlled by the displacement sensor, and at least one electrical conductor configured to connect to a lamp fixture socket that is wired to connect to either alternate current (AC) mains or ballasts; a full-wave rectifier connected to the at least one electrical conductor in each lamp base and configured to convert an input AC voltage into a direct current (DC) voltage; at least one LED printed circuit board (LED PCB) disposed between the two ends of the housing, the at least one LED PCB comprising one or more LED arrays disposed thereon; and an LED driving circuit comprising an input filter, one or more start-up resistors, a driver comprising a low voltage input, and an electrical jumper pair, the one or more start-up resistors configured to provide a low DC voltage to couple to the low voltage input of the driver via the electrical jumper pair, wherein: the at least one pair of electrical contacts in each of the two lamp bases are connected in series and connected to the electrical jumper pair so as to loop between the one or more start-up resistors and the low voltage input of the driver; when either one of the at least one pair of electrical contacts are not electrically connected, a through-lamp electric shock current does not flow into the driver; and when the at least one electrical conductor in each of the two lamp bases is inserted into the lamp fixture socket, the at least one pair of electrical contacts are actuated by the displacement sensor in each lamp base to deliver the low DC voltage to the driver, thereby operating the driver and powering the one or more LED arrays.","13.The linear LED tube lamp of claim 12, wherein the driver further comprises a high voltage input configured to receive a filtered DC voltage from the input filter, a power factor correction (PFC) and control device, a switch controlled by the PFC and control device, a current sensing resistor, a diode, an inductor with current charging and discharging thereof controlled by the switch, a resistor, an output capacitor in parallel with the resistor and connected to the inductor to build up an output voltage and to power the one or more LED arrays, and a voltage feedback module coupled to draw partial power from the output voltage to sustain an operation of the PFC and control devices, and wherein, responsive to detecting zero current in the inductor within an AC cycle of the input voltage, the PFC and control device generates a zero current detection signal to control the switch turning on and off.","14.The linear LED tube lamp of claim 13, wherein the voltage feedback module comprises a diode.","15.The linear LED tube lamp of claim 13, wherein the switch in the driver operates at a switching frequency greater than or equal to 45 KHz.","16.The linear LED tube lamp of claim 13, wherein the inductor in the driver is of an autotransformer type.","17.The linear LED tube lamp of claim 13, wherein the inductor in the driver is part of a transformer.","18.The linear LED tube lamp of claim 13, wherein the PFC and control device operates in a range approximately between 11 V and 35 VDC."],["<SOH> BACKGROUND <EOH>"],["<SOH> SUMMARY <EOH>A linear light-emitting diode (LED)-based solid-state tube (LLT) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, at least one conductor protruding outwards from each lamp base, and at least two pairs of electrical contacts controlled by the at least two proximity sensors, is used to replace a fluorescent tube or a conventional LED tube lamp without the at least two proximity sensors and the at least two pairs of electrical contacts.","The at least two proximity sensors and the at least two pairs of electrical contacts are configured to respectively perform proximity sensing between the two lamp bases and two sockets in an existing lamp fixture.","When both two lamp bases are inserted in the two sockets, the at least two pairs of electrical contacts are driven by the at least two proximity sensors to make an electrical connection between the full-wave rectifier and the LED driving circuit, rather than between an alternate current (AC) voltage input and the full-wave rectifier, to power the LED driving circuit and the one or more LED arrays.","When either one of the two lamp bases is not inserted in one of the two sockets, the at least two pairs of electrical contacts are disabled so as to disconnect a direct current (DC) current flow from the full-wave rectifier to the LED driving circuit.","Without such DC current flowing to power the LED driving circuit, a substantial through-lamp electric shock current is considered not to exist.","Furthermore, the at least two pairs of electrical contacts are interconnected between the full-wave rectifier and the LED driving circuit, the DC voltage provided to the LED driving circuit can be made small by using a voltage divider.","In such a case, no high voltage at a high frequency from a ballast is present at any open/closed electrical contacts in the LLT lamp, thus no internal fire possible.","The scheme can effectively reduce a risk of electric shock and a fire hazard to users during relamping or maintenance.","In one embodiment, the LLT lamp further comprises at least two magnets and at least two Hall effect sensors configured to form at least two magnetic proximity sensor pairs at the two ends of the LLT lamp and to provide a non-contact actuation of the at least two pairs of electrical contacts.","When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.","In this case, both the at least two pairs of electrical contacts are electrically connected by the non-contact actuation of the at least two magnetic proximity sensor pairs, whereas a low DC voltage is applied to the LED driving circuit to control a substantial electric current to flow into the one or more LED arrays.","However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.","In this case, the respective one of the at least two magnetic proximity sensor pairs associated with the exposed lamp base is not actuated with respective one of the at least two electrical contacts not electrically connected.","Because the at least two electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.","No substantial electric shock current can possibly be leaked out of exposed at least one electrical conductor.","In other words, once the at least one electrical conductor is exposed during relamping, the driving circuit will not receive a proper voltage to operate.","Thus, an overall through-lamp electric shock current may be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.","A controlling electronic circuit, which only supports an actuation of an electronic switch, indeed, has a much smaller power consumption than the one or more LED arrays do.","Experimental results show that such a through-lamp electric shock current not going through the one or more LED arrays can be controlled to an acceptable level according to a safety standard UL 935.In another embodiment, the LLT lamp may further comprise at least two displacement sensors configured to sense if the two ends of the LLT lamp are between the two sockets in the fixture.","When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.","In this case, both the at least two pairs of electrical contacts are electrically connected by an actuation of displacement sensors, whereas a low DC voltage is applied to the LED driving circuit, controlling electric current to flow into the one or more LED arrays.","However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.","In this case, the respective one of the at least two displacement sensors associated with the exposed lamp base is not actuated with respective one of the at least two pairs of electrical contacts not electrically connected.","Because at least two pairs of electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.","No substantial electric shock current can possibly be leaked out of the exposed at least one electrical conductor.","In other words, once the at least one electrical conductor is exposed during relamping, the LED driving circuit will not receive a proper voltage to operate.","Thus, an overall through-lamp electric shock current can be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.","Furthermore, the use of the low DC voltage in controlling electrical contacts to be on or off has one of unique advantages.","That is, no matter whether AC sources is AC mains from an electrical grid or power supplies from various ballasts, no significant arc can be observed due to a low DC current associated with the low DC voltage.","In other words, an internal arcing and firing will never occur using this approach, thus eliminating any internal fire hazard and enhancing operation reliability."],["CROSS-REFERENCE TO RELATED APPLICATIONS The present disclosure is part of a continuation-in-part (CIP) application of U.S. patent application Ser.","No.","15/836,170, filed 8 Dec. 2017, which is a CIP application of U.S. patent application of Ser.","No.","15/649,392 filed 13 Jul.","2017, which is a CIP application of U.S. patent application Ser.","No.","15/444,536, filed 28 Feb. 2017 and issued as U.S. Pat.","No.","9,826,595 on 21 Nov. 2017, which is a CIP application of U.S. patent application Ser.","No.","15/362,772, filed 28 Nov. 2016, which is a CIP application of U.S. patent application Ser.","No.","15/225,748, filed 1 Aug. 2016 and issued as U.S. Pat.","No.","9,743,484 on 22 Aug. 2017, which is a CIP application of U.S. patent application Ser.","No.","14/818,041, filed 4 Aug. 2015 and issued as U.S. Pat.","No.","9,420,663 on 16 Aug. 2016, which is a CIP application of U.S. patent application Ser.","No.","14/688,841, filed 16 Apr.","2015 and issued as U.S. Pat.","No.","9,288,867 on 15 Mar.","2016, which is a CIP application of U.S. patent application Ser.","No.","14/465,174, filed 21 Aug. 2014 and issued as U.S. Pat.","No.","9,277,603 on 1 Mar.","2016, which is a CIP application of U.S. patent application Ser.","No.","14/135,116, filed 19 Dec. 2013 and issued as U.S. Pat.","No.","9,163,818 on 20 Oct. 2015, which is a CIP application of U.S. patent application Ser.","No.","13/525,249, filed 15 Jun.","2012 and issued as U.S. Pat.","No.","8,749,167 on 10 Jun.","2014.Contents of the above-identified applications are incorporated herein by reference in their entirety.","BACKGROUND Technical Field The present disclosure relates to linear light-emitting diode (LED) lamps and more particularly to a linear LED lamp with a low voltage control configured to eliminate electric arcing that may cause internal fire when used with ballasts and to prevent electric shock current from reaching ground through a person's body when used with AC mains.","Description of the Related Art Solid-state lighting from semiconductor light-emitting diodes (LEDs) has received much attention in general lighting applications today.","Because of its potential for more energy savings, better environmental protection (no hazardous materials used), higher efficiency, smaller size, and much longer lifetime than conventional incandescent bulbs and fluorescent tubes, the LED-based solid-state lighting will be a mainstream for general lighting in the near future.","As LED technologies develop with the drive for energy efficiency and clean technologies worldwide, more families and organizations will adopt LED lighting for their illumination applications.","In this trend, the potential safety concerns such as risk of electric shock and fire become especially important and need to be well addressed.","In today's retrofit application of a linear LED tube (LLT) lamp to replace an existing fluorescent tube, consumers may choose either to adopt a ballast-compatible LLT lamp with an existing ballast used to operate the fluorescent tube or to employ an AC mains-operable LED lamp by removing/bypassing the ballast.","Either application has its advantages and disadvantages.","In the former case, although the ballast consumes extra power, it is straightforward to replace the fluorescent tube without rewiring, which consumers may have a first impression that it is the best alternative to fluorescent tube lamps.","But the fact is that total cost of ownership for this approach is high regardless of very low initial cost.","For example, the ballast-compatible LLT lamps work only with particular types of ballasts.","If the existing ballast is not compatible with the ballast-compatible LLT lamp, the consumers will have to replace the ballast.","Some facilities built long time ago incorporate different types of fixtures, which requires extensive labor for both identifying ballasts and replacing incompatible ones.","Moreover, a ballast-compatible LLT lamp can operate longer than the ballast.","When an old ballast fails, a new ballast will be needed to replace in order to keep the ballast-compatible LLT lamps working.","Maintenance will be complicated, sometimes for lamps and sometimes for ballasts.","The incurred cost will preponderate over the initial cost savings by changeover to the ballast-compatible LLT lamps for hundreds of fixtures throughout a facility.","When the ballast in a fixture dies, all the ballast-compatible tube lamps in the fixture go out until the ballast is replaced.","In addition, replacing a failed ballast requires a certified electrician.","The labor costs and long-term maintenance costs will be unacceptable to end users.","From energy saving point of view, a ballast constantly draws power, even when the ballast-compatible LLT lamps are dead or not installed.","In this sense, any energy saved while using the ballast-compatible LLT lamps becomes meaningless with the constant energy use by the ballast.","In the long run, ballast-compatible LLT lamps are more expensive and less efficient than self-sustaining AC mains-operable LLT lamps.","On the contrary, an AC mains-operable LLT lamp does not require a ballast to operate.","Before use of an AC mains-operable LLT lamp, the ballast in a fixture must be removed or bypassed.","Removing or bypassing the ballast does not require an electrician and can be replaced by end users.","Each AC mains-operable LLT lamp is self-sustaining.","If one AC mains-operable tube lamp in a fixture goes out, other lamps in the fixture are not affected.","Once installed, the AC mains-operable LLT lamps will only need to be replaced after 50,000 hours.","In view of above advantages and disadvantages of both ballast-compatible LLT lamps and AC mains-operable LLT lamps, it seems that market needs a most cost-effective solution by using a universal LLT lamp that can be used with the AC mains and is compatible with a ballast so that LLT lamp users can save an initial cost by changeover to such a universal LLT lamp followed by retrofitting the lamp fixture to be used with the AC mains when the ballast dies.","In the U.S. patent application Ser.","No.","14/688,841, filed Apr.","16, 2015, two shock prevention switches and an all-in-one driving circuit are adopted in an LLT lamp such that AC power from either a ballast or the AC mains can operate the LLT lamp without operational uncertainty and electric shock hazards.","In other words, no matter what a lamp fixture is configured as the AC mains- or a ballast-compatible fashion, the LLT lamp automatically detects configurations and works for either one.","All of such LLT lamps, no matter whether AC mains-operable or ballast-compatible, are electrically wired as double-ended and have one construction issue related to product safety and needed to be resolved prior to wide field deployment.","This kind of LLT lamps, if no shock prevention scheme is adopted in, always fails a safety test, which measures a through-lamp electric shock current.","Because an AC-mains voltage applies to both opposite ends of the LLT lamps, the measurement of current leakage from one end to the other consistently results in a substantial current flow, which may present a risk of an electric shock during re-lamping.","Due to this potential shock risk to the person who replaces the LLT lamps in an existing fluorescent tube fixture, Underwriters Laboratories (UL) uses its safety standard, UL 935, Risk of Shock During Relamping (Through Lamp), to do a current leakage test and to determine if the LLT lamps meet the consumer safety requirement.","Although the LLT lamps used with a ballast can pass the current leakage test, some kinds of electric shock hazards do exist.","Experimental results show that the skin of the person who touches an exposed bi-pin may be burned due to such an electric shock.","Fortunately, a mechanism of double shock prevention switches used in applications with the AC mains is also effective in applications with the ballasts to prevent the electric shock from occurring, thus protecting consumers from such a hazard, no matter whether input voltage is from the AC mains or the ballast.","Therefore, a universal LLT lamp that can work with either the AC mains or the ballast makes sense.","The effectiveness of using double shock prevention switches for applications in the AC mains has been well addressed in U.S. Pat.","No.","8,147,091, issued on Apr.","3, 2012.However, a conventional shock prevention switch has an inherent issue related to an electric arc when operated with a ballast.","Unlike an AC voltage of 120 or 277 V/50-60 Hz from the AC mains, the output AC voltage and current from the ballast presents a negative resistance characteristic.","The feature that originally supports a fluorescent tube to function properly becomes extremely detrimental to the conventional shock prevention switch due to the electric arc likely occurring between two electrical contacts that have a high electrical potential difference with a high frequency, such as 600 V/50 kHz.","Once a consumer fails to follow installation instructions to install or uninstall linear LED tube lamps such that one of two ends of the tube lamp is in the fixture socket connected to a powered ballast, and the other end is tweaked to connect to or disconnect from the associated socket, an internal electric arcing may occur between the electrical contacts in the associated switch.","The arcing even in a short period such as several seconds can generate high heat, burning and melting electrical contacts and neighboring plastic enclosures, creating a fire hazard.","The AC voltage of 120 or 277 V/50-60 Hz from the AC mains does not have such an issue because its voltage is relatively low compared with the ballast output voltage of 600 V. Moreover, the AC frequency of 60 Hz automatically extinguishes an electric arc every 1/60 seconds, if existed.","That is why a utility switch can be used in an electrical appliance to turn power on and off without any problem.","However when used with the ballast, the electrical contacts used in the conventional shock prevention switch can easily be burned out due to the high-voltage and high-frequency arcing introduced between each gap of each pair of the electrical contacts in the conventional shock prevention switch when someone tries to abusively tweak to remove the tube lamp from the fixture with the ballast that has a power on it.","Although such a situation is rare, an internal arcing, if occurred, does cause burning and even welding of the electrical contacts and melting of the plastic enclosure, so called internal fire, creating consumer safety issues.","Today, such LLT lamps are mostly used in a ceiling light fixture with a wall-mount power switch.","The ceiling light fixture could be an existing one used with fluorescent tubes but retrofitted for LLT lamps or a specific LLT lamp fixture.","The drivers that provide a proper voltage and current to LED arrays could be internal or external ones.","Not like LLT lamps with an external driver that is inherently electric-shock free if the driver can pass a dielectric withstand test used in the industry, LLT lamps with an internal driver could have a shock hazard during relamping or maintenance, when the substantial through-lamp electric shock current flows from any one of AC voltage inputs through the internal driver connecting to LED arrays to the earth ground.","Despite this disadvantage, LLT lamps with the internal driver still receive wide acceptance because they provide a stand-alone functionality and an easy retrofit for an LLT lamp fixture.","As consumerism develops, consumer product safety becomes extremely important.","Any products with electric shock or fire hazards and risk of injuries or deaths are absolutely not acceptable for consumers.","However, commercially available LLT lamps with internal drivers, single-ended or double-ended, fail to provide effective solutions to the problems of possible electric shock and internal arcing and fire.","In the prior art mentioned above, the double shock protection switches with mechanical actuation mechanisms protruding outwards from both ends of the LLT lamp are proposed to control a line voltage from the AC mains or high voltages from the ballasts to connect to the LLT lamp.","However, a length control of the LLT lamp becomes critical to operate the LLT lamp because sometimes the double shock protection switches may not be actuated by the mechanical actuation mechanisms.","Also, the double shock protection switches directly control AC voltages such as 120 or 277 V/50˜60 Hz from the AC mains or 600 V/45˜65 kHz from the ballasts, which makes the conventional LLT lamp so vulnerable because such high voltages working on the double shock protection switches may easily cause internal fire if consumers abusively tweak the mechanical actuation mechanisms at both ends of the LLT lamp operable with a ballast during relamping.","Another prior art may involve an electronic approach to eliminating electric shock.","However, such an electronic approach may not be as reliable as expected, especially in real applications where the electronic approach continues to fail in electric shock and arcing situations.","It is, therefore, the purpose of the present disclosure to disclose a novel low-voltage control approach to be used in the LLT lamp to eliminate above-mentioned electric shock and internal fire hazards and to work more reliably to protect consumers.","SUMMARY A linear light-emitting diode (LED)-based solid-state tube (LLT) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, at least one conductor protruding outwards from each lamp base, and at least two pairs of electrical contacts controlled by the at least two proximity sensors, is used to replace a fluorescent tube or a conventional LED tube lamp without the at least two proximity sensors and the at least two pairs of electrical contacts.","The at least two proximity sensors and the at least two pairs of electrical contacts are configured to respectively perform proximity sensing between the two lamp bases and two sockets in an existing lamp fixture.","When both two lamp bases are inserted in the two sockets, the at least two pairs of electrical contacts are driven by the at least two proximity sensors to make an electrical connection between the full-wave rectifier and the LED driving circuit, rather than between an alternate current (AC) voltage input and the full-wave rectifier, to power the LED driving circuit and the one or more LED arrays.","When either one of the two lamp bases is not inserted in one of the two sockets, the at least two pairs of electrical contacts are disabled so as to disconnect a direct current (DC) current flow from the full-wave rectifier to the LED driving circuit.","Without such DC current flowing to power the LED driving circuit, a substantial through-lamp electric shock current is considered not to exist.","Furthermore, the at least two pairs of electrical contacts are interconnected between the full-wave rectifier and the LED driving circuit, the DC voltage provided to the LED driving circuit can be made small by using a voltage divider.","In such a case, no high voltage at a high frequency from a ballast is present at any open/closed electrical contacts in the LLT lamp, thus no internal fire possible.","The scheme can effectively reduce a risk of electric shock and a fire hazard to users during relamping or maintenance.","In one embodiment, the LLT lamp further comprises at least two magnets and at least two Hall effect sensors configured to form at least two magnetic proximity sensor pairs at the two ends of the LLT lamp and to provide a non-contact actuation of the at least two pairs of electrical contacts.","When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.","In this case, both the at least two pairs of electrical contacts are electrically connected by the non-contact actuation of the at least two magnetic proximity sensor pairs, whereas a low DC voltage is applied to the LED driving circuit to control a substantial electric current to flow into the one or more LED arrays.","However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.","In this case, the respective one of the at least two magnetic proximity sensor pairs associated with the exposed lamp base is not actuated with respective one of the at least two electrical contacts not electrically connected.","Because the at least two electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.","No substantial electric shock current can possibly be leaked out of exposed at least one electrical conductor.","In other words, once the at least one electrical conductor is exposed during relamping, the driving circuit will not receive a proper voltage to operate.","Thus, an overall through-lamp electric shock current may be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.","A controlling electronic circuit, which only supports an actuation of an electronic switch, indeed, has a much smaller power consumption than the one or more LED arrays do.","Experimental results show that such a through-lamp electric shock current not going through the one or more LED arrays can be controlled to an acceptable level according to a safety standard UL 935.In another embodiment, the LLT lamp may further comprise at least two displacement sensors configured to sense if the two ends of the LLT lamp are between the two sockets in the fixture.","When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.","In this case, both the at least two pairs of electrical contacts are electrically connected by an actuation of displacement sensors, whereas a low DC voltage is applied to the LED driving circuit, controlling electric current to flow into the one or more LED arrays.","However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.","In this case, the respective one of the at least two displacement sensors associated with the exposed lamp base is not actuated with respective one of the at least two pairs of electrical contacts not electrically connected.","Because at least two pairs of electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.","No substantial electric shock current can possibly be leaked out of the exposed at least one electrical conductor.","In other words, once the at least one electrical conductor is exposed during relamping, the LED driving circuit will not receive a proper voltage to operate.","Thus, an overall through-lamp electric shock current can be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.","Furthermore, the use of the low DC voltage in controlling electrical contacts to be on or off has one of unique advantages.","That is, no matter whether AC sources is AC mains from an electrical grid or power supplies from various ballasts, no significant arc can be observed due to a low DC current associated with the low DC voltage.","In other words, an internal arcing and firing will never occur using this approach, thus eliminating any internal fire hazard and enhancing operation reliability.","BRIEF DESCRIPTION OF THE DRAWINGS Non-limiting and non-exhaustive embodiments of the present disclosure are described with reference to the following figures, wherein like reference numerals refer to like parts throughout the various figures unless otherwise specified.","FIG.","1 is an embodiment of an LLT lamp installed in lamp fixture sockets connected with AC sources that include AC mains and ballasts according to the present disclosure.","FIG.","2 is another embodiment of an LLT lamp installed in lamp fixture sockets connected with AC sources that include AC mains and ballasts according to the present disclosure.","FIG.","3 is a block diagram of an LED driving circuit used in an LLT lamp depicted in FIG.","2 operable with either the AC mains or ballasts according to the present disclosure.","FIG.","4 is a block diagram of another embodiment of an LED driving circuit used in an LLT lamp depicted in FIG.","2 operable with either the AC mains or ballasts according to the present disclosure.","DETAILED DESCRIPTION OF THE INVENTION FIG.","1 is an embodiment of a linear LED tube (LLT) lamp installed in lamp fixture sockets connected with alternate current (AC) sources that include AC mains and ballasts according to the present disclosure.","The LLT lamp 500 comprises a housing having two ends; two lamp bases 660 and 760 each having at least one electrical conductor 250 and 350 at each end of the housing; a first magnetic proximity sensor pair 310 close to the lamp base 660; a second magnetic proximity sensor pair 320 close to the lamp base 760; a controller 330; an LED driving circuit 100; and one or more LED arrays 214 disposed on an LED PCB 617 with the one or more LED arrays 214 connected to the LED driving circuit 100.The controller 330 comprises a set of voltage dividers and regulators 340, a switch control unit 360, at least one switch 370, and a full-wave rectifier 603 consisting of diodes 611, 612, 613, and 614 interconnected at ports 402, 404, 503, and 504.The first magnetic proximity sensor pair 310 comprises a magnet 380 and a Hall effect sensor 381.Similarly, the second magnetic proximity sensor pair 320 comprises a magnet 382 and a Hall effect sensor 383.The full-wave rectifier 603 is configured to convert an AC voltage from the AC mains or the ballasts into a direct current (DC) voltage with a voltage of V+ at the port 503 applied to the LED driving circuit 100.The set of voltage dividers and regulators 340 receives the DC voltage from the full-wave rectifier 603 via a diode 384 configured to block an electric current backward flowing to the at least one full-wave rectifier 603 and converts it into a low DC voltage to operate the Hall effect sensors 381 and 383 and the switch control unit 360.When both two lamp bases 660 and 760 are in fixture sockets 810 and 820, there is no exposed at least one conductor 250 or 350 that installers can possibly touch, creating an electric shock hazard.","In this case, both the magnets 380 and 382 are respectively in close proximity to the Hall effect sensors 381 and 383, and the magnetic proximity sensor pairs 310 and 320 are actuated to respectively output low-level signals 385 and 386.Such a non-contact actuation of the magnetic proximity sensor pairs 310 and 320 increases operating reliability.","The switch control unit 360 comprises a transistor 387 and a logic circuit 388 configured to control the transistor 387, further maneuvering the at least one switch 370 to control a current returned from the LED driving circuit 100.The low-level signals 385 and 386 are inputted to the logic circuit 388 to turn on the at least one switch 370, enabling the current returned from the LED driving circuit 100 back to the port 504, thus completing a power transfer to the one or more LED arrays 214.When either one of the two lamp bases of the LLT lamp is not in the respective socket, there is a risk of electric shock for installers.","In this case, one of the two magnets, say 382, is not in close proximity to the respective Hall effect sensor 383 whereas the other magnet 380 is in close proximity to the other respective Hall effect sensor 381 and ready to operate.","However, both Hall effect sensors 381 and 383 need power to operate.","At the instant when an installer touches the exposed at least one conductor 350, both Hall effect sensors 381 and 383 are energized, but only the magnetic proximity sensor pair 310 is actuated.","That is, only the Hall effect sensors 381 sends a low-level signal to the logic circuit 388, whereas the Hall effect sensor 383 sends a high-level signal to the logic circuit 388 because the magnet 382 is not in close proximity to the Hall effect sensor 383.The logic circuit 388 determines that there is an electric shock risk and controls the transistor 387 to electrically conduct the collector and the emitter of the transistor 387, subsequently turning off the at least one switch 370.No substantial electric current returned from the LED driving circuit 100 and the at least one or more LED arrays 214 can possibly leak out from the port 504, further flowing to the exposed at least one conductor 350.Thus, the LLT lamp does not light up.","In other words, once the at least one electrical conductor 250 and 350 is exposed during relamping, the LED driving circuit 100 will not receive power to operate.","Thus, an overall through-lamp electric shock current may be limited to a small amount that needs at least to operate the set of voltage dividers and regulators 340, the logic circuit 388, the two Hall effect sensors 381 and 383, the transistor 387, and the at least one switch 370, rather than a substantial electric shock current flowing through the LED driving circuit 100 and the one or more LED arrays 214.Indeed, power consumption of the control electronics, which supports the electric shock detection and actuation of at least one switch 370, is much smaller than that of the LED driving circuit 100 powering one or more LED arrays 214.Experimental results show that the through-lamp electric shock current can be controlled to an acceptable level according to a safety standard UL 935.In FIG.","1, the full-wave rectifier 603 is always connected to the at least one electrical conductor 250 and the at least one electrical conductor 350 and receives AC power from the AC mains or the ballasts.","This is different from prior art, which uses double safety switches to control the at least one electrical conductor 250 and the at least one electrical conductor 350 to make connections to the full-wave rectifier 603.In FIG.","1, the LED driving circuit 100 directly connects to the full-wave rectifier 603, receiving the DC voltage V+ from the port 503.The LED driving circuit 100 may comprise its own full-wave rectifier to energize the one or more LED arrays 214.Only when both the first and the second magnetic proximity sensor pairs are actuated, can the at least one switch 370 controlled by the switch control unit 360 conduct an electric current returned from the LED driving circuit 100 to the full-wave rectifier 603, completing a power transfer.","Specifically, when both the at least one electrical conductor 250 and the at least one electrical conductor 350 in each lamp base are inserted into the lamp fixture sockets 810 and 820, the controller 330 receives power from the AC sources and operates to individually actuate the first and the second magnetic proximity sensor pairs 310 and 320.For a positive cycle, the electric current from one port of the AC sources, AC mains or ballasts, can flow from the electrical contact 401 of the at least one electrical conductor 250, the full-wave rectifier 603 through the diode 611 to the port 503 of the LED driving circuit 100, further down into the one or more LED arrays 214, and return to a port 505 of the LED driving circuit 100.Because both the first and the second magnetic proximity sensor pairs 310 and 320 are actuated, the at least one switch 370 is “on”.","The electric current continues to flow through the port 504, the diode 614 of the full-wave rectifier 603, the electrical contact 405 of the at least one electrical conductor 350 to the other port of the AC sources, completing the positive half cycle power transfer.","For a negative half cycle, the electric current from one port of the AC sources can flow from the electrical contact 405 of the at least one electrical conductor 350, the full-wave rectifier 603 through the diode 612 to the port 503 of the LED driving circuit 100, further down into the one or more LED arrays 214, and return to the port 505 of the LED driving circuit 100.The electric current continues to flow through the diode 613 of the full-wave rectifier 603, the electrical contact 401 of the at least one electrical conductor 250 to the other port of the AC sources, completing the negative half cycle power transfer.","When the lamp base 660 is inserted in the lamp socket 810, which connects to one port of the AC sources (say, the left side in FIG.","1), the LLT lamp 500 is energized.","If the first and the second magnetic proximity sensor pairs 310 and 320 do not exist to control the electric current return, a substantial through-lamp electric shock current from the LED driving circuit 100 and the one or more LED arrays 214 can always come out through the at least one electrical conductor 350, which may be exposed to a user for an electric shock.","The electric shock may be fatal depending on impedance between the user's body and the earth ground.","On the other hand, if the first and the second magnetic proximity sensor pairs 310 and 320 exist and send the low-level signals to the controller 330 to control the electric current returned from the LED driving circuit 100, then the through-lamp electric shock current from the LED driving circuit 100 and the one or more LED arrays 214 is zero.","However, the through-lamp electric shock current can come out from the controller 330 that needs power to actuate the first and the second magnetic proximity sensor pairs 310 and 320, to determine for the logic circuit 388 if the electric shock hazard occurs, and to control the at least one switch 370.Because such a load is a fraction of one from the one or more LED arrays 214, the through-lamp electric shock current in this case can be controlled to an acceptable level not exceeding a specific value defined in the safety standard UL 935, no fatal electric shock possible.","In a normal operation when the at least one electrical conductor 250 and the at least one electrical conductor 350 are connected to the AC mains or the ballast in a double-ended wiring lamp fixture, the LED driving circuit 100 can receive power to drive the one or more LED arrays 214.As can be seen in FIG.","1, two sockets in each of the external fixture lamp sockets 810 and 820 are shunted, meaning that as long as the at least one electrical conductor 250 in the lamp base 660 and the at least one electrical conductor 350 in the lamp base 760 are connected to the AC sources, the LLT lamp using the approach depicted in FIG.","1 can operate with an acceptable through-lamp electric shock current, which is deemed safe for users.","In FIG.","1, the LED driving circuit 100 may comprise a second at least one full-wave rectifier configured to receive the DC voltage from the at least one full-wave rectifier 603 and to operate the one or more LED arrays 214.The at least one switch 370 may comprise a metal-oxide-semiconductor field-effect transistor (MOSFET), a transistor, a back-to-back thyristor, a silicon-controlled rectifier (SCR), a relay, or a combination thereof.","Also such devices may be connected with some snubber circuits to maintain their functionality under voltage spikes.","The low DC voltage used to operate the magnetic proximity sensor pairs 310 and 320 meets voltage requirements of a Class 2 circuit, which is considered safe from a fire initiation viewpoint and provides an acceptable level of protection from electrical shock.","FIG.","2 is another embodiment of an LLT lamp installed in lamp fixture sockets connected with AC sources that include AC mains and ballasts according to the present disclosure.","The LLT lamp 600 comprises a housing having two ends; two lamp bases 660 and 760 each having at least one electrical conductor 250 and 350 at each end of the housing; a first displacement sensor pair 511 close to the lamp base 660 comprising a displacement sensor 516 and a first pair of electrical contacts 301 and 302; a second displacement sensor pair 512 close to the lamp base 760 comprising a displacement sensor 517 and a second pair of electrical contacts 303 and 304; a full-wave rectifier 603 comprising diodes 611, 612, 613, and 614 interconnected at ports 402, 404, 503, and 504; an LED driving circuit 110; and one or more LED arrays 214 disposed on an LED PCB 617 with the one or more LED arrays 214 connected to the LED driving circuit 110.The LED driving circuit 110 comprises an input filter 102 connected to the port 503 of the full-wave rectifier 603, one or more start-up resistors 104 connected to the input filter 102, and a driver 400 connected to the one or more LED arrays 214.The driver 400 comprises a low voltage input 513, a high voltage input 514 connected to a port 518 of the input filter 102, and a common port 515 connected to the port 504 of the full-wave rectifier 603.The high voltage input 514 is configured to connect to a Buck converter (in FIGS.","3 and 4), whereas the low voltage input 513 is originally configured to connect to the one or more start-up resistors 104 and to control the Buck converter to provide a proper current and voltage to drive the one or more LED arrays 214.In FIG.","2, the first and the second pairs of electrical contacts 301, 302, 303, and 304 are interconnected in series and looped between the one or more start-up resistors 104 and the low voltage input 513 of the driver 400.The full-wave rectifier 603 is always connected to the at least one electrical conductor 250 and the at least one electrical conductor 350 and receives AC power from the AC mains or the ballasts.","As in FIG.","1, this is different from prior art, which uses double safety switches to make connections between the at least one electrical conductors 250 and 350 and the full-wave rectifier 603.In FIG.","2, the LED driving circuit 110 directly connects to the full-wave rectifier 603, receiving the DC voltage V+ from the port 503.When the first and the second pairs of electrical contacts 301, 302, 303, and 304 are not individually electrically connected, the one or more start-up resistors 104 is not connected to the low voltage input 513 of the driver 400, thus disabling the driver 400 to power one or more LED arrays 214.Without electric current returned from one or more LED arrays 214 to reach an exposed at least one electrical conductor 250 or 350, no electric shock hazard will occur even though the at least one electrical conductor 250 and the at least one electrical conductor 350 are electrically connected with the full-wave rectifier 603, which energizes the LED driving circuit 110.When both the at least one electrical conductor 250 and the at least one electrical conductor 350 in each lamp base are respectively inserted into the lamp fixture sockets 810 and 820, the one or more start-up resistors 104 provides a low DC voltage to individually actuate the first and the second pairs of electrical contacts 301, 302, 303, and 304 in a way that an electric current can conduct between the first pair of electrical contacts 301 and 302 and between the second pair of electrical contacts 303 and 304.The electric current can flow from an output port 519 of the one or more start-up resistors 104, the first pair of electrical contacts 301 and 302, the second pair of electrical contacts 303 and 304, entering the low voltage input port 513 of the driver 400.For a positive cycle, the electric current from one port of the AC sources can flow from the electrical contact 401 of the at least one electrical conductor 250, the full-wave rectifier 603 through the diode 611 to the port 503 of the LED driving circuit 110, going through the input filter 102.The low DC voltage from the one or more start-up resistors 104 is applied to the first pair of electrical contacts 301 and 302, the second pair of electrical contacts 303 and 304, entering the low voltage input port 513 of the driver 400.Whereas the high voltage input port 514 of the driver 400 is already energized, the low DC voltage from the one or more start-up resistors 104 starts to operate the driver 400, powering the one or more LED arrays 214.The current returns to the common port 515 of the driver 400, continuing to flow through the diode 614 of the full-wave rectifier 603, the electrical contact 405 of the at least one electrical conductor 350 to the other port of the AC sources, completing the positive half cycle power transfer.","For a negative half cycle, the electric current from one port of the AC sources can flow from the electrical contact 405 of the at least one electrical conductor 350, the full-wave rectifier 603 through the diode 612 to the port 503 of the LED driving circuit 110.Similar to the current flow in the LED driving circuit 110 for positive cycle, the electric current continues to flow through the diode 613 of the full-wave rectifier 603, the electrical contact 401 of the at least one electrical conductor 250 to the other port of the AC sources, completing the negative half cycle power transfer.","When the lamp base 660 is inserted in the lamp socket 810, which connects to one port of the AC sources (say, the left side in FIG.","1), the LLT lamp 600 is energized.","If the first and the second pairs of electrical contacts 301, 302, 303, and 304 do not exist to control the electric current conduction, a substantial through-lamp electric shock current from the LED driving circuit 110 and the one or more LED arrays 214 can always come out through the at least one electrical conductor 350, which may be exposed to a user for an electric shock.","The electric shock may be fatal depending on impedance between the user's body and the earth ground.","On the other hand, if the first and the second pairs of electrical contacts 301, 302, 303, and 304 exist and are connected in series and looped between the one or more start-up resistors 104 and the driver 400, then the through-lamp electric shock current from the LED driving circuit 100 and the one or more LED arrays 214 can be set to zero.","However, a small amount of the through-lamp electric shock current will come out from the input filter 102 and some safety varistors and capacitors (not shown in FIG.","2) in front of the full-wave rectifier 603, which need power to operate.","Because such a load is a fraction of the load from the one or more LED arrays 214, its through-lamp electric shock current can be controlled to an acceptable level not exceeding a specific value defined in the safety standard UL 935, no fatal electric shock possible.","In a normal operation when the at least one electrical conductor 250 and the at least one electrical conductor 350 are connected to the AC mains or the ballasts in a double-ended wiring lamp fixture, the LED driving circuit 110 can receive power to drive the one or more LED arrays 214.As can be seen in FIG.","2, two sockets in each of the external fixture lamp sockets 810 and 820 are shunted, meaning that as long as the at least one electrical conductor 250 in the lamp base 660 and the at least one electrical conductor 350 in the lamp base 760 are connected to the AC sources, the LLT lamp adopting the approach depicted in FIG.","2 can operate with an acceptable through-lamp electric shock current, which is deemed safe for users.","FIG.","3 is a block diagram of an LED driving circuit used in an LLT lamp depicted in FIG.","2 operable with either the AC mains or the ballasts according to the present disclosure.","A full-wave rectifier 603 connecting to an AC source, either the AC mains or the ballast, converts an AC voltage into a DC voltage.","An LED driving circuit 110, connecting to the full-wave rectifier 603, comprises an input filter 102 used to filter the input voltage and to suppress EMI noise created in the LED driving circuit 110, one or more start-up resistors 104, a driver 400, an electrical jumper pair 109 connecting between the one or more start-up resistors 104 and the driver 400 with a terminal module 500 outside the LED driving circuit 110, The driver 400 comprises a power factor correction (PFC) and control device 103, a Buck converter 200 in communicating with the PFC and control device 103, an output capacitor 105 in parallel with a resistor 106 connected to the Buck converter 200 to build up an output voltage and to power the one or more LED arrays 214, a current sensing resistor 107, and a voltage feedback module 300 extracting partial energy from the output voltage to sustain the PFC and control device 103.The driver 400 has a high voltage input port 108 and a low voltage input port 501.The terminal module 500 comprises the first pair of electrical contacts 301 and 302 and the second pair of electrical contacts 303 and 304 interconnected in series, as depicted in FIG.","2.Either one of the two pairs of electrical contacts not electrically connected results in a lost connection at the low voltage input port 501 and renders an electrical disconnection between the one or more start-up resistors 104 and the driver 400.The full-wave rectifier 603 has four input/output ports, among which a high electric potential appears at the input/output port 503 as V+, and a low electric potential appears at the input/output port 504 as V−, respectively connecting to the high side and the low side of the input filter 102 with the low electric potential port 504 as a common ground.","The Buck converter 200 comprises a switch 201 controlled by the PFC and control device 103, a diode 202, and an inductor 203 with its current charging and discharging controlled by the switch 201.When both two pairs of electrical contacts are individually connected, the electrical jumper pair 109 connecting to the terminal module 500 conducts so that a low DC voltage from the one or more start-up resistors 104 applies to the PFC and control device 103 to sustain its operation.","Then the driver 400 can detect zero current in the inductor 203 within an AC cycle of an input voltage generating a zero current detection signal and controls the switch 201 on and off with a constant on-time and a varied off-time controlled by the zero current detection signal.","By adapting switching frequencies for a high frequency associated with a ballast and a low frequency associated with the AC mains, the PFC and control device 103 controls the switch 201 on and off in a way that the inductor 203 is charged during on-time and discharged during off-time, and that a desired output voltage Vo across the one or more LED arrays 214 is reached to light up the one or more LED arrays 214.The average inductor current is thus equal to the output current that flows into the LED array 214.When the switch 201 is on, the diode 202 is reverse-biased, and an input current flows from an output port 108 in the input filter 102, the switch 201, the first port 204 of the current sensing resistor 107, the current sensing resistor 107 itself, and the second port 205 of the current sensing resistor 107, into the inductor 203.When the current flowing into the inductor 203 increases, the voltage across the current sensing resistor 107 increases.","The second port 205 of the current sensing resistor 107 connects with the PFC and control device 103, which continuously receives signals and adjusts the off-time such that the output voltage and current to the one or more LED arrays 214 are regulated to meet the output requirements.","The output capacitor 105 in parallel with the resistor 106 connects to the inductor 203, receiving energy to build up an output voltage and to power the one or more LED arrays 214.The inductor 203 configured as an autotransformer has a center-tapped port connecting to the first port 301 of the voltage feedback module 300 comprising a diode.","The voltage feedback module 300 has two connection ports 305 and 306, with the first connection port 305 connecting to the center-tapped port of center-tapped inductor 203 and with the second connection port 306 connecting to the PFC and control device 103.The PFC and control device 103 has an input capacitor (not shown) with a voltage built up to supply an internal logic control circuit (not shown) in the PFC and control device 103 When the voltage decreases due to its increased internal operations and controls, and when the voltage at the center-tapped port of the inductor 203 is higher than the supplying voltage, the diode in the voltage feedback module 300 conducts to supply a current to the PFC and control device 103 and sustain its operations.","The function of the voltage feedback module 300 is essential because the LED driving circuit 110 has a wide range of operating voltages not only 110 and 277 VAC for AC mains but also 375˜400 VAC for a ballast.","The one or more start-up resistor 104 is so designed to operate a LLT lamp at the lowest input voltage 110 VAC.","When the highest voltage 400 VAC from the ballast comes in, a higher proportional voltage appears at an input of the internal logic control circuit.","Therefore an operating voltage for the internal logic control circuit must be in a wide range such as 11˜35 VDC rather than 5˜15 VDC as in a conventional logic control device.","To meet requirements of start-up time and current without turn-on failure or flickering occurred at the lamp start-up, the input capacitor in the PFC and control device 103 with a minimum capacitance is designed and used at the input of the internal logic control circuit.","The voltage feedback module 300 is thus needed to pump in energy in time and to sustain the operating voltage and ensure no flickering occurred when operating the LLT lamp.","When the switch 201 is off, the diode 202 is forward-biased, and the inductor 203 discharges with a loop current flowing from the one or more LED arrays 214, the diode 202, the current sensing resistor 107, back to the inductor 203.The current sensing resistor 107 keeps track of the output current and feedbacks to the PFC and control device 103 to further control the switch 201 on and off.","The closed loop operation in both on-time and off-time of the switch 201 ensures the output current to be accurately controlled within 4%.","FIG.","4 is a block diagram of another embodiment of an LED driving circuit used in an LLT lamp depicted in FIG.","2 operable with either the AC mains or the ballasts according to the present disclosure.","The LED driving circuit 120 in FIG.","4 has all the components as the LED driving circuit 110 in FIG.","3, except that interconnections are different, and a transformer 206 in FIG.","4 replaces the center-tapped inductor 203 in FIG.","3.In FIG.","4, the same numerals are used for the same components as in FIG.","3.As in FIG.","3, the LED driving circuit 120, connecting to the full-wave rectifier 603, comprises an input filter 102, one or more start-up resistors 104, a driver 400, an electrical jumper pair 109 connecting between the one or more start-up resistors 104 and the driver 400 with a terminal module 500 outside the LED driving circuit 120, The driver 400 comprises a PFC and control device 103, a Buck converter 200 in communicating with the PFC and control device 103, an output capacitor 105 in parallel with a resistor 106 connected to the Buck converter 200 to build up an output voltage and to power the one or more LED arrays 214, a current sensing resistor 107, and a voltage feedback module 300 extracting partial energy from the output voltage to sustain the PFC and control device 103.The terminal module 500 comprises the first pair of electrical contacts 301 and 302 and the second pairs of electrical contacts 303 and 304 interconnected in series, as depicted in FIG.","2.Either one of the two pairs of electrical contacts not electrically connected renders an electrical disconnection between the one or more start-up resistors 104 and the driver 400.In FIG.","4, the driver 400 has a high voltage input port 108 and a low voltage input port 501.When the power is on, the high voltage input port 108 of the driver 400 receives an input current via the input filter 102, and the switch 201 controlled by the PFC and control device 103 is ready to be turned on to control the Buck converter 200.However, when the terminal module 500 is off, the low voltage input port 501 loses a connection, meaning that the driver 103 is not yet operable.","Only when the first pair of electrical contacts 301 and 302 and the second pairs of electrical contacts 303 and 304 in the terminal module 500 are individually connected, can the switch 201 be controlled to turn on or off.","When the switch 201 is on, the diode 202 is reverse-biased, and the input current goes from the resistor 106, a primary side of the transformer 206, the switch 201, and the current sensing resistor 107 to the common ground 504, completing an AC cycle.","When the input current goes into the primary side of the transformer 206, energy is stored in it.","The PFC and control device 103 detects the input voltage level and control the switch 201 on and off in a way that a desired output voltage Vo across the one or more LED arrays 214 is reached to light up the one or more LED arrays 214.When the switch 201 is off, the diode 202 is forward-biased, and the primary side of the transformer 206 releases the energy stored, resulting in a loop current flowing from the diode 202 and the one or more LED arrays 214, back to the primary side of the transformer 206, completing the energy transfer to the one or more LED arrays 214.When the switch 201 is on, the input current flows into the one or more LED arrays 214, the primary side of the transformer 206, the switch 201, and the current sensing resistor 107, creating a voltage drop across the current sensing resistor 107.The voltage appearing at the port 204 of the current sensing resistor 107 inputs to the PFC and control device 103 to control the off-time of the switch 201.The voltage feedback module 300 has two connection ports 305 and 306, with the first connection port 305 connecting to a high side of a secondary winding 207 in the transformer 206 and with the second connection port 306 connecting to the PFC and control device 103, as in FIG.","3.The voltage feedback module 300 continuously monitors the output voltage by using the secondary winding 207 in the transformer 206.When the voltage at the high side of the secondary winding 207 is higher than a becoming lower operating voltage in the PFC and control device 103 due to increased internal operations, the diode (not shown) in the voltage feedback module 300 conducts to supply energy in time through the second connection port 306 to sustain the operating voltage in the PFC and control device 103.In FIGS.","1-4, the low DC voltage are used to control the through-lamp electric shock current flowing out from the LED driving circuit and the one or more LED arrays to reduce a risk of electric shock.","The use of such a low DC voltage in controlling electrical contacts to be on or off has one of unique advantages.","That is, no matter whether AC sources is AC mains from an electrical grid or power supplies from various ballasts, no significant arc can be observed due to a low current associated with the low voltage.","In other words, an internal arcing and firing will never occur using this approach, thus eliminating any internal fire hazard and enhancing operation reliability.","Whereas preferred embodiments of the present disclosure have been shown and described, it will be realized that alterations, modifications, and improvements may be made thereto without departing from the scope of the following claims.","Another kind of the electric shock and internal fire prevention schemes in an LED-based lamp using various kinds of combinations to accomplish the same or different objectives could be easily adapted for use from the present disclosure.","Accordingly, the foregoing descriptions and attached drawings are by way of example only, and are not intended to be limiting."]],"string":"[\n [\n \"Linear Solid-State Lighting With Low Voltage Control Free Of Electric Shock And Fire Hazard\",\n \"A linear light-emitting diode (LED) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, and at least two pairs of electrical contacts controlled by the at least two proximity sensors, is used to replace a fluorescent tube or a conventional LED tube lamp.\",\n \"The at least two proximity sensors and the at least two pairs of electrical contacts configured to respectively perform proximity sensing between the two lamp bases and two sockets in an existing lamp fixture are operated by using a low DC voltage.\",\n \"When both two lamp bases are inserted in the two sockets, the at least two pairs of electrical contacts are driven to make an electrical coupling between the full-wave rectifier and the LED driving circuit.\"\n ],\n [\n \"1.A linear light-emitting diode (LED) tube lamp, comprising: a housing having two ends; at least one LED printed circuit board (LED PCB) disposed between the two ends of the housing, the at least one LED PCB comprising one or more LED arrays disposed thereon; two lamp bases respectively connected to the two ends of the housing, each lamp base comprising a magnetic proximity sensor pair and at least one electrical conductor configured to connect to a lamp fixture socket that is wired to connect to either alternate current (AC) mains or ballasts; a controller comprising a first full-wave rectifier configured to convert an input AC voltage into a direct current (DC) voltage, a set of voltage dividers and regulators configured to convert the DC voltage into a low DC voltage, a switch control unit coupled to receive signals from the magnetic proximity sensor pair in each lamp base, and at least one switch controlled by the switch control unit; and an LED driving circuit configured to receive the DC voltage and to return an electric current via the at least one switch enabled by the controller so as to drive and to light up the one or more LED arrays; wherein: the low DC voltage is configured to operate the magnetic proximity sensor pair in each lamp base; when either one of the two lamp bases is out of the lamp fixture socket, the at least one switch disables an electric current flow from the LED driving circuit, thereby disconnecting an electric shock current returned from the one or more LED arrays to reach the at least one full-wave rectifier; and when the at least one electrical conductor in each lamp base is inserted into the respective lamp fixture socket, the controller enables the LED driving circuit to deliver electrical power to the one or more LED arrays.\",\n \"2.The linear LED tube lamp of claim 1, wherein the LED driving circuit comprises a second full-wave rectifier configured to receive the DC voltage from the first full-wave rectifier and to operate the one or more LED arrays.\",\n \"3.The linear LED tube lamp of claim 1, wherein the controller further comprises a diode configured to block an electric current backward flowing to the first full-wave rectifier.\",\n \"4.The linear LED tube lamp of claim 1, wherein the at least one switch comprises a metal-oxide-semiconductor field-effect transistor (MOSFET), a transistor, a back-to-back thyristor, a silicon-controlled rectifier (SCR), a relay, or a combination thereof.\",\n \"5.The linear LED tube lamp of claim 1, wherein the low DC voltage meets voltage requirements of a Class 2 circuit.\",\n \"6.The linear LED tube lamp of claim 1, wherein the switch control unit comprises a transistor configured to control the at least one switch turning on and off.\",\n \"7.The linear LED tube lamp of claim 1, wherein the switch control unit comprises a logic circuit configured to receive signals from the magnetic proximity sensor pair in each lamp base and to control the at least one switch turning on and off.\",\n \"8.The linear LED tube lamp of claim 7, wherein the logic circuit comprises one or more logic gates.\",\n \"9.The linear LED tube lamp of claim 8, wherein the one or more logic gates are implemented by one or more transistors.\",\n \"10.The linear LED tube lamp of claim 1, wherein the magnetic proximity sensor pair in each lamp base comprises a magnet and a Hall effect sensor.\",\n \"11.The linear LED tube lamp of claim 10, wherein the magnetic proximity sensor pair in each lamp base operates when the respective magnet is in close proximity to the respective Hall effect sensor.\",\n \"12.A linear light-emitting diode (LED) tube lamp, comprising: a housing having two ends; two lamp bases respectively connected to the two ends of the housing, each lamp base comprising a displacement sensor, at least one pair of electrical contacts controlled by the displacement sensor, and at least one electrical conductor configured to connect to a lamp fixture socket that is wired to connect to either alternate current (AC) mains or ballasts; a full-wave rectifier connected to the at least one electrical conductor in each lamp base and configured to convert an input AC voltage into a direct current (DC) voltage; at least one LED printed circuit board (LED PCB) disposed between the two ends of the housing, the at least one LED PCB comprising one or more LED arrays disposed thereon; and an LED driving circuit comprising an input filter, one or more start-up resistors, a driver comprising a low voltage input, and an electrical jumper pair, the one or more start-up resistors configured to provide a low DC voltage to couple to the low voltage input of the driver via the electrical jumper pair, wherein: the at least one pair of electrical contacts in each of the two lamp bases are connected in series and connected to the electrical jumper pair so as to loop between the one or more start-up resistors and the low voltage input of the driver; when either one of the at least one pair of electrical contacts are not electrically connected, a through-lamp electric shock current does not flow into the driver; and when the at least one electrical conductor in each of the two lamp bases is inserted into the lamp fixture socket, the at least one pair of electrical contacts are actuated by the displacement sensor in each lamp base to deliver the low DC voltage to the driver, thereby operating the driver and powering the one or more LED arrays.\",\n \"13.The linear LED tube lamp of claim 12, wherein the driver further comprises a high voltage input configured to receive a filtered DC voltage from the input filter, a power factor correction (PFC) and control device, a switch controlled by the PFC and control device, a current sensing resistor, a diode, an inductor with current charging and discharging thereof controlled by the switch, a resistor, an output capacitor in parallel with the resistor and connected to the inductor to build up an output voltage and to power the one or more LED arrays, and a voltage feedback module coupled to draw partial power from the output voltage to sustain an operation of the PFC and control devices, and wherein, responsive to detecting zero current in the inductor within an AC cycle of the input voltage, the PFC and control device generates a zero current detection signal to control the switch turning on and off.\",\n \"14.The linear LED tube lamp of claim 13, wherein the voltage feedback module comprises a diode.\",\n \"15.The linear LED tube lamp of claim 13, wherein the switch in the driver operates at a switching frequency greater than or equal to 45 KHz.\",\n \"16.The linear LED tube lamp of claim 13, wherein the inductor in the driver is of an autotransformer type.\",\n \"17.The linear LED tube lamp of claim 13, wherein the inductor in the driver is part of a transformer.\",\n \"18.The linear LED tube lamp of claim 13, wherein the PFC and control device operates in a range approximately between 11 V and 35 VDC.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>\"\n ],\n [\n \"<SOH> SUMMARY <EOH>A linear light-emitting diode (LED)-based solid-state tube (LLT) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, at least one conductor protruding outwards from each lamp base, and at least two pairs of electrical contacts controlled by the at least two proximity sensors, is used to replace a fluorescent tube or a conventional LED tube lamp without the at least two proximity sensors and the at least two pairs of electrical contacts.\",\n \"The at least two proximity sensors and the at least two pairs of electrical contacts are configured to respectively perform proximity sensing between the two lamp bases and two sockets in an existing lamp fixture.\",\n \"When both two lamp bases are inserted in the two sockets, the at least two pairs of electrical contacts are driven by the at least two proximity sensors to make an electrical connection between the full-wave rectifier and the LED driving circuit, rather than between an alternate current (AC) voltage input and the full-wave rectifier, to power the LED driving circuit and the one or more LED arrays.\",\n \"When either one of the two lamp bases is not inserted in one of the two sockets, the at least two pairs of electrical contacts are disabled so as to disconnect a direct current (DC) current flow from the full-wave rectifier to the LED driving circuit.\",\n \"Without such DC current flowing to power the LED driving circuit, a substantial through-lamp electric shock current is considered not to exist.\",\n \"Furthermore, the at least two pairs of electrical contacts are interconnected between the full-wave rectifier and the LED driving circuit, the DC voltage provided to the LED driving circuit can be made small by using a voltage divider.\",\n \"In such a case, no high voltage at a high frequency from a ballast is present at any open/closed electrical contacts in the LLT lamp, thus no internal fire possible.\",\n \"The scheme can effectively reduce a risk of electric shock and a fire hazard to users during relamping or maintenance.\",\n \"In one embodiment, the LLT lamp further comprises at least two magnets and at least two Hall effect sensors configured to form at least two magnetic proximity sensor pairs at the two ends of the LLT lamp and to provide a non-contact actuation of the at least two pairs of electrical contacts.\",\n \"When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.\",\n \"In this case, both the at least two pairs of electrical contacts are electrically connected by the non-contact actuation of the at least two magnetic proximity sensor pairs, whereas a low DC voltage is applied to the LED driving circuit to control a substantial electric current to flow into the one or more LED arrays.\",\n \"However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.\",\n \"In this case, the respective one of the at least two magnetic proximity sensor pairs associated with the exposed lamp base is not actuated with respective one of the at least two electrical contacts not electrically connected.\",\n \"Because the at least two electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.\",\n \"No substantial electric shock current can possibly be leaked out of exposed at least one electrical conductor.\",\n \"In other words, once the at least one electrical conductor is exposed during relamping, the driving circuit will not receive a proper voltage to operate.\",\n \"Thus, an overall through-lamp electric shock current may be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.\",\n \"A controlling electronic circuit, which only supports an actuation of an electronic switch, indeed, has a much smaller power consumption than the one or more LED arrays do.\",\n \"Experimental results show that such a through-lamp electric shock current not going through the one or more LED arrays can be controlled to an acceptable level according to a safety standard UL 935.In another embodiment, the LLT lamp may further comprise at least two displacement sensors configured to sense if the two ends of the LLT lamp are between the two sockets in the fixture.\",\n \"When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.\",\n \"In this case, both the at least two pairs of electrical contacts are electrically connected by an actuation of displacement sensors, whereas a low DC voltage is applied to the LED driving circuit, controlling electric current to flow into the one or more LED arrays.\",\n \"However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.\",\n \"In this case, the respective one of the at least two displacement sensors associated with the exposed lamp base is not actuated with respective one of the at least two pairs of electrical contacts not electrically connected.\",\n \"Because at least two pairs of electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.\",\n \"No substantial electric shock current can possibly be leaked out of the exposed at least one electrical conductor.\",\n \"In other words, once the at least one electrical conductor is exposed during relamping, the LED driving circuit will not receive a proper voltage to operate.\",\n \"Thus, an overall through-lamp electric shock current can be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.\",\n \"Furthermore, the use of the low DC voltage in controlling electrical contacts to be on or off has one of unique advantages.\",\n \"That is, no matter whether AC sources is AC mains from an electrical grid or power supplies from various ballasts, no significant arc can be observed due to a low DC current associated with the low DC voltage.\",\n \"In other words, an internal arcing and firing will never occur using this approach, thus eliminating any internal fire hazard and enhancing operation reliability.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS The present disclosure is part of a continuation-in-part (CIP) application of U.S. patent application Ser.\",\n \"No.\",\n \"15/836,170, filed 8 Dec. 2017, which is a CIP application of U.S. patent application of Ser.\",\n \"No.\",\n \"15/649,392 filed 13 Jul.\",\n \"2017, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"15/444,536, filed 28 Feb. 2017 and issued as U.S. Pat.\",\n \"No.\",\n \"9,826,595 on 21 Nov. 2017, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"15/362,772, filed 28 Nov. 2016, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"15/225,748, filed 1 Aug. 2016 and issued as U.S. Pat.\",\n \"No.\",\n \"9,743,484 on 22 Aug. 2017, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"14/818,041, filed 4 Aug. 2015 and issued as U.S. Pat.\",\n \"No.\",\n \"9,420,663 on 16 Aug. 2016, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"14/688,841, filed 16 Apr.\",\n \"2015 and issued as U.S. Pat.\",\n \"No.\",\n \"9,288,867 on 15 Mar.\",\n \"2016, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"14/465,174, filed 21 Aug. 2014 and issued as U.S. Pat.\",\n \"No.\",\n \"9,277,603 on 1 Mar.\",\n \"2016, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"14/135,116, filed 19 Dec. 2013 and issued as U.S. Pat.\",\n \"No.\",\n \"9,163,818 on 20 Oct. 2015, which is a CIP application of U.S. patent application Ser.\",\n \"No.\",\n \"13/525,249, filed 15 Jun.\",\n \"2012 and issued as U.S. Pat.\",\n \"No.\",\n \"8,749,167 on 10 Jun.\",\n \"2014.Contents of the above-identified applications are incorporated herein by reference in their entirety.\",\n \"BACKGROUND Technical Field The present disclosure relates to linear light-emitting diode (LED) lamps and more particularly to a linear LED lamp with a low voltage control configured to eliminate electric arcing that may cause internal fire when used with ballasts and to prevent electric shock current from reaching ground through a person's body when used with AC mains.\",\n \"Description of the Related Art Solid-state lighting from semiconductor light-emitting diodes (LEDs) has received much attention in general lighting applications today.\",\n \"Because of its potential for more energy savings, better environmental protection (no hazardous materials used), higher efficiency, smaller size, and much longer lifetime than conventional incandescent bulbs and fluorescent tubes, the LED-based solid-state lighting will be a mainstream for general lighting in the near future.\",\n \"As LED technologies develop with the drive for energy efficiency and clean technologies worldwide, more families and organizations will adopt LED lighting for their illumination applications.\",\n \"In this trend, the potential safety concerns such as risk of electric shock and fire become especially important and need to be well addressed.\",\n \"In today's retrofit application of a linear LED tube (LLT) lamp to replace an existing fluorescent tube, consumers may choose either to adopt a ballast-compatible LLT lamp with an existing ballast used to operate the fluorescent tube or to employ an AC mains-operable LED lamp by removing/bypassing the ballast.\",\n \"Either application has its advantages and disadvantages.\",\n \"In the former case, although the ballast consumes extra power, it is straightforward to replace the fluorescent tube without rewiring, which consumers may have a first impression that it is the best alternative to fluorescent tube lamps.\",\n \"But the fact is that total cost of ownership for this approach is high regardless of very low initial cost.\",\n \"For example, the ballast-compatible LLT lamps work only with particular types of ballasts.\",\n \"If the existing ballast is not compatible with the ballast-compatible LLT lamp, the consumers will have to replace the ballast.\",\n \"Some facilities built long time ago incorporate different types of fixtures, which requires extensive labor for both identifying ballasts and replacing incompatible ones.\",\n \"Moreover, a ballast-compatible LLT lamp can operate longer than the ballast.\",\n \"When an old ballast fails, a new ballast will be needed to replace in order to keep the ballast-compatible LLT lamps working.\",\n \"Maintenance will be complicated, sometimes for lamps and sometimes for ballasts.\",\n \"The incurred cost will preponderate over the initial cost savings by changeover to the ballast-compatible LLT lamps for hundreds of fixtures throughout a facility.\",\n \"When the ballast in a fixture dies, all the ballast-compatible tube lamps in the fixture go out until the ballast is replaced.\",\n \"In addition, replacing a failed ballast requires a certified electrician.\",\n \"The labor costs and long-term maintenance costs will be unacceptable to end users.\",\n \"From energy saving point of view, a ballast constantly draws power, even when the ballast-compatible LLT lamps are dead or not installed.\",\n \"In this sense, any energy saved while using the ballast-compatible LLT lamps becomes meaningless with the constant energy use by the ballast.\",\n \"In the long run, ballast-compatible LLT lamps are more expensive and less efficient than self-sustaining AC mains-operable LLT lamps.\",\n \"On the contrary, an AC mains-operable LLT lamp does not require a ballast to operate.\",\n \"Before use of an AC mains-operable LLT lamp, the ballast in a fixture must be removed or bypassed.\",\n \"Removing or bypassing the ballast does not require an electrician and can be replaced by end users.\",\n \"Each AC mains-operable LLT lamp is self-sustaining.\",\n \"If one AC mains-operable tube lamp in a fixture goes out, other lamps in the fixture are not affected.\",\n \"Once installed, the AC mains-operable LLT lamps will only need to be replaced after 50,000 hours.\",\n \"In view of above advantages and disadvantages of both ballast-compatible LLT lamps and AC mains-operable LLT lamps, it seems that market needs a most cost-effective solution by using a universal LLT lamp that can be used with the AC mains and is compatible with a ballast so that LLT lamp users can save an initial cost by changeover to such a universal LLT lamp followed by retrofitting the lamp fixture to be used with the AC mains when the ballast dies.\",\n \"In the U.S. patent application Ser.\",\n \"No.\",\n \"14/688,841, filed Apr.\",\n \"16, 2015, two shock prevention switches and an all-in-one driving circuit are adopted in an LLT lamp such that AC power from either a ballast or the AC mains can operate the LLT lamp without operational uncertainty and electric shock hazards.\",\n \"In other words, no matter what a lamp fixture is configured as the AC mains- or a ballast-compatible fashion, the LLT lamp automatically detects configurations and works for either one.\",\n \"All of such LLT lamps, no matter whether AC mains-operable or ballast-compatible, are electrically wired as double-ended and have one construction issue related to product safety and needed to be resolved prior to wide field deployment.\",\n \"This kind of LLT lamps, if no shock prevention scheme is adopted in, always fails a safety test, which measures a through-lamp electric shock current.\",\n \"Because an AC-mains voltage applies to both opposite ends of the LLT lamps, the measurement of current leakage from one end to the other consistently results in a substantial current flow, which may present a risk of an electric shock during re-lamping.\",\n \"Due to this potential shock risk to the person who replaces the LLT lamps in an existing fluorescent tube fixture, Underwriters Laboratories (UL) uses its safety standard, UL 935, Risk of Shock During Relamping (Through Lamp), to do a current leakage test and to determine if the LLT lamps meet the consumer safety requirement.\",\n \"Although the LLT lamps used with a ballast can pass the current leakage test, some kinds of electric shock hazards do exist.\",\n \"Experimental results show that the skin of the person who touches an exposed bi-pin may be burned due to such an electric shock.\",\n \"Fortunately, a mechanism of double shock prevention switches used in applications with the AC mains is also effective in applications with the ballasts to prevent the electric shock from occurring, thus protecting consumers from such a hazard, no matter whether input voltage is from the AC mains or the ballast.\",\n \"Therefore, a universal LLT lamp that can work with either the AC mains or the ballast makes sense.\",\n \"The effectiveness of using double shock prevention switches for applications in the AC mains has been well addressed in U.S. Pat.\",\n \"No.\",\n \"8,147,091, issued on Apr.\",\n \"3, 2012.However, a conventional shock prevention switch has an inherent issue related to an electric arc when operated with a ballast.\",\n \"Unlike an AC voltage of 120 or 277 V/50-60 Hz from the AC mains, the output AC voltage and current from the ballast presents a negative resistance characteristic.\",\n \"The feature that originally supports a fluorescent tube to function properly becomes extremely detrimental to the conventional shock prevention switch due to the electric arc likely occurring between two electrical contacts that have a high electrical potential difference with a high frequency, such as 600 V/50 kHz.\",\n \"Once a consumer fails to follow installation instructions to install or uninstall linear LED tube lamps such that one of two ends of the tube lamp is in the fixture socket connected to a powered ballast, and the other end is tweaked to connect to or disconnect from the associated socket, an internal electric arcing may occur between the electrical contacts in the associated switch.\",\n \"The arcing even in a short period such as several seconds can generate high heat, burning and melting electrical contacts and neighboring plastic enclosures, creating a fire hazard.\",\n \"The AC voltage of 120 or 277 V/50-60 Hz from the AC mains does not have such an issue because its voltage is relatively low compared with the ballast output voltage of 600 V. Moreover, the AC frequency of 60 Hz automatically extinguishes an electric arc every 1/60 seconds, if existed.\",\n \"That is why a utility switch can be used in an electrical appliance to turn power on and off without any problem.\",\n \"However when used with the ballast, the electrical contacts used in the conventional shock prevention switch can easily be burned out due to the high-voltage and high-frequency arcing introduced between each gap of each pair of the electrical contacts in the conventional shock prevention switch when someone tries to abusively tweak to remove the tube lamp from the fixture with the ballast that has a power on it.\",\n \"Although such a situation is rare, an internal arcing, if occurred, does cause burning and even welding of the electrical contacts and melting of the plastic enclosure, so called internal fire, creating consumer safety issues.\",\n \"Today, such LLT lamps are mostly used in a ceiling light fixture with a wall-mount power switch.\",\n \"The ceiling light fixture could be an existing one used with fluorescent tubes but retrofitted for LLT lamps or a specific LLT lamp fixture.\",\n \"The drivers that provide a proper voltage and current to LED arrays could be internal or external ones.\",\n \"Not like LLT lamps with an external driver that is inherently electric-shock free if the driver can pass a dielectric withstand test used in the industry, LLT lamps with an internal driver could have a shock hazard during relamping or maintenance, when the substantial through-lamp electric shock current flows from any one of AC voltage inputs through the internal driver connecting to LED arrays to the earth ground.\",\n \"Despite this disadvantage, LLT lamps with the internal driver still receive wide acceptance because they provide a stand-alone functionality and an easy retrofit for an LLT lamp fixture.\",\n \"As consumerism develops, consumer product safety becomes extremely important.\",\n \"Any products with electric shock or fire hazards and risk of injuries or deaths are absolutely not acceptable for consumers.\",\n \"However, commercially available LLT lamps with internal drivers, single-ended or double-ended, fail to provide effective solutions to the problems of possible electric shock and internal arcing and fire.\",\n \"In the prior art mentioned above, the double shock protection switches with mechanical actuation mechanisms protruding outwards from both ends of the LLT lamp are proposed to control a line voltage from the AC mains or high voltages from the ballasts to connect to the LLT lamp.\",\n \"However, a length control of the LLT lamp becomes critical to operate the LLT lamp because sometimes the double shock protection switches may not be actuated by the mechanical actuation mechanisms.\",\n \"Also, the double shock protection switches directly control AC voltages such as 120 or 277 V/50˜60 Hz from the AC mains or 600 V/45˜65 kHz from the ballasts, which makes the conventional LLT lamp so vulnerable because such high voltages working on the double shock protection switches may easily cause internal fire if consumers abusively tweak the mechanical actuation mechanisms at both ends of the LLT lamp operable with a ballast during relamping.\",\n \"Another prior art may involve an electronic approach to eliminating electric shock.\",\n \"However, such an electronic approach may not be as reliable as expected, especially in real applications where the electronic approach continues to fail in electric shock and arcing situations.\",\n \"It is, therefore, the purpose of the present disclosure to disclose a novel low-voltage control approach to be used in the LLT lamp to eliminate above-mentioned electric shock and internal fire hazards and to work more reliably to protect consumers.\",\n \"SUMMARY A linear light-emitting diode (LED)-based solid-state tube (LLT) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, at least one conductor protruding outwards from each lamp base, and at least two pairs of electrical contacts controlled by the at least two proximity sensors, is used to replace a fluorescent tube or a conventional LED tube lamp without the at least two proximity sensors and the at least two pairs of electrical contacts.\",\n \"The at least two proximity sensors and the at least two pairs of electrical contacts are configured to respectively perform proximity sensing between the two lamp bases and two sockets in an existing lamp fixture.\",\n \"When both two lamp bases are inserted in the two sockets, the at least two pairs of electrical contacts are driven by the at least two proximity sensors to make an electrical connection between the full-wave rectifier and the LED driving circuit, rather than between an alternate current (AC) voltage input and the full-wave rectifier, to power the LED driving circuit and the one or more LED arrays.\",\n \"When either one of the two lamp bases is not inserted in one of the two sockets, the at least two pairs of electrical contacts are disabled so as to disconnect a direct current (DC) current flow from the full-wave rectifier to the LED driving circuit.\",\n \"Without such DC current flowing to power the LED driving circuit, a substantial through-lamp electric shock current is considered not to exist.\",\n \"Furthermore, the at least two pairs of electrical contacts are interconnected between the full-wave rectifier and the LED driving circuit, the DC voltage provided to the LED driving circuit can be made small by using a voltage divider.\",\n \"In such a case, no high voltage at a high frequency from a ballast is present at any open/closed electrical contacts in the LLT lamp, thus no internal fire possible.\",\n \"The scheme can effectively reduce a risk of electric shock and a fire hazard to users during relamping or maintenance.\",\n \"In one embodiment, the LLT lamp further comprises at least two magnets and at least two Hall effect sensors configured to form at least two magnetic proximity sensor pairs at the two ends of the LLT lamp and to provide a non-contact actuation of the at least two pairs of electrical contacts.\",\n \"When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.\",\n \"In this case, both the at least two pairs of electrical contacts are electrically connected by the non-contact actuation of the at least two magnetic proximity sensor pairs, whereas a low DC voltage is applied to the LED driving circuit to control a substantial electric current to flow into the one or more LED arrays.\",\n \"However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.\",\n \"In this case, the respective one of the at least two magnetic proximity sensor pairs associated with the exposed lamp base is not actuated with respective one of the at least two electrical contacts not electrically connected.\",\n \"Because the at least two electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.\",\n \"No substantial electric shock current can possibly be leaked out of exposed at least one electrical conductor.\",\n \"In other words, once the at least one electrical conductor is exposed during relamping, the driving circuit will not receive a proper voltage to operate.\",\n \"Thus, an overall through-lamp electric shock current may be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.\",\n \"A controlling electronic circuit, which only supports an actuation of an electronic switch, indeed, has a much smaller power consumption than the one or more LED arrays do.\",\n \"Experimental results show that such a through-lamp electric shock current not going through the one or more LED arrays can be controlled to an acceptable level according to a safety standard UL 935.In another embodiment, the LLT lamp may further comprise at least two displacement sensors configured to sense if the two ends of the LLT lamp are between the two sockets in the fixture.\",\n \"When both two lamp bases of the LLT lamp are in the sockets, there is no exposed at least one conductor that installers can possibly touch, creating an electric shock hazard.\",\n \"In this case, both the at least two pairs of electrical contacts are electrically connected by an actuation of displacement sensors, whereas a low DC voltage is applied to the LED driving circuit, controlling electric current to flow into the one or more LED arrays.\",\n \"However, when either one of the two lamp bases of the LLT lamp is not in the respective socket, the electric shock hazard occurs.\",\n \"In this case, the respective one of the at least two displacement sensors associated with the exposed lamp base is not actuated with respective one of the at least two pairs of electrical contacts not electrically connected.\",\n \"Because at least two pairs of electrical contacts are interconnected at a low voltage input of the LED driving circuit, the low DC voltage does not apply to the LED driving circuit, disabling operation of the LED driving circuit.\",\n \"No substantial electric shock current can possibly be leaked out of the exposed at least one electrical conductor.\",\n \"In other words, once the at least one electrical conductor is exposed during relamping, the LED driving circuit will not receive a proper voltage to operate.\",\n \"Thus, an overall through-lamp electric shock current can be limited to a small amount rather than the substantial electric shock current flowing through the LED driving circuit and the one or more LED arrays.\",\n \"Furthermore, the use of the low DC voltage in controlling electrical contacts to be on or off has one of unique advantages.\",\n \"That is, no matter whether AC sources is AC mains from an electrical grid or power supplies from various ballasts, no significant arc can be observed due to a low DC current associated with the low DC voltage.\",\n \"In other words, an internal arcing and firing will never occur using this approach, thus eliminating any internal fire hazard and enhancing operation reliability.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Non-limiting and non-exhaustive embodiments of the present disclosure are described with reference to the following figures, wherein like reference numerals refer to like parts throughout the various figures unless otherwise specified.\",\n \"FIG.\",\n \"1 is an embodiment of an LLT lamp installed in lamp fixture sockets connected with AC sources that include AC mains and ballasts according to the present disclosure.\",\n \"FIG.\",\n \"2 is another embodiment of an LLT lamp installed in lamp fixture sockets connected with AC sources that include AC mains and ballasts according to the present disclosure.\",\n \"FIG.\",\n \"3 is a block diagram of an LED driving circuit used in an LLT lamp depicted in FIG.\",\n \"2 operable with either the AC mains or ballasts according to the present disclosure.\",\n \"FIG.\",\n \"4 is a block diagram of another embodiment of an LED driving circuit used in an LLT lamp depicted in FIG.\",\n \"2 operable with either the AC mains or ballasts according to the present disclosure.\",\n \"DETAILED DESCRIPTION OF THE INVENTION FIG.\",\n \"1 is an embodiment of a linear LED tube (LLT) lamp installed in lamp fixture sockets connected with alternate current (AC) sources that include AC mains and ballasts according to the present disclosure.\",\n \"The LLT lamp 500 comprises a housing having two ends; two lamp bases 660 and 760 each having at least one electrical conductor 250 and 350 at each end of the housing; a first magnetic proximity sensor pair 310 close to the lamp base 660; a second magnetic proximity sensor pair 320 close to the lamp base 760; a controller 330; an LED driving circuit 100; and one or more LED arrays 214 disposed on an LED PCB 617 with the one or more LED arrays 214 connected to the LED driving circuit 100.The controller 330 comprises a set of voltage dividers and regulators 340, a switch control unit 360, at least one switch 370, and a full-wave rectifier 603 consisting of diodes 611, 612, 613, and 614 interconnected at ports 402, 404, 503, and 504.The first magnetic proximity sensor pair 310 comprises a magnet 380 and a Hall effect sensor 381.Similarly, the second magnetic proximity sensor pair 320 comprises a magnet 382 and a Hall effect sensor 383.The full-wave rectifier 603 is configured to convert an AC voltage from the AC mains or the ballasts into a direct current (DC) voltage with a voltage of V+ at the port 503 applied to the LED driving circuit 100.The set of voltage dividers and regulators 340 receives the DC voltage from the full-wave rectifier 603 via a diode 384 configured to block an electric current backward flowing to the at least one full-wave rectifier 603 and converts it into a low DC voltage to operate the Hall effect sensors 381 and 383 and the switch control unit 360.When both two lamp bases 660 and 760 are in fixture sockets 810 and 820, there is no exposed at least one conductor 250 or 350 that installers can possibly touch, creating an electric shock hazard.\",\n \"In this case, both the magnets 380 and 382 are respectively in close proximity to the Hall effect sensors 381 and 383, and the magnetic proximity sensor pairs 310 and 320 are actuated to respectively output low-level signals 385 and 386.Such a non-contact actuation of the magnetic proximity sensor pairs 310 and 320 increases operating reliability.\",\n \"The switch control unit 360 comprises a transistor 387 and a logic circuit 388 configured to control the transistor 387, further maneuvering the at least one switch 370 to control a current returned from the LED driving circuit 100.The low-level signals 385 and 386 are inputted to the logic circuit 388 to turn on the at least one switch 370, enabling the current returned from the LED driving circuit 100 back to the port 504, thus completing a power transfer to the one or more LED arrays 214.When either one of the two lamp bases of the LLT lamp is not in the respective socket, there is a risk of electric shock for installers.\",\n \"In this case, one of the two magnets, say 382, is not in close proximity to the respective Hall effect sensor 383 whereas the other magnet 380 is in close proximity to the other respective Hall effect sensor 381 and ready to operate.\",\n \"However, both Hall effect sensors 381 and 383 need power to operate.\",\n \"At the instant when an installer touches the exposed at least one conductor 350, both Hall effect sensors 381 and 383 are energized, but only the magnetic proximity sensor pair 310 is actuated.\",\n \"That is, only the Hall effect sensors 381 sends a low-level signal to the logic circuit 388, whereas the Hall effect sensor 383 sends a high-level signal to the logic circuit 388 because the magnet 382 is not in close proximity to the Hall effect sensor 383.The logic circuit 388 determines that there is an electric shock risk and controls the transistor 387 to electrically conduct the collector and the emitter of the transistor 387, subsequently turning off the at least one switch 370.No substantial electric current returned from the LED driving circuit 100 and the at least one or more LED arrays 214 can possibly leak out from the port 504, further flowing to the exposed at least one conductor 350.Thus, the LLT lamp does not light up.\",\n \"In other words, once the at least one electrical conductor 250 and 350 is exposed during relamping, the LED driving circuit 100 will not receive power to operate.\",\n \"Thus, an overall through-lamp electric shock current may be limited to a small amount that needs at least to operate the set of voltage dividers and regulators 340, the logic circuit 388, the two Hall effect sensors 381 and 383, the transistor 387, and the at least one switch 370, rather than a substantial electric shock current flowing through the LED driving circuit 100 and the one or more LED arrays 214.Indeed, power consumption of the control electronics, which supports the electric shock detection and actuation of at least one switch 370, is much smaller than that of the LED driving circuit 100 powering one or more LED arrays 214.Experimental results show that the through-lamp electric shock current can be controlled to an acceptable level according to a safety standard UL 935.In FIG.\",\n \"1, the full-wave rectifier 603 is always connected to the at least one electrical conductor 250 and the at least one electrical conductor 350 and receives AC power from the AC mains or the ballasts.\",\n \"This is different from prior art, which uses double safety switches to control the at least one electrical conductor 250 and the at least one electrical conductor 350 to make connections to the full-wave rectifier 603.In FIG.\",\n \"1, the LED driving circuit 100 directly connects to the full-wave rectifier 603, receiving the DC voltage V+ from the port 503.The LED driving circuit 100 may comprise its own full-wave rectifier to energize the one or more LED arrays 214.Only when both the first and the second magnetic proximity sensor pairs are actuated, can the at least one switch 370 controlled by the switch control unit 360 conduct an electric current returned from the LED driving circuit 100 to the full-wave rectifier 603, completing a power transfer.\",\n \"Specifically, when both the at least one electrical conductor 250 and the at least one electrical conductor 350 in each lamp base are inserted into the lamp fixture sockets 810 and 820, the controller 330 receives power from the AC sources and operates to individually actuate the first and the second magnetic proximity sensor pairs 310 and 320.For a positive cycle, the electric current from one port of the AC sources, AC mains or ballasts, can flow from the electrical contact 401 of the at least one electrical conductor 250, the full-wave rectifier 603 through the diode 611 to the port 503 of the LED driving circuit 100, further down into the one or more LED arrays 214, and return to a port 505 of the LED driving circuit 100.Because both the first and the second magnetic proximity sensor pairs 310 and 320 are actuated, the at least one switch 370 is “on”.\",\n \"The electric current continues to flow through the port 504, the diode 614 of the full-wave rectifier 603, the electrical contact 405 of the at least one electrical conductor 350 to the other port of the AC sources, completing the positive half cycle power transfer.\",\n \"For a negative half cycle, the electric current from one port of the AC sources can flow from the electrical contact 405 of the at least one electrical conductor 350, the full-wave rectifier 603 through the diode 612 to the port 503 of the LED driving circuit 100, further down into the one or more LED arrays 214, and return to the port 505 of the LED driving circuit 100.The electric current continues to flow through the diode 613 of the full-wave rectifier 603, the electrical contact 401 of the at least one electrical conductor 250 to the other port of the AC sources, completing the negative half cycle power transfer.\",\n \"When the lamp base 660 is inserted in the lamp socket 810, which connects to one port of the AC sources (say, the left side in FIG.\",\n \"1), the LLT lamp 500 is energized.\",\n \"If the first and the second magnetic proximity sensor pairs 310 and 320 do not exist to control the electric current return, a substantial through-lamp electric shock current from the LED driving circuit 100 and the one or more LED arrays 214 can always come out through the at least one electrical conductor 350, which may be exposed to a user for an electric shock.\",\n \"The electric shock may be fatal depending on impedance between the user's body and the earth ground.\",\n \"On the other hand, if the first and the second magnetic proximity sensor pairs 310 and 320 exist and send the low-level signals to the controller 330 to control the electric current returned from the LED driving circuit 100, then the through-lamp electric shock current from the LED driving circuit 100 and the one or more LED arrays 214 is zero.\",\n \"However, the through-lamp electric shock current can come out from the controller 330 that needs power to actuate the first and the second magnetic proximity sensor pairs 310 and 320, to determine for the logic circuit 388 if the electric shock hazard occurs, and to control the at least one switch 370.Because such a load is a fraction of one from the one or more LED arrays 214, the through-lamp electric shock current in this case can be controlled to an acceptable level not exceeding a specific value defined in the safety standard UL 935, no fatal electric shock possible.\",\n \"In a normal operation when the at least one electrical conductor 250 and the at least one electrical conductor 350 are connected to the AC mains or the ballast in a double-ended wiring lamp fixture, the LED driving circuit 100 can receive power to drive the one or more LED arrays 214.As can be seen in FIG.\",\n \"1, two sockets in each of the external fixture lamp sockets 810 and 820 are shunted, meaning that as long as the at least one electrical conductor 250 in the lamp base 660 and the at least one electrical conductor 350 in the lamp base 760 are connected to the AC sources, the LLT lamp using the approach depicted in FIG.\",\n \"1 can operate with an acceptable through-lamp electric shock current, which is deemed safe for users.\",\n \"In FIG.\",\n \"1, the LED driving circuit 100 may comprise a second at least one full-wave rectifier configured to receive the DC voltage from the at least one full-wave rectifier 603 and to operate the one or more LED arrays 214.The at least one switch 370 may comprise a metal-oxide-semiconductor field-effect transistor (MOSFET), a transistor, a back-to-back thyristor, a silicon-controlled rectifier (SCR), a relay, or a combination thereof.\",\n \"Also such devices may be connected with some snubber circuits to maintain their functionality under voltage spikes.\",\n \"The low DC voltage used to operate the magnetic proximity sensor pairs 310 and 320 meets voltage requirements of a Class 2 circuit, which is considered safe from a fire initiation viewpoint and provides an acceptable level of protection from electrical shock.\",\n \"FIG.\",\n \"2 is another embodiment of an LLT lamp installed in lamp fixture sockets connected with AC sources that include AC mains and ballasts according to the present disclosure.\",\n \"The LLT lamp 600 comprises a housing having two ends; two lamp bases 660 and 760 each having at least one electrical conductor 250 and 350 at each end of the housing; a first displacement sensor pair 511 close to the lamp base 660 comprising a displacement sensor 516 and a first pair of electrical contacts 301 and 302; a second displacement sensor pair 512 close to the lamp base 760 comprising a displacement sensor 517 and a second pair of electrical contacts 303 and 304; a full-wave rectifier 603 comprising diodes 611, 612, 613, and 614 interconnected at ports 402, 404, 503, and 504; an LED driving circuit 110; and one or more LED arrays 214 disposed on an LED PCB 617 with the one or more LED arrays 214 connected to the LED driving circuit 110.The LED driving circuit 110 comprises an input filter 102 connected to the port 503 of the full-wave rectifier 603, one or more start-up resistors 104 connected to the input filter 102, and a driver 400 connected to the one or more LED arrays 214.The driver 400 comprises a low voltage input 513, a high voltage input 514 connected to a port 518 of the input filter 102, and a common port 515 connected to the port 504 of the full-wave rectifier 603.The high voltage input 514 is configured to connect to a Buck converter (in FIGS.\",\n \"3 and 4), whereas the low voltage input 513 is originally configured to connect to the one or more start-up resistors 104 and to control the Buck converter to provide a proper current and voltage to drive the one or more LED arrays 214.In FIG.\",\n \"2, the first and the second pairs of electrical contacts 301, 302, 303, and 304 are interconnected in series and looped between the one or more start-up resistors 104 and the low voltage input 513 of the driver 400.The full-wave rectifier 603 is always connected to the at least one electrical conductor 250 and the at least one electrical conductor 350 and receives AC power from the AC mains or the ballasts.\",\n \"As in FIG.\",\n \"1, this is different from prior art, which uses double safety switches to make connections between the at least one electrical conductors 250 and 350 and the full-wave rectifier 603.In FIG.\",\n \"2, the LED driving circuit 110 directly connects to the full-wave rectifier 603, receiving the DC voltage V+ from the port 503.When the first and the second pairs of electrical contacts 301, 302, 303, and 304 are not individually electrically connected, the one or more start-up resistors 104 is not connected to the low voltage input 513 of the driver 400, thus disabling the driver 400 to power one or more LED arrays 214.Without electric current returned from one or more LED arrays 214 to reach an exposed at least one electrical conductor 250 or 350, no electric shock hazard will occur even though the at least one electrical conductor 250 and the at least one electrical conductor 350 are electrically connected with the full-wave rectifier 603, which energizes the LED driving circuit 110.When both the at least one electrical conductor 250 and the at least one electrical conductor 350 in each lamp base are respectively inserted into the lamp fixture sockets 810 and 820, the one or more start-up resistors 104 provides a low DC voltage to individually actuate the first and the second pairs of electrical contacts 301, 302, 303, and 304 in a way that an electric current can conduct between the first pair of electrical contacts 301 and 302 and between the second pair of electrical contacts 303 and 304.The electric current can flow from an output port 519 of the one or more start-up resistors 104, the first pair of electrical contacts 301 and 302, the second pair of electrical contacts 303 and 304, entering the low voltage input port 513 of the driver 400.For a positive cycle, the electric current from one port of the AC sources can flow from the electrical contact 401 of the at least one electrical conductor 250, the full-wave rectifier 603 through the diode 611 to the port 503 of the LED driving circuit 110, going through the input filter 102.The low DC voltage from the one or more start-up resistors 104 is applied to the first pair of electrical contacts 301 and 302, the second pair of electrical contacts 303 and 304, entering the low voltage input port 513 of the driver 400.Whereas the high voltage input port 514 of the driver 400 is already energized, the low DC voltage from the one or more start-up resistors 104 starts to operate the driver 400, powering the one or more LED arrays 214.The current returns to the common port 515 of the driver 400, continuing to flow through the diode 614 of the full-wave rectifier 603, the electrical contact 405 of the at least one electrical conductor 350 to the other port of the AC sources, completing the positive half cycle power transfer.\",\n \"For a negative half cycle, the electric current from one port of the AC sources can flow from the electrical contact 405 of the at least one electrical conductor 350, the full-wave rectifier 603 through the diode 612 to the port 503 of the LED driving circuit 110.Similar to the current flow in the LED driving circuit 110 for positive cycle, the electric current continues to flow through the diode 613 of the full-wave rectifier 603, the electrical contact 401 of the at least one electrical conductor 250 to the other port of the AC sources, completing the negative half cycle power transfer.\",\n \"When the lamp base 660 is inserted in the lamp socket 810, which connects to one port of the AC sources (say, the left side in FIG.\",\n \"1), the LLT lamp 600 is energized.\",\n \"If the first and the second pairs of electrical contacts 301, 302, 303, and 304 do not exist to control the electric current conduction, a substantial through-lamp electric shock current from the LED driving circuit 110 and the one or more LED arrays 214 can always come out through the at least one electrical conductor 350, which may be exposed to a user for an electric shock.\",\n \"The electric shock may be fatal depending on impedance between the user's body and the earth ground.\",\n \"On the other hand, if the first and the second pairs of electrical contacts 301, 302, 303, and 304 exist and are connected in series and looped between the one or more start-up resistors 104 and the driver 400, then the through-lamp electric shock current from the LED driving circuit 100 and the one or more LED arrays 214 can be set to zero.\",\n \"However, a small amount of the through-lamp electric shock current will come out from the input filter 102 and some safety varistors and capacitors (not shown in FIG.\",\n \"2) in front of the full-wave rectifier 603, which need power to operate.\",\n \"Because such a load is a fraction of the load from the one or more LED arrays 214, its through-lamp electric shock current can be controlled to an acceptable level not exceeding a specific value defined in the safety standard UL 935, no fatal electric shock possible.\",\n \"In a normal operation when the at least one electrical conductor 250 and the at least one electrical conductor 350 are connected to the AC mains or the ballasts in a double-ended wiring lamp fixture, the LED driving circuit 110 can receive power to drive the one or more LED arrays 214.As can be seen in FIG.\",\n \"2, two sockets in each of the external fixture lamp sockets 810 and 820 are shunted, meaning that as long as the at least one electrical conductor 250 in the lamp base 660 and the at least one electrical conductor 350 in the lamp base 760 are connected to the AC sources, the LLT lamp adopting the approach depicted in FIG.\",\n \"2 can operate with an acceptable through-lamp electric shock current, which is deemed safe for users.\",\n \"FIG.\",\n \"3 is a block diagram of an LED driving circuit used in an LLT lamp depicted in FIG.\",\n \"2 operable with either the AC mains or the ballasts according to the present disclosure.\",\n \"A full-wave rectifier 603 connecting to an AC source, either the AC mains or the ballast, converts an AC voltage into a DC voltage.\",\n \"An LED driving circuit 110, connecting to the full-wave rectifier 603, comprises an input filter 102 used to filter the input voltage and to suppress EMI noise created in the LED driving circuit 110, one or more start-up resistors 104, a driver 400, an electrical jumper pair 109 connecting between the one or more start-up resistors 104 and the driver 400 with a terminal module 500 outside the LED driving circuit 110, The driver 400 comprises a power factor correction (PFC) and control device 103, a Buck converter 200 in communicating with the PFC and control device 103, an output capacitor 105 in parallel with a resistor 106 connected to the Buck converter 200 to build up an output voltage and to power the one or more LED arrays 214, a current sensing resistor 107, and a voltage feedback module 300 extracting partial energy from the output voltage to sustain the PFC and control device 103.The driver 400 has a high voltage input port 108 and a low voltage input port 501.The terminal module 500 comprises the first pair of electrical contacts 301 and 302 and the second pair of electrical contacts 303 and 304 interconnected in series, as depicted in FIG.\",\n \"2.Either one of the two pairs of electrical contacts not electrically connected results in a lost connection at the low voltage input port 501 and renders an electrical disconnection between the one or more start-up resistors 104 and the driver 400.The full-wave rectifier 603 has four input/output ports, among which a high electric potential appears at the input/output port 503 as V+, and a low electric potential appears at the input/output port 504 as V−, respectively connecting to the high side and the low side of the input filter 102 with the low electric potential port 504 as a common ground.\",\n \"The Buck converter 200 comprises a switch 201 controlled by the PFC and control device 103, a diode 202, and an inductor 203 with its current charging and discharging controlled by the switch 201.When both two pairs of electrical contacts are individually connected, the electrical jumper pair 109 connecting to the terminal module 500 conducts so that a low DC voltage from the one or more start-up resistors 104 applies to the PFC and control device 103 to sustain its operation.\",\n \"Then the driver 400 can detect zero current in the inductor 203 within an AC cycle of an input voltage generating a zero current detection signal and controls the switch 201 on and off with a constant on-time and a varied off-time controlled by the zero current detection signal.\",\n \"By adapting switching frequencies for a high frequency associated with a ballast and a low frequency associated with the AC mains, the PFC and control device 103 controls the switch 201 on and off in a way that the inductor 203 is charged during on-time and discharged during off-time, and that a desired output voltage Vo across the one or more LED arrays 214 is reached to light up the one or more LED arrays 214.The average inductor current is thus equal to the output current that flows into the LED array 214.When the switch 201 is on, the diode 202 is reverse-biased, and an input current flows from an output port 108 in the input filter 102, the switch 201, the first port 204 of the current sensing resistor 107, the current sensing resistor 107 itself, and the second port 205 of the current sensing resistor 107, into the inductor 203.When the current flowing into the inductor 203 increases, the voltage across the current sensing resistor 107 increases.\",\n \"The second port 205 of the current sensing resistor 107 connects with the PFC and control device 103, which continuously receives signals and adjusts the off-time such that the output voltage and current to the one or more LED arrays 214 are regulated to meet the output requirements.\",\n \"The output capacitor 105 in parallel with the resistor 106 connects to the inductor 203, receiving energy to build up an output voltage and to power the one or more LED arrays 214.The inductor 203 configured as an autotransformer has a center-tapped port connecting to the first port 301 of the voltage feedback module 300 comprising a diode.\",\n \"The voltage feedback module 300 has two connection ports 305 and 306, with the first connection port 305 connecting to the center-tapped port of center-tapped inductor 203 and with the second connection port 306 connecting to the PFC and control device 103.The PFC and control device 103 has an input capacitor (not shown) with a voltage built up to supply an internal logic control circuit (not shown) in the PFC and control device 103 When the voltage decreases due to its increased internal operations and controls, and when the voltage at the center-tapped port of the inductor 203 is higher than the supplying voltage, the diode in the voltage feedback module 300 conducts to supply a current to the PFC and control device 103 and sustain its operations.\",\n \"The function of the voltage feedback module 300 is essential because the LED driving circuit 110 has a wide range of operating voltages not only 110 and 277 VAC for AC mains but also 375˜400 VAC for a ballast.\",\n \"The one or more start-up resistor 104 is so designed to operate a LLT lamp at the lowest input voltage 110 VAC.\",\n \"When the highest voltage 400 VAC from the ballast comes in, a higher proportional voltage appears at an input of the internal logic control circuit.\",\n \"Therefore an operating voltage for the internal logic control circuit must be in a wide range such as 11˜35 VDC rather than 5˜15 VDC as in a conventional logic control device.\",\n \"To meet requirements of start-up time and current without turn-on failure or flickering occurred at the lamp start-up, the input capacitor in the PFC and control device 103 with a minimum capacitance is designed and used at the input of the internal logic control circuit.\",\n \"The voltage feedback module 300 is thus needed to pump in energy in time and to sustain the operating voltage and ensure no flickering occurred when operating the LLT lamp.\",\n \"When the switch 201 is off, the diode 202 is forward-biased, and the inductor 203 discharges with a loop current flowing from the one or more LED arrays 214, the diode 202, the current sensing resistor 107, back to the inductor 203.The current sensing resistor 107 keeps track of the output current and feedbacks to the PFC and control device 103 to further control the switch 201 on and off.\",\n \"The closed loop operation in both on-time and off-time of the switch 201 ensures the output current to be accurately controlled within 4%.\",\n \"FIG.\",\n \"4 is a block diagram of another embodiment of an LED driving circuit used in an LLT lamp depicted in FIG.\",\n \"2 operable with either the AC mains or the ballasts according to the present disclosure.\",\n \"The LED driving circuit 120 in FIG.\",\n \"4 has all the components as the LED driving circuit 110 in FIG.\",\n \"3, except that interconnections are different, and a transformer 206 in FIG.\",\n \"4 replaces the center-tapped inductor 203 in FIG.\",\n \"3.In FIG.\",\n \"4, the same numerals are used for the same components as in FIG.\",\n \"3.As in FIG.\",\n \"3, the LED driving circuit 120, connecting to the full-wave rectifier 603, comprises an input filter 102, one or more start-up resistors 104, a driver 400, an electrical jumper pair 109 connecting between the one or more start-up resistors 104 and the driver 400 with a terminal module 500 outside the LED driving circuit 120, The driver 400 comprises a PFC and control device 103, a Buck converter 200 in communicating with the PFC and control device 103, an output capacitor 105 in parallel with a resistor 106 connected to the Buck converter 200 to build up an output voltage and to power the one or more LED arrays 214, a current sensing resistor 107, and a voltage feedback module 300 extracting partial energy from the output voltage to sustain the PFC and control device 103.The terminal module 500 comprises the first pair of electrical contacts 301 and 302 and the second pairs of electrical contacts 303 and 304 interconnected in series, as depicted in FIG.\",\n \"2.Either one of the two pairs of electrical contacts not electrically connected renders an electrical disconnection between the one or more start-up resistors 104 and the driver 400.In FIG.\",\n \"4, the driver 400 has a high voltage input port 108 and a low voltage input port 501.When the power is on, the high voltage input port 108 of the driver 400 receives an input current via the input filter 102, and the switch 201 controlled by the PFC and control device 103 is ready to be turned on to control the Buck converter 200.However, when the terminal module 500 is off, the low voltage input port 501 loses a connection, meaning that the driver 103 is not yet operable.\",\n \"Only when the first pair of electrical contacts 301 and 302 and the second pairs of electrical contacts 303 and 304 in the terminal module 500 are individually connected, can the switch 201 be controlled to turn on or off.\",\n \"When the switch 201 is on, the diode 202 is reverse-biased, and the input current goes from the resistor 106, a primary side of the transformer 206, the switch 201, and the current sensing resistor 107 to the common ground 504, completing an AC cycle.\",\n \"When the input current goes into the primary side of the transformer 206, energy is stored in it.\",\n \"The PFC and control device 103 detects the input voltage level and control the switch 201 on and off in a way that a desired output voltage Vo across the one or more LED arrays 214 is reached to light up the one or more LED arrays 214.When the switch 201 is off, the diode 202 is forward-biased, and the primary side of the transformer 206 releases the energy stored, resulting in a loop current flowing from the diode 202 and the one or more LED arrays 214, back to the primary side of the transformer 206, completing the energy transfer to the one or more LED arrays 214.When the switch 201 is on, the input current flows into the one or more LED arrays 214, the primary side of the transformer 206, the switch 201, and the current sensing resistor 107, creating a voltage drop across the current sensing resistor 107.The voltage appearing at the port 204 of the current sensing resistor 107 inputs to the PFC and control device 103 to control the off-time of the switch 201.The voltage feedback module 300 has two connection ports 305 and 306, with the first connection port 305 connecting to a high side of a secondary winding 207 in the transformer 206 and with the second connection port 306 connecting to the PFC and control device 103, as in FIG.\",\n \"3.The voltage feedback module 300 continuously monitors the output voltage by using the secondary winding 207 in the transformer 206.When the voltage at the high side of the secondary winding 207 is higher than a becoming lower operating voltage in the PFC and control device 103 due to increased internal operations, the diode (not shown) in the voltage feedback module 300 conducts to supply energy in time through the second connection port 306 to sustain the operating voltage in the PFC and control device 103.In FIGS.\",\n \"1-4, the low DC voltage are used to control the through-lamp electric shock current flowing out from the LED driving circuit and the one or more LED arrays to reduce a risk of electric shock.\",\n \"The use of such a low DC voltage in controlling electrical contacts to be on or off has one of unique advantages.\",\n \"That is, no matter whether AC sources is AC mains from an electrical grid or power supplies from various ballasts, no significant arc can be observed due to a low current associated with the low voltage.\",\n \"In other words, an internal arcing and firing will never occur using this approach, thus eliminating any internal fire hazard and enhancing operation reliability.\",\n \"Whereas preferred embodiments of the present disclosure have been shown and described, it will be realized that alterations, modifications, and improvements may be made thereto without departing from the scope of the following claims.\",\n \"Another kind of the electric shock and internal fire prevention schemes in an LED-based lamp using various kinds of combinations to accomplish the same or different objectives could be easily adapted for use from the present disclosure.\",\n \"Accordingly, the foregoing descriptions and attached drawings are by way of example only, and are not intended to be limiting.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874752"}}},{"rowIdx":4494687,"cells":{"text":{"kind":"list like","value":[["HIGH CONDUCTIVITY GRAPHENE-METAL COMPOSITE","Embodiments of the present technology include graphene-metal composites.","An example graphene-metal composite comprises a porous metal foam substrate, a graphene layer deposited to the porous metal foam substrate, a metal layer applied to the graphene layer, and another graphene layer deposited to the metal layer; the multilayered porous metal foam substrate being compressed to form a graphene-metal composite."],["1.A graphene-metal composite comprising: a porous metal foam substrate and a graphene layer deposited to the porous metal foam substrate, the porous metal foam substrate and graphene being compressed to form a graphene-metal composite.","2.The graphene-metal composite according to claim 1, wherein the porous metal foam substrate is nickel or copper foam.","3.The graphene-metal composite according to claim 1, wherein the porosity of the porous metal foam substrate is at least 70%.","4.The graphene-metal composite according to claim 1, wherein the graphene layer is deposited to the porous metal foam substrate by chemical vapor deposition.","5.The graphene-metal composite according to claim 1, wherein the porous metal foam substrate with graphene applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with graphene applied thinner than the thickness of the non-compressed porous metal foam substrate.","6.A graphene-metal composite comprising: a porous metal foam substrate; a first graphene layer deposited to the porous metal foam substrate; a metal layer applied to the first graphene layer; and a second graphene layer deposited to the metal layer, at least some of the layers being compressed to form a graphene-metal composite.","7.The graphene-metal composite according to claim 6, wherein at least a second metal layer is applied to the second graphene layer and at least a third graphene layer is deposited to the second metal layer.","8.The graphene-metal composite according to claim 6, wherein the first graphene layer is deposited to the porous metal foam substrate by chemical vapor deposition.","9.The graphene-metal composite according to claim 6, wherein the porous metal foam substrate with the first graphene layer applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with the first graphene layer applied thinner than the thickness of the non-compressed porous metal foam substrate.","10.A stanene-metal composite comprising: a porous metal foam substrate and a first stanene layer deposited to the porous metal foam substrate, the porous metal foam substrate and first stanene layer being compressed to form a stanene-metal composite.","11.The stanene-metal composite according to claim 10, wherein at least a second metal layer is applied to the first stanene layer and at least a second stanene layer is deposited to the second metal layer.","12.The stanene-metal composite according to claim 10, wherein the stanene layer is deposited to the porous metal foam substrate by chemical vapor deposition.","13.The stanene-metal composite according to claim 10, wherein the porous metal foam substrate with stanene applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with stanene applied thinner than the thickness of the non-compressed porous metal foam substrate.","14.A stanene-metal composite comprising: a porous metal foam substrate; a stanene layer deposited to the porous metal foam substrate; a metal layer applied to the stanene layer; and another stanene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a stanene-metal composite.","15.The stanene-metal composite according to claim 14, wherein at least a second metal layer is applied to the first stanene layer and at least a second stanene layer is deposited to the second metal layer.","16.The stanene-metal composite according to claim 14, wherein the first stanene layer is deposited to the porous metal foam substrate by chemical vapor deposition.","17.The stanene-metal composite according to claim 14, wherein the porous metal foam substrate with stanene applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with stanene applied thinner than the thickness of the non-compressed porous metal foam substrate."],["<SOH> FIELD OF THE PRESENT TECHNOLOGY <EOH>The present technology relates generally to manufacturing methods, and more particularly but not by limitation, to methods that produce a graphene-metal composite or a stanene-metal composite to provide substantial heat and electrical transfer properties from materials such as graphene or stanene deposited on porous metal foam followed by compression to increase heat and electrical transfer properties."],["<SOH> SUMMARY <EOH>Embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate and a graphene layer deposited to the porous metal foam substrate, the porous metal foam substrate with graphene being compressed into a graphene-metal composite.","Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate and a stanene layer deposited to the porous metal foam substrate, the porous metal foam substrate with stanene being compressed into a stanene-metal composite.","In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing graphene or stanene onto a porous metal foam substrate and compressing the porous metal foam substrate with graphene or stanene applied to form a graphene-metal composite or stanene-metal composite.","In some embodiments, graphene or stanene is deposited onto the porous metal foam substrate by chemical vapor deposition.","Other embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate; a graphene layer deposited to the porous metal foam substrate; a metal layer applied to the graphene layer; and another graphene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a graphene-metal composite.","Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate; a stanene layer deposited to the porous metal foam substrate; a metal layer applied to the stanene layer; and another stanene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a stanene-metal composite.","In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing a layer of graphene or stanene onto a porous metal foam substrate; applying a layer of metal on top of the layer of graphene or stanene; depositing another layer of graphene or stanene onto the layer of metal; and compressing the multilayered porous metal foam substrate to form a graphene-metal composite or stanene-metal composite."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional application of and claims the priority benefit of U.S. patent application Ser.","No.","14/947,951 filed Nov. 20, 2015, entitled “High Conductivity Graphene-Metal Composite and Methods of Manufacture,” the disclosure of which is incorporated herein by reference.","FIELD OF THE PRESENT TECHNOLOGY The present technology relates generally to manufacturing methods, and more particularly but not by limitation, to methods that produce a graphene-metal composite or a stanene-metal composite to provide substantial heat and electrical transfer properties from materials such as graphene or stanene deposited on porous metal foam followed by compression to increase heat and electrical transfer properties.","SUMMARY Embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate and a graphene layer deposited to the porous metal foam substrate, the porous metal foam substrate with graphene being compressed into a graphene-metal composite.","Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate and a stanene layer deposited to the porous metal foam substrate, the porous metal foam substrate with stanene being compressed into a stanene-metal composite.","In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing graphene or stanene onto a porous metal foam substrate and compressing the porous metal foam substrate with graphene or stanene applied to form a graphene-metal composite or stanene-metal composite.","In some embodiments, graphene or stanene is deposited onto the porous metal foam substrate by chemical vapor deposition.","Other embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate; a graphene layer deposited to the porous metal foam substrate; a metal layer applied to the graphene layer; and another graphene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a graphene-metal composite.","Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate; a stanene layer deposited to the porous metal foam substrate; a metal layer applied to the stanene layer; and another stanene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a stanene-metal composite.","In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing a layer of graphene or stanene onto a porous metal foam substrate; applying a layer of metal on top of the layer of graphene or stanene; depositing another layer of graphene or stanene onto the layer of metal; and compressing the multilayered porous metal foam substrate to form a graphene-metal composite or stanene-metal composite.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1A is a SEM (scanning electron microscope) micrograph of a nickel foam structure.","FIG.","1B is a conceptual drawing showing an open-cell metal foam substrate such as nickel foam.","FIG.","2 illustrates the chemical structure of graphene.","FIG.","3 is a conceptual drawing showing the result of chemical vapor deposition of graphene in an open-cell metal foam substrate to form an example open-cell graphene-metal composite.","FIG.","4 illustrates an example of a chemical vapor deposition (CVD) manufacturing process.","FIG.","5 is a flow diagram illustrating an example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.","FIG.","6 is a cross sectional view of an embodiment of clad material with enhanced graphene according to exemplary embodiments of the present technology.","FIG.","7 is a cross sectional view of an embodiment of roll bonded nickel and copper foil enhanced with graphene according to exemplary embodiments of the present technology.","FIG.","8 illustrates die casting enhanced nickel foam into a frame according to exemplary embodiments of the present technology.","FIG.","9 is a flow diagram illustrating another example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.","FIG.","10 is a schematic diagram of an example computer system that can be utilized to implement aspects of the present technology.","FIG.","11 is a flow diagram illustrating another example method of manufacturing a graphane-metal composite according to exemplary embodiments of the present technology.","FIG.","12 is a schematic diagram of an example computer system that can be utilized to implement aspects of the present technology.","FIG.","13 is a flowchart of an example method for both creating a graphane-metal composite and coating an outer surface of the graphane-metal composite with a thin metal coating using chemical or physical vapor deposition.","FIG.","14 is a flowchart of an example method for both creating a graphane-metal composite and coating an outer surface of the graphane-metal composite with a thin metal coating using chemical vapor deposition using plasma injection and/or alternatively evaporative processes in physical vapor deposition DETAILED DESCRIPTION In the following description, for purposes of explanation and not limitation, specific details are set forth, such as particular embodiments, procedures, techniques, etc.","in order to provide a thorough understanding of the present invention.","However, it will be apparent to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details.","The present disclosure is directed to graphene-metal composites, stanine-metal composites and methods of manufacture.","Graphene is the strongest material, best electrical conductor, and is very light weight.","Graphene can be used in various applications such as batteries for electric drive automobiles, filter material for water filters, bendable LCD screens for consumer electronics, nanoelectronics, or light weight body panels for commercial aircrafts.","Production techniques for graphene and components and systems integrating graphene are growing rapidly.","Stanene is an ultrathin superconductor.","Stanene could be integrated into computer chips at critical junctions to improve speed and energy efficiency.","Since graphene is a two dimensional layer of carbon atoms only one carbon thick and stanene is a two dimensional single layer of tin atoms with the possible addition of fluorine atoms, graphene and stanene have large surface to volume ratios and very little capacity because they are so thin.","However, because graphene transmits heat very efficiently, it is desirable to use graphene as a thermal heat sink in order to dissipate heat.","When graphene is layered upon another layer of graphene, it forms graphite which is very brittle and less conductive.","There is a need to solve the problem of increasing thermal and electrical capacity of graphene.","Stanene, comprised of the heavy atom tin, may be a topological insulator and 100% efficient in the transfer of electrons at or above room temperature.","Moreover, by adding fluorine atoms to the tin structure, stanene may be super conductive at around the boiling point of water.","In the present technology, graphene is deposited onto a porous metal foam substrate, for example, by chemical vapor deposition.","An alternative material, stanene, may be used in place of graphene throughout the present technology.","Any metal foam may be used in the present technology, including, but not limited to, nickel foam and copper foam.","In some embodiments, chemical vapor deposition can coat the internal voids and metal bridges within nickel foam with graphene.","By compressing the nickel foam deposited with graphene with a compressive force, a graphene-metal composite is created with a flattened graphene matrix for current to travel across.","Even before compression, additional layers of graphene can be deposited, but the graphene cannot be deposited directly onto carbon atoms, which would form graphite.","Instead a layer of metal, such as copper, nickel, palladium, gold, or any other metal, can be flash coated over graphene or by any other plating mechanism in order for another layer of graphene to be grown on top of the metal followed by compression after a desired number of layers of graphene have been deposited.","In some embodiments, the porous metal foam enhanced with graphene or stanene can be used in fiber optics to increase thermal, electrical, and shielding properties.","These and other advantages of the present technology will be described with reference to the collective drawings.","Referring now to FIGS.","1A and 1B, which collectively illustrate an embodiment of nickel foam, FIG.","1A is a SEM micrograph depicting an exemplary microstructure of foamed nickel.","FIG.","1B is a conceptual drawing showing an open-cell metal foam substrate.","An open-cell metal foam refers to the structure formed by a plurality of cells where inside surfaces of the cells are accessible from neighboring cells in contrast to closed-cell structure where individual cells may be self-contained, for example, in a bubble-like structure.","The open-cell metal foam structure 100 of FIG.","1B comprises metal foam 110 formed with void spaces 120.According to exemplary embodiments, open-cell metal foam structure 100 is comprised of nickel.","Nickel foam is a low density permeable material with a very high porosity.","Nickel foam can be made in a wide porosity range, for example, ranging from 70% to 98% by volume.","In some embodiments, the porosity of nickel foam used in the present technology is where at least 95% of the volume consists of void spaces or higher.","In some embodiments, the nickel foam utilized in the present technology can be produced by coating polyurethane foam with nickel metal, for example, by chemical vapor deposition (CVD).","The nickel-coated polyurethane foam is heated to remove the polymer substrate, leaving the porous nickel as the finished product.","The pore size is determined by the pore size of the polymer template.","The CVD process is unique in that it allows a uniform 3-D distribution of nickel on the polymer substrate over a wide range of thicknesses of the nickel.","The thickness of the nickel is determined by residence time inside a plating chamber.","FIG.","2 illustrates the chemical structure of graphene.","Graphene is a two dimensional sheet of carbon arranged in hexagonal honeycomb lattice that has highly desirable physical properties.","Graphene is the strongest material compared to other materials in Table 1, having a Young's modulus of 1000 GPa, yet it is extremely flexible, quite stable, and mechanically resilient.","Graphene can also be transferred onto any shaped surface, flat or irregular.","Graphene is also the best electrical conductor compared to other materials in Table 1, having a theoretical conductivity of 5020 W/m*K, and graphene transmits heat very efficiently.","Graphene, being a single atomic layer thick, has a large surface to volume ratio; however, the thinness of graphene results in very little capacity.","Other carbon allotropes that comprise variations on the lattice structure of graphene are graphite, diamond, and carbon nanotubes.","Graphite comprises many layers of graphene stacked on top of each other.","While each layer of carbon atoms are tightly bound, only weak bonds known as van der Waals bonds exist between the layers.","These weak van der Waals bonds enable the layers to slide laterally, making graphite slippery and brittle.","As seen in Table 1, the conductivity of graphene can be almost 3 times higher or more than the conductivity of graphite.","Diamond is the most stable form of pure carbon.","There are two ways, in order to achieve its tetrahedral lattice structure, very high pressure and high temperature or chemical vapor deposition, making diamonds difficult to make.","Diamond is about 15 times denser than graphene, but graphene has a higher tensile strength with a similar Young's modulus described in Table 1.Carbon nanotubes are layers of graphene that have been grown into a tube.","While carbon nanotubes can have diameters only in nanometers, carbon nanotubes can grow to millimeters in length.","Carbon nanotubes are one of the strongest fibers with high conductivity like graphene.","Some carbon nanotubes have diameters of 1.3 to 3 nanometers, which are microscopic and much smaller than the smallest voids in nickel foam.","Unlike single layers of graphene, carbon nanotubes are able to switch on and off using three times less power than traditional silicon transistors.","TABLE 1 Strength Properties and Thermal Conductivity of Various Materials.","Tensile Young Conductivity Density strength Modules Material (W/m*k) (g/cm3) (MPa) (GPa) Stainless Steel 16 8.74 2000 210 Tin 67 7.3 15-200 47 Nickel 91 8.908 140-195 170 Aluminum 210 2.71 40-50 70 Brass 115 8.5 550 97 (70Cu—30Zn) Copper 398 8.94 220 130 Gold 315 19.32 100 79 Silver 428 10.49 170 83 Diamond 2500 3.51 60000 1050 Graphite 300-1500 1.3-1.95 6.9 to 100 8 to 15 (pyrolytic, some planes) Graphene 5020 .215 130000 1000 (theoretical) Carbon 3500 0.116 11000-63000 N/A Nanotubes (theoretcal) Carbon Fiber 21-180 N/A 1600 for N/A laminates, 4137 for fibers alone FIG.","3 is a conceptual drawing showing chemical vapor deposition of graphene in an open-cell metal foam substrate 110 to form an open-cell graphene-metal foam 300 arranged according to embodiments described herein.","Graphene layer 310 may be deposited by a CVD process on metal foam 110 to form a graphene-metal foam 300.For example, graphene layer 310 may be deposited on the inner surfaces of metal foam 110 in metal foam void spaces 120, resulting in graphene-metal foam void spaces 320.The CVD process illustrated in FIG.","4 may use any suitable materials and conditions for forming graphene by CVD.","For example, in a sealed center chamber comprising an inner tube 410 and an outer tube 420, at least two gases, such as methane (CH4) and hydrogen (H2) can be flowed such that the at least two gasses can meet at a vortex in the center.","A roll of a metal foam substrate 430, such as nickel foam, can be sent through the sealed chamber.","As the roll of metal foam substrate 430 is heated inside the sealed center chamber at annealing zone 440 and methane gas is flowed through inner tube 410 and hydrogen gas flowed through outer tube 320, the hydrogen catalyzes a reaction between methane and the surface and voids of the roll of metal foam substrate 430, causing carbon atoms from the methane to be deposited onto and within the voids of the metal foam substrate 430.Once a carbon atom occupies a position on the surface of the metal substrate, it pushes other carbons to the side, creating a one atom thick layer of carbon.","As the sealed center chamber is quickly cooled at growth stage 450, the deposited carbon layer is crystalized into a continuous graphene layer on metal foam substrate 430, and the deposited carbon layer is kept from aggregating into bulk graphite.","In some embodiments, a payout and take up mechanism moves the roll of metal foam substrate 430 through the sealed center changer, resulting in a roll of metal foam substrate deposited with graphene 460.CVD of graphene on a metal foam substrate provides a much larger surface area to be coated with graphene compared to a single layer of graphene that is deposited on a solid metal film.","For example, a 1 inch by 1 inch by 0.003 inch piece of solid nickel film coated by graphene could have two layers of graphene per side, which would be 0.0000000078 inches thick and 46×1015 atoms per side based on the two layers.","Based on the amount of atoms, the graphene weight in grams can be calculated.","Similarly, the weight of atoms deposited onto a 1 inch by 1 inch by 0.062 inch thick piece of nickel foam before compression can be calculated based on the porosity of the metal foam.","FIG.","5 is a flow diagram illustrating an example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.","FIG.","5 illustrates a method 500 for manufacturing a graphene-metal composite.","At step 510, method 500 begins by depositing graphene onto a porous metal foam substrate.","In some embodiments, the porous metal foam substrate is nickel foam where the nickel foam has a high porosity of at least 95% or more.","In various embodiments, graphene can be deposited onto the nickel foam by the chemical vaporization deposition process described in FIG.","4.Various different methods can also be used to produce graphene.","According to some embodiment, graphene can be chemically synthesized by using chemicals to purify graphite and heat to reshape and reform the carbon atoms into nano-structured configuration which can be processed into sheets, added onto nickel foam, or processed into carbon nanotubes.","Carbon nanotube ropes can be grown throughout the porous structure of a metal foam using a catalyst material and a heated carbon-rich gas flowing over the metal surface.","These carbon nanotube ropes would occupy the voids within the metal foam, and when the desired amount of carbon nanotubes is produced, the foam can be compressed, leaving a thermal and electrical super highway through the materials.","In some embodiments, graphene can be produced from graphite using ultrasonic irradiation.","Graphite is added in a mixture of dilute organic acid, alcohol, and water, and the mixture is exposed to ultrasonic irradiation.","The acid separates the graphene sheets head together by van der Waals bonds, resulting in a large quantity of undamaged, high-quality graphene dispersed into water.","In an exemplary embodiment depicted in FIG.","6, graphene-enhanced nickel foam 602 can be roll bonded to the surface of a structural material 604, filling pre-stamped openings to allow for a thermal and electrical conduit to pass through the structural material.","This will allow thermal, electrical, and shielding properties to travel in a co-planar direction as well as a trans-planar path, thus adding more capacity to the mass and amplifying the composite's ability to act as a super conduit.","By having relief areas in the structural member before roll bonding the structural member to the graphene-enhanced foam, thermal pathways can be created to help dissipate heat through the structural member and out of a device through the metal foam composite.","See, e.g., U.S. patent application Ser.","No.","14/876,733, filed Oct. 6, 2015, titled “Multiple Layered Alloy/Non Alloy Clad Materials and Methods of Manufacture”, the disclosure of which is incorporate herein by reference in its entirety for all purposes.","The present application discloses additional embodiments of roll bonded clad material.","According to some embodiments as depicted in FIG.","7, layers of copper foil 702 coated with graphene can be roll bonded.","For example, a 0.003 inch thick roll bonded material may comprise two outers layers of nickel 702 each 0.0004 inch think and six 0.0004 inch layers of copper 704 between the layers of nickel 702.Coating the outside of two layers of nickel foil 702 yields eight layers of graphene and 12 more layers of graphene are added to the six copper layers 704, giving a total of 20 layers of graphene within the 0.03 inch of roll bonded material.","In some embodiments, graphene can be grown on thin sheets of nickel, copper, tin, or any other metal.","After the growth process, the thin metal sheets are atomically bonded together by a cladding process.","The resultant composite has many layers of metal and graphene, adding more capacity to the mass, allowing for greater thermal, electrical, and shielding properties of the composite.","In another embodiment, metals, thermal plastics, or conductive elastomers can be 3D printed into the voids of nickel foam.","Injection molding, compression molding, and die casting are additional methods of introducing thermal plastics or metals on the surface or into the voids of nickel foam.","According to exemplary embodiments, thermal paths can be selectively added to certain areas of the nickel foam, making the selected area conductive, while other particular areas would be selected to be insulated within the nickel foam.","After the selective addition of thermal paths, the nickel foam can be compressed.","In some embodiments, enhanced graphene-nickel foam 802 that may have at least one layer of graphene deposited onto a metal foam substrate can be die casted or injection molded into a frame 804, such as an aluminum mobile phone frame, any aluminum frame, zinc frame, plastic frame, or frame of any material, as depicted in FIG.","8.After die casting nickel foam 802 into an aluminum casing 804, there would be very little stress between the nickel foam 802 and aluminum casing.","The nickel foam 802 could then be compressed to a thickness of 0.1 mm to 0.45 mm while keeping the surface of the foam uniform and flat and parallel to the die cast frame 804.At step 520, the metal foam substrate deposited with graphene is compressed to a desired level of thickness using any desired means of compression.","In some embodiments, the metal foam substrate deposited with graphene is compressed substantially closing the voids within the metal foam substrate and making the metal foam substrate with graphene thinner than the thickness of the non-compressed metal foam substrate.","For example, nickel foam with thickness of 0.200 inches can be coated with graphene by CVD.","Then, the coated nickel foam is rolled or compressed to form a graphene-nickel composite with a thickness of 0.010 inches, twenty times thinner than the thickness of the non-compressed nickel foam.","In various embodiments, the amount of compression can be used to control the elastomeric properties of the graphene-metal composite.","The graphene-nickel composite comprises a matrix of graphene inside the nickel foam such that the composite is 40 times more efficient than a single layer of graphene.","The properties of the nickel foam are tremendously enhanced by the compression, creating a thermal and electrical conduit.","Since graphene is elastic and stretchy, it can be compressed.","However, graphene should not be subjected to high heat (over 700° C. in the presence of oxygen) or else it will decompose and convert to carbon dioxide.","Also, graphene has been reported to be as brittle as ceramics and can crack.","Graphene can even crack while it is manufactured.","FIG.","9 is a flow diagram illustrating another example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.","FIG.","9 illustrates a method 900 for manufacturing a graphene-metal composite where the metal foam substrate can be coated with a plurality of layers of graphene.","Similar to method 500, method 900 begins at step 910 by depositing graphene onto a porous metal substrate.","In some embodiments, the graphene is deposited by chemical vapor deposition, the graphene is chemically synthesized, or any other method of synthesizing and depositing graphene.","At step 920, a layer of metal is applied to the metal foam substrate deposited with graphene.","In some embodiments, the metal is flash coated or plated over the graphene.","In order for graphene to be layered on the metal foam substrate, a metal layer needs to be applied between graphene layers because as previously discussed direct layers of graphene will create graphite, which is brittle and has less desirable thermal properties than graphene.","By adding multiple layers graphene and metal to a metal foam substrate, the thermal and electrical properties of the graphene-metal composite could be increased exponentially.","Additionally, in various embodiments, the metal that is applied between the layer of graphene can be any metal, including, but not limited to copper, nickel, palladium or gold.","Furthermore, any substrate upon which graphene can be grown can be used in the present technology, such as glass and ceramic, although their conductivity is low.","Nickel has better properties for growing graphene allowing two layers of graphene per side to be grown in a single process.","It is also very malleable, has good corrosion quality, but it is not very strong and its conductivity is about four times lower than copper.","Copper is soft, malleable, and has great thermal characteristics.","At step 930, graphene is deposited onto the layer of metal using chemical vapor deposition, the graphene is chemically synthesized, or any other method of synthesizing and depositing graphene.","Then steps 920 and 930 can be repeated to deposit a desired number of layers of graphene.","For example, steps 920 and 930 can be repeated 6, 7, or 8 times.","Once the desired number of layers of graphene is deposited, the multilayered metal foam substrate is then compressed or rolled at step 940 to a desired level of thickness, resulting in a graphene-metal composite.","FIG.","10 illustrates an example computer system 1 that can be utilized to control the chemical vapor deposition machine and compression machine.","That is, the computer system 1 can select thermal profiles to control the heating and cooling during graphene deposition.","The computer system 1, within which a set of instructions for causing the machine to perform any one or more of the methodologies discussed herein may be executed.","In various example embodiments, the machine operates as a standalone device or may be connected (e.g., networked) to other machines.","In a networked deployment, the machine may operate in the capacity of a server or a client machine in a server-client network environment, or as a peer machine in a peer-to-peer (or distributed) network environment.","The machine may be a robotic construction marking device, a base station, a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a cellular telephone, a portable music player (e.g., a portable hard drive audio device such as an Moving Picture Experts Group Audio Layer 3 (MP3) player), a web appliance, a network router, switch or bridge, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine.","Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein.","The example computer system 1 includes a processor or multiple processors 5 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), or both), and a main memory 10 and static memory 15, which communicate with each other via a bus 20.The computer system 1 may further include a video display 35 (e.g., a liquid crystal display (LCD)).","The computer system 1 may also include an alpha-numeric input device(s) 30 (e.g., a keyboard), a cursor control device (e.g., a mouse), a voice recognition or biometric verification unit (not shown), a drive unit 37 (also referred to as disk drive unit), a signal generation device 40 (e.g., a speaker), and a network interface device 45.The computer system 1 may further include a data encryption module (not shown) to encrypt data.","The drive unit 37 includes a computer or machine-readable medium 50 on which is stored one or more sets of instructions and data structures (e.g., instructions 55) embodying or utilizing any one or more of the methodologies or functions described herein.","The instructions 55 may also reside, completely or at least partially, within the main memory 10 and/or within the processors 5 during execution thereof by the computer system 1.The main memory 10 and the processors 5 may also constitute machine-readable media.","The instructions 55 may further be transmitted or received over a network via the network interface device 45 utilizing any one of a number of well-known transfer protocols (e.g., Hyper Text Transfer Protocol (HTTP)).","While the machine-readable medium 50 is shown in an example embodiment to be a single medium, the term “computer-readable medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database and/or associated caches and servers) that store the one or more sets of instructions.","The term “computer-readable medium” shall also be taken to include any medium that is capable of storing, encoding, or carrying a set of instructions for execution by the machine and that causes the machine to perform any one or more of the methodologies of the present application, or that is capable of storing, encoding, or carrying data structures utilized by or associated with such a set of instructions.","The term “computer-readable medium” shall accordingly be taken to include, but not be limited to, solid-state memories, optical and magnetic media, and carrier wave signals.","Such media may also include, without limitation, hard disks, floppy disks, flash memory cards, digital video disks, random access memory (RAM), read only memory (ROM), and the like.","The example embodiments described herein may be implemented in an operating environment comprising software installed on a computer, in hardware, or in a combination of software and hardware.","Not all components of the computer system 1 are required and thus portions of the computer system 1 can be removed if not needed, such as Input/Output (I/O) devices (e.g., input device(s) 30).","One skilled in the art will recognize that the Internet service may be configured to provide Internet access to one or more computing devices that are coupled to the Internet service, and that the computing devices may include one or more processors, buses, memory devices, display devices, input/output devices, and the like.","Furthermore, those skilled in the art may appreciate that the Internet service may be coupled to one or more databases, repositories, servers, and the like, which may be utilized in order to implement any of the embodiments of the disclosure as described herein.","Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention.","Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” or “according to one embodiment” (or other phrases having similar import) at various places throughout this specification are not necessarily all referring to the same embodiment.","Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.","Furthermore, depending on the context of discussion herein, a singular term may include its plural forms and a plural term may include its singular form.","Similarly, a hyphenated term (e.g., “on-demand”) may be occasionally interchangeably used with its non-hyphenated version (e.g., “on demand”), a capitalized entry (e.g., “Software”) may be interchangeably used with its non-capitalized version (e.g., “software”), a plural term may be indicated with or without an apostrophe (e.g., PE's or PEs), and an italicized term (e.g., “N+1”) may be interchangeably used with its non-italicized version (e.g., “N+1”).","Such occasional interchangeable uses shall not be considered inconsistent with each other.","Also, some embodiments may be described in terms of “means for” performing a task or set of tasks.","It will be understood that a “means for” may be expressed herein in terms of a structure, such as a processor, a memory, an I/O device such as a camera, or combinations thereof.","Alternatively, the “means for” may include an algorithm that is descriptive of a function or method step, while in yet other embodiments the “means for” is expressed in terms of a mathematical formula, prose, or as a flow chart or signal diagram.","The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.","As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.","It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.","While specific embodiments of, and examples for, the system are described above for illustrative purposes, various equivalent modifications are possible within the scope of the system, as those skilled in the relevant art will recognize.","For example, while processes or steps are presented in a given order, alternative embodiments may perform routines having steps in a different order, and some processes or steps may be deleted, moved, added, subdivided, combined, and/or modified to provide alternative or sub-combinations.","Each of these processes or steps may be implemented in a variety of different ways.","Also, while processes or steps are at times shown as being performed in series, these processes or steps may instead be performed in parallel, or may be performed at different times.","While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation.","The descriptions are not intended to limit the scope of the invention to the particular forms set forth herein.","To the contrary, the present descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and otherwise appreciated by one of ordinary skill in the art.","Thus, the breadth and scope of a preferred embodiment should not be limited by any of the above-described exemplary embodiments."]],"string":"[\n [\n \"HIGH CONDUCTIVITY GRAPHENE-METAL COMPOSITE\",\n \"Embodiments of the present technology include graphene-metal composites.\",\n \"An example graphene-metal composite comprises a porous metal foam substrate, a graphene layer deposited to the porous metal foam substrate, a metal layer applied to the graphene layer, and another graphene layer deposited to the metal layer; the multilayered porous metal foam substrate being compressed to form a graphene-metal composite.\"\n ],\n [\n \"1.A graphene-metal composite comprising: a porous metal foam substrate and a graphene layer deposited to the porous metal foam substrate, the porous metal foam substrate and graphene being compressed to form a graphene-metal composite.\",\n \"2.The graphene-metal composite according to claim 1, wherein the porous metal foam substrate is nickel or copper foam.\",\n \"3.The graphene-metal composite according to claim 1, wherein the porosity of the porous metal foam substrate is at least 70%.\",\n \"4.The graphene-metal composite according to claim 1, wherein the graphene layer is deposited to the porous metal foam substrate by chemical vapor deposition.\",\n \"5.The graphene-metal composite according to claim 1, wherein the porous metal foam substrate with graphene applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with graphene applied thinner than the thickness of the non-compressed porous metal foam substrate.\",\n \"6.A graphene-metal composite comprising: a porous metal foam substrate; a first graphene layer deposited to the porous metal foam substrate; a metal layer applied to the first graphene layer; and a second graphene layer deposited to the metal layer, at least some of the layers being compressed to form a graphene-metal composite.\",\n \"7.The graphene-metal composite according to claim 6, wherein at least a second metal layer is applied to the second graphene layer and at least a third graphene layer is deposited to the second metal layer.\",\n \"8.The graphene-metal composite according to claim 6, wherein the first graphene layer is deposited to the porous metal foam substrate by chemical vapor deposition.\",\n \"9.The graphene-metal composite according to claim 6, wherein the porous metal foam substrate with the first graphene layer applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with the first graphene layer applied thinner than the thickness of the non-compressed porous metal foam substrate.\",\n \"10.A stanene-metal composite comprising: a porous metal foam substrate and a first stanene layer deposited to the porous metal foam substrate, the porous metal foam substrate and first stanene layer being compressed to form a stanene-metal composite.\",\n \"11.The stanene-metal composite according to claim 10, wherein at least a second metal layer is applied to the first stanene layer and at least a second stanene layer is deposited to the second metal layer.\",\n \"12.The stanene-metal composite according to claim 10, wherein the stanene layer is deposited to the porous metal foam substrate by chemical vapor deposition.\",\n \"13.The stanene-metal composite according to claim 10, wherein the porous metal foam substrate with stanene applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with stanene applied thinner than the thickness of the non-compressed porous metal foam substrate.\",\n \"14.A stanene-metal composite comprising: a porous metal foam substrate; a stanene layer deposited to the porous metal foam substrate; a metal layer applied to the stanene layer; and another stanene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a stanene-metal composite.\",\n \"15.The stanene-metal composite according to claim 14, wherein at least a second metal layer is applied to the first stanene layer and at least a second stanene layer is deposited to the second metal layer.\",\n \"16.The stanene-metal composite according to claim 14, wherein the first stanene layer is deposited to the porous metal foam substrate by chemical vapor deposition.\",\n \"17.The stanene-metal composite according to claim 14, wherein the porous metal foam substrate with stanene applied is compressed to substantially close the voids in the porous metal foam substrate and make the compressed porous metal foam substrate with stanene applied thinner than the thickness of the non-compressed porous metal foam substrate.\"\n ],\n [\n \"<SOH> FIELD OF THE PRESENT TECHNOLOGY <EOH>The present technology relates generally to manufacturing methods, and more particularly but not by limitation, to methods that produce a graphene-metal composite or a stanene-metal composite to provide substantial heat and electrical transfer properties from materials such as graphene or stanene deposited on porous metal foam followed by compression to increase heat and electrical transfer properties.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>Embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate and a graphene layer deposited to the porous metal foam substrate, the porous metal foam substrate with graphene being compressed into a graphene-metal composite.\",\n \"Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate and a stanene layer deposited to the porous metal foam substrate, the porous metal foam substrate with stanene being compressed into a stanene-metal composite.\",\n \"In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing graphene or stanene onto a porous metal foam substrate and compressing the porous metal foam substrate with graphene or stanene applied to form a graphene-metal composite or stanene-metal composite.\",\n \"In some embodiments, graphene or stanene is deposited onto the porous metal foam substrate by chemical vapor deposition.\",\n \"Other embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate; a graphene layer deposited to the porous metal foam substrate; a metal layer applied to the graphene layer; and another graphene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a graphene-metal composite.\",\n \"Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate; a stanene layer deposited to the porous metal foam substrate; a metal layer applied to the stanene layer; and another stanene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a stanene-metal composite.\",\n \"In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing a layer of graphene or stanene onto a porous metal foam substrate; applying a layer of metal on top of the layer of graphene or stanene; depositing another layer of graphene or stanene onto the layer of metal; and compressing the multilayered porous metal foam substrate to form a graphene-metal composite or stanene-metal composite.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional application of and claims the priority benefit of U.S. patent application Ser.\",\n \"No.\",\n \"14/947,951 filed Nov. 20, 2015, entitled “High Conductivity Graphene-Metal Composite and Methods of Manufacture,” the disclosure of which is incorporated herein by reference.\",\n \"FIELD OF THE PRESENT TECHNOLOGY The present technology relates generally to manufacturing methods, and more particularly but not by limitation, to methods that produce a graphene-metal composite or a stanene-metal composite to provide substantial heat and electrical transfer properties from materials such as graphene or stanene deposited on porous metal foam followed by compression to increase heat and electrical transfer properties.\",\n \"SUMMARY Embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate and a graphene layer deposited to the porous metal foam substrate, the porous metal foam substrate with graphene being compressed into a graphene-metal composite.\",\n \"Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate and a stanene layer deposited to the porous metal foam substrate, the porous metal foam substrate with stanene being compressed into a stanene-metal composite.\",\n \"In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing graphene or stanene onto a porous metal foam substrate and compressing the porous metal foam substrate with graphene or stanene applied to form a graphene-metal composite or stanene-metal composite.\",\n \"In some embodiments, graphene or stanene is deposited onto the porous metal foam substrate by chemical vapor deposition.\",\n \"Other embodiments of the present technology include a graphene-metal composite comprising: a porous metal foam substrate; a graphene layer deposited to the porous metal foam substrate; a metal layer applied to the graphene layer; and another graphene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a graphene-metal composite.\",\n \"Another embodiment of the present technology includes a stanene-metal composite comprising: a porous metal foam substrate; a stanene layer deposited to the porous metal foam substrate; a metal layer applied to the stanene layer; and another stanene layer deposited to the metal layer, the multilayered porous metal foam substrate being compressed to form a stanene-metal composite.\",\n \"In some embodiments, the graphene-metal composite or stanene-metal composite can be manufactured by depositing a layer of graphene or stanene onto a porous metal foam substrate; applying a layer of metal on top of the layer of graphene or stanene; depositing another layer of graphene or stanene onto the layer of metal; and compressing the multilayered porous metal foam substrate to form a graphene-metal composite or stanene-metal composite.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1A is a SEM (scanning electron microscope) micrograph of a nickel foam structure.\",\n \"FIG.\",\n \"1B is a conceptual drawing showing an open-cell metal foam substrate such as nickel foam.\",\n \"FIG.\",\n \"2 illustrates the chemical structure of graphene.\",\n \"FIG.\",\n \"3 is a conceptual drawing showing the result of chemical vapor deposition of graphene in an open-cell metal foam substrate to form an example open-cell graphene-metal composite.\",\n \"FIG.\",\n \"4 illustrates an example of a chemical vapor deposition (CVD) manufacturing process.\",\n \"FIG.\",\n \"5 is a flow diagram illustrating an example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"6 is a cross sectional view of an embodiment of clad material with enhanced graphene according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"7 is a cross sectional view of an embodiment of roll bonded nickel and copper foil enhanced with graphene according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"8 illustrates die casting enhanced nickel foam into a frame according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"9 is a flow diagram illustrating another example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"10 is a schematic diagram of an example computer system that can be utilized to implement aspects of the present technology.\",\n \"FIG.\",\n \"11 is a flow diagram illustrating another example method of manufacturing a graphane-metal composite according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"12 is a schematic diagram of an example computer system that can be utilized to implement aspects of the present technology.\",\n \"FIG.\",\n \"13 is a flowchart of an example method for both creating a graphane-metal composite and coating an outer surface of the graphane-metal composite with a thin metal coating using chemical or physical vapor deposition.\",\n \"FIG.\",\n \"14 is a flowchart of an example method for both creating a graphane-metal composite and coating an outer surface of the graphane-metal composite with a thin metal coating using chemical vapor deposition using plasma injection and/or alternatively evaporative processes in physical vapor deposition DETAILED DESCRIPTION In the following description, for purposes of explanation and not limitation, specific details are set forth, such as particular embodiments, procedures, techniques, etc.\",\n \"in order to provide a thorough understanding of the present invention.\",\n \"However, it will be apparent to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details.\",\n \"The present disclosure is directed to graphene-metal composites, stanine-metal composites and methods of manufacture.\",\n \"Graphene is the strongest material, best electrical conductor, and is very light weight.\",\n \"Graphene can be used in various applications such as batteries for electric drive automobiles, filter material for water filters, bendable LCD screens for consumer electronics, nanoelectronics, or light weight body panels for commercial aircrafts.\",\n \"Production techniques for graphene and components and systems integrating graphene are growing rapidly.\",\n \"Stanene is an ultrathin superconductor.\",\n \"Stanene could be integrated into computer chips at critical junctions to improve speed and energy efficiency.\",\n \"Since graphene is a two dimensional layer of carbon atoms only one carbon thick and stanene is a two dimensional single layer of tin atoms with the possible addition of fluorine atoms, graphene and stanene have large surface to volume ratios and very little capacity because they are so thin.\",\n \"However, because graphene transmits heat very efficiently, it is desirable to use graphene as a thermal heat sink in order to dissipate heat.\",\n \"When graphene is layered upon another layer of graphene, it forms graphite which is very brittle and less conductive.\",\n \"There is a need to solve the problem of increasing thermal and electrical capacity of graphene.\",\n \"Stanene, comprised of the heavy atom tin, may be a topological insulator and 100% efficient in the transfer of electrons at or above room temperature.\",\n \"Moreover, by adding fluorine atoms to the tin structure, stanene may be super conductive at around the boiling point of water.\",\n \"In the present technology, graphene is deposited onto a porous metal foam substrate, for example, by chemical vapor deposition.\",\n \"An alternative material, stanene, may be used in place of graphene throughout the present technology.\",\n \"Any metal foam may be used in the present technology, including, but not limited to, nickel foam and copper foam.\",\n \"In some embodiments, chemical vapor deposition can coat the internal voids and metal bridges within nickel foam with graphene.\",\n \"By compressing the nickel foam deposited with graphene with a compressive force, a graphene-metal composite is created with a flattened graphene matrix for current to travel across.\",\n \"Even before compression, additional layers of graphene can be deposited, but the graphene cannot be deposited directly onto carbon atoms, which would form graphite.\",\n \"Instead a layer of metal, such as copper, nickel, palladium, gold, or any other metal, can be flash coated over graphene or by any other plating mechanism in order for another layer of graphene to be grown on top of the metal followed by compression after a desired number of layers of graphene have been deposited.\",\n \"In some embodiments, the porous metal foam enhanced with graphene or stanene can be used in fiber optics to increase thermal, electrical, and shielding properties.\",\n \"These and other advantages of the present technology will be described with reference to the collective drawings.\",\n \"Referring now to FIGS.\",\n \"1A and 1B, which collectively illustrate an embodiment of nickel foam, FIG.\",\n \"1A is a SEM micrograph depicting an exemplary microstructure of foamed nickel.\",\n \"FIG.\",\n \"1B is a conceptual drawing showing an open-cell metal foam substrate.\",\n \"An open-cell metal foam refers to the structure formed by a plurality of cells where inside surfaces of the cells are accessible from neighboring cells in contrast to closed-cell structure where individual cells may be self-contained, for example, in a bubble-like structure.\",\n \"The open-cell metal foam structure 100 of FIG.\",\n \"1B comprises metal foam 110 formed with void spaces 120.According to exemplary embodiments, open-cell metal foam structure 100 is comprised of nickel.\",\n \"Nickel foam is a low density permeable material with a very high porosity.\",\n \"Nickel foam can be made in a wide porosity range, for example, ranging from 70% to 98% by volume.\",\n \"In some embodiments, the porosity of nickel foam used in the present technology is where at least 95% of the volume consists of void spaces or higher.\",\n \"In some embodiments, the nickel foam utilized in the present technology can be produced by coating polyurethane foam with nickel metal, for example, by chemical vapor deposition (CVD).\",\n \"The nickel-coated polyurethane foam is heated to remove the polymer substrate, leaving the porous nickel as the finished product.\",\n \"The pore size is determined by the pore size of the polymer template.\",\n \"The CVD process is unique in that it allows a uniform 3-D distribution of nickel on the polymer substrate over a wide range of thicknesses of the nickel.\",\n \"The thickness of the nickel is determined by residence time inside a plating chamber.\",\n \"FIG.\",\n \"2 illustrates the chemical structure of graphene.\",\n \"Graphene is a two dimensional sheet of carbon arranged in hexagonal honeycomb lattice that has highly desirable physical properties.\",\n \"Graphene is the strongest material compared to other materials in Table 1, having a Young's modulus of 1000 GPa, yet it is extremely flexible, quite stable, and mechanically resilient.\",\n \"Graphene can also be transferred onto any shaped surface, flat or irregular.\",\n \"Graphene is also the best electrical conductor compared to other materials in Table 1, having a theoretical conductivity of 5020 W/m*K, and graphene transmits heat very efficiently.\",\n \"Graphene, being a single atomic layer thick, has a large surface to volume ratio; however, the thinness of graphene results in very little capacity.\",\n \"Other carbon allotropes that comprise variations on the lattice structure of graphene are graphite, diamond, and carbon nanotubes.\",\n \"Graphite comprises many layers of graphene stacked on top of each other.\",\n \"While each layer of carbon atoms are tightly bound, only weak bonds known as van der Waals bonds exist between the layers.\",\n \"These weak van der Waals bonds enable the layers to slide laterally, making graphite slippery and brittle.\",\n \"As seen in Table 1, the conductivity of graphene can be almost 3 times higher or more than the conductivity of graphite.\",\n \"Diamond is the most stable form of pure carbon.\",\n \"There are two ways, in order to achieve its tetrahedral lattice structure, very high pressure and high temperature or chemical vapor deposition, making diamonds difficult to make.\",\n \"Diamond is about 15 times denser than graphene, but graphene has a higher tensile strength with a similar Young's modulus described in Table 1.Carbon nanotubes are layers of graphene that have been grown into a tube.\",\n \"While carbon nanotubes can have diameters only in nanometers, carbon nanotubes can grow to millimeters in length.\",\n \"Carbon nanotubes are one of the strongest fibers with high conductivity like graphene.\",\n \"Some carbon nanotubes have diameters of 1.3 to 3 nanometers, which are microscopic and much smaller than the smallest voids in nickel foam.\",\n \"Unlike single layers of graphene, carbon nanotubes are able to switch on and off using three times less power than traditional silicon transistors.\",\n \"TABLE 1 Strength Properties and Thermal Conductivity of Various Materials.\",\n \"Tensile Young Conductivity Density strength Modules Material (W/m*k) (g/cm3) (MPa) (GPa) Stainless Steel 16 8.74 2000 210 Tin 67 7.3 15-200 47 Nickel 91 8.908 140-195 170 Aluminum 210 2.71 40-50 70 Brass 115 8.5 550 97 (70Cu—30Zn) Copper 398 8.94 220 130 Gold 315 19.32 100 79 Silver 428 10.49 170 83 Diamond 2500 3.51 60000 1050 Graphite 300-1500 1.3-1.95 6.9 to 100 8 to 15 (pyrolytic, some planes) Graphene 5020 .215 130000 1000 (theoretical) Carbon 3500 0.116 11000-63000 N/A Nanotubes (theoretcal) Carbon Fiber 21-180 N/A 1600 for N/A laminates, 4137 for fibers alone FIG.\",\n \"3 is a conceptual drawing showing chemical vapor deposition of graphene in an open-cell metal foam substrate 110 to form an open-cell graphene-metal foam 300 arranged according to embodiments described herein.\",\n \"Graphene layer 310 may be deposited by a CVD process on metal foam 110 to form a graphene-metal foam 300.For example, graphene layer 310 may be deposited on the inner surfaces of metal foam 110 in metal foam void spaces 120, resulting in graphene-metal foam void spaces 320.The CVD process illustrated in FIG.\",\n \"4 may use any suitable materials and conditions for forming graphene by CVD.\",\n \"For example, in a sealed center chamber comprising an inner tube 410 and an outer tube 420, at least two gases, such as methane (CH4) and hydrogen (H2) can be flowed such that the at least two gasses can meet at a vortex in the center.\",\n \"A roll of a metal foam substrate 430, such as nickel foam, can be sent through the sealed chamber.\",\n \"As the roll of metal foam substrate 430 is heated inside the sealed center chamber at annealing zone 440 and methane gas is flowed through inner tube 410 and hydrogen gas flowed through outer tube 320, the hydrogen catalyzes a reaction between methane and the surface and voids of the roll of metal foam substrate 430, causing carbon atoms from the methane to be deposited onto and within the voids of the metal foam substrate 430.Once a carbon atom occupies a position on the surface of the metal substrate, it pushes other carbons to the side, creating a one atom thick layer of carbon.\",\n \"As the sealed center chamber is quickly cooled at growth stage 450, the deposited carbon layer is crystalized into a continuous graphene layer on metal foam substrate 430, and the deposited carbon layer is kept from aggregating into bulk graphite.\",\n \"In some embodiments, a payout and take up mechanism moves the roll of metal foam substrate 430 through the sealed center changer, resulting in a roll of metal foam substrate deposited with graphene 460.CVD of graphene on a metal foam substrate provides a much larger surface area to be coated with graphene compared to a single layer of graphene that is deposited on a solid metal film.\",\n \"For example, a 1 inch by 1 inch by 0.003 inch piece of solid nickel film coated by graphene could have two layers of graphene per side, which would be 0.0000000078 inches thick and 46×1015 atoms per side based on the two layers.\",\n \"Based on the amount of atoms, the graphene weight in grams can be calculated.\",\n \"Similarly, the weight of atoms deposited onto a 1 inch by 1 inch by 0.062 inch thick piece of nickel foam before compression can be calculated based on the porosity of the metal foam.\",\n \"FIG.\",\n \"5 is a flow diagram illustrating an example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"5 illustrates a method 500 for manufacturing a graphene-metal composite.\",\n \"At step 510, method 500 begins by depositing graphene onto a porous metal foam substrate.\",\n \"In some embodiments, the porous metal foam substrate is nickel foam where the nickel foam has a high porosity of at least 95% or more.\",\n \"In various embodiments, graphene can be deposited onto the nickel foam by the chemical vaporization deposition process described in FIG.\",\n \"4.Various different methods can also be used to produce graphene.\",\n \"According to some embodiment, graphene can be chemically synthesized by using chemicals to purify graphite and heat to reshape and reform the carbon atoms into nano-structured configuration which can be processed into sheets, added onto nickel foam, or processed into carbon nanotubes.\",\n \"Carbon nanotube ropes can be grown throughout the porous structure of a metal foam using a catalyst material and a heated carbon-rich gas flowing over the metal surface.\",\n \"These carbon nanotube ropes would occupy the voids within the metal foam, and when the desired amount of carbon nanotubes is produced, the foam can be compressed, leaving a thermal and electrical super highway through the materials.\",\n \"In some embodiments, graphene can be produced from graphite using ultrasonic irradiation.\",\n \"Graphite is added in a mixture of dilute organic acid, alcohol, and water, and the mixture is exposed to ultrasonic irradiation.\",\n \"The acid separates the graphene sheets head together by van der Waals bonds, resulting in a large quantity of undamaged, high-quality graphene dispersed into water.\",\n \"In an exemplary embodiment depicted in FIG.\",\n \"6, graphene-enhanced nickel foam 602 can be roll bonded to the surface of a structural material 604, filling pre-stamped openings to allow for a thermal and electrical conduit to pass through the structural material.\",\n \"This will allow thermal, electrical, and shielding properties to travel in a co-planar direction as well as a trans-planar path, thus adding more capacity to the mass and amplifying the composite's ability to act as a super conduit.\",\n \"By having relief areas in the structural member before roll bonding the structural member to the graphene-enhanced foam, thermal pathways can be created to help dissipate heat through the structural member and out of a device through the metal foam composite.\",\n \"See, e.g., U.S. patent application Ser.\",\n \"No.\",\n \"14/876,733, filed Oct. 6, 2015, titled “Multiple Layered Alloy/Non Alloy Clad Materials and Methods of Manufacture”, the disclosure of which is incorporate herein by reference in its entirety for all purposes.\",\n \"The present application discloses additional embodiments of roll bonded clad material.\",\n \"According to some embodiments as depicted in FIG.\",\n \"7, layers of copper foil 702 coated with graphene can be roll bonded.\",\n \"For example, a 0.003 inch thick roll bonded material may comprise two outers layers of nickel 702 each 0.0004 inch think and six 0.0004 inch layers of copper 704 between the layers of nickel 702.Coating the outside of two layers of nickel foil 702 yields eight layers of graphene and 12 more layers of graphene are added to the six copper layers 704, giving a total of 20 layers of graphene within the 0.03 inch of roll bonded material.\",\n \"In some embodiments, graphene can be grown on thin sheets of nickel, copper, tin, or any other metal.\",\n \"After the growth process, the thin metal sheets are atomically bonded together by a cladding process.\",\n \"The resultant composite has many layers of metal and graphene, adding more capacity to the mass, allowing for greater thermal, electrical, and shielding properties of the composite.\",\n \"In another embodiment, metals, thermal plastics, or conductive elastomers can be 3D printed into the voids of nickel foam.\",\n \"Injection molding, compression molding, and die casting are additional methods of introducing thermal plastics or metals on the surface or into the voids of nickel foam.\",\n \"According to exemplary embodiments, thermal paths can be selectively added to certain areas of the nickel foam, making the selected area conductive, while other particular areas would be selected to be insulated within the nickel foam.\",\n \"After the selective addition of thermal paths, the nickel foam can be compressed.\",\n \"In some embodiments, enhanced graphene-nickel foam 802 that may have at least one layer of graphene deposited onto a metal foam substrate can be die casted or injection molded into a frame 804, such as an aluminum mobile phone frame, any aluminum frame, zinc frame, plastic frame, or frame of any material, as depicted in FIG.\",\n \"8.After die casting nickel foam 802 into an aluminum casing 804, there would be very little stress between the nickel foam 802 and aluminum casing.\",\n \"The nickel foam 802 could then be compressed to a thickness of 0.1 mm to 0.45 mm while keeping the surface of the foam uniform and flat and parallel to the die cast frame 804.At step 520, the metal foam substrate deposited with graphene is compressed to a desired level of thickness using any desired means of compression.\",\n \"In some embodiments, the metal foam substrate deposited with graphene is compressed substantially closing the voids within the metal foam substrate and making the metal foam substrate with graphene thinner than the thickness of the non-compressed metal foam substrate.\",\n \"For example, nickel foam with thickness of 0.200 inches can be coated with graphene by CVD.\",\n \"Then, the coated nickel foam is rolled or compressed to form a graphene-nickel composite with a thickness of 0.010 inches, twenty times thinner than the thickness of the non-compressed nickel foam.\",\n \"In various embodiments, the amount of compression can be used to control the elastomeric properties of the graphene-metal composite.\",\n \"The graphene-nickel composite comprises a matrix of graphene inside the nickel foam such that the composite is 40 times more efficient than a single layer of graphene.\",\n \"The properties of the nickel foam are tremendously enhanced by the compression, creating a thermal and electrical conduit.\",\n \"Since graphene is elastic and stretchy, it can be compressed.\",\n \"However, graphene should not be subjected to high heat (over 700° C. in the presence of oxygen) or else it will decompose and convert to carbon dioxide.\",\n \"Also, graphene has been reported to be as brittle as ceramics and can crack.\",\n \"Graphene can even crack while it is manufactured.\",\n \"FIG.\",\n \"9 is a flow diagram illustrating another example method of manufacturing a graphene-metal composite according to exemplary embodiments of the present technology.\",\n \"FIG.\",\n \"9 illustrates a method 900 for manufacturing a graphene-metal composite where the metal foam substrate can be coated with a plurality of layers of graphene.\",\n \"Similar to method 500, method 900 begins at step 910 by depositing graphene onto a porous metal substrate.\",\n \"In some embodiments, the graphene is deposited by chemical vapor deposition, the graphene is chemically synthesized, or any other method of synthesizing and depositing graphene.\",\n \"At step 920, a layer of metal is applied to the metal foam substrate deposited with graphene.\",\n \"In some embodiments, the metal is flash coated or plated over the graphene.\",\n \"In order for graphene to be layered on the metal foam substrate, a metal layer needs to be applied between graphene layers because as previously discussed direct layers of graphene will create graphite, which is brittle and has less desirable thermal properties than graphene.\",\n \"By adding multiple layers graphene and metal to a metal foam substrate, the thermal and electrical properties of the graphene-metal composite could be increased exponentially.\",\n \"Additionally, in various embodiments, the metal that is applied between the layer of graphene can be any metal, including, but not limited to copper, nickel, palladium or gold.\",\n \"Furthermore, any substrate upon which graphene can be grown can be used in the present technology, such as glass and ceramic, although their conductivity is low.\",\n \"Nickel has better properties for growing graphene allowing two layers of graphene per side to be grown in a single process.\",\n \"It is also very malleable, has good corrosion quality, but it is not very strong and its conductivity is about four times lower than copper.\",\n \"Copper is soft, malleable, and has great thermal characteristics.\",\n \"At step 930, graphene is deposited onto the layer of metal using chemical vapor deposition, the graphene is chemically synthesized, or any other method of synthesizing and depositing graphene.\",\n \"Then steps 920 and 930 can be repeated to deposit a desired number of layers of graphene.\",\n \"For example, steps 920 and 930 can be repeated 6, 7, or 8 times.\",\n \"Once the desired number of layers of graphene is deposited, the multilayered metal foam substrate is then compressed or rolled at step 940 to a desired level of thickness, resulting in a graphene-metal composite.\",\n \"FIG.\",\n \"10 illustrates an example computer system 1 that can be utilized to control the chemical vapor deposition machine and compression machine.\",\n \"That is, the computer system 1 can select thermal profiles to control the heating and cooling during graphene deposition.\",\n \"The computer system 1, within which a set of instructions for causing the machine to perform any one or more of the methodologies discussed herein may be executed.\",\n \"In various example embodiments, the machine operates as a standalone device or may be connected (e.g., networked) to other machines.\",\n \"In a networked deployment, the machine may operate in the capacity of a server or a client machine in a server-client network environment, or as a peer machine in a peer-to-peer (or distributed) network environment.\",\n \"The machine may be a robotic construction marking device, a base station, a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a cellular telephone, a portable music player (e.g., a portable hard drive audio device such as an Moving Picture Experts Group Audio Layer 3 (MP3) player), a web appliance, a network router, switch or bridge, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine.\",\n \"Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein.\",\n \"The example computer system 1 includes a processor or multiple processors 5 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), or both), and a main memory 10 and static memory 15, which communicate with each other via a bus 20.The computer system 1 may further include a video display 35 (e.g., a liquid crystal display (LCD)).\",\n \"The computer system 1 may also include an alpha-numeric input device(s) 30 (e.g., a keyboard), a cursor control device (e.g., a mouse), a voice recognition or biometric verification unit (not shown), a drive unit 37 (also referred to as disk drive unit), a signal generation device 40 (e.g., a speaker), and a network interface device 45.The computer system 1 may further include a data encryption module (not shown) to encrypt data.\",\n \"The drive unit 37 includes a computer or machine-readable medium 50 on which is stored one or more sets of instructions and data structures (e.g., instructions 55) embodying or utilizing any one or more of the methodologies or functions described herein.\",\n \"The instructions 55 may also reside, completely or at least partially, within the main memory 10 and/or within the processors 5 during execution thereof by the computer system 1.The main memory 10 and the processors 5 may also constitute machine-readable media.\",\n \"The instructions 55 may further be transmitted or received over a network via the network interface device 45 utilizing any one of a number of well-known transfer protocols (e.g., Hyper Text Transfer Protocol (HTTP)).\",\n \"While the machine-readable medium 50 is shown in an example embodiment to be a single medium, the term “computer-readable medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database and/or associated caches and servers) that store the one or more sets of instructions.\",\n \"The term “computer-readable medium” shall also be taken to include any medium that is capable of storing, encoding, or carrying a set of instructions for execution by the machine and that causes the machine to perform any one or more of the methodologies of the present application, or that is capable of storing, encoding, or carrying data structures utilized by or associated with such a set of instructions.\",\n \"The term “computer-readable medium” shall accordingly be taken to include, but not be limited to, solid-state memories, optical and magnetic media, and carrier wave signals.\",\n \"Such media may also include, without limitation, hard disks, floppy disks, flash memory cards, digital video disks, random access memory (RAM), read only memory (ROM), and the like.\",\n \"The example embodiments described herein may be implemented in an operating environment comprising software installed on a computer, in hardware, or in a combination of software and hardware.\",\n \"Not all components of the computer system 1 are required and thus portions of the computer system 1 can be removed if not needed, such as Input/Output (I/O) devices (e.g., input device(s) 30).\",\n \"One skilled in the art will recognize that the Internet service may be configured to provide Internet access to one or more computing devices that are coupled to the Internet service, and that the computing devices may include one or more processors, buses, memory devices, display devices, input/output devices, and the like.\",\n \"Furthermore, those skilled in the art may appreciate that the Internet service may be coupled to one or more databases, repositories, servers, and the like, which may be utilized in order to implement any of the embodiments of the disclosure as described herein.\",\n \"Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention.\",\n \"Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” or “according to one embodiment” (or other phrases having similar import) at various places throughout this specification are not necessarily all referring to the same embodiment.\",\n \"Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.\",\n \"Furthermore, depending on the context of discussion herein, a singular term may include its plural forms and a plural term may include its singular form.\",\n \"Similarly, a hyphenated term (e.g., “on-demand”) may be occasionally interchangeably used with its non-hyphenated version (e.g., “on demand”), a capitalized entry (e.g., “Software”) may be interchangeably used with its non-capitalized version (e.g., “software”), a plural term may be indicated with or without an apostrophe (e.g., PE's or PEs), and an italicized term (e.g., “N+1”) may be interchangeably used with its non-italicized version (e.g., “N+1”).\",\n \"Such occasional interchangeable uses shall not be considered inconsistent with each other.\",\n \"Also, some embodiments may be described in terms of “means for” performing a task or set of tasks.\",\n \"It will be understood that a “means for” may be expressed herein in terms of a structure, such as a processor, a memory, an I/O device such as a camera, or combinations thereof.\",\n \"Alternatively, the “means for” may include an algorithm that is descriptive of a function or method step, while in yet other embodiments the “means for” is expressed in terms of a mathematical formula, prose, or as a flow chart or signal diagram.\",\n \"The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.\",\n \"As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.\",\n \"It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.\",\n \"While specific embodiments of, and examples for, the system are described above for illustrative purposes, various equivalent modifications are possible within the scope of the system, as those skilled in the relevant art will recognize.\",\n \"For example, while processes or steps are presented in a given order, alternative embodiments may perform routines having steps in a different order, and some processes or steps may be deleted, moved, added, subdivided, combined, and/or modified to provide alternative or sub-combinations.\",\n \"Each of these processes or steps may be implemented in a variety of different ways.\",\n \"Also, while processes or steps are at times shown as being performed in series, these processes or steps may instead be performed in parallel, or may be performed at different times.\",\n \"While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation.\",\n \"The descriptions are not intended to limit the scope of the invention to the particular forms set forth herein.\",\n \"To the contrary, the present descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and otherwise appreciated by one of ordinary skill in the art.\",\n \"Thus, the breadth and scope of a preferred embodiment should not be limited by any of the above-described exemplary embodiments.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874753"}}},{"rowIdx":4494688,"cells":{"text":{"kind":"list like","value":[["JUICE EXTRACTION MODULE FOR JUICER","A juice extraction module for a juicer is provided, which includes a container formed with a juice discharge port, a sieve positioned inside of the container, a screw positioned inside of the sieve to extract juice from a material, and a lid coupled to a top end of the container and formed with a input port through which the material is input.","The juice extraction module includes a crushing portion formed on a top end of the screw to be narrowed upward, the crushing portion having a crushing blade formed thereon; and a crushing processing portion connected to the input port and formed in a bottom of the lid to be concave for accommodating the crushing portion."],["1.A juice extraction module for a juicer, the juice extraction module including: a container comprising a juice discharge port; a sieve positioned inside of the container; a screw to extract juice from a material, the screw being rotatable about a rotational axis and having top and bottom portions vertically arranged along the rotational axis, the bottom portion of the screw being accommodated within the sieve and the top portion of the screw extending out of the sieve; a lid coupled to a top end of the container, the lid having: a top portion that includes an input port through which said material is input into the juice extraction module, and a bottom portion that receives said material from the input port, wherein the top portion of the screw has a spiral blade formed thereon and extends above a top end of the sieve to narrow toward a top end of the screw, wherein the bottom portion of the lid includes a screw accommodating portion configured to accommodate the top portion of the screw, wherein a first material processing zone in which said material is subjected to crushing, in use, is defined between the top portion of the screw and an interior surface of the lid above the top end of the sieve, wherein a second material processing zone in which said material is subjected to juicing, in use, is defined between the bottom portion of the screw and the sieve, and wherein the input port is proportioned to accommodate material of up to a first diameter in size, the first diameter being greater than the shortest distance between the rotational axis of the screw and an inner circumferential surface of the top end of the sieve.","2.The juice extraction module according to claim 1, wherein the first material processing zone reduces in size between its upstream and downstream ends.","3.The juice extraction module according to claim 1, wherein the screw is of unitary one-piece construction.","4.A juice extraction module for a juicer, which includes a container formed with a juice discharge port, a sieve positioned inside of the container, a screw positioned inside of the sieve to rotate about a rotational axis and extract juice from a material, and a lid coupled to a top end of the container and formed with a input port through which the material is input, the juice extraction module comprising: a top portion of the screw defining a crushing portion, the crushing portion comprising a crushing blade formed thereon; and a crushing processing portion connected to the input port and defined in a bottom portion of the lid, the crushing processing portion accommodating the crushing portion of the screw, an inner surface of the crushing processing portion including a crushing processing surface and a material guide surface, wherein the input port is an opening formed in a top portion of the lid, and wherein the material guide surface continues from the input port and is inclined toward the rotational axis, whereby the material guide surface guides the material so that the material begins to be crushed by the crushing blade, and wherein the crushing blade crushes the material within the crushing processing portion formed in the bottom of the lid, in advance of the material reaching the sieve.","5.The juice extraction module according to claim 4, wherein the screw is of unitary one-piece construction.","6.A juice extraction module for a juicer, comprising: a container comprising a juice discharge port; a sieve positioned inside of the container; a screw positioned inside of the sieve to rotate about a rotational axis and extract juice from a material, a top portion of the screw defining a crushing portion which includes a crushing blade formed thereon; and a lid coupled to a top end of the container and comprising an input port through which the material is input, a bottom portion of the lid comprising a crushing processing portion connected to the input port, the crushing processing portion accommodating the crushing portion of the screw and having an inner surface that includes a crushing processing surface, wherein the input port is an opening formed in the lid, and wherein the crushing blade crushes the material within the crushing processing portion formed in the bottom of the lid, in advance of the material reaching the sieve.","7.The juice extraction module according to claim 6, wherein the screw is of unitary one-piece construction."],["<SOH> BACKGROUND <EOH>"],["<SOH> BRIEF SUMMARY <EOH>Embodiments of the present invention provide a juice extraction module for a juicer, in which a structure of crushing a material in advance is provided in a lid and a screw to eliminate an inconvenient procedure of chopping or cutting a material in advance before inputting the material.","According to an aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a juice discharge port 101 , a sieve 200 positioned inside of the container 100 , a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input.","The juice extraction module includes a crushing portion 500 formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon; and a crushing processing portion 600 connected to the input port 410 and formed in a bottom of the lid 400 to be concave for accommodating the crushing portion 500 , wherein the crushing blade 510 crushes the material in advance within the crushing processing portion 600 .","According to one embodiment, the crushing blade 510 is formed so that the material input through the input port 410 is crushed while a lateral side of the material is pushed outwards, and the crushing processing portion 600 is provided with an inner surface to hold the material pushed outwards by the crushing blade 510 , whereby the material can be crushed between the crushing blade 510 and the inner surface of the crushing processing portion 600 .","According to one embodiment, the crushing processing portion 600 is formed to cover an entire bottom region of the input port 410 at the height of the crushing processing portion 600 connected to a bottom end of the input port 410 .","According to one embodiment, a bottom region of the input port 410 is positioned to be offset within a semicircle region of a circle having a diameter corresponding to a diameter of the crushing processing portion 600 with a central shaft 310 of the screw 300 as a center.","According to one embodiment, the inner surface of the crushing processing portion 600 comprises a crushing processing surface 610 formed to be gradually close to the crushing blade 510 in a direction in which the crushing blade 510 runs from the input port 410 .","According to one embodiment, the inner surface of the crushing processing portion 600 comprises a material guide surface 620 continuing from the input port 410 and formed to be inclined toward a central axis of the crushing portion 500 , whereby the material guide surface 620 guides the material so that a lateral side of the material begins to be crushed by the crushing blade 510 .","According to one embodiment, a bottom end of the material guide surface 620 may conform to an inner surface of the sieve 200 .","According to one embodiment, the crushing portion 500 passes over a top end of the sieve 200 and is accommodated in the crushing processing portion 600 , and the crushing blade 510 cooperates with the crushing processing portion 600 to crush the material.","According to another aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a residue discharge port 102 and a juice discharge port 101 ; a sieve 200 positioned inside of the container 100 ; a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input, wherein a crushing portion 500 is formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon, wherein the lid 400 is formed with a crushing processing portion 600 , the crushing processing portion 600 being connected to the input port 410 and accommodating the crushing portion 500 , wherein the input port 410 is disposed to be offset outwards from a central axis of the screw 300 and has a width larger than the shortest distance from the central axis of the screw 300 to an inner circumferential surface of a top end of the sieve 200 , wherein the crushing processing portion 600 is formed with a material guide surface for assisting guidance of the material from the input port 410 to the sieve 200 .","The crushing blade 510 and the crushing processing portion 600 are formed so that a distance between the crushing blade 510 and an inner surface of the crushing processing portion 600 is gradually reduced by the rotation of the crushing blade 510 The crushing processing portion 600 comprises a crushing processing surface 610 , the crushing processing surface 610 is formed with at least one milling blade 630 .","A conventional juicer has inconvenience and difficulty in that an increase in length of a screw blade increases an entire outer diameter of a screw, and thus, a sieve, a container and a lid should be manufactured large so as to be fitted to the screw.","However, according to embodiments of the present invention, a material having a diameter larger than a length of a screw blade can be used, and the material can be crushed into a size suitable for extracting juice without increasing an outer diameter of a screw by a crushing processing portion formed to be concave in a bottom of a lid and a crushing portion accommodated in the crushing processing portion and cooperating with the crushing processing portion.","Thus, embodiments of the present invention eliminate the inconvenience and cumbersomeness that a user should chop a material before the material is input.","In addition, a space between the crushing blade and the crushing processing portion is gradually narrowed and the material is caught and simultaneously dragged into between the crushing blade and the crushing processing portion, so that the material is effectively crushed while being automatically supplied to the screw without inconveniently pushing the material."],["BACKGROUND Technical Field The present disclosure relates to a juice extraction module for a juicer, and more specifically, to a juice extraction module for a juicer having an improved structure capable of eliminating the inconvenience that a material should be chopped before the material is input into the juicer.","Description of the Related Art In general, a juicer includes a main body, and a juice extraction module mounted onto the main body.","The juice extraction module includes a container having a juice extraction space, a lid having an input port through which a material is input into the container, a screw for extracting juice from the material in the container, and a sieve for separating juice and residues from each other.","The main body includes a driving motor for rotating the screw, and a shaft of the driving motor is connected to the screw in the juice extraction module.","In the conventional juicer, the material should be chopped into such a size that the screw can extract juice.","As an example, Korean Patent No.","10-0793852 discloses a juicer configured to cut or sever a material by a screw blade protruding from a central axis of a screw toward a lateral side of an uppermost end.","However, in the above technique, when a material has a size larger than the length of the screw blade, the material should be chopped in advance into a size smaller than the length of the screw blade.","In addition, Korean Patent No.","10-0966607 discloses a juicer having a grater provided in an entire upper surface over a screw to crush a material just before juice is extracted.","However, there are problems in that the crush using the grater is achieved at a speed higher than an ordinary low speed of the juicer and also a user should press the material against the grater by a large force in order to prevent the rotation of the material due to the high speed of the grater.","Also, since the conventional juicer cuts the material and then mills the cut pieces of the material while they are pressed against a sieve in a juice extraction process, the sieve may be deformed in a moment by the pressed cut pieces.","Such deformation destroys a molding for holding a shape of the sieve or decreases the bond between the molding and the sieve to generate a gap between the molding and the sieve causing a leakage of residues and a decrease in juice extraction efficiency.","BRIEF SUMMARY Embodiments of the present invention provide a juice extraction module for a juicer, in which a structure of crushing a material in advance is provided in a lid and a screw to eliminate an inconvenient procedure of chopping or cutting a material in advance before inputting the material.","According to an aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a juice discharge port 101, a sieve 200 positioned inside of the container 100, a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input.","The juice extraction module includes a crushing portion 500 formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon; and a crushing processing portion 600 connected to the input port 410 and formed in a bottom of the lid 400 to be concave for accommodating the crushing portion 500, wherein the crushing blade 510 crushes the material in advance within the crushing processing portion 600.According to one embodiment, the crushing blade 510 is formed so that the material input through the input port 410 is crushed while a lateral side of the material is pushed outwards, and the crushing processing portion 600 is provided with an inner surface to hold the material pushed outwards by the crushing blade 510, whereby the material can be crushed between the crushing blade 510 and the inner surface of the crushing processing portion 600.According to one embodiment, the crushing processing portion 600 is formed to cover an entire bottom region of the input port 410 at the height of the crushing processing portion 600 connected to a bottom end of the input port 410.According to one embodiment, a bottom region of the input port 410 is positioned to be offset within a semicircle region of a circle having a diameter corresponding to a diameter of the crushing processing portion 600 with a central shaft 310 of the screw 300 as a center.","According to one embodiment, the inner surface of the crushing processing portion 600 comprises a crushing processing surface 610 formed to be gradually close to the crushing blade 510 in a direction in which the crushing blade 510 runs from the input port 410.According to one embodiment, the inner surface of the crushing processing portion 600 comprises a material guide surface 620 continuing from the input port 410 and formed to be inclined toward a central axis of the crushing portion 500, whereby the material guide surface 620 guides the material so that a lateral side of the material begins to be crushed by the crushing blade 510.According to one embodiment, a bottom end of the material guide surface 620 may conform to an inner surface of the sieve 200.According to one embodiment, the crushing portion 500 passes over a top end of the sieve 200 and is accommodated in the crushing processing portion 600, and the crushing blade 510 cooperates with the crushing processing portion 600 to crush the material.","According to another aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a residue discharge port 102 and a juice discharge port 101; a sieve 200 positioned inside of the container 100; a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input, wherein a crushing portion 500 is formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon, wherein the lid 400 is formed with a crushing processing portion 600, the crushing processing portion 600 being connected to the input port 410 and accommodating the crushing portion 500, wherein the input port 410 is disposed to be offset outwards from a central axis of the screw 300 and has a width larger than the shortest distance from the central axis of the screw 300 to an inner circumferential surface of a top end of the sieve 200, wherein the crushing processing portion 600 is formed with a material guide surface for assisting guidance of the material from the input port 410 to the sieve 200.The crushing blade 510 and the crushing processing portion 600 are formed so that a distance between the crushing blade 510 and an inner surface of the crushing processing portion 600 is gradually reduced by the rotation of the crushing blade 510 The crushing processing portion 600 comprises a crushing processing surface 610, the crushing processing surface 610 is formed with at least one milling blade 630.A conventional juicer has inconvenience and difficulty in that an increase in length of a screw blade increases an entire outer diameter of a screw, and thus, a sieve, a container and a lid should be manufactured large so as to be fitted to the screw.","However, according to embodiments of the present invention, a material having a diameter larger than a length of a screw blade can be used, and the material can be crushed into a size suitable for extracting juice without increasing an outer diameter of a screw by a crushing processing portion formed to be concave in a bottom of a lid and a crushing portion accommodated in the crushing processing portion and cooperating with the crushing processing portion.","Thus, embodiments of the present invention eliminate the inconvenience and cumbersomeness that a user should chop a material before the material is input.","In addition, a space between the crushing blade and the crushing processing portion is gradually narrowed and the material is caught and simultaneously dragged into between the crushing blade and the crushing processing portion, so that the material is effectively crushed while being automatically supplied to the screw without inconveniently pushing the material.","BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS FIG.","1 is a perspective view showing a juice extraction module for a juicer according to one embodiment of the present invention; FIG.","2 is a sectional view showing the juice extraction module according to the embodiment of the present invention; FIG.","3 is a plan view showing a lid of the juice extraction module shown in FIG.","1; FIG.","4 is a sectional view of the lid taken along line A-A of FIG.","3; FIG.","5 is a sectional view of the lid taken along line B-B of FIG.","3; and FIG.","6 is a front view showing a screw having a crushing portion provided on a top end thereof as a portion of juice extraction module shown in FIG.","1.DETAILED DESCRIPTION Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.","The following embodiments are provided only for illustrative purposes.","Therefore, the present invention is not limited to the following embodiments but may be implemented in other forms.","In the drawings, the widths, lengths, thicknesses and the like of elements may be exaggerated for convenience of illustration.","FIG.","1 is a perspective view showing a juice extraction module for a juicer according to one embodiment of the present invention; FIG.","2 is a sectional view showing the juice extraction module according to the embodiment of the present invention; FIG.","3 is a plan view showing a lid of the juice extraction module shown in FIG.","1; FIG.","4 is a sectional view of the lid taken along line A-A of FIG.","3; FIG.","5 is a sectional view of the lid taken along line B-B of FIG.","3; and FIG.","6 is a front view showing a screw having a crushing portion provided on a top end thereof as a portion of juice extraction module shown in FIG.","1.Referring to FIGS.","1 to 6, a juice extraction module for a juicer according to one embodiment of the present invention includes a container 100 having a juice extraction space defined therein and having a juice discharge port 101 and a residue discharge port 102 respectively formed in one and another sides of an outer surface thereof, a sieve 200 installed inside of the container 100 to separate juice from material residues generated in juice extraction, a screw 300 installed inside of the sieve 200 to extract juice from the material, and a lid 400 installed to a top end of the container 100 and formed with an input port 410, through which a material is input.","Although not shown, an opening/closing means for selectively opening and closing the juice discharge port 101 of the container 100 may be applied to the juice extraction module.","As the opening/closing means, a cock valve may be used.","The cock valve includes a valve body moving forward or backward in the juice discharge port 101, wherein a leading end of the valve body is preferably oriented toward the juice discharge port 101.In addition, the cock valve may include a juice discharge cock, which may be selectively connected to the juice discharge port 101 by the valve body.","As a means for opening and closing the juice discharge port 101, a variety of means may be employed in addition to the above structure.","A crushing portion 500 is formed on a top end of the screw 300 to have a shape narrowed upward.","The crushing portion 500 has further a crushing blade 510 formed thereon, wherein the crushing blade 510 extends in the shape of a spiral having a width gradually narrowed upward, more preferably toward a top apex of the crushing portion 500.A central shaft 310 of the screw 300 may be formed on the top apex of the crushing portion 500.The lid 400 has a crushing processing portion 600 formed in a bottom thereof to be concave upward from a face coupled with the container 100 in order to accommodate the crushing portion 500.The crushing processing portion 600 has a shape gradually narrowed toward a top apex corresponding to the crushing portion 500.In addition, the top apex of the crushing processing portion 600 is formed with a shaft hole, into which the central shaft 310 of the screw 300 is rotatably fitted.","While being connected with the input port 410, the crushing processing portion 600 cooperates with the crushing portion 500 to serve to crush the material input through the input port 410.The crushing blade 510 is inserted and positioned in the crushing processing portion 600, and the crushing blade 510 cooperates with a specific shape of an inner surface of the crushing processing portion 600 to crush the material.","The input port 410 is offset toward one side with respect to a central axis of the screw 300 and simultaneously should have such a large bottom width W (or inner diameter) that a large-sized material such as an apple is allowed to be input without being chopped.","The sieve 200 has the largest inner diameter at the top end thereof, and thus, a distance from the central axis of the screw 300 to the sieve 200 is set up to be largest at the top end of the sieve 200.The bottom width of the input port 410 is set up to be larger than the shortest distance from the central axis of the screw 300 to an inner circumferential surface of the top end of the sieve 200.Accordingly, as viewed from the top, a region of the input port 410 partially overlaps with a top end region of the sieve 200 and is out of the top end region of the sieve 200.Embodiments of the present invention have a large difference in that a conventional juicer has a small-sized input port so as to be generally positioned inside of a region of a sieve.","Also, the crushing processing portion 600 is formed to cover the entire bottom region of the input port 410 at the height of the crushing processing portion 600 connected to the bottom end of the input port 410.Further, the input port 410 is within a circle region having a diameter corresponding to the diameter of the crushing processing portion 600 with the central shaft 310 of the screw 300 as the center, and more preferably, is positioned to be offset within one side of semicircle regions into which the circle region is divided by a line passing through the central shaft 310.In addition, the inner surface of the crushing processing portion 600, particularly an inner crushing processing surface 610 is formed to be gradually close to the crushing blade 510 of the crushing portion 500 in a direction in which the crushing blade 510 runs from the bottom end of the input port 410.Accordingly, when the material is expelled out by the crushing blade 510, the material is held by the inner surface of the crushing processing portion 600, so that a lateral side of the material is crushed by the crushing blade 510, and the material is dragged into the crushing processing portion according to the rotation of the crushing portion.","This provides an effect of automatically crushing the material even if a user inputs the material and then does not push the material again.","The crushing portion 500 further has one or more auxiliary crushing blades formed thereon so that they assist the crushing blade 510 to crush the material more effectively.","In such a case, the crushing blade 510 first crushes the material, and the auxiliary crushing blades may crush the material more finely.","Also, as the material is dragged into the crushing processing portion, the force of pressing the screw downward is generated, so that there is an effect of suppressing the upward movement of the screw generated by permeation of material residues between a bottom surface of the screw and a floor surface of the container.","As mentioned above, since a portion of the input port 410 extends out of the top end region of the sieve 200, a material guide surface 620 is provided on the inner surface of the crushing processing portion 600 so that the material input through the input port 410 can be guided to the sieve 200.That is, the material guide surface 620 is provided as an element for smoothly connecting the sieve 200 and the input port 410 extending to the outside to such an extent as to use an uncut apple as it is.","Also, the material guide surface 620 continues from the input port 410 while overlapping with the input port 410 and is formed to be inclined toward the central axis of the crushing portion 500, thereby causing a lateral side of the material to begin to be crushed by the crushing blade 510.In order to improve crushing processibility, one or more milling blades 630 may be further formed on the crushing processing surface 610.In this embodiment, the plurality of milling blades 630 are spaced apart from each other and extend from an upper portion of the crushing processing surface 610 to a lower portion thereof, and each of the milling blades 630 is gradually close to the crushing blade 510 as it goes from the upper portion toward the lower portion.","The crushing portion 500 passes over the top end of the container 100 and sieve 200 and is accommodated and positioned in the crushing processing portion 600 positioned in the lid 400.The crushing portion 500 and the crushing processing portion 600 cooperate with each other to fully crush the material input through the input port 410, thereby making it possible to smoothly extract juice from the material even if the user does not chop the material in advance.","Since the juice is extracted from the material fully crushed as above in the sieve 200, there is an effect of preventing the sieve 200 from being deformed.","In addition, a lateral side of the material is processed by the crushing blade 510, which can be performed only by forming the crushing portion 500 to have a length suitable for the height of the material.","Thus, the protruding length of the screw blade need not extend in order to cut the material itself.","Further, a sieve insertion step 420 may be formed in a bottom of the crushing processing portion 600 to be snugly fitted to the top end of the sieve 200.The bottom end of the material guide surface 620 meets the sieve insertion step 420 in a stepwise manner, wherein the bottom end of the material guide surface 620 is formed to conform to an inner surface of the top end of the sieve 200.Accordingly, the material crushed through the crushing processing portion 600 is smoothly guided into the sieve 200 along the material guide surface 620.The various embodiments described above can be combined to provide further embodiments.","All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety.","Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments.","These and other changes can be made to the embodiments in light of the above-detailed description.","In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled.","Accordingly, the claims are not limited by the disclosure."]],"string":"[\n [\n \"JUICE EXTRACTION MODULE FOR JUICER\",\n \"A juice extraction module for a juicer is provided, which includes a container formed with a juice discharge port, a sieve positioned inside of the container, a screw positioned inside of the sieve to extract juice from a material, and a lid coupled to a top end of the container and formed with a input port through which the material is input.\",\n \"The juice extraction module includes a crushing portion formed on a top end of the screw to be narrowed upward, the crushing portion having a crushing blade formed thereon; and a crushing processing portion connected to the input port and formed in a bottom of the lid to be concave for accommodating the crushing portion.\"\n ],\n [\n \"1.A juice extraction module for a juicer, the juice extraction module including: a container comprising a juice discharge port; a sieve positioned inside of the container; a screw to extract juice from a material, the screw being rotatable about a rotational axis and having top and bottom portions vertically arranged along the rotational axis, the bottom portion of the screw being accommodated within the sieve and the top portion of the screw extending out of the sieve; a lid coupled to a top end of the container, the lid having: a top portion that includes an input port through which said material is input into the juice extraction module, and a bottom portion that receives said material from the input port, wherein the top portion of the screw has a spiral blade formed thereon and extends above a top end of the sieve to narrow toward a top end of the screw, wherein the bottom portion of the lid includes a screw accommodating portion configured to accommodate the top portion of the screw, wherein a first material processing zone in which said material is subjected to crushing, in use, is defined between the top portion of the screw and an interior surface of the lid above the top end of the sieve, wherein a second material processing zone in which said material is subjected to juicing, in use, is defined between the bottom portion of the screw and the sieve, and wherein the input port is proportioned to accommodate material of up to a first diameter in size, the first diameter being greater than the shortest distance between the rotational axis of the screw and an inner circumferential surface of the top end of the sieve.\",\n \"2.The juice extraction module according to claim 1, wherein the first material processing zone reduces in size between its upstream and downstream ends.\",\n \"3.The juice extraction module according to claim 1, wherein the screw is of unitary one-piece construction.\",\n \"4.A juice extraction module for a juicer, which includes a container formed with a juice discharge port, a sieve positioned inside of the container, a screw positioned inside of the sieve to rotate about a rotational axis and extract juice from a material, and a lid coupled to a top end of the container and formed with a input port through which the material is input, the juice extraction module comprising: a top portion of the screw defining a crushing portion, the crushing portion comprising a crushing blade formed thereon; and a crushing processing portion connected to the input port and defined in a bottom portion of the lid, the crushing processing portion accommodating the crushing portion of the screw, an inner surface of the crushing processing portion including a crushing processing surface and a material guide surface, wherein the input port is an opening formed in a top portion of the lid, and wherein the material guide surface continues from the input port and is inclined toward the rotational axis, whereby the material guide surface guides the material so that the material begins to be crushed by the crushing blade, and wherein the crushing blade crushes the material within the crushing processing portion formed in the bottom of the lid, in advance of the material reaching the sieve.\",\n \"5.The juice extraction module according to claim 4, wherein the screw is of unitary one-piece construction.\",\n \"6.A juice extraction module for a juicer, comprising: a container comprising a juice discharge port; a sieve positioned inside of the container; a screw positioned inside of the sieve to rotate about a rotational axis and extract juice from a material, a top portion of the screw defining a crushing portion which includes a crushing blade formed thereon; and a lid coupled to a top end of the container and comprising an input port through which the material is input, a bottom portion of the lid comprising a crushing processing portion connected to the input port, the crushing processing portion accommodating the crushing portion of the screw and having an inner surface that includes a crushing processing surface, wherein the input port is an opening formed in the lid, and wherein the crushing blade crushes the material within the crushing processing portion formed in the bottom of the lid, in advance of the material reaching the sieve.\",\n \"7.The juice extraction module according to claim 6, wherein the screw is of unitary one-piece construction.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>\"\n ],\n [\n \"<SOH> BRIEF SUMMARY <EOH>Embodiments of the present invention provide a juice extraction module for a juicer, in which a structure of crushing a material in advance is provided in a lid and a screw to eliminate an inconvenient procedure of chopping or cutting a material in advance before inputting the material.\",\n \"According to an aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a juice discharge port 101 , a sieve 200 positioned inside of the container 100 , a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input.\",\n \"The juice extraction module includes a crushing portion 500 formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon; and a crushing processing portion 600 connected to the input port 410 and formed in a bottom of the lid 400 to be concave for accommodating the crushing portion 500 , wherein the crushing blade 510 crushes the material in advance within the crushing processing portion 600 .\",\n \"According to one embodiment, the crushing blade 510 is formed so that the material input through the input port 410 is crushed while a lateral side of the material is pushed outwards, and the crushing processing portion 600 is provided with an inner surface to hold the material pushed outwards by the crushing blade 510 , whereby the material can be crushed between the crushing blade 510 and the inner surface of the crushing processing portion 600 .\",\n \"According to one embodiment, the crushing processing portion 600 is formed to cover an entire bottom region of the input port 410 at the height of the crushing processing portion 600 connected to a bottom end of the input port 410 .\",\n \"According to one embodiment, a bottom region of the input port 410 is positioned to be offset within a semicircle region of a circle having a diameter corresponding to a diameter of the crushing processing portion 600 with a central shaft 310 of the screw 300 as a center.\",\n \"According to one embodiment, the inner surface of the crushing processing portion 600 comprises a crushing processing surface 610 formed to be gradually close to the crushing blade 510 in a direction in which the crushing blade 510 runs from the input port 410 .\",\n \"According to one embodiment, the inner surface of the crushing processing portion 600 comprises a material guide surface 620 continuing from the input port 410 and formed to be inclined toward a central axis of the crushing portion 500 , whereby the material guide surface 620 guides the material so that a lateral side of the material begins to be crushed by the crushing blade 510 .\",\n \"According to one embodiment, a bottom end of the material guide surface 620 may conform to an inner surface of the sieve 200 .\",\n \"According to one embodiment, the crushing portion 500 passes over a top end of the sieve 200 and is accommodated in the crushing processing portion 600 , and the crushing blade 510 cooperates with the crushing processing portion 600 to crush the material.\",\n \"According to another aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a residue discharge port 102 and a juice discharge port 101 ; a sieve 200 positioned inside of the container 100 ; a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input, wherein a crushing portion 500 is formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon, wherein the lid 400 is formed with a crushing processing portion 600 , the crushing processing portion 600 being connected to the input port 410 and accommodating the crushing portion 500 , wherein the input port 410 is disposed to be offset outwards from a central axis of the screw 300 and has a width larger than the shortest distance from the central axis of the screw 300 to an inner circumferential surface of a top end of the sieve 200 , wherein the crushing processing portion 600 is formed with a material guide surface for assisting guidance of the material from the input port 410 to the sieve 200 .\",\n \"The crushing blade 510 and the crushing processing portion 600 are formed so that a distance between the crushing blade 510 and an inner surface of the crushing processing portion 600 is gradually reduced by the rotation of the crushing blade 510 The crushing processing portion 600 comprises a crushing processing surface 610 , the crushing processing surface 610 is formed with at least one milling blade 630 .\",\n \"A conventional juicer has inconvenience and difficulty in that an increase in length of a screw blade increases an entire outer diameter of a screw, and thus, a sieve, a container and a lid should be manufactured large so as to be fitted to the screw.\",\n \"However, according to embodiments of the present invention, a material having a diameter larger than a length of a screw blade can be used, and the material can be crushed into a size suitable for extracting juice without increasing an outer diameter of a screw by a crushing processing portion formed to be concave in a bottom of a lid and a crushing portion accommodated in the crushing processing portion and cooperating with the crushing processing portion.\",\n \"Thus, embodiments of the present invention eliminate the inconvenience and cumbersomeness that a user should chop a material before the material is input.\",\n \"In addition, a space between the crushing blade and the crushing processing portion is gradually narrowed and the material is caught and simultaneously dragged into between the crushing blade and the crushing processing portion, so that the material is effectively crushed while being automatically supplied to the screw without inconveniently pushing the material.\"\n ],\n [\n \"BACKGROUND Technical Field The present disclosure relates to a juice extraction module for a juicer, and more specifically, to a juice extraction module for a juicer having an improved structure capable of eliminating the inconvenience that a material should be chopped before the material is input into the juicer.\",\n \"Description of the Related Art In general, a juicer includes a main body, and a juice extraction module mounted onto the main body.\",\n \"The juice extraction module includes a container having a juice extraction space, a lid having an input port through which a material is input into the container, a screw for extracting juice from the material in the container, and a sieve for separating juice and residues from each other.\",\n \"The main body includes a driving motor for rotating the screw, and a shaft of the driving motor is connected to the screw in the juice extraction module.\",\n \"In the conventional juicer, the material should be chopped into such a size that the screw can extract juice.\",\n \"As an example, Korean Patent No.\",\n \"10-0793852 discloses a juicer configured to cut or sever a material by a screw blade protruding from a central axis of a screw toward a lateral side of an uppermost end.\",\n \"However, in the above technique, when a material has a size larger than the length of the screw blade, the material should be chopped in advance into a size smaller than the length of the screw blade.\",\n \"In addition, Korean Patent No.\",\n \"10-0966607 discloses a juicer having a grater provided in an entire upper surface over a screw to crush a material just before juice is extracted.\",\n \"However, there are problems in that the crush using the grater is achieved at a speed higher than an ordinary low speed of the juicer and also a user should press the material against the grater by a large force in order to prevent the rotation of the material due to the high speed of the grater.\",\n \"Also, since the conventional juicer cuts the material and then mills the cut pieces of the material while they are pressed against a sieve in a juice extraction process, the sieve may be deformed in a moment by the pressed cut pieces.\",\n \"Such deformation destroys a molding for holding a shape of the sieve or decreases the bond between the molding and the sieve to generate a gap between the molding and the sieve causing a leakage of residues and a decrease in juice extraction efficiency.\",\n \"BRIEF SUMMARY Embodiments of the present invention provide a juice extraction module for a juicer, in which a structure of crushing a material in advance is provided in a lid and a screw to eliminate an inconvenient procedure of chopping or cutting a material in advance before inputting the material.\",\n \"According to an aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a juice discharge port 101, a sieve 200 positioned inside of the container 100, a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input.\",\n \"The juice extraction module includes a crushing portion 500 formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon; and a crushing processing portion 600 connected to the input port 410 and formed in a bottom of the lid 400 to be concave for accommodating the crushing portion 500, wherein the crushing blade 510 crushes the material in advance within the crushing processing portion 600.According to one embodiment, the crushing blade 510 is formed so that the material input through the input port 410 is crushed while a lateral side of the material is pushed outwards, and the crushing processing portion 600 is provided with an inner surface to hold the material pushed outwards by the crushing blade 510, whereby the material can be crushed between the crushing blade 510 and the inner surface of the crushing processing portion 600.According to one embodiment, the crushing processing portion 600 is formed to cover an entire bottom region of the input port 410 at the height of the crushing processing portion 600 connected to a bottom end of the input port 410.According to one embodiment, a bottom region of the input port 410 is positioned to be offset within a semicircle region of a circle having a diameter corresponding to a diameter of the crushing processing portion 600 with a central shaft 310 of the screw 300 as a center.\",\n \"According to one embodiment, the inner surface of the crushing processing portion 600 comprises a crushing processing surface 610 formed to be gradually close to the crushing blade 510 in a direction in which the crushing blade 510 runs from the input port 410.According to one embodiment, the inner surface of the crushing processing portion 600 comprises a material guide surface 620 continuing from the input port 410 and formed to be inclined toward a central axis of the crushing portion 500, whereby the material guide surface 620 guides the material so that a lateral side of the material begins to be crushed by the crushing blade 510.According to one embodiment, a bottom end of the material guide surface 620 may conform to an inner surface of the sieve 200.According to one embodiment, the crushing portion 500 passes over a top end of the sieve 200 and is accommodated in the crushing processing portion 600, and the crushing blade 510 cooperates with the crushing processing portion 600 to crush the material.\",\n \"According to another aspect of the present invention, there is provided a juice extraction module for a juicer, which includes a container 100 formed with a residue discharge port 102 and a juice discharge port 101; a sieve 200 positioned inside of the container 100; a screw 300 positioned inside of the sieve 200 to extract juice from a material, and a lid 400 coupled to a top end of the container 100 and formed with a input port 410 through which the material is input, wherein a crushing portion 500 is formed on a top end of the screw 300 to be narrowed upward, the crushing portion 500 having a crushing blade 510 formed thereon, wherein the lid 400 is formed with a crushing processing portion 600, the crushing processing portion 600 being connected to the input port 410 and accommodating the crushing portion 500, wherein the input port 410 is disposed to be offset outwards from a central axis of the screw 300 and has a width larger than the shortest distance from the central axis of the screw 300 to an inner circumferential surface of a top end of the sieve 200, wherein the crushing processing portion 600 is formed with a material guide surface for assisting guidance of the material from the input port 410 to the sieve 200.The crushing blade 510 and the crushing processing portion 600 are formed so that a distance between the crushing blade 510 and an inner surface of the crushing processing portion 600 is gradually reduced by the rotation of the crushing blade 510 The crushing processing portion 600 comprises a crushing processing surface 610, the crushing processing surface 610 is formed with at least one milling blade 630.A conventional juicer has inconvenience and difficulty in that an increase in length of a screw blade increases an entire outer diameter of a screw, and thus, a sieve, a container and a lid should be manufactured large so as to be fitted to the screw.\",\n \"However, according to embodiments of the present invention, a material having a diameter larger than a length of a screw blade can be used, and the material can be crushed into a size suitable for extracting juice without increasing an outer diameter of a screw by a crushing processing portion formed to be concave in a bottom of a lid and a crushing portion accommodated in the crushing processing portion and cooperating with the crushing processing portion.\",\n \"Thus, embodiments of the present invention eliminate the inconvenience and cumbersomeness that a user should chop a material before the material is input.\",\n \"In addition, a space between the crushing blade and the crushing processing portion is gradually narrowed and the material is caught and simultaneously dragged into between the crushing blade and the crushing processing portion, so that the material is effectively crushed while being automatically supplied to the screw without inconveniently pushing the material.\",\n \"BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS FIG.\",\n \"1 is a perspective view showing a juice extraction module for a juicer according to one embodiment of the present invention; FIG.\",\n \"2 is a sectional view showing the juice extraction module according to the embodiment of the present invention; FIG.\",\n \"3 is a plan view showing a lid of the juice extraction module shown in FIG.\",\n \"1; FIG.\",\n \"4 is a sectional view of the lid taken along line A-A of FIG.\",\n \"3; FIG.\",\n \"5 is a sectional view of the lid taken along line B-B of FIG.\",\n \"3; and FIG.\",\n \"6 is a front view showing a screw having a crushing portion provided on a top end thereof as a portion of juice extraction module shown in FIG.\",\n \"1.DETAILED DESCRIPTION Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.\",\n \"The following embodiments are provided only for illustrative purposes.\",\n \"Therefore, the present invention is not limited to the following embodiments but may be implemented in other forms.\",\n \"In the drawings, the widths, lengths, thicknesses and the like of elements may be exaggerated for convenience of illustration.\",\n \"FIG.\",\n \"1 is a perspective view showing a juice extraction module for a juicer according to one embodiment of the present invention; FIG.\",\n \"2 is a sectional view showing the juice extraction module according to the embodiment of the present invention; FIG.\",\n \"3 is a plan view showing a lid of the juice extraction module shown in FIG.\",\n \"1; FIG.\",\n \"4 is a sectional view of the lid taken along line A-A of FIG.\",\n \"3; FIG.\",\n \"5 is a sectional view of the lid taken along line B-B of FIG.\",\n \"3; and FIG.\",\n \"6 is a front view showing a screw having a crushing portion provided on a top end thereof as a portion of juice extraction module shown in FIG.\",\n \"1.Referring to FIGS.\",\n \"1 to 6, a juice extraction module for a juicer according to one embodiment of the present invention includes a container 100 having a juice extraction space defined therein and having a juice discharge port 101 and a residue discharge port 102 respectively formed in one and another sides of an outer surface thereof, a sieve 200 installed inside of the container 100 to separate juice from material residues generated in juice extraction, a screw 300 installed inside of the sieve 200 to extract juice from the material, and a lid 400 installed to a top end of the container 100 and formed with an input port 410, through which a material is input.\",\n \"Although not shown, an opening/closing means for selectively opening and closing the juice discharge port 101 of the container 100 may be applied to the juice extraction module.\",\n \"As the opening/closing means, a cock valve may be used.\",\n \"The cock valve includes a valve body moving forward or backward in the juice discharge port 101, wherein a leading end of the valve body is preferably oriented toward the juice discharge port 101.In addition, the cock valve may include a juice discharge cock, which may be selectively connected to the juice discharge port 101 by the valve body.\",\n \"As a means for opening and closing the juice discharge port 101, a variety of means may be employed in addition to the above structure.\",\n \"A crushing portion 500 is formed on a top end of the screw 300 to have a shape narrowed upward.\",\n \"The crushing portion 500 has further a crushing blade 510 formed thereon, wherein the crushing blade 510 extends in the shape of a spiral having a width gradually narrowed upward, more preferably toward a top apex of the crushing portion 500.A central shaft 310 of the screw 300 may be formed on the top apex of the crushing portion 500.The lid 400 has a crushing processing portion 600 formed in a bottom thereof to be concave upward from a face coupled with the container 100 in order to accommodate the crushing portion 500.The crushing processing portion 600 has a shape gradually narrowed toward a top apex corresponding to the crushing portion 500.In addition, the top apex of the crushing processing portion 600 is formed with a shaft hole, into which the central shaft 310 of the screw 300 is rotatably fitted.\",\n \"While being connected with the input port 410, the crushing processing portion 600 cooperates with the crushing portion 500 to serve to crush the material input through the input port 410.The crushing blade 510 is inserted and positioned in the crushing processing portion 600, and the crushing blade 510 cooperates with a specific shape of an inner surface of the crushing processing portion 600 to crush the material.\",\n \"The input port 410 is offset toward one side with respect to a central axis of the screw 300 and simultaneously should have such a large bottom width W (or inner diameter) that a large-sized material such as an apple is allowed to be input without being chopped.\",\n \"The sieve 200 has the largest inner diameter at the top end thereof, and thus, a distance from the central axis of the screw 300 to the sieve 200 is set up to be largest at the top end of the sieve 200.The bottom width of the input port 410 is set up to be larger than the shortest distance from the central axis of the screw 300 to an inner circumferential surface of the top end of the sieve 200.Accordingly, as viewed from the top, a region of the input port 410 partially overlaps with a top end region of the sieve 200 and is out of the top end region of the sieve 200.Embodiments of the present invention have a large difference in that a conventional juicer has a small-sized input port so as to be generally positioned inside of a region of a sieve.\",\n \"Also, the crushing processing portion 600 is formed to cover the entire bottom region of the input port 410 at the height of the crushing processing portion 600 connected to the bottom end of the input port 410.Further, the input port 410 is within a circle region having a diameter corresponding to the diameter of the crushing processing portion 600 with the central shaft 310 of the screw 300 as the center, and more preferably, is positioned to be offset within one side of semicircle regions into which the circle region is divided by a line passing through the central shaft 310.In addition, the inner surface of the crushing processing portion 600, particularly an inner crushing processing surface 610 is formed to be gradually close to the crushing blade 510 of the crushing portion 500 in a direction in which the crushing blade 510 runs from the bottom end of the input port 410.Accordingly, when the material is expelled out by the crushing blade 510, the material is held by the inner surface of the crushing processing portion 600, so that a lateral side of the material is crushed by the crushing blade 510, and the material is dragged into the crushing processing portion according to the rotation of the crushing portion.\",\n \"This provides an effect of automatically crushing the material even if a user inputs the material and then does not push the material again.\",\n \"The crushing portion 500 further has one or more auxiliary crushing blades formed thereon so that they assist the crushing blade 510 to crush the material more effectively.\",\n \"In such a case, the crushing blade 510 first crushes the material, and the auxiliary crushing blades may crush the material more finely.\",\n \"Also, as the material is dragged into the crushing processing portion, the force of pressing the screw downward is generated, so that there is an effect of suppressing the upward movement of the screw generated by permeation of material residues between a bottom surface of the screw and a floor surface of the container.\",\n \"As mentioned above, since a portion of the input port 410 extends out of the top end region of the sieve 200, a material guide surface 620 is provided on the inner surface of the crushing processing portion 600 so that the material input through the input port 410 can be guided to the sieve 200.That is, the material guide surface 620 is provided as an element for smoothly connecting the sieve 200 and the input port 410 extending to the outside to such an extent as to use an uncut apple as it is.\",\n \"Also, the material guide surface 620 continues from the input port 410 while overlapping with the input port 410 and is formed to be inclined toward the central axis of the crushing portion 500, thereby causing a lateral side of the material to begin to be crushed by the crushing blade 510.In order to improve crushing processibility, one or more milling blades 630 may be further formed on the crushing processing surface 610.In this embodiment, the plurality of milling blades 630 are spaced apart from each other and extend from an upper portion of the crushing processing surface 610 to a lower portion thereof, and each of the milling blades 630 is gradually close to the crushing blade 510 as it goes from the upper portion toward the lower portion.\",\n \"The crushing portion 500 passes over the top end of the container 100 and sieve 200 and is accommodated and positioned in the crushing processing portion 600 positioned in the lid 400.The crushing portion 500 and the crushing processing portion 600 cooperate with each other to fully crush the material input through the input port 410, thereby making it possible to smoothly extract juice from the material even if the user does not chop the material in advance.\",\n \"Since the juice is extracted from the material fully crushed as above in the sieve 200, there is an effect of preventing the sieve 200 from being deformed.\",\n \"In addition, a lateral side of the material is processed by the crushing blade 510, which can be performed only by forming the crushing portion 500 to have a length suitable for the height of the material.\",\n \"Thus, the protruding length of the screw blade need not extend in order to cut the material itself.\",\n \"Further, a sieve insertion step 420 may be formed in a bottom of the crushing processing portion 600 to be snugly fitted to the top end of the sieve 200.The bottom end of the material guide surface 620 meets the sieve insertion step 420 in a stepwise manner, wherein the bottom end of the material guide surface 620 is formed to conform to an inner surface of the top end of the sieve 200.Accordingly, the material crushed through the crushing processing portion 600 is smoothly guided into the sieve 200 along the material guide surface 620.The various embodiments described above can be combined to provide further embodiments.\",\n \"All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety.\",\n \"Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments.\",\n \"These and other changes can be made to the embodiments in light of the above-detailed description.\",\n \"In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled.\",\n \"Accordingly, the claims are not limited by the disclosure.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874756"}}},{"rowIdx":4494689,"cells":{"text":{"kind":"list like","value":[["POSTERIOR CAPSULOTOMY USING LASER TECHNIQUES","A system and method are provided for removing a natural lens and inserting an Intraocular Lens (IOL) into the lens capsule of an eye.","Specifically, this is accomplished by inserting the IOL through an opening on the posterior capsule that is created using a focused laser beam.","The system includes a laser unit, a detector for creating images of the interior of the eye, and a computer that controls the cooperative functions of the detector and the laser unit.","Based on images of the posterior capsule provided by the detector, the computer is used to control movements of the focal point through tissue of the posterior capsule to perform Laser Induced Optical Breakdown (LIOB) on posterior capsule tissue.","The result is a laser capsulotomy that creates an opening through the posterior capsule allowing the natural lens to be removed and the IOL to be implanted."],["1.A method for performing ophthalmic surgery inside an eye which comprises the steps of: performing Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule of the eye to create a section of separated tissue defining an opening into the lens capsule of the eye; removing the section of separated tissue from the lens capsule to establish the opening; extracting the lens of the eye from the lens capsule of the eye through the opening in the posterior capsule; and implanting an optical device in the lens capsule through the opening in the posterior capsule to replace the extracted lens.","2.A method as recited in claim 1 wherein the performing step comprises the steps of: generating a pulsed laser beam; focusing the pulsed laser beam to a focal point; and directing the focal point of the pulsed laser beam onto tissue of the posterior capsule inside the eye.","3.A method as recited in claim 2 wherein the performing step further comprises the steps of: creating images of the inside of the eye; and using an image from the creating step to control movements of the focal point through tissue of the posterior capsule to create the opening.","4.A method as recited in claim 3 wherein the creating step is accomplished using imaging techniques selected from a group comprising Optical Coherence Tomography (OCT), Scheimpfiug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.","5.A method as recited in claim 1 wherein the removing step comprises the steps of: incising the sclera to establish an access port to the vitreous body of the eye; advancing a probe through the access port for engagement of the probe with the section of separated tissue; and withdrawing the separated section of tissue from the eye with the probe to establish the opening.","6.A method as recited in claim 1 wherein the optical device is an Intraocular Lens (IOL).","7.A method as recited in claim 6 further comprising the step of establishing LIOB marks on the lens capsule to assist in aligning the IOL in the lens capsule.","8.A method as recited in claim 6 further comprising the step of dimensioning the opening to receive a specific IOL into the lens capsule via the opening.","9.A method for performing ophthalmic laser surgery inside an eye which comprises the steps of: generating a pulsed laser beam; creating images of the inside of the eye; using images from the creating step to control movements of the focal point of the laser beam through tissue of the posterior capsule to perform Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule to create an opening into the lens capsule of the eye; extracting the lens of the eye from the lens capsule of the eye through the opening in the posterior capsule; and implanting an optical device in the lens capsule through the opening in the posterior capsule to replace the extracted lens.","10.The method of claim 9 further comprising the step of preparing the lens of the eye for removal from the posterior capsule prior to the extracting step.","11.The method of claim 10 wherein the preparing step is accomplished by a procedure selected from the group consisting of hydrodissection, phacoemulsification and lens fragmentation.","12.The method of claim 9 further comprising the steps of: incising the sclera to establish an access port into the vitreous body of the eye; and advancing a probe through the access port to accomplish the extracting step.","13.The method of claim 9 wherein the optical device is an Intraocular Lens (IOL).","14.The method of claim 13 further comprising the step of establishing LIOB marks on the lens capsule to assist in aligning the IOL in the lens capsule.","15.The method of claim 14 further comprising the step of dimensioning the opening to receive a specific IOL into the lens capsule via the opening."],["<SOH> BACKGROUND OF THE INVENTION <EOH>A common treatment for a cataract involves removal of the diseased lens from a patient's eye followed by replacement with an Intraocular Lens (IOL).","Originally, the entire lens and capsule were removed and replaced.","More modernly, the lens is removed from the capsule, in situ, and the new IOL is inserted into the capsule.","In a typical cataract procedure, access to the lens is obtained and the lens is fragmented and/or emulsified.","For example, the lens can be emulsified using a traditional ultrasonic handpiece (a process known as “phacoemulsification”), or, more modernly, the lens can be fragmented using a femtosecond laser.","Once fragmented or emulsified, the lens material can be removed from the capsule, for example, by aspirating the material using an aspiration needle.","Once the lens material has been removed, an IOL can be inserted into the remaining portion of the lens capsule.","To perform the procedures described above, an opening in the lens capsule is required.","Two possibilities for this opening include an anterior capsulotomy in which an opening is made on the anterior surface of the lens capsule and a posterior capsulotomy in which an opening is made on the posterior surface of the lens capsule.","Typically, for an anterior capsulotomy, the surgeon gains access to the capsule and lens through incisions that are made on the cornea or limbus.","However, these incisions can adversely affect the refractive properties of the eye, including the inducement of undesirable astigmatism.","Another drawback associated with a typical anterior capsulotomy procedure involves anatomical considerations.","In more detail, access to the anterior capsule surface necessarily involves transit through the relatively small anterior chamber of the eye.","Unfortunately, there are a number of surgical problems associated with passing tools, such as the phacoemulsification probe and aspiration needle, through the small anterior chamber of the eye.","Moreover, the anterior capsulotomy procedure can disturb other fragile anatomical structures that are anterior to the crystalline lens.","Unlike the anterior capsulotomy, access for a posterior capsulotomy can be obtained using incisions through the sclera on the side of the eye.","These incisions do not, in general, affect the refractive properties of the eye like the incisions described above that are made on the cornea or limbus.","In addition, there is more operating room on the posterior side of the crystalline lens than the small anterior chamber of the eye.","And, in many instances, additional room for tool manipulation can be made on the posterior side of the crystalline lens by performing a partial vitrectomy.","Another advantage of a posterior capsulotomy is that the optical barrier (e.g.","the anterior surface of the capsule) is maintained intact during a surgical procedure.","Lastly, the use of a posterior capsulotomy can provide flexibility for combining the capsulotomy procedure with other surgical procedures in the back of the eye.","In light of the above, it is an object of the present invention to provide a system and method for performing a posterior capsulotomy.","Another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure to accommodate the insertion of an Intraocular Lens (IOL) into the lens capsule of an eye.","Still another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure using laser techniques which is simple to implement and is relatively cost effective."],["<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the present invention, a system and method are provided for inserting an Intraocular Lens (IOL) into the lens capsule of an eye.","Specifically, this is accomplished by inserting the IOL through an opening that is created through the posterior capsule of the eye.","In overview, the system includes a detector for creating images of the interior of the eye, and it includes a laser unit for generating and focusing a laser beam to a focal point.","The system further includes a computer that controls the cooperative functions of the detector and the laser unit.","For an operation of the present invention, the computer processes images that are provided by the detector.","Specifically, these images are of tissue inside the eye and their processing by the computer is accomplished to establish an accurate location for the posterior capsule of the eye.","As envisioned for the present invention, the detector is preferably an imaging unit that employs imaging techniques selected from a group comprising Optical Coherence Tomography (OCT), Scheimpflug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.","In addition to receiving images from the detector, the computer also operates the laser unit to generate and focus a laser beam.","In detail, the laser beam is preferably a pulsed laser beam wherein each pulse has a duration less than one millisecond.","Furthermore, it is necessary that the energy at the focal point of the laser beam be capable of performing Laser Induced Optical Breakdown (LIOB) of tissue of the posterior capsule.","Based on images of the posterior capsule that have been provided by the detector (imaging unit), the computer is used to control movements of the focal point through tissue of the posterior capsule.","As indicated above, this is done for the purpose of performing Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule.","As envisioned for the present invention, the condition of tissue of the posterior capsule is of interest only insofar as it may affect the laser operation.","Stated differently, the present invention pertains regardless whether the posterior capsule is initially intact, or somehow torn.","In either case, the intent here is to create an opening through the posterior capsule that can be used for inserting the IOL into the lens capsule.","Importantly, in this process, the opening is dimensioned and customized to receive a specific IOL into the lens capsule via the opening.","In accordance with a methodology for the present invention, the crystalline lens of an eye is prepared for its removal from the lens capsule at an appropriate time in the particular procedure.","As will be appreciated by the skilled artisan, preparation of the lens can be done in any of several different ways that are well known in the pertinent art.","For example, techniques such as hydrodissection and phacoemulsification may be used for this purpose.","Preferably, laser techniques such as disclosed in U.S. application Ser.","No.","13/436,352, which was filed on Mar.","30, 2012 for an invention entitled “System and Method for Performing Lens Fragmentation,” can be useful for this same purpose.","At an appropriate time in the procedure, Laser Induced Optical Breakdown (LIOB) is performed on tissue of the posterior capsule of the eye to create a section of separated tissue.","In effect, this involves a laser capsulotomy that creates an opening through the posterior capsule, into the lens capsule of the eye.","The section of separated tissue is then removed from the lens capsule to establish the opening.","As envisioned for the present invention, this removal of the separated tissue section will be accomplished by first incising the sclera to establish an access port to the vitreous body of the eye.","A probe can then be advanced through the access port for engagement of the probe with the section of separated tissue.","After the probe has engaged with the separated section of tissue, the separated section of tissue can be removed from the eye by the probe to establish the opening.","Once an opening has been established through the posterior capsule of the eye, the crystalline lens of the eye can be extracted (removed) from the lens capsule of the eye.","The extracted lens can then be removed from the eye through the access port that has been created through the sclera.","Specifically, this may include removing the whole lens through the scleral incision using mechanical cutters and macelators such as scissors, lassos, guillotine cutters, cautery devices, aqua-jets, ultrasonic blades, a combination of a laser and another extraction device, or any other device or technique sufficient to remove the lens.","Once the crystalline lens has been extracted (removed), an IOL can be introduced through the sclera and inserted through the opening in the posterior capsule to replace the extracted lens.","As an additional feature of the present invention, LIOB marks can be established on the lens capsule during the procedure to assist in aligning the IOL in the lens capsule.","Such feature may be particularly useful for properly orienting a toric IOL that is to be used for the correction of astigmatism."],["This application is a divisional of application Ser.","No.","14/412,168, filed Dec. 30, 2014, which is currently pending.","Application Ser.","No.","14/412,168 is a 371 of International Application No.","PCT/US2013/031394, filed Mar.","14, 2013, which is expired and which claims the benefit of U.S.","Provisional Patent Application Ser.","No.","61/671,312, filed Jul.","13, 2012, which is expired.","FIELD OF THE INVENTION The present invention pertains generally to ocular laser surgery.","More particularly, the present invention pertains to capsulotomy procedures that employ a femtosecond laser.","The present invention is particularly, but not exclusively, useful for performing a posterior capsulotomy procedure to insert an Intraocular Lens (IOL) into the lens capsule of an eye.","BACKGROUND OF THE INVENTION A common treatment for a cataract involves removal of the diseased lens from a patient's eye followed by replacement with an Intraocular Lens (IOL).","Originally, the entire lens and capsule were removed and replaced.","More modernly, the lens is removed from the capsule, in situ, and the new IOL is inserted into the capsule.","In a typical cataract procedure, access to the lens is obtained and the lens is fragmented and/or emulsified.","For example, the lens can be emulsified using a traditional ultrasonic handpiece (a process known as “phacoemulsification”), or, more modernly, the lens can be fragmented using a femtosecond laser.","Once fragmented or emulsified, the lens material can be removed from the capsule, for example, by aspirating the material using an aspiration needle.","Once the lens material has been removed, an IOL can be inserted into the remaining portion of the lens capsule.","To perform the procedures described above, an opening in the lens capsule is required.","Two possibilities for this opening include an anterior capsulotomy in which an opening is made on the anterior surface of the lens capsule and a posterior capsulotomy in which an opening is made on the posterior surface of the lens capsule.","Typically, for an anterior capsulotomy, the surgeon gains access to the capsule and lens through incisions that are made on the cornea or limbus.","However, these incisions can adversely affect the refractive properties of the eye, including the inducement of undesirable astigmatism.","Another drawback associated with a typical anterior capsulotomy procedure involves anatomical considerations.","In more detail, access to the anterior capsule surface necessarily involves transit through the relatively small anterior chamber of the eye.","Unfortunately, there are a number of surgical problems associated with passing tools, such as the phacoemulsification probe and aspiration needle, through the small anterior chamber of the eye.","Moreover, the anterior capsulotomy procedure can disturb other fragile anatomical structures that are anterior to the crystalline lens.","Unlike the anterior capsulotomy, access for a posterior capsulotomy can be obtained using incisions through the sclera on the side of the eye.","These incisions do not, in general, affect the refractive properties of the eye like the incisions described above that are made on the cornea or limbus.","In addition, there is more operating room on the posterior side of the crystalline lens than the small anterior chamber of the eye.","And, in many instances, additional room for tool manipulation can be made on the posterior side of the crystalline lens by performing a partial vitrectomy.","Another advantage of a posterior capsulotomy is that the optical barrier (e.g.","the anterior surface of the capsule) is maintained intact during a surgical procedure.","Lastly, the use of a posterior capsulotomy can provide flexibility for combining the capsulotomy procedure with other surgical procedures in the back of the eye.","In light of the above, it is an object of the present invention to provide a system and method for performing a posterior capsulotomy.","Another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure to accommodate the insertion of an Intraocular Lens (IOL) into the lens capsule of an eye.","Still another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure using laser techniques which is simple to implement and is relatively cost effective.","SUMMARY OF THE INVENTION In accordance with the present invention, a system and method are provided for inserting an Intraocular Lens (IOL) into the lens capsule of an eye.","Specifically, this is accomplished by inserting the IOL through an opening that is created through the posterior capsule of the eye.","In overview, the system includes a detector for creating images of the interior of the eye, and it includes a laser unit for generating and focusing a laser beam to a focal point.","The system further includes a computer that controls the cooperative functions of the detector and the laser unit.","For an operation of the present invention, the computer processes images that are provided by the detector.","Specifically, these images are of tissue inside the eye and their processing by the computer is accomplished to establish an accurate location for the posterior capsule of the eye.","As envisioned for the present invention, the detector is preferably an imaging unit that employs imaging techniques selected from a group comprising Optical Coherence Tomography (OCT), Scheimpflug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.","In addition to receiving images from the detector, the computer also operates the laser unit to generate and focus a laser beam.","In detail, the laser beam is preferably a pulsed laser beam wherein each pulse has a duration less than one millisecond.","Furthermore, it is necessary that the energy at the focal point of the laser beam be capable of performing Laser Induced Optical Breakdown (LIOB) of tissue of the posterior capsule.","Based on images of the posterior capsule that have been provided by the detector (imaging unit), the computer is used to control movements of the focal point through tissue of the posterior capsule.","As indicated above, this is done for the purpose of performing Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule.","As envisioned for the present invention, the condition of tissue of the posterior capsule is of interest only insofar as it may affect the laser operation.","Stated differently, the present invention pertains regardless whether the posterior capsule is initially intact, or somehow torn.","In either case, the intent here is to create an opening through the posterior capsule that can be used for inserting the IOL into the lens capsule.","Importantly, in this process, the opening is dimensioned and customized to receive a specific IOL into the lens capsule via the opening.","In accordance with a methodology for the present invention, the crystalline lens of an eye is prepared for its removal from the lens capsule at an appropriate time in the particular procedure.","As will be appreciated by the skilled artisan, preparation of the lens can be done in any of several different ways that are well known in the pertinent art.","For example, techniques such as hydrodissection and phacoemulsification may be used for this purpose.","Preferably, laser techniques such as disclosed in U.S. application Ser.","No.","13/436,352, which was filed on Mar.","30, 2012 for an invention entitled “System and Method for Performing Lens Fragmentation,” can be useful for this same purpose.","At an appropriate time in the procedure, Laser Induced Optical Breakdown (LIOB) is performed on tissue of the posterior capsule of the eye to create a section of separated tissue.","In effect, this involves a laser capsulotomy that creates an opening through the posterior capsule, into the lens capsule of the eye.","The section of separated tissue is then removed from the lens capsule to establish the opening.","As envisioned for the present invention, this removal of the separated tissue section will be accomplished by first incising the sclera to establish an access port to the vitreous body of the eye.","A probe can then be advanced through the access port for engagement of the probe with the section of separated tissue.","After the probe has engaged with the separated section of tissue, the separated section of tissue can be removed from the eye by the probe to establish the opening.","Once an opening has been established through the posterior capsule of the eye, the crystalline lens of the eye can be extracted (removed) from the lens capsule of the eye.","The extracted lens can then be removed from the eye through the access port that has been created through the sclera.","Specifically, this may include removing the whole lens through the scleral incision using mechanical cutters and macelators such as scissors, lassos, guillotine cutters, cautery devices, aqua-jets, ultrasonic blades, a combination of a laser and another extraction device, or any other device or technique sufficient to remove the lens.","Once the crystalline lens has been extracted (removed), an IOL can be introduced through the sclera and inserted through the opening in the posterior capsule to replace the extracted lens.","As an additional feature of the present invention, LIOB marks can be established on the lens capsule during the procedure to assist in aligning the IOL in the lens capsule.","Such feature may be particularly useful for properly orienting a toric IOL that is to be used for the correction of astigmatism.","BRIEF DESCRIPTION OF THE DRAWINGS The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which: FIG.","1 is a schematic presentation of components for the system of the present invention; FIG.","2A is a cross section view of the anterior portion of an eye showing the removal of tissue from the posterior capsule of the eye to create an opening into the lens capsule; and FIG.","2B is a cross section view of the anterior portion of the eye as seen in FIG.","2A, showing the insertion of an Intraocular Lens (IOL) through the opening into the lens capsule of the eye, after the crystalline lens of the eye has been removed from the lens capsule.","DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring initially to FIG.","1, a system in accordance with the present invention is shown and is generally designated 10.As shown, the system 10 includes a laser unit 12 and a computer 14.As shown, the computer 14 is connected with the laser unit 12 for the purposes of guiding and controlling the movement of a laser beam 16 that is generated and focused by the laser unit 12.Necessarily, the laser unit 12 is of a type that generates a pulsed laser beam 16 which is capable of performing Laser Induced Optical Breakdown (LIOB) on sub-surface anatomical tissue.","Preferably, the laser beam 16 will have laser pulses with pulse durations in the femtosecond range.","FIG.","1 also shows that the system 10 can include a detector 18 for creating images of the interior of the eye 20.For example, the detector 18 can include an imaging unit that employs imaging techniques such as Optical Coherence Tomography (OCT), Scheimpflug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.","As shown, the computer 14 is connected to the detector 18 to receive and process image data from the detector 18 and control the operation of the detector 18.More specifically, images of tissue inside the eye 20 can be processed by the computer 14 to establish an accurate location for the crystalline lens 22 and posterior capsule 24 of the eye 20.FIG.","2A illustrates a procedure for creating a section of separated tissue 26 and removing the tissue 26 from the posterior capsule 24 of the eye 20 to create an opening 28 into the posterior capsule 24.For this procedure, images of the posterior capsule 24 (FIG.","1) are provided by the detector 18 to the computer 14 which uses the image data to control movements of the focal point through tissue of the posterior capsule 24.As this is done, Laser Induced Optical Breakdown (LIOB) occurs on tissue of the posterior capsule 24 to create a section of separated tissue 26.Once the separated tissue is removed, an opening 28 is established through the posterior capsule 24 that can be used for removing the lens 22 and/or inserting an IOL 30 (FIG.","2B) into the lens capsule 31.For this process, the opening 28 can be dimensioned and customized to allow a specific IOL 30 (FIG.","2B) to pass through the opening 28 and be implanted into the lens capsule 31.Continuing with FIG.","2A, it can be seen that the separated tissue 26 can be removed from the eye 20, by first incising the sclera 32 to establish an access port 34 to the vitreous body 36 of the eye 20.As shown, a probe 38 can then be advanced through the access port 34 for engagement of the probe 38 with the section of separated tissue 26.After the probe 38 has engaged with the separated section of tissue 26, the separated section of tissue 26 can be removed from the eye 20 by the probe 38 (in the direction of arrow 40) and through access port 34 to establish the opening 28.Once an opening 28 has been established through the posterior capsule 24 of the eye 20, as shown, the crystalline lens 22 can be extracted from the lens capsule 31 and removed from the eye 20 through the access port 34.FIG.","2B shows that an IOL 30 can be introduced through the access port 34 in the sclera 32 and inserted through the opening 28 (in the direction of arrow 42 and into the lens capsule 31.As shown, probe 44 can be used to place the IOL 30 into the lens capsule 31.As an additional feature of the present invention, LIOB marks (not shown) can be established on the lens capsule 31 during the procedure to assist in aligning the IOL 30 in the lens capsule 31.For example, these LIOB marks may be used to properly orient a toric IOL (not shown) that is to be used for the correction of astigmatism.","While the particular Posterior Capsulotomy Using Laser Techniques as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims."]],"string":"[\n [\n \"POSTERIOR CAPSULOTOMY USING LASER TECHNIQUES\",\n \"A system and method are provided for removing a natural lens and inserting an Intraocular Lens (IOL) into the lens capsule of an eye.\",\n \"Specifically, this is accomplished by inserting the IOL through an opening on the posterior capsule that is created using a focused laser beam.\",\n \"The system includes a laser unit, a detector for creating images of the interior of the eye, and a computer that controls the cooperative functions of the detector and the laser unit.\",\n \"Based on images of the posterior capsule provided by the detector, the computer is used to control movements of the focal point through tissue of the posterior capsule to perform Laser Induced Optical Breakdown (LIOB) on posterior capsule tissue.\",\n \"The result is a laser capsulotomy that creates an opening through the posterior capsule allowing the natural lens to be removed and the IOL to be implanted.\"\n ],\n [\n \"1.A method for performing ophthalmic surgery inside an eye which comprises the steps of: performing Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule of the eye to create a section of separated tissue defining an opening into the lens capsule of the eye; removing the section of separated tissue from the lens capsule to establish the opening; extracting the lens of the eye from the lens capsule of the eye through the opening in the posterior capsule; and implanting an optical device in the lens capsule through the opening in the posterior capsule to replace the extracted lens.\",\n \"2.A method as recited in claim 1 wherein the performing step comprises the steps of: generating a pulsed laser beam; focusing the pulsed laser beam to a focal point; and directing the focal point of the pulsed laser beam onto tissue of the posterior capsule inside the eye.\",\n \"3.A method as recited in claim 2 wherein the performing step further comprises the steps of: creating images of the inside of the eye; and using an image from the creating step to control movements of the focal point through tissue of the posterior capsule to create the opening.\",\n \"4.A method as recited in claim 3 wherein the creating step is accomplished using imaging techniques selected from a group comprising Optical Coherence Tomography (OCT), Scheimpfiug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.\",\n \"5.A method as recited in claim 1 wherein the removing step comprises the steps of: incising the sclera to establish an access port to the vitreous body of the eye; advancing a probe through the access port for engagement of the probe with the section of separated tissue; and withdrawing the separated section of tissue from the eye with the probe to establish the opening.\",\n \"6.A method as recited in claim 1 wherein the optical device is an Intraocular Lens (IOL).\",\n \"7.A method as recited in claim 6 further comprising the step of establishing LIOB marks on the lens capsule to assist in aligning the IOL in the lens capsule.\",\n \"8.A method as recited in claim 6 further comprising the step of dimensioning the opening to receive a specific IOL into the lens capsule via the opening.\",\n \"9.A method for performing ophthalmic laser surgery inside an eye which comprises the steps of: generating a pulsed laser beam; creating images of the inside of the eye; using images from the creating step to control movements of the focal point of the laser beam through tissue of the posterior capsule to perform Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule to create an opening into the lens capsule of the eye; extracting the lens of the eye from the lens capsule of the eye through the opening in the posterior capsule; and implanting an optical device in the lens capsule through the opening in the posterior capsule to replace the extracted lens.\",\n \"10.The method of claim 9 further comprising the step of preparing the lens of the eye for removal from the posterior capsule prior to the extracting step.\",\n \"11.The method of claim 10 wherein the preparing step is accomplished by a procedure selected from the group consisting of hydrodissection, phacoemulsification and lens fragmentation.\",\n \"12.The method of claim 9 further comprising the steps of: incising the sclera to establish an access port into the vitreous body of the eye; and advancing a probe through the access port to accomplish the extracting step.\",\n \"13.The method of claim 9 wherein the optical device is an Intraocular Lens (IOL).\",\n \"14.The method of claim 13 further comprising the step of establishing LIOB marks on the lens capsule to assist in aligning the IOL in the lens capsule.\",\n \"15.The method of claim 14 further comprising the step of dimensioning the opening to receive a specific IOL into the lens capsule via the opening.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>A common treatment for a cataract involves removal of the diseased lens from a patient's eye followed by replacement with an Intraocular Lens (IOL).\",\n \"Originally, the entire lens and capsule were removed and replaced.\",\n \"More modernly, the lens is removed from the capsule, in situ, and the new IOL is inserted into the capsule.\",\n \"In a typical cataract procedure, access to the lens is obtained and the lens is fragmented and/or emulsified.\",\n \"For example, the lens can be emulsified using a traditional ultrasonic handpiece (a process known as “phacoemulsification”), or, more modernly, the lens can be fragmented using a femtosecond laser.\",\n \"Once fragmented or emulsified, the lens material can be removed from the capsule, for example, by aspirating the material using an aspiration needle.\",\n \"Once the lens material has been removed, an IOL can be inserted into the remaining portion of the lens capsule.\",\n \"To perform the procedures described above, an opening in the lens capsule is required.\",\n \"Two possibilities for this opening include an anterior capsulotomy in which an opening is made on the anterior surface of the lens capsule and a posterior capsulotomy in which an opening is made on the posterior surface of the lens capsule.\",\n \"Typically, for an anterior capsulotomy, the surgeon gains access to the capsule and lens through incisions that are made on the cornea or limbus.\",\n \"However, these incisions can adversely affect the refractive properties of the eye, including the inducement of undesirable astigmatism.\",\n \"Another drawback associated with a typical anterior capsulotomy procedure involves anatomical considerations.\",\n \"In more detail, access to the anterior capsule surface necessarily involves transit through the relatively small anterior chamber of the eye.\",\n \"Unfortunately, there are a number of surgical problems associated with passing tools, such as the phacoemulsification probe and aspiration needle, through the small anterior chamber of the eye.\",\n \"Moreover, the anterior capsulotomy procedure can disturb other fragile anatomical structures that are anterior to the crystalline lens.\",\n \"Unlike the anterior capsulotomy, access for a posterior capsulotomy can be obtained using incisions through the sclera on the side of the eye.\",\n \"These incisions do not, in general, affect the refractive properties of the eye like the incisions described above that are made on the cornea or limbus.\",\n \"In addition, there is more operating room on the posterior side of the crystalline lens than the small anterior chamber of the eye.\",\n \"And, in many instances, additional room for tool manipulation can be made on the posterior side of the crystalline lens by performing a partial vitrectomy.\",\n \"Another advantage of a posterior capsulotomy is that the optical barrier (e.g.\",\n \"the anterior surface of the capsule) is maintained intact during a surgical procedure.\",\n \"Lastly, the use of a posterior capsulotomy can provide flexibility for combining the capsulotomy procedure with other surgical procedures in the back of the eye.\",\n \"In light of the above, it is an object of the present invention to provide a system and method for performing a posterior capsulotomy.\",\n \"Another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure to accommodate the insertion of an Intraocular Lens (IOL) into the lens capsule of an eye.\",\n \"Still another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure using laser techniques which is simple to implement and is relatively cost effective.\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the present invention, a system and method are provided for inserting an Intraocular Lens (IOL) into the lens capsule of an eye.\",\n \"Specifically, this is accomplished by inserting the IOL through an opening that is created through the posterior capsule of the eye.\",\n \"In overview, the system includes a detector for creating images of the interior of the eye, and it includes a laser unit for generating and focusing a laser beam to a focal point.\",\n \"The system further includes a computer that controls the cooperative functions of the detector and the laser unit.\",\n \"For an operation of the present invention, the computer processes images that are provided by the detector.\",\n \"Specifically, these images are of tissue inside the eye and their processing by the computer is accomplished to establish an accurate location for the posterior capsule of the eye.\",\n \"As envisioned for the present invention, the detector is preferably an imaging unit that employs imaging techniques selected from a group comprising Optical Coherence Tomography (OCT), Scheimpflug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.\",\n \"In addition to receiving images from the detector, the computer also operates the laser unit to generate and focus a laser beam.\",\n \"In detail, the laser beam is preferably a pulsed laser beam wherein each pulse has a duration less than one millisecond.\",\n \"Furthermore, it is necessary that the energy at the focal point of the laser beam be capable of performing Laser Induced Optical Breakdown (LIOB) of tissue of the posterior capsule.\",\n \"Based on images of the posterior capsule that have been provided by the detector (imaging unit), the computer is used to control movements of the focal point through tissue of the posterior capsule.\",\n \"As indicated above, this is done for the purpose of performing Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule.\",\n \"As envisioned for the present invention, the condition of tissue of the posterior capsule is of interest only insofar as it may affect the laser operation.\",\n \"Stated differently, the present invention pertains regardless whether the posterior capsule is initially intact, or somehow torn.\",\n \"In either case, the intent here is to create an opening through the posterior capsule that can be used for inserting the IOL into the lens capsule.\",\n \"Importantly, in this process, the opening is dimensioned and customized to receive a specific IOL into the lens capsule via the opening.\",\n \"In accordance with a methodology for the present invention, the crystalline lens of an eye is prepared for its removal from the lens capsule at an appropriate time in the particular procedure.\",\n \"As will be appreciated by the skilled artisan, preparation of the lens can be done in any of several different ways that are well known in the pertinent art.\",\n \"For example, techniques such as hydrodissection and phacoemulsification may be used for this purpose.\",\n \"Preferably, laser techniques such as disclosed in U.S. application Ser.\",\n \"No.\",\n \"13/436,352, which was filed on Mar.\",\n \"30, 2012 for an invention entitled “System and Method for Performing Lens Fragmentation,” can be useful for this same purpose.\",\n \"At an appropriate time in the procedure, Laser Induced Optical Breakdown (LIOB) is performed on tissue of the posterior capsule of the eye to create a section of separated tissue.\",\n \"In effect, this involves a laser capsulotomy that creates an opening through the posterior capsule, into the lens capsule of the eye.\",\n \"The section of separated tissue is then removed from the lens capsule to establish the opening.\",\n \"As envisioned for the present invention, this removal of the separated tissue section will be accomplished by first incising the sclera to establish an access port to the vitreous body of the eye.\",\n \"A probe can then be advanced through the access port for engagement of the probe with the section of separated tissue.\",\n \"After the probe has engaged with the separated section of tissue, the separated section of tissue can be removed from the eye by the probe to establish the opening.\",\n \"Once an opening has been established through the posterior capsule of the eye, the crystalline lens of the eye can be extracted (removed) from the lens capsule of the eye.\",\n \"The extracted lens can then be removed from the eye through the access port that has been created through the sclera.\",\n \"Specifically, this may include removing the whole lens through the scleral incision using mechanical cutters and macelators such as scissors, lassos, guillotine cutters, cautery devices, aqua-jets, ultrasonic blades, a combination of a laser and another extraction device, or any other device or technique sufficient to remove the lens.\",\n \"Once the crystalline lens has been extracted (removed), an IOL can be introduced through the sclera and inserted through the opening in the posterior capsule to replace the extracted lens.\",\n \"As an additional feature of the present invention, LIOB marks can be established on the lens capsule during the procedure to assist in aligning the IOL in the lens capsule.\",\n \"Such feature may be particularly useful for properly orienting a toric IOL that is to be used for the correction of astigmatism.\"\n ],\n [\n \"This application is a divisional of application Ser.\",\n \"No.\",\n \"14/412,168, filed Dec. 30, 2014, which is currently pending.\",\n \"Application Ser.\",\n \"No.\",\n \"14/412,168 is a 371 of International Application No.\",\n \"PCT/US2013/031394, filed Mar.\",\n \"14, 2013, which is expired and which claims the benefit of U.S.\",\n \"Provisional Patent Application Ser.\",\n \"No.\",\n \"61/671,312, filed Jul.\",\n \"13, 2012, which is expired.\",\n \"FIELD OF THE INVENTION The present invention pertains generally to ocular laser surgery.\",\n \"More particularly, the present invention pertains to capsulotomy procedures that employ a femtosecond laser.\",\n \"The present invention is particularly, but not exclusively, useful for performing a posterior capsulotomy procedure to insert an Intraocular Lens (IOL) into the lens capsule of an eye.\",\n \"BACKGROUND OF THE INVENTION A common treatment for a cataract involves removal of the diseased lens from a patient's eye followed by replacement with an Intraocular Lens (IOL).\",\n \"Originally, the entire lens and capsule were removed and replaced.\",\n \"More modernly, the lens is removed from the capsule, in situ, and the new IOL is inserted into the capsule.\",\n \"In a typical cataract procedure, access to the lens is obtained and the lens is fragmented and/or emulsified.\",\n \"For example, the lens can be emulsified using a traditional ultrasonic handpiece (a process known as “phacoemulsification”), or, more modernly, the lens can be fragmented using a femtosecond laser.\",\n \"Once fragmented or emulsified, the lens material can be removed from the capsule, for example, by aspirating the material using an aspiration needle.\",\n \"Once the lens material has been removed, an IOL can be inserted into the remaining portion of the lens capsule.\",\n \"To perform the procedures described above, an opening in the lens capsule is required.\",\n \"Two possibilities for this opening include an anterior capsulotomy in which an opening is made on the anterior surface of the lens capsule and a posterior capsulotomy in which an opening is made on the posterior surface of the lens capsule.\",\n \"Typically, for an anterior capsulotomy, the surgeon gains access to the capsule and lens through incisions that are made on the cornea or limbus.\",\n \"However, these incisions can adversely affect the refractive properties of the eye, including the inducement of undesirable astigmatism.\",\n \"Another drawback associated with a typical anterior capsulotomy procedure involves anatomical considerations.\",\n \"In more detail, access to the anterior capsule surface necessarily involves transit through the relatively small anterior chamber of the eye.\",\n \"Unfortunately, there are a number of surgical problems associated with passing tools, such as the phacoemulsification probe and aspiration needle, through the small anterior chamber of the eye.\",\n \"Moreover, the anterior capsulotomy procedure can disturb other fragile anatomical structures that are anterior to the crystalline lens.\",\n \"Unlike the anterior capsulotomy, access for a posterior capsulotomy can be obtained using incisions through the sclera on the side of the eye.\",\n \"These incisions do not, in general, affect the refractive properties of the eye like the incisions described above that are made on the cornea or limbus.\",\n \"In addition, there is more operating room on the posterior side of the crystalline lens than the small anterior chamber of the eye.\",\n \"And, in many instances, additional room for tool manipulation can be made on the posterior side of the crystalline lens by performing a partial vitrectomy.\",\n \"Another advantage of a posterior capsulotomy is that the optical barrier (e.g.\",\n \"the anterior surface of the capsule) is maintained intact during a surgical procedure.\",\n \"Lastly, the use of a posterior capsulotomy can provide flexibility for combining the capsulotomy procedure with other surgical procedures in the back of the eye.\",\n \"In light of the above, it is an object of the present invention to provide a system and method for performing a posterior capsulotomy.\",\n \"Another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure to accommodate the insertion of an Intraocular Lens (IOL) into the lens capsule of an eye.\",\n \"Still another object of the present invention is to provide a system and method for performing a posterior capsulotomy procedure using laser techniques which is simple to implement and is relatively cost effective.\",\n \"SUMMARY OF THE INVENTION In accordance with the present invention, a system and method are provided for inserting an Intraocular Lens (IOL) into the lens capsule of an eye.\",\n \"Specifically, this is accomplished by inserting the IOL through an opening that is created through the posterior capsule of the eye.\",\n \"In overview, the system includes a detector for creating images of the interior of the eye, and it includes a laser unit for generating and focusing a laser beam to a focal point.\",\n \"The system further includes a computer that controls the cooperative functions of the detector and the laser unit.\",\n \"For an operation of the present invention, the computer processes images that are provided by the detector.\",\n \"Specifically, these images are of tissue inside the eye and their processing by the computer is accomplished to establish an accurate location for the posterior capsule of the eye.\",\n \"As envisioned for the present invention, the detector is preferably an imaging unit that employs imaging techniques selected from a group comprising Optical Coherence Tomography (OCT), Scheimpflug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.\",\n \"In addition to receiving images from the detector, the computer also operates the laser unit to generate and focus a laser beam.\",\n \"In detail, the laser beam is preferably a pulsed laser beam wherein each pulse has a duration less than one millisecond.\",\n \"Furthermore, it is necessary that the energy at the focal point of the laser beam be capable of performing Laser Induced Optical Breakdown (LIOB) of tissue of the posterior capsule.\",\n \"Based on images of the posterior capsule that have been provided by the detector (imaging unit), the computer is used to control movements of the focal point through tissue of the posterior capsule.\",\n \"As indicated above, this is done for the purpose of performing Laser Induced Optical Breakdown (LIOB) on tissue of the posterior capsule.\",\n \"As envisioned for the present invention, the condition of tissue of the posterior capsule is of interest only insofar as it may affect the laser operation.\",\n \"Stated differently, the present invention pertains regardless whether the posterior capsule is initially intact, or somehow torn.\",\n \"In either case, the intent here is to create an opening through the posterior capsule that can be used for inserting the IOL into the lens capsule.\",\n \"Importantly, in this process, the opening is dimensioned and customized to receive a specific IOL into the lens capsule via the opening.\",\n \"In accordance with a methodology for the present invention, the crystalline lens of an eye is prepared for its removal from the lens capsule at an appropriate time in the particular procedure.\",\n \"As will be appreciated by the skilled artisan, preparation of the lens can be done in any of several different ways that are well known in the pertinent art.\",\n \"For example, techniques such as hydrodissection and phacoemulsification may be used for this purpose.\",\n \"Preferably, laser techniques such as disclosed in U.S. application Ser.\",\n \"No.\",\n \"13/436,352, which was filed on Mar.\",\n \"30, 2012 for an invention entitled “System and Method for Performing Lens Fragmentation,” can be useful for this same purpose.\",\n \"At an appropriate time in the procedure, Laser Induced Optical Breakdown (LIOB) is performed on tissue of the posterior capsule of the eye to create a section of separated tissue.\",\n \"In effect, this involves a laser capsulotomy that creates an opening through the posterior capsule, into the lens capsule of the eye.\",\n \"The section of separated tissue is then removed from the lens capsule to establish the opening.\",\n \"As envisioned for the present invention, this removal of the separated tissue section will be accomplished by first incising the sclera to establish an access port to the vitreous body of the eye.\",\n \"A probe can then be advanced through the access port for engagement of the probe with the section of separated tissue.\",\n \"After the probe has engaged with the separated section of tissue, the separated section of tissue can be removed from the eye by the probe to establish the opening.\",\n \"Once an opening has been established through the posterior capsule of the eye, the crystalline lens of the eye can be extracted (removed) from the lens capsule of the eye.\",\n \"The extracted lens can then be removed from the eye through the access port that has been created through the sclera.\",\n \"Specifically, this may include removing the whole lens through the scleral incision using mechanical cutters and macelators such as scissors, lassos, guillotine cutters, cautery devices, aqua-jets, ultrasonic blades, a combination of a laser and another extraction device, or any other device or technique sufficient to remove the lens.\",\n \"Once the crystalline lens has been extracted (removed), an IOL can be introduced through the sclera and inserted through the opening in the posterior capsule to replace the extracted lens.\",\n \"As an additional feature of the present invention, LIOB marks can be established on the lens capsule during the procedure to assist in aligning the IOL in the lens capsule.\",\n \"Such feature may be particularly useful for properly orienting a toric IOL that is to be used for the correction of astigmatism.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which: FIG.\",\n \"1 is a schematic presentation of components for the system of the present invention; FIG.\",\n \"2A is a cross section view of the anterior portion of an eye showing the removal of tissue from the posterior capsule of the eye to create an opening into the lens capsule; and FIG.\",\n \"2B is a cross section view of the anterior portion of the eye as seen in FIG.\",\n \"2A, showing the insertion of an Intraocular Lens (IOL) through the opening into the lens capsule of the eye, after the crystalline lens of the eye has been removed from the lens capsule.\",\n \"DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring initially to FIG.\",\n \"1, a system in accordance with the present invention is shown and is generally designated 10.As shown, the system 10 includes a laser unit 12 and a computer 14.As shown, the computer 14 is connected with the laser unit 12 for the purposes of guiding and controlling the movement of a laser beam 16 that is generated and focused by the laser unit 12.Necessarily, the laser unit 12 is of a type that generates a pulsed laser beam 16 which is capable of performing Laser Induced Optical Breakdown (LIOB) on sub-surface anatomical tissue.\",\n \"Preferably, the laser beam 16 will have laser pulses with pulse durations in the femtosecond range.\",\n \"FIG.\",\n \"1 also shows that the system 10 can include a detector 18 for creating images of the interior of the eye 20.For example, the detector 18 can include an imaging unit that employs imaging techniques such as Optical Coherence Tomography (OCT), Scheimpflug imaging, confocal imaging, two-photon imaging, laser (optical) range finding and acoustical imaging.\",\n \"As shown, the computer 14 is connected to the detector 18 to receive and process image data from the detector 18 and control the operation of the detector 18.More specifically, images of tissue inside the eye 20 can be processed by the computer 14 to establish an accurate location for the crystalline lens 22 and posterior capsule 24 of the eye 20.FIG.\",\n \"2A illustrates a procedure for creating a section of separated tissue 26 and removing the tissue 26 from the posterior capsule 24 of the eye 20 to create an opening 28 into the posterior capsule 24.For this procedure, images of the posterior capsule 24 (FIG.\",\n \"1) are provided by the detector 18 to the computer 14 which uses the image data to control movements of the focal point through tissue of the posterior capsule 24.As this is done, Laser Induced Optical Breakdown (LIOB) occurs on tissue of the posterior capsule 24 to create a section of separated tissue 26.Once the separated tissue is removed, an opening 28 is established through the posterior capsule 24 that can be used for removing the lens 22 and/or inserting an IOL 30 (FIG.\",\n \"2B) into the lens capsule 31.For this process, the opening 28 can be dimensioned and customized to allow a specific IOL 30 (FIG.\",\n \"2B) to pass through the opening 28 and be implanted into the lens capsule 31.Continuing with FIG.\",\n \"2A, it can be seen that the separated tissue 26 can be removed from the eye 20, by first incising the sclera 32 to establish an access port 34 to the vitreous body 36 of the eye 20.As shown, a probe 38 can then be advanced through the access port 34 for engagement of the probe 38 with the section of separated tissue 26.After the probe 38 has engaged with the separated section of tissue 26, the separated section of tissue 26 can be removed from the eye 20 by the probe 38 (in the direction of arrow 40) and through access port 34 to establish the opening 28.Once an opening 28 has been established through the posterior capsule 24 of the eye 20, as shown, the crystalline lens 22 can be extracted from the lens capsule 31 and removed from the eye 20 through the access port 34.FIG.\",\n \"2B shows that an IOL 30 can be introduced through the access port 34 in the sclera 32 and inserted through the opening 28 (in the direction of arrow 42 and into the lens capsule 31.As shown, probe 44 can be used to place the IOL 30 into the lens capsule 31.As an additional feature of the present invention, LIOB marks (not shown) can be established on the lens capsule 31 during the procedure to assist in aligning the IOL 30 in the lens capsule 31.For example, these LIOB marks may be used to properly orient a toric IOL (not shown) that is to be used for the correction of astigmatism.\",\n \"While the particular Posterior Capsulotomy Using Laser Techniques as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874759"}}},{"rowIdx":4494690,"cells":{"text":{"kind":"list like","value":[["APPLIANCE, MOTOR OR STATOR","A motor suited for use in a direct drive laundry machine.","The described motor has a stator core including an annular ring with an inner diameter between 120 mm and 250 mm, a radial width between 5 mm and 15 mm, and 24 or 27 stator poles projecting outward from the annular ring a distance of between 15 mm and 40 mm.","Each stator pole is associated with one of three phase windings.","A rotor for the motor has inwardly facing permanent magnet poles whereby the ratio of rotor poles to stator poles is 4:3."],["1.A stator comprising: a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, a plurality of radiating extending poles spaced around the outer circumference of the annular ring, the poles extending outward from the annular ring between 15 mm and 40 mm, three phase windings, each winding comprising a plurality of coils, each coil arranged on ⅓ of the poles, an insulator insulating the poles from the windings, a plurality of fastening locations for fastening the stator to a machine, each fastening location being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the poles extend beyond the outer circumference of the annular ring, and more than 40 mm from the centre of the stator.","2.The stator as claimed in claim 1, wherein the fastening locations are between 40 mm and 80 mm from the centre of the stator.","3.The stator as claimed in claim 1, wherein the fastening locations are between 50 mm and 75 mm from the centre of the stator.","4.The stator as claimed in claim 1, wherein the fastening locations are between 60 mm and 70 mm from the centre of the stator.","5.The stator as claimed in claim 1, wherein the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the inner circumference of the ring and that includes the fastening locations.","6.The stator as claimed in claim 5, wherein the fastening locations comprise apertures through the diaphragm portion.","7.The stator as claimed in claim 5, wherein the diaphragm portion is annular and occupies an area between the annular ring and an inner aperture spaced inward of the fastening locations.","8.The stator as claimed in claim 5, wherein the diaphragm includes at least one substantially frustoconical surface in a region between the fastening locations and the annular ring.","9.The stator as claimed in claim 5, wherein the diaphragm includes at least two substantially frustoconical portions between the fastening locations and the annular ring, the frustoconical portions joining to form a circular ridge when viewed from one side of the stator and a circular valley when viewed from the other side of the stator.","10.The stator as claimed in claim 9, wherein the height of the ridge or depth of the valley is less than the height of the annular ring.","11.A motor for use in a washing machine, said motor comprising: a stator as claimed in claim 1, and a rotor concentric with said stator with a permanent magnet ring outside said stator and rotor poles facing the ends of said stator poles.","12.The motor as claimed in claim 11, wherein the rotor comprises: a plurality of magnet elements with two lateral edges each with magnetic domains aligned anisotropically to form a domain alignment pattern, the plurality of magnet elements being arranged to form the permanent magnet ring with an inner face and an outer face, and a rigid support holding said magnet elements in said permanent magnet ring, wherein the magnetic domain alignment pattern in each magnet element has an orientation that varies substantially continuously across at least part of the magnet element between its lateral edges from an orientation that has a predominant radial component at a pole of the magnet element to an orientation that has a least some tangential component at one lateral edge of the magnet element, and wherein the magnet elements are magnetised to produce a resulting magnetic flux field.","13.The motor according to claim 12, wherein one or more of the magnet elements have a chamfer at the intersection of each lateral edge with a front edge, wherein the front edge is the edge at the inner face of the permanent magnet ring.","14.The motor according to claim 12, wherein at both lateral edges of each magnet element the orientation of the magnetic domain alignment pattern has a significant tangential component which results in the magnetic domain alignment pattern having an orientation of at least 15 degrees with respect to the lateral edges.","15.The motor according to claim 12, wherein the orientation of the magnetic domain alignment pattern varies substantially non-linearly over the magnet element.","16.The motor according to claim 12, wherein the resulting magnetic flux field of the permanent magnet ring has poles with alternating polarity spaced around the permanent magnet ring, the poles being aligned radially with respect to the permanent magnet ring, and wherein the resulting magnetic flux field traverses between adjacent poles of opposite polarities and between those poles is focused to extend beyond the boundary defined by the inner face, but remain at least partially constrained within the boundary defined by the outer face of the permanent magnet ring.","17.The motor according to claim 16, wherein the portion of the resulting magnetic flux field between adjacent poles extending beyond the boundary defined by the inner face of the permanent magnet ring has an orientation that varies continuously wherein: between the poles, the orientation varies from an orientation that has a predominant radial component at a pole to an orientation that has a predominant tangential component at the mid-point between poles, and extending radially from the inner face, the orientation varies from an orientation that has a predominant radial component at the inner face to an orientation that has an increasingly tangential component with distance from the inner face.","18.A washing machine including a motor as claimed in claim 11, said stator being coupled to a non-rotating tub or housing of the washing machine, said rotor being coupled to a rotating drum of the washing machine.","19.The washing machine according to claim 18, wherein the washing machine is a top loading washing machine and/or a horizontal axis washing machine comprising: an outer wrapper, the non-rotating tub or housing suspended in the outer wrapper, and the rotating drum in the tub."],["<SOH> BACKGROUND TO THE INVENTION <EOH>The present invention relates to motors for particular use in laundry machines.","The motors are of a type including an internal stator with radially extending stator poles and an external rotor with inwardly facing rotor poles.","In motors having a 4:3 ratio of rotor poles to stator poles, for use with direct drive laundry washing machines, more than 30 stator poles has been typical."],["<SOH> SUMMARY OF THE INVENTION <EOH>An object of the present invention is to provide a stator, a motor including the stator, or a laundry machine including the motor, which improve on the prior art, or which will at least provide the public or industry with a useful choice.","In one aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, 24 or 27 radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring a distance between 15 mm and 40 mm, three phase windings, each winding comprising a plurality of coils arranged on one third of the pole cores, the windings arranged on the pole cores such that each pole core is associated with only one winding, which is different from the winding associated with each of the two immediately adjacent pole cores and the two immediately adjacent pole cores are associated with different windings, an insulator insulating the pole cores from the windings.","According to a further aspect, the core has a depth between 10 mm and 35 mm.","According to a further aspect, the annular ring is at least largely encapsulated by an insulator.","According to a further aspect, the insulator over the pole cores and annular ring is an over moulded plastic material.","According to a further aspect, the diameter of the inner circumference of the annular ring is between 150 mm and 230 mm.","According to a further aspect, the diameter of the inner circumference of the annular ring is between 200 mm and 220 mm.","According to a further aspect, the width of the annular ring is between 5 mm and 10 mm.","According to a further aspect, the width of the annular ring is between 7 mm and 10 mm.","According to a further aspect, the depth or thickness of the annular ring is between 12 mm and 15 mm.","According to a further aspect, the depth or thickness of the annular ring is between 17 mm and 23 mm.","According to a further aspect, the core comprises at least one stack of laminations, each lamination lying in a plane substantially parallel to the plane of the annular ring.","According to a further aspect, the stack or stacks of laminations comprise a stack formed from a helical coil of steel strip such that each layer in the stack comprises a turn in the helix.","According to a further aspect, the steel strip includes a band forming the annular ring and extended portions forming the pole cores.","According to a further aspect, the stack or stacks of laminations comprises multiple stacks joined at their ends, each stack including a segment of the annular ring and one or more extending pole cores.","According to a further aspect, each segment of the annular ring joins with adjacent segments of the annular ring by interlocking shapes at the abutting ends (such as a dove tail joint).","According to a further aspect, each segment includes a plurality of radially extending pole cores.","According to a further aspect, the stator includes 27 radially extending pole cores and the core comprises 6 stacks, 3 stacks having 5 radially extending pole cores each and 3 stacks having 4 radially extending pole cores each.","According to a further aspect, the stator has only 27 radially extending pole cores.","According to a further aspect, the stator includes a plurality of fastening locations for mounting the stator to a machine, each fastening location being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring.","According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.","According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.","According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.","According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.","According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.","According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).","According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.","In a further aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, a plurality of radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring between 15 mm and 40 mm, 3 phase windings, each winding comprising a plurality of coils arranged on ⅓ of the pole cores, an insulator insulating the pole cores from the windings, a plurality of mounting points for mounting the stator to a machine, each mounting point being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring, and more than 40 mm from the centre of the stator.","According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.","According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.","According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.","According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.","According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.","According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).","According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.","In a further aspect, the present invention may broadly be said to consist in a motor for use in a washing machine, said motor comprising a stator as described above, a rotor concentric with said stator with a permanent magnet ring outside said stator and rotor poles facing the ends of said stator poles.","According to a further aspect, the rotor comprises a plurality of magnet elements with two lateral edges each with magnetic domains aligned anisotropically to form a domain alignment pattern, the plurality of magnets being arranged to form a permanent magnet ring with an inner face and an outer face, a rigid support holding said magnet elements in said ring arrangement, wherein the magnetic domain alignment pattern in each magnet element has an orientation that varies substantially continuously across at least part of the magnet element between its lateral edges from an orientation that has a predominant radial component at a pole of the magnet element to an orientation that has a least some tangential component at one lateral edge of the magnet element, wherein the magnet elements are magnetised to produce a resulting magnetic flux field.","According to a further aspect, one or more of the magnet elements have a chamfer at the intersection of each lateral edge with the front edge, wherein the front edge is the edge at the inner face of the rotor.","According to a further aspect, at both lateral edges the orientation of the magnetic domain alignment pattern has significant tangential component which result in the magnetic domain alignment pattern having an orientation of at least 15 degrees with respect to the lateral edges.","According to a further aspect, the orientation varies substantially non-linearly over the magnet element.","According to a further aspect, the resulting magnetic flux field has poles with alternating polarity spaced around the ring, the poles being aligned radially with respect to the permanent magnet ring, and wherein the resulting magnetic flux field of the permanent magnet ring traverses between adjacent poles of opposite polarities and between those poles is focused to extend beyond the boundary defined by the inner face, but remain at least partially constrained within the boundary defined by the outer face of the permanent magnet ring, According to a further aspect, the portion of the resulting magnetic flux field between adjacent poles extending beyond the boundary defined by the inner face of the permanent magnet ring magnet element has an orientation that varies continuously wherein between the poles, the orientation varies from an orientation that has a predominant radial component at the pole to an orientation that has a predominant tangential component at the mid-point between the poles, and extending radially from the inner face, the orientation varies from an orientation that has a predominant radial component at an inner face to an orientation that has an increasingly tangential component with distance from the inner face.","In a further aspect, the present invention may broadly be said to consist in a washing machine including an electronically commutated motor as described above, said stator being coupled to a non-rotating tub or housing of the washing machine, said rotor being coupled to a rotating drum of the washing machine.","According to a further aspect, washing machine is a top loading washing machine comprising: an outer wrapper, a tub suspended in the outer wrapper, and a rotating drum in the tub.","According to a further aspect, the washing machine is a horizontal axis machine comprising: an outer wrapper, a rotating drum housing, and a rotating drum in the housing.","According to a further aspect, the washing machine is a horizontal axis machine with top loading access comprising: an outer wrapper, a tub, and a rotating drum in the tub.","In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention.","Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.","The term “comprising” as used in this specification means “consisting at least in part of”.","Related terms such as “comprise” and “comprised” are to be interpreted in the same manner.","It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7).","To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended claims.","The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting"],["INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application are hereby incorporated by reference under 37 C.F.R.","§ 1.57 and made a part of the present disclosure.","FIELD OF THE INVENTION The present invention relates to electric motors and magnet elements for use in such motors, and particularly motors having an external rotor of a type that are used as the main drive motor for a domestic laundry machine or other apparatus.","BACKGROUND TO THE INVENTION The present invention relates to motors for particular use in laundry machines.","The motors are of a type including an internal stator with radially extending stator poles and an external rotor with inwardly facing rotor poles.","In motors having a 4:3 ratio of rotor poles to stator poles, for use with direct drive laundry washing machines, more than 30 stator poles has been typical.","SUMMARY OF THE INVENTION An object of the present invention is to provide a stator, a motor including the stator, or a laundry machine including the motor, which improve on the prior art, or which will at least provide the public or industry with a useful choice.","In one aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, 24 or 27 radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring a distance between 15 mm and 40 mm, three phase windings, each winding comprising a plurality of coils arranged on one third of the pole cores, the windings arranged on the pole cores such that each pole core is associated with only one winding, which is different from the winding associated with each of the two immediately adjacent pole cores and the two immediately adjacent pole cores are associated with different windings, an insulator insulating the pole cores from the windings.","According to a further aspect, the core has a depth between 10 mm and 35 mm.","According to a further aspect, the annular ring is at least largely encapsulated by an insulator.","According to a further aspect, the insulator over the pole cores and annular ring is an over moulded plastic material.","According to a further aspect, the diameter of the inner circumference of the annular ring is between 150 mm and 230 mm.","According to a further aspect, the diameter of the inner circumference of the annular ring is between 200 mm and 220 mm.","According to a further aspect, the width of the annular ring is between 5 mm and 10 mm.","According to a further aspect, the width of the annular ring is between 7 mm and 10 mm.","According to a further aspect, the depth or thickness of the annular ring is between 12 mm and 15 mm.","According to a further aspect, the depth or thickness of the annular ring is between 17 mm and 23 mm.","According to a further aspect, the core comprises at least one stack of laminations, each lamination lying in a plane substantially parallel to the plane of the annular ring.","According to a further aspect, the stack or stacks of laminations comprise a stack formed from a helical coil of steel strip such that each layer in the stack comprises a turn in the helix.","According to a further aspect, the steel strip includes a band forming the annular ring and extended portions forming the pole cores.","According to a further aspect, the stack or stacks of laminations comprises multiple stacks joined at their ends, each stack including a segment of the annular ring and one or more extending pole cores.","According to a further aspect, each segment of the annular ring joins with adjacent segments of the annular ring by interlocking shapes at the abutting ends (such as a dove tail joint).","According to a further aspect, each segment includes a plurality of radially extending pole cores.","According to a further aspect, the stator includes 27 radially extending pole cores and the core comprises 6 stacks, 3 stacks having 5 radially extending pole cores each and 3 stacks having 4 radially extending pole cores each.","According to a further aspect, the stator has only 27 radially extending pole cores.","According to a further aspect, the stator includes a plurality of fastening locations for mounting the stator to a machine, each fastening location being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring.","According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.","According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.","According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.","According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.","According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.","According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).","According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.","In a further aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, a plurality of radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring between 15 mm and 40 mm, 3 phase windings, each winding comprising a plurality of coils arranged on ⅓ of the pole cores, an insulator insulating the pole cores from the windings, a plurality of mounting points for mounting the stator to a machine, each mounting point being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring, and more than 40 mm from the centre of the stator.","According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.","According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.","According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.","According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.","According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.","According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.","According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).","According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.","In a further aspect, the present invention may broadly be said to consist in a motor for use in a washing machine, said motor comprising a stator as described above, a rotor concentric with said stator with a permanent magnet ring outside said stator and rotor poles facing the ends of said stator poles.","According to a further aspect, the rotor comprises a plurality of magnet elements with two lateral edges each with magnetic domains aligned anisotropically to form a domain alignment pattern, the plurality of magnets being arranged to form a permanent magnet ring with an inner face and an outer face, a rigid support holding said magnet elements in said ring arrangement, wherein the magnetic domain alignment pattern in each magnet element has an orientation that varies substantially continuously across at least part of the magnet element between its lateral edges from an orientation that has a predominant radial component at a pole of the magnet element to an orientation that has a least some tangential component at one lateral edge of the magnet element, wherein the magnet elements are magnetised to produce a resulting magnetic flux field.","According to a further aspect, one or more of the magnet elements have a chamfer at the intersection of each lateral edge with the front edge, wherein the front edge is the edge at the inner face of the rotor.","According to a further aspect, at both lateral edges the orientation of the magnetic domain alignment pattern has significant tangential component which result in the magnetic domain alignment pattern having an orientation of at least 15 degrees with respect to the lateral edges.","According to a further aspect, the orientation varies substantially non-linearly over the magnet element.","According to a further aspect, the resulting magnetic flux field has poles with alternating polarity spaced around the ring, the poles being aligned radially with respect to the permanent magnet ring, and wherein the resulting magnetic flux field of the permanent magnet ring traverses between adjacent poles of opposite polarities and between those poles is focused to extend beyond the boundary defined by the inner face, but remain at least partially constrained within the boundary defined by the outer face of the permanent magnet ring, According to a further aspect, the portion of the resulting magnetic flux field between adjacent poles extending beyond the boundary defined by the inner face of the permanent magnet ring magnet element has an orientation that varies continuously wherein between the poles, the orientation varies from an orientation that has a predominant radial component at the pole to an orientation that has a predominant tangential component at the mid-point between the poles, and extending radially from the inner face, the orientation varies from an orientation that has a predominant radial component at an inner face to an orientation that has an increasingly tangential component with distance from the inner face.","In a further aspect, the present invention may broadly be said to consist in a washing machine including an electronically commutated motor as described above, said stator being coupled to a non-rotating tub or housing of the washing machine, said rotor being coupled to a rotating drum of the washing machine.","According to a further aspect, washing machine is a top loading washing machine comprising: an outer wrapper, a tub suspended in the outer wrapper, and a rotating drum in the tub.","According to a further aspect, the washing machine is a horizontal axis machine comprising: an outer wrapper, a rotating drum housing, and a rotating drum in the housing.","According to a further aspect, the washing machine is a horizontal axis machine with top loading access comprising: an outer wrapper, a tub, and a rotating drum in the tub.","In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention.","Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.","The term “comprising” as used in this specification means “consisting at least in part of”.","Related terms such as “comprise” and “comprised” are to be interpreted in the same manner.","It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7).","To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended claims.","The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a perspective view of a stator according to one embodiment of the present invention.","FIG.","2 is a plan view from below of the stator of FIG.","1.FIG.","3 is a side elevation of the stator of FIG.","2.FIG.","4 is a cross section through line BB of FIG.","3.FIG.","5 is a cross section through line CC of FIG.","4.FIG.","6 is a plan view of a laminated core suitable for the stator of FIG.","1.FIG.","7 is a plan view of an alternative laminated stator core suitable for the stator of FIG.","1.FIG.","8 is a perspective view from one side of the rotor suitable (for adaption to the number of rotor poles) for use with the stator of FIG.","1.FIG.","9 is a perspective view of the rotor of FIG.","8 from the other side.","FIG.","10 is a perspective view of another rotor suitable (with adaptation of the number of rotor poles) for use with the stator of FIG.","1.FIG.","11 is a perspective view of another rotor suitable (With adaptation of the number of rotor poles) for use with the stator of FIG.","1.FIG.","12 shows a diagrammatic cutaway view of a washing machine of a vertical axis type that may incorporate a stator and/or motor according to the present invention.","FIG.","13 shows a diagrammatic view of a horizontal axis washing machine with front access that may incorporate the stator and/or motor according to the present invention.","FIG.","14 shows a diagrammatic view of a horizontal axis washing machine with top or tilt access that may incorporate the stator and/or motor according to the present invention.","FIG.","15 shows a diagrammatic view of a horizontal axis laundry machine with tilt access that may incorporate the stator and/or motor according to the present invention.","FIG.","16 is a perspective view of a prior art stator.","FIG.","17 is a perspective view of a prior art rotor.","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A stator according to one embodiment of the present invention is illustrated in FIGS.","1 to 5.The stator 100 has 27 poles 102.The stator generally includes an annular ring portion 104, a mounting portion 106 inside the ring portion, and a plurality of poles 102 extending radially from the outside surface of the annular ring portion 104.In construction, the stator generally comprises a magnetically permeable core 108, an insulator structure 113 surrounding the core, or surrounding most of the core, and conductive windings arranged on the poles 102.In the illustrated embodiment, the insulating structure 113 comprises a layer of plastic over moulded over the magnetically permeable core.","The over moulded plastic covers at least those parts of the core which support and locate the conductive windings.","In the illustrated embodiment, the plastic covers all of the radially extending pole cores except the outer end surfaces 118.In an alternative embodiment, the insulating plastic may also cover the end surfaces of the pole cores.","Holes or partial holes 110 may extend through the plastic at the annular ring portion of the stator.","These may result from pins or other locating devices used to hold the stator core in place during the moulding process.","The magnetically permeable core 108 may be formed of any suitable material, including for example a sintered ferritic powder, but most preferably is formed from steel laminations 115.In general form, laminations of the laminated steel lie in planes substantially parallel to the plane of the annular ring of the stator.","The plan view of FIG.","4 illustrates the outline shapes of the laminations 115 while the cross section of FIG.","5 illustrates edges of the laminations 115.The lamination steel may be, for example, a fully processed non-oriented grain lamination steel with a nominal loss of about 7 w/kg.","The plastic material over moulding the core may be any suitable plastic.","For example, one suitable material is a polybutylene terephthalate (PBT) sold as “CRASTIN” by Dupont Corporation.","The stator mounting portion 106 includes mounting locations generally designated 112.In the illustrated embodiment, each fastening location 112 includes a fastening hole 114.The fastening holes 114 may be slotted or otherwise larger than the outside diameter of the fastener intended to pass through the fastening holes.","This allows for manufacturing tolerance in the machine to which the stator will be secured.","The mounting portion 106 may include a locating portion 116 in addition to the fastening locations 112.The locating portion 116 may provide for aligning the stator concentrically with a shaft of the motor.","For example, the locating portion 116 may comprise a circular opening 120 at the centre of the stator.","A lip or rim 122 of the opening 120 may locate on a corresponding feature or features of a bearing housing or bearing supporting the drive shaft.","The fastening locations 112 (with fastening holes 114) are located in the mounting portion 106 between the opening 120 and the annular ring portion 104.In the illustrated embodiment, these fastening locations and fastening holes are centred more than 40 mm from the centre of the stator.","In some embodiments, they may be more than 45 mm from the centre of the stator, more than 50 mm from the centre of the stator, more than 55 mm from the centre of the stator, more than 60 mm from the centre of the stator and preferably more than 65 mm from the centre of the stator, or about 68 mm from the centre of the stator.","The mounting locations and fastening holes 114 are centred a distance from the inside surface of the annular ring portion 111 of the core 108 that is greater than the distance that the radially extending pole portions 109 of the core 108 extend beyond the outer surface of the annular ring portion of the core 108.For example, in one embodiment, the fastening holes may be centred more than 30 mm from the inside surface of the annular ring portion of the core 108, more than 32 mm, more than 34 mm and preferably more than 35 mm from the inside surface of the stator core annular ring portion.","Whereas the pole portions may extend less than 30 mm from the outside surface of the annular ring portion of the core 108, and most preferably less than 27 mm.","In other embodiments, the pole portions may extend more than 30 mm from the outside surface of the annular ring, for example up to 40 mm, in which case the fastening holes may be more than 40 mm from the inside surface of the annular ring.","The pole portions may extend much less than 30 mm from the outer surface over the annular ring, for example, only 15 mm.","In plan view, each pole portion is T-shaped, with a cross bar portion of each pole portion supported spaced apart from the annular ring portion of the stator by a trunk portion of each pole portion.","The mounting portion 106 of the stator may be formed entirely from plastic.","The mounting portion 106 may be formed in one operation with over moulding of the core 108.The mounting portion may include one or more frustoconical portions concentric with the annular ring portion of the stator.","The illustrated stator includes an inner frustoconical portion 124 and an outer frustoconical portion 126.Together, the frustoconical portions 124 and 126 form a circular ridge 128 (when viewed from one side of the stator as in FIG.","1) and circular valley 130 (when viewed from the other side of the stator as in FIG.","2).","The overall diameter 132 of the stator may be about 280 mm.","In other embodiments, the diameter may be between 320 and 270, between 290 and 270 or between 290 and 240.The width 134 of the annular ring portion of the stator core may be about 9 mm.","In other embodiments, the width of the annular ring portion of the stator core may be between 5 mm and 15 mm.","The diameter 131 of the inner surface of the stator core 108 may be about 208 mm.","In other embodiments, the diameter may be between 230 mm and 190 mm or between 250 mm and 120 mm.","The radial distance 133 of the fastening locations from the centre of the stator may be about 68 mm.","In other embodiments, the radial distance may be between 40 mm and 80 mm.","The thickness of the plastic insulator 113 in the region of the radially projecting pole cores may be about 1.5 mm.","The thickness of the mounting portion 106 may be about 4 mm in the vicinity of the mounting locations 112 and about 3 mm adjacent the annular portion 104 of the stator.","The thickness of the mounting portion 106 may be about 2 mm in the region of the frustoconical portions 124 and 126.Preferably, the motor is wound such that each projecting pole includes a discreet conductor coil, with each pole being associated with one of three phase windings of the motor.","Each phase winding is therefore associated with ⅓ of the poles of the stator.","The coils of each pole associated with a particular phase winding are connected in series.","The coils of a phase winding may be wound from a single continuous conductor, the conductor forming a coil of each respective pole in series.","In the Figures, the coils of the windings are illustrated as amorphous blocks of material.","This is to simplify the illustration.","In practice, each illustrated block is a coil of conductor.","Additional portions of conductor (not illustrated) interconnect the coils for a particular phase winding.","These portions of conductor interconnecting the coils are located in the vicinity of the annular ring portion 104.A framework 125 of guideposts 127 and supporting surfaces 129 assist the arrangement of the interconnecting portions of conductor.","According to this arrangement, first ends of the conductor of each phase winding terminate together at a connector 117.Second ends of the conductor of each phase winding terminate together at connectors 119.In different electrical configurations for the motor, it may be preferable for pairs of ends to terminate together.","In one electrical arrangement for the motor, the phase windings are connected in a star configuration.","In this configuration, an end of each of the three windings is connected together at a common connector 117.Referring to FIGS.","6 and 7, alternative cores according to different methods of manufacturing a lamination stack 115 are illustrated.","In the arrangement illustrated in FIG.","6, the stator core comprises a lamination formed from a helically, edgewise wound strip 600.The strip includes a band portion 602 and radially extending pole portions 604 at regular intervals.","As the strip is wound edgewise, the pole portions splay apart slightly.","And the turns of strip stack up to form the laminated stator core.","The helical stack of turns may be secured by a plurality of rivets 608 or alternatively by interlocking punch down portions (not illustrated) where a tab of each layer of strip is punched into a recess in the layer below, the recess being formed by punching down the tab in that layer.","One end 606 of the helically wound strip sits on the top of the stack.","The other end of the helically wound strip sits on the bottom of the stack.","FIG.","7 illustrates an alternative embodiment in which the core is formed from multiple stacks of laminations.","Each stack of laminations includes a segment 702 or 704 of the annular ring portion of the stator core and a plurality of radially extending pole core portions 706.For a stator with 27 poles, the core preferably comprises 3 lamination stacks having 5 pole cores each, and 3 lamination stacks having 4 pole cores each.","The 5-pole stacks 710 and the 4-pole stacks 708 may be assembled to form the stator core, with stacks 708 and 710 alternating around the stator core.","The individual lamination stacks may be joined in any suitable fashion.","For example the stacks may be butt-welded, or they may be simply restrained in place and held together abutting one another by the moulded plastic insulating layer.","However, preferably, they are joined by interconnecting shapes at the butting ends of the annular ring portion 702, 704.For example, the interlocking shapes may form a dove-tail connection.","The laminations within each stack may be riveted, or otherwise secured together.","For example they may be secured by an adhesive, or in some temporary fashion until the plastic over moulding, or they may be interlocked by appropriate punched connections between layers of the lamination.","The height of the lamination stack may vary depending on the torque requirement of the motor.","For example, the height of the lamination stack may be between 10 mm and 35 mm depending on the output requirement for the motor.","Each lamination of the lamination stack may be about 0.5 mm thickness.","For example, a lamination stack of 27 layers would have a stator core thickness of 13.5 mm.","A stack of 38 layers would have a stator core thickness of 19 mm.","The inventors have found that the described stator, intended for use in application in a laundry machine, provides lower noise than conventional stators such as are illustrated in FIGS.","16 and 17 and (labelled “prior art”), with rotation speeds up to 1600 rpm.","The described stator is for use with an external rotor having a ring of magnets facing inward toward the outer surfaces of the pole ends of the stator.","For example, rotors are illustrated in FIGS.","8 to 11.In use, the stator is secure on the machine, with a shaft of the machine passing through the inner aperture 120 of the stator mounting portion.","The rotor is secured to the shaft.","The stator is intended for a motor with a 4:3 rotor pole to stator pole ratio.","Accordingly, the rotor for use with a 27 pole stator as illustrated should have 36 poles.","As an alternative, the inventors believe a stator with 24 poles may achieve some of the benefits of the described stator.","The corresponding rotor would have 32 poles.","Referring to FIGS.","8 to 11, the rotor 36 comprises a number of, hard ferrite or neodymium-iron-boron permanent magnet elements 37, arranged to form a permanent magnet ring 38 of such elements.","The permanent magnet elements 37 could also be comprised of a blend of hard ferrite and neodymium-iron-boron material or other magnetic material such as, but not limited to, Samarium-cobalt.","Alternatively the permanent magnet elements 37 could comprise a blend of these magnet materials and plastic material.","The ring 38 of magnetic material can be supported by a rigid rotor support or housing 39.This may comprise an over moulded plastics annular ring, with a plastics hub.","Alternatively, the housing could comprise pressed steel 39a (as in the rotor of FIG.","10) with the magnet elements attached therein.","A single or multiple piece or multiple layer laminated backing ring 40 (see FIG.","8) could optionally be provided to increase the resulting magnetic flux field produced by the magnetic material.","Preferably, the ring of permanent magnetic material 38 has an internal diameter just larger than the outside diameter of the stator.","The combination achieves an air gap of between 2.5 mm and 0.5 mm.","Each section (and the ring) is preferably less than 20 mm thick.","It will be appreciated by those skilled in the art that there are many possible variations on the construction of a rotor 36 for use in a washing machine motor.","FIGS.","8 and 9 show just one possibility in a general form for exemplary purposes.","FIGS.","10 and 11 show an alternative possible rotor.","Further details of possible rotor constructions are described in our U.S. Pat.","No.","5,040,285, our PCT international publication WO2009/017430 and in our pending US patent application U.S. 61/358,746.The whole content of each application is hereby incorporated by reference.","The preferred motor has a magnet to stator pole ratio of 4:3.The number of rotor magnets shown FIGS.","10 and 11 are illustrative only to demonstrate the physical nature of the rotor/stator.","The actual number of magnets might be different.","As described in our WO2009/017430, the rotor 36 may be magnetised to produce a Halbach-style resulting magnetic flux field the same or similar to that produced by a standard Halbach array.","As described in WO2009/017430, each permanent magnet element 37 in the rotor may be produced in a manner such that it comprises magnetic domains pre-aligned into a magnetic domain alignment pattern.","The term “magnetic domain alignment pattern” refers to the orientation of the magnetic domains 41 occurring as a result of the manufacture process.","Multiple magnet elements can be arranged together to create magnetic material with pre-aligned magnetic domains that enable production of a Halbach-style resulting magnetic flux field when the magnet material is subsequently magnetised by a magnetisation pattern.","A ring of such magnet elements can be assembled to produce a permanent magnet ring of the rotor.","This can be magnetised to have a Halbach-style resulting magnetic flux field.","This field is stronger than if isotropic or radially aligned anisotropic magnetic material is magnetised with the same flux field.","A rotor with Halbach-style resulting magnetic flux field is the desired field in order to produce improved operating characteristics of the motor.","The magnet elements of the permanent magnet ring might be curved commensurate with the curvature of the rotor.","“Halbach style” refers to a resulting magnetic flux field that is the same as or is similar to a magnetic flux field produced by a traditional Halbach array magnet arrangement.","The term “magnetisation pattern” refers to the external magnetic flux field employed to energise the magnet element according to the domain alignment pattern, causing the magnets to become magnetised.","The term “resulting magnetic flux field” refers to the magnetic flux field that exists in the magnet elements (and surrounding structure, where applicable) after production, assembly and magnetisation.","Further detail, alternatives and options concerning the magnet elements, which may be used in some embodiments of a rotor for the motor herein, are set forth in WO2009/017430.An embodiment of the invention might comprise a washing machine with a motor as described above, or another embodiment might comprise the motor itself, or the stator itself.","Alternatively, the motor or stator could be used in another application, such as a power generation apparatus.","A washing machine using the motor described could take one of many forms.","For example, referring to FIG.","12, one embodiment comprises a top loading washing machine with an outer wrapper and a tub suspended within the wrapper.","A rotating drum with perforated walls is disposed in and rotatable within the suspended tub.","A motor, comprising a stator and rotor as previously desired, is coupled to the rotating drum via a rotational shaft.","The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.","The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.","These may make the motor as a whole less expensive or operate with less noise.","Referring to FIG.","13, another embodiment comprises a front loading horizontal axis washing machine with an outer wrapper and a rotating drum housing suspended in the outer wrapper.","A rotating drum is disposed in and rotatable within the rotating drum housing.","A door provides access to the rotating drum for introducing or removing clothing to be washed.","A gasket may be included to provide a seal between the door and the rotating drum.","A rotor is coupled to the rotating drum via a rotational shaft and the stator is coupled to the rear of the tub.","The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.","The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.","These may make the motor as a whole less expensive or operate with less noise.","Referring to FIG.","14, another embodiment comprises a top loading or tilt access horizontal axis washing machine.","The washing machine has an outer wrapper and a tub suspended within the outer wrapper.","A rotating drum can rotate within the tub.","Clothes can be introduced and taken from the rotating drum through an opening in the top of the drum.","A motor, comprising a stator and rotor as previously desired, is arranged to drive the rotating drum via a rotational shaft.","The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.","The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.","These may make the motor as a whole less expensive or operate with less noise.","FIG.","15 shows a tilt loading horizontal axis washing machine.","The washing machine has an outer wrapper and a tub suspended within the outer wrapper.","A rotating drum can rotate within the tub.","Clothes can be introduced and taken from the rotating drum by tilting the drum.","A motor, comprising a stator and rotor as previously desired, is arranged to drive the rotating drum via a rotational shaft.","The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.","The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.","These may make the motor as a whole less expensive or operate with less noise.","It will be appreciated that FIGS.","9 to 12 show just four examples of washing machines that could utilise a motor with a rotor containing magnetic elements produced in the manner described above.","Other embodiments of the present invention could comprise other washing machines, operated by a motor as described above."]],"string":"[\n [\n \"APPLIANCE, MOTOR OR STATOR\",\n \"A motor suited for use in a direct drive laundry machine.\",\n \"The described motor has a stator core including an annular ring with an inner diameter between 120 mm and 250 mm, a radial width between 5 mm and 15 mm, and 24 or 27 stator poles projecting outward from the annular ring a distance of between 15 mm and 40 mm.\",\n \"Each stator pole is associated with one of three phase windings.\",\n \"A rotor for the motor has inwardly facing permanent magnet poles whereby the ratio of rotor poles to stator poles is 4:3.\"\n ],\n [\n \"1.A stator comprising: a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, a plurality of radiating extending poles spaced around the outer circumference of the annular ring, the poles extending outward from the annular ring between 15 mm and 40 mm, three phase windings, each winding comprising a plurality of coils, each coil arranged on ⅓ of the poles, an insulator insulating the poles from the windings, a plurality of fastening locations for fastening the stator to a machine, each fastening location being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the poles extend beyond the outer circumference of the annular ring, and more than 40 mm from the centre of the stator.\",\n \"2.The stator as claimed in claim 1, wherein the fastening locations are between 40 mm and 80 mm from the centre of the stator.\",\n \"3.The stator as claimed in claim 1, wherein the fastening locations are between 50 mm and 75 mm from the centre of the stator.\",\n \"4.The stator as claimed in claim 1, wherein the fastening locations are between 60 mm and 70 mm from the centre of the stator.\",\n \"5.The stator as claimed in claim 1, wherein the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the inner circumference of the ring and that includes the fastening locations.\",\n \"6.The stator as claimed in claim 5, wherein the fastening locations comprise apertures through the diaphragm portion.\",\n \"7.The stator as claimed in claim 5, wherein the diaphragm portion is annular and occupies an area between the annular ring and an inner aperture spaced inward of the fastening locations.\",\n \"8.The stator as claimed in claim 5, wherein the diaphragm includes at least one substantially frustoconical surface in a region between the fastening locations and the annular ring.\",\n \"9.The stator as claimed in claim 5, wherein the diaphragm includes at least two substantially frustoconical portions between the fastening locations and the annular ring, the frustoconical portions joining to form a circular ridge when viewed from one side of the stator and a circular valley when viewed from the other side of the stator.\",\n \"10.The stator as claimed in claim 9, wherein the height of the ridge or depth of the valley is less than the height of the annular ring.\",\n \"11.A motor for use in a washing machine, said motor comprising: a stator as claimed in claim 1, and a rotor concentric with said stator with a permanent magnet ring outside said stator and rotor poles facing the ends of said stator poles.\",\n \"12.The motor as claimed in claim 11, wherein the rotor comprises: a plurality of magnet elements with two lateral edges each with magnetic domains aligned anisotropically to form a domain alignment pattern, the plurality of magnet elements being arranged to form the permanent magnet ring with an inner face and an outer face, and a rigid support holding said magnet elements in said permanent magnet ring, wherein the magnetic domain alignment pattern in each magnet element has an orientation that varies substantially continuously across at least part of the magnet element between its lateral edges from an orientation that has a predominant radial component at a pole of the magnet element to an orientation that has a least some tangential component at one lateral edge of the magnet element, and wherein the magnet elements are magnetised to produce a resulting magnetic flux field.\",\n \"13.The motor according to claim 12, wherein one or more of the magnet elements have a chamfer at the intersection of each lateral edge with a front edge, wherein the front edge is the edge at the inner face of the permanent magnet ring.\",\n \"14.The motor according to claim 12, wherein at both lateral edges of each magnet element the orientation of the magnetic domain alignment pattern has a significant tangential component which results in the magnetic domain alignment pattern having an orientation of at least 15 degrees with respect to the lateral edges.\",\n \"15.The motor according to claim 12, wherein the orientation of the magnetic domain alignment pattern varies substantially non-linearly over the magnet element.\",\n \"16.The motor according to claim 12, wherein the resulting magnetic flux field of the permanent magnet ring has poles with alternating polarity spaced around the permanent magnet ring, the poles being aligned radially with respect to the permanent magnet ring, and wherein the resulting magnetic flux field traverses between adjacent poles of opposite polarities and between those poles is focused to extend beyond the boundary defined by the inner face, but remain at least partially constrained within the boundary defined by the outer face of the permanent magnet ring.\",\n \"17.The motor according to claim 16, wherein the portion of the resulting magnetic flux field between adjacent poles extending beyond the boundary defined by the inner face of the permanent magnet ring has an orientation that varies continuously wherein: between the poles, the orientation varies from an orientation that has a predominant radial component at a pole to an orientation that has a predominant tangential component at the mid-point between poles, and extending radially from the inner face, the orientation varies from an orientation that has a predominant radial component at the inner face to an orientation that has an increasingly tangential component with distance from the inner face.\",\n \"18.A washing machine including a motor as claimed in claim 11, said stator being coupled to a non-rotating tub or housing of the washing machine, said rotor being coupled to a rotating drum of the washing machine.\",\n \"19.The washing machine according to claim 18, wherein the washing machine is a top loading washing machine and/or a horizontal axis washing machine comprising: an outer wrapper, the non-rotating tub or housing suspended in the outer wrapper, and the rotating drum in the tub.\"\n ],\n [\n \"<SOH> BACKGROUND TO THE INVENTION <EOH>The present invention relates to motors for particular use in laundry machines.\",\n \"The motors are of a type including an internal stator with radially extending stator poles and an external rotor with inwardly facing rotor poles.\",\n \"In motors having a 4:3 ratio of rotor poles to stator poles, for use with direct drive laundry washing machines, more than 30 stator poles has been typical.\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>An object of the present invention is to provide a stator, a motor including the stator, or a laundry machine including the motor, which improve on the prior art, or which will at least provide the public or industry with a useful choice.\",\n \"In one aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, 24 or 27 radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring a distance between 15 mm and 40 mm, three phase windings, each winding comprising a plurality of coils arranged on one third of the pole cores, the windings arranged on the pole cores such that each pole core is associated with only one winding, which is different from the winding associated with each of the two immediately adjacent pole cores and the two immediately adjacent pole cores are associated with different windings, an insulator insulating the pole cores from the windings.\",\n \"According to a further aspect, the core has a depth between 10 mm and 35 mm.\",\n \"According to a further aspect, the annular ring is at least largely encapsulated by an insulator.\",\n \"According to a further aspect, the insulator over the pole cores and annular ring is an over moulded plastic material.\",\n \"According to a further aspect, the diameter of the inner circumference of the annular ring is between 150 mm and 230 mm.\",\n \"According to a further aspect, the diameter of the inner circumference of the annular ring is between 200 mm and 220 mm.\",\n \"According to a further aspect, the width of the annular ring is between 5 mm and 10 mm.\",\n \"According to a further aspect, the width of the annular ring is between 7 mm and 10 mm.\",\n \"According to a further aspect, the depth or thickness of the annular ring is between 12 mm and 15 mm.\",\n \"According to a further aspect, the depth or thickness of the annular ring is between 17 mm and 23 mm.\",\n \"According to a further aspect, the core comprises at least one stack of laminations, each lamination lying in a plane substantially parallel to the plane of the annular ring.\",\n \"According to a further aspect, the stack or stacks of laminations comprise a stack formed from a helical coil of steel strip such that each layer in the stack comprises a turn in the helix.\",\n \"According to a further aspect, the steel strip includes a band forming the annular ring and extended portions forming the pole cores.\",\n \"According to a further aspect, the stack or stacks of laminations comprises multiple stacks joined at their ends, each stack including a segment of the annular ring and one or more extending pole cores.\",\n \"According to a further aspect, each segment of the annular ring joins with adjacent segments of the annular ring by interlocking shapes at the abutting ends (such as a dove tail joint).\",\n \"According to a further aspect, each segment includes a plurality of radially extending pole cores.\",\n \"According to a further aspect, the stator includes 27 radially extending pole cores and the core comprises 6 stacks, 3 stacks having 5 radially extending pole cores each and 3 stacks having 4 radially extending pole cores each.\",\n \"According to a further aspect, the stator has only 27 radially extending pole cores.\",\n \"According to a further aspect, the stator includes a plurality of fastening locations for mounting the stator to a machine, each fastening location being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring.\",\n \"According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.\",\n \"According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.\",\n \"According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.\",\n \"According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.\",\n \"According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.\",\n \"According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).\",\n \"According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.\",\n \"In a further aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, a plurality of radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring between 15 mm and 40 mm, 3 phase windings, each winding comprising a plurality of coils arranged on ⅓ of the pole cores, an insulator insulating the pole cores from the windings, a plurality of mounting points for mounting the stator to a machine, each mounting point being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring, and more than 40 mm from the centre of the stator.\",\n \"According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.\",\n \"According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.\",\n \"According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.\",\n \"According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.\",\n \"According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.\",\n \"According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).\",\n \"According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.\",\n \"In a further aspect, the present invention may broadly be said to consist in a motor for use in a washing machine, said motor comprising a stator as described above, a rotor concentric with said stator with a permanent magnet ring outside said stator and rotor poles facing the ends of said stator poles.\",\n \"According to a further aspect, the rotor comprises a plurality of magnet elements with two lateral edges each with magnetic domains aligned anisotropically to form a domain alignment pattern, the plurality of magnets being arranged to form a permanent magnet ring with an inner face and an outer face, a rigid support holding said magnet elements in said ring arrangement, wherein the magnetic domain alignment pattern in each magnet element has an orientation that varies substantially continuously across at least part of the magnet element between its lateral edges from an orientation that has a predominant radial component at a pole of the magnet element to an orientation that has a least some tangential component at one lateral edge of the magnet element, wherein the magnet elements are magnetised to produce a resulting magnetic flux field.\",\n \"According to a further aspect, one or more of the magnet elements have a chamfer at the intersection of each lateral edge with the front edge, wherein the front edge is the edge at the inner face of the rotor.\",\n \"According to a further aspect, at both lateral edges the orientation of the magnetic domain alignment pattern has significant tangential component which result in the magnetic domain alignment pattern having an orientation of at least 15 degrees with respect to the lateral edges.\",\n \"According to a further aspect, the orientation varies substantially non-linearly over the magnet element.\",\n \"According to a further aspect, the resulting magnetic flux field has poles with alternating polarity spaced around the ring, the poles being aligned radially with respect to the permanent magnet ring, and wherein the resulting magnetic flux field of the permanent magnet ring traverses between adjacent poles of opposite polarities and between those poles is focused to extend beyond the boundary defined by the inner face, but remain at least partially constrained within the boundary defined by the outer face of the permanent magnet ring, According to a further aspect, the portion of the resulting magnetic flux field between adjacent poles extending beyond the boundary defined by the inner face of the permanent magnet ring magnet element has an orientation that varies continuously wherein between the poles, the orientation varies from an orientation that has a predominant radial component at the pole to an orientation that has a predominant tangential component at the mid-point between the poles, and extending radially from the inner face, the orientation varies from an orientation that has a predominant radial component at an inner face to an orientation that has an increasingly tangential component with distance from the inner face.\",\n \"In a further aspect, the present invention may broadly be said to consist in a washing machine including an electronically commutated motor as described above, said stator being coupled to a non-rotating tub or housing of the washing machine, said rotor being coupled to a rotating drum of the washing machine.\",\n \"According to a further aspect, washing machine is a top loading washing machine comprising: an outer wrapper, a tub suspended in the outer wrapper, and a rotating drum in the tub.\",\n \"According to a further aspect, the washing machine is a horizontal axis machine comprising: an outer wrapper, a rotating drum housing, and a rotating drum in the housing.\",\n \"According to a further aspect, the washing machine is a horizontal axis machine with top loading access comprising: an outer wrapper, a tub, and a rotating drum in the tub.\",\n \"In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention.\",\n \"Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.\",\n \"The term “comprising” as used in this specification means “consisting at least in part of”.\",\n \"Related terms such as “comprise” and “comprised” are to be interpreted in the same manner.\",\n \"It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7).\",\n \"To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended claims.\",\n \"The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting\"\n ],\n [\n \"INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application are hereby incorporated by reference under 37 C.F.R.\",\n \"§ 1.57 and made a part of the present disclosure.\",\n \"FIELD OF THE INVENTION The present invention relates to electric motors and magnet elements for use in such motors, and particularly motors having an external rotor of a type that are used as the main drive motor for a domestic laundry machine or other apparatus.\",\n \"BACKGROUND TO THE INVENTION The present invention relates to motors for particular use in laundry machines.\",\n \"The motors are of a type including an internal stator with radially extending stator poles and an external rotor with inwardly facing rotor poles.\",\n \"In motors having a 4:3 ratio of rotor poles to stator poles, for use with direct drive laundry washing machines, more than 30 stator poles has been typical.\",\n \"SUMMARY OF THE INVENTION An object of the present invention is to provide a stator, a motor including the stator, or a laundry machine including the motor, which improve on the prior art, or which will at least provide the public or industry with a useful choice.\",\n \"In one aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, 24 or 27 radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring a distance between 15 mm and 40 mm, three phase windings, each winding comprising a plurality of coils arranged on one third of the pole cores, the windings arranged on the pole cores such that each pole core is associated with only one winding, which is different from the winding associated with each of the two immediately adjacent pole cores and the two immediately adjacent pole cores are associated with different windings, an insulator insulating the pole cores from the windings.\",\n \"According to a further aspect, the core has a depth between 10 mm and 35 mm.\",\n \"According to a further aspect, the annular ring is at least largely encapsulated by an insulator.\",\n \"According to a further aspect, the insulator over the pole cores and annular ring is an over moulded plastic material.\",\n \"According to a further aspect, the diameter of the inner circumference of the annular ring is between 150 mm and 230 mm.\",\n \"According to a further aspect, the diameter of the inner circumference of the annular ring is between 200 mm and 220 mm.\",\n \"According to a further aspect, the width of the annular ring is between 5 mm and 10 mm.\",\n \"According to a further aspect, the width of the annular ring is between 7 mm and 10 mm.\",\n \"According to a further aspect, the depth or thickness of the annular ring is between 12 mm and 15 mm.\",\n \"According to a further aspect, the depth or thickness of the annular ring is between 17 mm and 23 mm.\",\n \"According to a further aspect, the core comprises at least one stack of laminations, each lamination lying in a plane substantially parallel to the plane of the annular ring.\",\n \"According to a further aspect, the stack or stacks of laminations comprise a stack formed from a helical coil of steel strip such that each layer in the stack comprises a turn in the helix.\",\n \"According to a further aspect, the steel strip includes a band forming the annular ring and extended portions forming the pole cores.\",\n \"According to a further aspect, the stack or stacks of laminations comprises multiple stacks joined at their ends, each stack including a segment of the annular ring and one or more extending pole cores.\",\n \"According to a further aspect, each segment of the annular ring joins with adjacent segments of the annular ring by interlocking shapes at the abutting ends (such as a dove tail joint).\",\n \"According to a further aspect, each segment includes a plurality of radially extending pole cores.\",\n \"According to a further aspect, the stator includes 27 radially extending pole cores and the core comprises 6 stacks, 3 stacks having 5 radially extending pole cores each and 3 stacks having 4 radially extending pole cores each.\",\n \"According to a further aspect, the stator has only 27 radially extending pole cores.\",\n \"According to a further aspect, the stator includes a plurality of fastening locations for mounting the stator to a machine, each fastening location being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring.\",\n \"According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.\",\n \"According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.\",\n \"According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.\",\n \"According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.\",\n \"According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.\",\n \"According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).\",\n \"According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.\",\n \"In a further aspect, the present invention may broadly be said to consist in a stator comprising a core of magnetically permeable material including an annular ring with an inner circumference between 120 mm diameter and 250 mm diameter and a width between 5 mm and 15 mm, a plurality of radiating extending poles spaced around the circumference of the annular ring, the poles extending outward from the annular ring between 15 mm and 40 mm, 3 phase windings, each winding comprising a plurality of coils arranged on ⅓ of the pole cores, an insulator insulating the pole cores from the windings, a plurality of mounting points for mounting the stator to a machine, each mounting point being centred a distance radially inside the inner surface of the annular ring of the core, this distance being greater than the length that the pole cores extend beyond the outer surface of the annular ring, and more than 40 mm from the centre of the stator.\",\n \"According to a further aspect, fastening locations for fastening the stator to the machine have centres more than 40 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 40 mm and 80 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 50 mm and 75 mm from the centre of the stator.\",\n \"According to a further aspect, the fastening locations are between 60 mm and 70 mm from the centre of the stator.\",\n \"According to a further aspect, the stator includes a diaphragm portion extending inward from the annular ring to occupy an area within the perimeter of the ring and that includes the fastening locations.\",\n \"According to a further aspect, the fastening locations comprise apertures through the diaphragm portion.\",\n \"According to a further aspect, the diaphragm portion is annular and occupies an area between the annular ring and a circular aperture spaced inward of the mounting locations.\",\n \"According to a further aspect, the diaphragm includes at least one substantially frustoconical surface in a region between the mounting locations and the annular ring.\",\n \"According to a further aspect, the diaphragm includes at least two substantially frustoconical portions between the mounting locations and the annular ring, the frustoconical portions joining to form a circular ridge (when viewed from one side of the stator) and valley (when viewed from the other side of the stator).\",\n \"According to a further aspect, the height of the ridge or valley is less than the height of the annular ring.\",\n \"In a further aspect, the present invention may broadly be said to consist in a motor for use in a washing machine, said motor comprising a stator as described above, a rotor concentric with said stator with a permanent magnet ring outside said stator and rotor poles facing the ends of said stator poles.\",\n \"According to a further aspect, the rotor comprises a plurality of magnet elements with two lateral edges each with magnetic domains aligned anisotropically to form a domain alignment pattern, the plurality of magnets being arranged to form a permanent magnet ring with an inner face and an outer face, a rigid support holding said magnet elements in said ring arrangement, wherein the magnetic domain alignment pattern in each magnet element has an orientation that varies substantially continuously across at least part of the magnet element between its lateral edges from an orientation that has a predominant radial component at a pole of the magnet element to an orientation that has a least some tangential component at one lateral edge of the magnet element, wherein the magnet elements are magnetised to produce a resulting magnetic flux field.\",\n \"According to a further aspect, one or more of the magnet elements have a chamfer at the intersection of each lateral edge with the front edge, wherein the front edge is the edge at the inner face of the rotor.\",\n \"According to a further aspect, at both lateral edges the orientation of the magnetic domain alignment pattern has significant tangential component which result in the magnetic domain alignment pattern having an orientation of at least 15 degrees with respect to the lateral edges.\",\n \"According to a further aspect, the orientation varies substantially non-linearly over the magnet element.\",\n \"According to a further aspect, the resulting magnetic flux field has poles with alternating polarity spaced around the ring, the poles being aligned radially with respect to the permanent magnet ring, and wherein the resulting magnetic flux field of the permanent magnet ring traverses between adjacent poles of opposite polarities and between those poles is focused to extend beyond the boundary defined by the inner face, but remain at least partially constrained within the boundary defined by the outer face of the permanent magnet ring, According to a further aspect, the portion of the resulting magnetic flux field between adjacent poles extending beyond the boundary defined by the inner face of the permanent magnet ring magnet element has an orientation that varies continuously wherein between the poles, the orientation varies from an orientation that has a predominant radial component at the pole to an orientation that has a predominant tangential component at the mid-point between the poles, and extending radially from the inner face, the orientation varies from an orientation that has a predominant radial component at an inner face to an orientation that has an increasingly tangential component with distance from the inner face.\",\n \"In a further aspect, the present invention may broadly be said to consist in a washing machine including an electronically commutated motor as described above, said stator being coupled to a non-rotating tub or housing of the washing machine, said rotor being coupled to a rotating drum of the washing machine.\",\n \"According to a further aspect, washing machine is a top loading washing machine comprising: an outer wrapper, a tub suspended in the outer wrapper, and a rotating drum in the tub.\",\n \"According to a further aspect, the washing machine is a horizontal axis machine comprising: an outer wrapper, a rotating drum housing, and a rotating drum in the housing.\",\n \"According to a further aspect, the washing machine is a horizontal axis machine with top loading access comprising: an outer wrapper, a tub, and a rotating drum in the tub.\",\n \"In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention.\",\n \"Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.\",\n \"The term “comprising” as used in this specification means “consisting at least in part of”.\",\n \"Related terms such as “comprise” and “comprised” are to be interpreted in the same manner.\",\n \"It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7).\",\n \"To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended claims.\",\n \"The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a perspective view of a stator according to one embodiment of the present invention.\",\n \"FIG.\",\n \"2 is a plan view from below of the stator of FIG.\",\n \"1.FIG.\",\n \"3 is a side elevation of the stator of FIG.\",\n \"2.FIG.\",\n \"4 is a cross section through line BB of FIG.\",\n \"3.FIG.\",\n \"5 is a cross section through line CC of FIG.\",\n \"4.FIG.\",\n \"6 is a plan view of a laminated core suitable for the stator of FIG.\",\n \"1.FIG.\",\n \"7 is a plan view of an alternative laminated stator core suitable for the stator of FIG.\",\n \"1.FIG.\",\n \"8 is a perspective view from one side of the rotor suitable (for adaption to the number of rotor poles) for use with the stator of FIG.\",\n \"1.FIG.\",\n \"9 is a perspective view of the rotor of FIG.\",\n \"8 from the other side.\",\n \"FIG.\",\n \"10 is a perspective view of another rotor suitable (with adaptation of the number of rotor poles) for use with the stator of FIG.\",\n \"1.FIG.\",\n \"11 is a perspective view of another rotor suitable (With adaptation of the number of rotor poles) for use with the stator of FIG.\",\n \"1.FIG.\",\n \"12 shows a diagrammatic cutaway view of a washing machine of a vertical axis type that may incorporate a stator and/or motor according to the present invention.\",\n \"FIG.\",\n \"13 shows a diagrammatic view of a horizontal axis washing machine with front access that may incorporate the stator and/or motor according to the present invention.\",\n \"FIG.\",\n \"14 shows a diagrammatic view of a horizontal axis washing machine with top or tilt access that may incorporate the stator and/or motor according to the present invention.\",\n \"FIG.\",\n \"15 shows a diagrammatic view of a horizontal axis laundry machine with tilt access that may incorporate the stator and/or motor according to the present invention.\",\n \"FIG.\",\n \"16 is a perspective view of a prior art stator.\",\n \"FIG.\",\n \"17 is a perspective view of a prior art rotor.\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A stator according to one embodiment of the present invention is illustrated in FIGS.\",\n \"1 to 5.The stator 100 has 27 poles 102.The stator generally includes an annular ring portion 104, a mounting portion 106 inside the ring portion, and a plurality of poles 102 extending radially from the outside surface of the annular ring portion 104.In construction, the stator generally comprises a magnetically permeable core 108, an insulator structure 113 surrounding the core, or surrounding most of the core, and conductive windings arranged on the poles 102.In the illustrated embodiment, the insulating structure 113 comprises a layer of plastic over moulded over the magnetically permeable core.\",\n \"The over moulded plastic covers at least those parts of the core which support and locate the conductive windings.\",\n \"In the illustrated embodiment, the plastic covers all of the radially extending pole cores except the outer end surfaces 118.In an alternative embodiment, the insulating plastic may also cover the end surfaces of the pole cores.\",\n \"Holes or partial holes 110 may extend through the plastic at the annular ring portion of the stator.\",\n \"These may result from pins or other locating devices used to hold the stator core in place during the moulding process.\",\n \"The magnetically permeable core 108 may be formed of any suitable material, including for example a sintered ferritic powder, but most preferably is formed from steel laminations 115.In general form, laminations of the laminated steel lie in planes substantially parallel to the plane of the annular ring of the stator.\",\n \"The plan view of FIG.\",\n \"4 illustrates the outline shapes of the laminations 115 while the cross section of FIG.\",\n \"5 illustrates edges of the laminations 115.The lamination steel may be, for example, a fully processed non-oriented grain lamination steel with a nominal loss of about 7 w/kg.\",\n \"The plastic material over moulding the core may be any suitable plastic.\",\n \"For example, one suitable material is a polybutylene terephthalate (PBT) sold as “CRASTIN” by Dupont Corporation.\",\n \"The stator mounting portion 106 includes mounting locations generally designated 112.In the illustrated embodiment, each fastening location 112 includes a fastening hole 114.The fastening holes 114 may be slotted or otherwise larger than the outside diameter of the fastener intended to pass through the fastening holes.\",\n \"This allows for manufacturing tolerance in the machine to which the stator will be secured.\",\n \"The mounting portion 106 may include a locating portion 116 in addition to the fastening locations 112.The locating portion 116 may provide for aligning the stator concentrically with a shaft of the motor.\",\n \"For example, the locating portion 116 may comprise a circular opening 120 at the centre of the stator.\",\n \"A lip or rim 122 of the opening 120 may locate on a corresponding feature or features of a bearing housing or bearing supporting the drive shaft.\",\n \"The fastening locations 112 (with fastening holes 114) are located in the mounting portion 106 between the opening 120 and the annular ring portion 104.In the illustrated embodiment, these fastening locations and fastening holes are centred more than 40 mm from the centre of the stator.\",\n \"In some embodiments, they may be more than 45 mm from the centre of the stator, more than 50 mm from the centre of the stator, more than 55 mm from the centre of the stator, more than 60 mm from the centre of the stator and preferably more than 65 mm from the centre of the stator, or about 68 mm from the centre of the stator.\",\n \"The mounting locations and fastening holes 114 are centred a distance from the inside surface of the annular ring portion 111 of the core 108 that is greater than the distance that the radially extending pole portions 109 of the core 108 extend beyond the outer surface of the annular ring portion of the core 108.For example, in one embodiment, the fastening holes may be centred more than 30 mm from the inside surface of the annular ring portion of the core 108, more than 32 mm, more than 34 mm and preferably more than 35 mm from the inside surface of the stator core annular ring portion.\",\n \"Whereas the pole portions may extend less than 30 mm from the outside surface of the annular ring portion of the core 108, and most preferably less than 27 mm.\",\n \"In other embodiments, the pole portions may extend more than 30 mm from the outside surface of the annular ring, for example up to 40 mm, in which case the fastening holes may be more than 40 mm from the inside surface of the annular ring.\",\n \"The pole portions may extend much less than 30 mm from the outer surface over the annular ring, for example, only 15 mm.\",\n \"In plan view, each pole portion is T-shaped, with a cross bar portion of each pole portion supported spaced apart from the annular ring portion of the stator by a trunk portion of each pole portion.\",\n \"The mounting portion 106 of the stator may be formed entirely from plastic.\",\n \"The mounting portion 106 may be formed in one operation with over moulding of the core 108.The mounting portion may include one or more frustoconical portions concentric with the annular ring portion of the stator.\",\n \"The illustrated stator includes an inner frustoconical portion 124 and an outer frustoconical portion 126.Together, the frustoconical portions 124 and 126 form a circular ridge 128 (when viewed from one side of the stator as in FIG.\",\n \"1) and circular valley 130 (when viewed from the other side of the stator as in FIG.\",\n \"2).\",\n \"The overall diameter 132 of the stator may be about 280 mm.\",\n \"In other embodiments, the diameter may be between 320 and 270, between 290 and 270 or between 290 and 240.The width 134 of the annular ring portion of the stator core may be about 9 mm.\",\n \"In other embodiments, the width of the annular ring portion of the stator core may be between 5 mm and 15 mm.\",\n \"The diameter 131 of the inner surface of the stator core 108 may be about 208 mm.\",\n \"In other embodiments, the diameter may be between 230 mm and 190 mm or between 250 mm and 120 mm.\",\n \"The radial distance 133 of the fastening locations from the centre of the stator may be about 68 mm.\",\n \"In other embodiments, the radial distance may be between 40 mm and 80 mm.\",\n \"The thickness of the plastic insulator 113 in the region of the radially projecting pole cores may be about 1.5 mm.\",\n \"The thickness of the mounting portion 106 may be about 4 mm in the vicinity of the mounting locations 112 and about 3 mm adjacent the annular portion 104 of the stator.\",\n \"The thickness of the mounting portion 106 may be about 2 mm in the region of the frustoconical portions 124 and 126.Preferably, the motor is wound such that each projecting pole includes a discreet conductor coil, with each pole being associated with one of three phase windings of the motor.\",\n \"Each phase winding is therefore associated with ⅓ of the poles of the stator.\",\n \"The coils of each pole associated with a particular phase winding are connected in series.\",\n \"The coils of a phase winding may be wound from a single continuous conductor, the conductor forming a coil of each respective pole in series.\",\n \"In the Figures, the coils of the windings are illustrated as amorphous blocks of material.\",\n \"This is to simplify the illustration.\",\n \"In practice, each illustrated block is a coil of conductor.\",\n \"Additional portions of conductor (not illustrated) interconnect the coils for a particular phase winding.\",\n \"These portions of conductor interconnecting the coils are located in the vicinity of the annular ring portion 104.A framework 125 of guideposts 127 and supporting surfaces 129 assist the arrangement of the interconnecting portions of conductor.\",\n \"According to this arrangement, first ends of the conductor of each phase winding terminate together at a connector 117.Second ends of the conductor of each phase winding terminate together at connectors 119.In different electrical configurations for the motor, it may be preferable for pairs of ends to terminate together.\",\n \"In one electrical arrangement for the motor, the phase windings are connected in a star configuration.\",\n \"In this configuration, an end of each of the three windings is connected together at a common connector 117.Referring to FIGS.\",\n \"6 and 7, alternative cores according to different methods of manufacturing a lamination stack 115 are illustrated.\",\n \"In the arrangement illustrated in FIG.\",\n \"6, the stator core comprises a lamination formed from a helically, edgewise wound strip 600.The strip includes a band portion 602 and radially extending pole portions 604 at regular intervals.\",\n \"As the strip is wound edgewise, the pole portions splay apart slightly.\",\n \"And the turns of strip stack up to form the laminated stator core.\",\n \"The helical stack of turns may be secured by a plurality of rivets 608 or alternatively by interlocking punch down portions (not illustrated) where a tab of each layer of strip is punched into a recess in the layer below, the recess being formed by punching down the tab in that layer.\",\n \"One end 606 of the helically wound strip sits on the top of the stack.\",\n \"The other end of the helically wound strip sits on the bottom of the stack.\",\n \"FIG.\",\n \"7 illustrates an alternative embodiment in which the core is formed from multiple stacks of laminations.\",\n \"Each stack of laminations includes a segment 702 or 704 of the annular ring portion of the stator core and a plurality of radially extending pole core portions 706.For a stator with 27 poles, the core preferably comprises 3 lamination stacks having 5 pole cores each, and 3 lamination stacks having 4 pole cores each.\",\n \"The 5-pole stacks 710 and the 4-pole stacks 708 may be assembled to form the stator core, with stacks 708 and 710 alternating around the stator core.\",\n \"The individual lamination stacks may be joined in any suitable fashion.\",\n \"For example the stacks may be butt-welded, or they may be simply restrained in place and held together abutting one another by the moulded plastic insulating layer.\",\n \"However, preferably, they are joined by interconnecting shapes at the butting ends of the annular ring portion 702, 704.For example, the interlocking shapes may form a dove-tail connection.\",\n \"The laminations within each stack may be riveted, or otherwise secured together.\",\n \"For example they may be secured by an adhesive, or in some temporary fashion until the plastic over moulding, or they may be interlocked by appropriate punched connections between layers of the lamination.\",\n \"The height of the lamination stack may vary depending on the torque requirement of the motor.\",\n \"For example, the height of the lamination stack may be between 10 mm and 35 mm depending on the output requirement for the motor.\",\n \"Each lamination of the lamination stack may be about 0.5 mm thickness.\",\n \"For example, a lamination stack of 27 layers would have a stator core thickness of 13.5 mm.\",\n \"A stack of 38 layers would have a stator core thickness of 19 mm.\",\n \"The inventors have found that the described stator, intended for use in application in a laundry machine, provides lower noise than conventional stators such as are illustrated in FIGS.\",\n \"16 and 17 and (labelled “prior art”), with rotation speeds up to 1600 rpm.\",\n \"The described stator is for use with an external rotor having a ring of magnets facing inward toward the outer surfaces of the pole ends of the stator.\",\n \"For example, rotors are illustrated in FIGS.\",\n \"8 to 11.In use, the stator is secure on the machine, with a shaft of the machine passing through the inner aperture 120 of the stator mounting portion.\",\n \"The rotor is secured to the shaft.\",\n \"The stator is intended for a motor with a 4:3 rotor pole to stator pole ratio.\",\n \"Accordingly, the rotor for use with a 27 pole stator as illustrated should have 36 poles.\",\n \"As an alternative, the inventors believe a stator with 24 poles may achieve some of the benefits of the described stator.\",\n \"The corresponding rotor would have 32 poles.\",\n \"Referring to FIGS.\",\n \"8 to 11, the rotor 36 comprises a number of, hard ferrite or neodymium-iron-boron permanent magnet elements 37, arranged to form a permanent magnet ring 38 of such elements.\",\n \"The permanent magnet elements 37 could also be comprised of a blend of hard ferrite and neodymium-iron-boron material or other magnetic material such as, but not limited to, Samarium-cobalt.\",\n \"Alternatively the permanent magnet elements 37 could comprise a blend of these magnet materials and plastic material.\",\n \"The ring 38 of magnetic material can be supported by a rigid rotor support or housing 39.This may comprise an over moulded plastics annular ring, with a plastics hub.\",\n \"Alternatively, the housing could comprise pressed steel 39a (as in the rotor of FIG.\",\n \"10) with the magnet elements attached therein.\",\n \"A single or multiple piece or multiple layer laminated backing ring 40 (see FIG.\",\n \"8) could optionally be provided to increase the resulting magnetic flux field produced by the magnetic material.\",\n \"Preferably, the ring of permanent magnetic material 38 has an internal diameter just larger than the outside diameter of the stator.\",\n \"The combination achieves an air gap of between 2.5 mm and 0.5 mm.\",\n \"Each section (and the ring) is preferably less than 20 mm thick.\",\n \"It will be appreciated by those skilled in the art that there are many possible variations on the construction of a rotor 36 for use in a washing machine motor.\",\n \"FIGS.\",\n \"8 and 9 show just one possibility in a general form for exemplary purposes.\",\n \"FIGS.\",\n \"10 and 11 show an alternative possible rotor.\",\n \"Further details of possible rotor constructions are described in our U.S. Pat.\",\n \"No.\",\n \"5,040,285, our PCT international publication WO2009/017430 and in our pending US patent application U.S. 61/358,746.The whole content of each application is hereby incorporated by reference.\",\n \"The preferred motor has a magnet to stator pole ratio of 4:3.The number of rotor magnets shown FIGS.\",\n \"10 and 11 are illustrative only to demonstrate the physical nature of the rotor/stator.\",\n \"The actual number of magnets might be different.\",\n \"As described in our WO2009/017430, the rotor 36 may be magnetised to produce a Halbach-style resulting magnetic flux field the same or similar to that produced by a standard Halbach array.\",\n \"As described in WO2009/017430, each permanent magnet element 37 in the rotor may be produced in a manner such that it comprises magnetic domains pre-aligned into a magnetic domain alignment pattern.\",\n \"The term “magnetic domain alignment pattern” refers to the orientation of the magnetic domains 41 occurring as a result of the manufacture process.\",\n \"Multiple magnet elements can be arranged together to create magnetic material with pre-aligned magnetic domains that enable production of a Halbach-style resulting magnetic flux field when the magnet material is subsequently magnetised by a magnetisation pattern.\",\n \"A ring of such magnet elements can be assembled to produce a permanent magnet ring of the rotor.\",\n \"This can be magnetised to have a Halbach-style resulting magnetic flux field.\",\n \"This field is stronger than if isotropic or radially aligned anisotropic magnetic material is magnetised with the same flux field.\",\n \"A rotor with Halbach-style resulting magnetic flux field is the desired field in order to produce improved operating characteristics of the motor.\",\n \"The magnet elements of the permanent magnet ring might be curved commensurate with the curvature of the rotor.\",\n \"“Halbach style” refers to a resulting magnetic flux field that is the same as or is similar to a magnetic flux field produced by a traditional Halbach array magnet arrangement.\",\n \"The term “magnetisation pattern” refers to the external magnetic flux field employed to energise the magnet element according to the domain alignment pattern, causing the magnets to become magnetised.\",\n \"The term “resulting magnetic flux field” refers to the magnetic flux field that exists in the magnet elements (and surrounding structure, where applicable) after production, assembly and magnetisation.\",\n \"Further detail, alternatives and options concerning the magnet elements, which may be used in some embodiments of a rotor for the motor herein, are set forth in WO2009/017430.An embodiment of the invention might comprise a washing machine with a motor as described above, or another embodiment might comprise the motor itself, or the stator itself.\",\n \"Alternatively, the motor or stator could be used in another application, such as a power generation apparatus.\",\n \"A washing machine using the motor described could take one of many forms.\",\n \"For example, referring to FIG.\",\n \"12, one embodiment comprises a top loading washing machine with an outer wrapper and a tub suspended within the wrapper.\",\n \"A rotating drum with perforated walls is disposed in and rotatable within the suspended tub.\",\n \"A motor, comprising a stator and rotor as previously desired, is coupled to the rotating drum via a rotational shaft.\",\n \"The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.\",\n \"The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.\",\n \"These may make the motor as a whole less expensive or operate with less noise.\",\n \"Referring to FIG.\",\n \"13, another embodiment comprises a front loading horizontal axis washing machine with an outer wrapper and a rotating drum housing suspended in the outer wrapper.\",\n \"A rotating drum is disposed in and rotatable within the rotating drum housing.\",\n \"A door provides access to the rotating drum for introducing or removing clothing to be washed.\",\n \"A gasket may be included to provide a seal between the door and the rotating drum.\",\n \"A rotor is coupled to the rotating drum via a rotational shaft and the stator is coupled to the rear of the tub.\",\n \"The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.\",\n \"The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.\",\n \"These may make the motor as a whole less expensive or operate with less noise.\",\n \"Referring to FIG.\",\n \"14, another embodiment comprises a top loading or tilt access horizontal axis washing machine.\",\n \"The washing machine has an outer wrapper and a tub suspended within the outer wrapper.\",\n \"A rotating drum can rotate within the tub.\",\n \"Clothes can be introduced and taken from the rotating drum through an opening in the top of the drum.\",\n \"A motor, comprising a stator and rotor as previously desired, is arranged to drive the rotating drum via a rotational shaft.\",\n \"The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.\",\n \"The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.\",\n \"These may make the motor as a whole less expensive or operate with less noise.\",\n \"FIG.\",\n \"15 shows a tilt loading horizontal axis washing machine.\",\n \"The washing machine has an outer wrapper and a tub suspended within the outer wrapper.\",\n \"A rotating drum can rotate within the tub.\",\n \"Clothes can be introduced and taken from the rotating drum by tilting the drum.\",\n \"A motor, comprising a stator and rotor as previously desired, is arranged to drive the rotating drum via a rotational shaft.\",\n \"The motor can be operated by a controller to spin and oscillate the rotating drum to carry out washing of clothes.\",\n \"The inventors have found the described stator of the motor to be less susceptible to resonance relative to prior art stators of similar size, weight and output.\",\n \"These may make the motor as a whole less expensive or operate with less noise.\",\n \"It will be appreciated that FIGS.\",\n \"9 to 12 show just four examples of washing machines that could utilise a motor with a rotor containing magnetic elements produced in the manner described above.\",\n \"Other embodiments of the present invention could comprise other washing machines, operated by a motor as described above.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874764"}}},{"rowIdx":4494691,"cells":{"text":{"kind":"list like","value":[["SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING","Methods for depositing nanolaminate protective layers over a core layer to enable deposition of high quality conformal films over the core layer for use in advanced multiple patterning schemes are provided.","In certain embodiments, the methods involve depositing a thin silicon oxide or titanium oxide film using plasma-based atomic layer deposition techniques with a low high frequency radio frequency (HFRF) plasma power, followed by depositing a conformal titanium oxide film or spacer with a high HFRF plasma power."],["1.A method of processing a substrate, the method comprising: depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer, wherein the nanolaminate layer comprises a stack comprising two or more sublayers, and wherein the nanolaminate layer comprises silicon oxide or titanium oxide.","2.The method of claim 1, wherein the core layer is a patterned layer.","3.The method of claim 1, wherein the core layer comprises amorphous carbon or a photoresist.","4.","(canceled) 5.The method of claim 1, wherein each of the more than one layer of the nanolaminate layer is deposited using plasma enhanced atomic layer deposition (PEALD) by: exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.","6.The method of claim 1, wherein the metal nitride or metal oxide layer comprises titanium oxide or silicon oxide.","7.The method of claim 1, wherein the metal nitride or metal oxide layer has etch selectivity to the core layer.","8.A method of processing a substrate, the method comprising: depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer, wherein the metal nitride or metal oxide layer is deposited using a metal-containing precursor by plasma enhance atomic layer deposition (PEALD), wherein the nanolaminate layer comprises a stack comprising two or more sublayers.","9-11.","(canceled) 12.The method of claim 8, wherein the metal-containing precursor is a titanium-containing precursor or a silicon-containing precursor and the PEALD is performed by exposing the substrate to the titanium-containing precursor or the silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.","13.The method of claim 12, wherein the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.14.The method of claim 12, wherein the nanolaminate layer is deposited at a temperature less than about 100° C. 15.A method of patterning a semiconductor substrate, the method comprising: prior to depositing a conformal film on a core layer, depositing a nanolaminate protective layer on a patterned core layer; depositing a conformal film on the nanolaminate protective layer; planarizing the conformal film to expose the patterned core layer; and selectively etching the patterned core layer to form a mask.","16.The method of claim 15, wherein the patterned core layer comprises amorphous carbon.","17.The method of claim 15, wherein the nanolaminate protective layer comprises silicon oxide or titanium oxide.","18.","(canceled) 19.The method of claim 15, wherein the nanolaminate protective layer is deposited using plasma enhanced atomic layer deposition (PEALD) by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a first plasma while the substrate is exposed to the oxidant.","20.The method of claim 19, wherein the nanolaminate protective layer is deposited at a temperature less than about 100° C. 21.The method of claim 19, wherein the nanolaminate protective layer is deposited at a temperature between about 50° C. and about 150° C. and the first plasma is initiated at a HFRF power per square millimeter of substrate area between about 1.768×10-4 per mm2 and about 1.768×10-3 per mm2.22.The method of claim 19, wherein the conformal film is deposited using PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a second plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.23.","(canceled) 24.The method of claim 8, wherein the metal nitride or metal oxide layer deposited using the metal-containing precursor by PEALD is performed by exposing the substrate to the metal-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.25.The method of claim 1, wherein the each of the two or more sublayers of the nanolaminate layer comprises silicon oxide or titanium oxide.","26.The method of claim 8, wherein the two or more sublayers have different compositions."],["<SOH> BACKGROUND <EOH>Fabrication of advanced integrated circuits often involve patterning of 1× nm half-pitch features in high volume manufacturing of semiconductors.","Multiple patterning techniques may enable feature size scaling based on lithographic techniques such as 193 nm immersion lithography.","Self-aligned double patterning is an example of a multiple patterning technique.","Extensions of order multiple patterning techniques to 11 nm half pitch and below present challenges."],["<SOH> SUMMARY <EOH>Provided herein are methods of processing semiconductor substrates to enable deposition of high quality conformal films for use in multiple patterning integration schemes.","One aspect involves a method of processing a semiconductor substrate by depositing a nanolaminate layer on the substrate and depositing a titanium oxide layer on the nanolaminate layer.","The nanolaminate layer may have a thickness between about 15 Å and about 200 Å and may have a density lower than the density of the titanium oxide layer.","In various embodiments, the method also includes depositing an amorphous carbon layer.","In some embodiments, the amorphous carbon layer is patterned.","In various embodiments, the nanolaminate layer includes a stack that includes two or more sublayers.","In some embodiments, the two or more sublayers include silicon oxide, or titanium oxide, or combinations thereof.","In certain embodiments, the stack includes only two sublayers.","In some embodiments, the nanolaminate layer includes a first sublayer of silicon oxide and a second sublayer of titanium oxide.","In various embodiments, the nanolaminate layer is silicon oxide or titanium oxide.","In certain embodiments, the nanolaminate layer is deposited using a plasma-based process such as plasma-enhanced atomic layer deposition (PEALD) by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.","In certain embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with a high frequency radio frequency (HFRF) power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 .","In certain embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. An example of a titanium-containing precursor that may be used with the methods disclosed herein is tetrakis(dimethylamino)titanium (TDMAT).","An example of a silicon-containing precursor is bis(tertiarybutylamino)silane (SiH 2 (NHC(CH 3 ) 3 ) 2 (BTBAS).","In various embodiments, the titanium oxide layer is deposited by PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .","Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or a combination thereof.","The titanium oxide layer may be deposited at a temperature between about 50° C. and about 400° C. in some embodiments.","Another aspect involves a method of processing a semiconductor substrate by depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer.","In some embodiments, the core layer is patterned.","In certain embodiments, the core layer may be amorphous carbon or a photoresist.","In various embodiments, the nanolaminate layer may be silicon oxide or titanium oxide.","In some embodiments, the thickness of the deposited nanolaminate layer is between about 15 Å and about 200 Å.","In certain embodiments, the nanolaminate layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.","In various embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with HFRF power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 .","In some embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. In various embodiments, the metal nitride or metal oxide layer includes titanium oxide or silicon oxide.","The metal nitride or metal oxide layer may have etch selectivity to the core.","In certain embodiments, the metal nitride or metal oxide layer is deposited using PEALD by exposing the substrate to a metal-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .","Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or combinations thereof.","In some embodiments, the metal nitride or metal oxide layer is deposited at a temperature between about 50° C. and about 400° C. Another aspect involves a method of processing a semiconductor substrate by (a) exposing the substrate to a first titanium-containing precursor or a silicon-containing precursor; (b) exposing the substrate to a first oxidant; (c) initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 ; (d) exposing the substrate to a second titanium-containing precursor; (e) exposing the substrate to a second oxidant; and (f) initiating a second plasma while the substrate is exposed to the second oxidant with a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .","In some embodiments, (a) through (c) are processed at temperature between about 50° C. and 150° C. In some embodiments, (d) through (f) are processed at temperature between about 50° C. and 400° C. In some embodiments, (d) through (f) are processed at a higher temperature than (a) through (c) such that transitioning from (c) to (d) includes raising the substrate temperature by at least about 50° C., at least about 100° C., at least about 150° C., or at least about 200° C. The first titanium-containing precursor and the second titanium-containing precursor may be the same precursor, e.g., TDMAT.","In some embodiments, the first oxidant may be the same as the second oxidant (e.g., nitrous oxide, oxygen, carbon dioxide or combinations thereof).","In some embodiments, it may be advantageous to use a different oxidant or mixture.","In some embodiments, the substrate includes amorphous carbon.","In some embodiments, the amorphous carbon is patterned.","In various embodiments, the method also includes after initiating the second plasma, planarizing the substrate to expose the amorphous carbon, and selectively etching the amorphous carbon to form a mask.","Another aspect involves a method of patterning a semiconductor substrate by, prior to depositing a conformal film on a core layer, depositing a nanolaminate protective layer on a patterned core layer; depositing a conformal film on the nanolaminate protective layer; planarizing the conformal film to expose the core; and selectively etching the core to form a mask.","In certain embodiments, the core layer includes amorphous carbon.","In various embodiments, the nanolaminate protective layer includes silicon oxide or titanium oxide.","In certain embodiments, the thickness of the nanolaminate protective layer is between about 15 Å and about 200 Å.","In many embodiments, the nanolaminate protective layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a first plasma while the substrate is exposed to the oxidant.","In some embodiments, the nanolaminate protective layer is deposited at a temperature less than about 100° C. In various embodiments, the nanolaminate protective layer is deposited at a temperature between about 50° C. and about 150° C. and the first plasma is initiated at a HFRF power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 .","In some embodiments, the titanium oxide layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a second plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .","Another aspect involves an apparatus for processing a semiconductor substrate including one or more process chambers; one or more gas inlets into the process chambers and associated flow-control hardware; a HFRF generator; and a controller having at least one processor and a memory, such that the at least one processer and the memory are communicatively connected with one another, the at least one processor is at least operatively connected with the flow-control hardware and HFRF generator, and the memory stores computer-executable instructions for: exposing the substrate to a metal-containing precursor; exposing the substrate to a first oxidant; initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power of between about 12.5 W and 125 W; exposing the substrate to a titanium-containing precursor; exposing the substrate to a second oxidant; and initiating a second plasma while the substrate is exposed to the second oxidant with HFRF power of at least about 125 W. These and other aspects are described further below with reference to the drawings."],["CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of U.S. patent application Ser.","No.","15/177,108, filed on Jun.","8, 2016, and titled “SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING,” which is a division of U.S. patent application Ser.","No.","14/194,324, filed on Feb. 28, 2014, and titled “SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING,” which is a continuation-in-part of U.S. patent application Ser.","No.","14/074,617 (now U.S. Pat.","No.","9,287,113), filed Nov. 7, 2013, issued Mar.","15, 2016, and titled “METHODS FOR DEPOSITING FILMS ON SENSITIVE SUBSTRATES,” which are incorporated by reference herein in their entireties and for all purposes.","BACKGROUND Fabrication of advanced integrated circuits often involve patterning of 1× nm half-pitch features in high volume manufacturing of semiconductors.","Multiple patterning techniques may enable feature size scaling based on lithographic techniques such as 193 nm immersion lithography.","Self-aligned double patterning is an example of a multiple patterning technique.","Extensions of order multiple patterning techniques to 11 nm half pitch and below present challenges.","SUMMARY Provided herein are methods of processing semiconductor substrates to enable deposition of high quality conformal films for use in multiple patterning integration schemes.","One aspect involves a method of processing a semiconductor substrate by depositing a nanolaminate layer on the substrate and depositing a titanium oxide layer on the nanolaminate layer.","The nanolaminate layer may have a thickness between about 15 Å and about 200 Å and may have a density lower than the density of the titanium oxide layer.","In various embodiments, the method also includes depositing an amorphous carbon layer.","In some embodiments, the amorphous carbon layer is patterned.","In various embodiments, the nanolaminate layer includes a stack that includes two or more sublayers.","In some embodiments, the two or more sublayers include silicon oxide, or titanium oxide, or combinations thereof.","In certain embodiments, the stack includes only two sublayers.","In some embodiments, the nanolaminate layer includes a first sublayer of silicon oxide and a second sublayer of titanium oxide.","In various embodiments, the nanolaminate layer is silicon oxide or titanium oxide.","In certain embodiments, the nanolaminate layer is deposited using a plasma-based process such as plasma-enhanced atomic layer deposition (PEALD) by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.","In certain embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with a high frequency radio frequency (HFRF) power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.In certain embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. An example of a titanium-containing precursor that may be used with the methods disclosed herein is tetrakis(dimethylamino)titanium (TDMAT).","An example of a silicon-containing precursor is bis(tertiarybutylamino)silane (SiH2(NHC(CH3)3)2 (BTBAS).","In various embodiments, the titanium oxide layer is deposited by PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or a combination thereof.","The titanium oxide layer may be deposited at a temperature between about 50° C. and about 400° C. in some embodiments.","Another aspect involves a method of processing a semiconductor substrate by depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer.","In some embodiments, the core layer is patterned.","In certain embodiments, the core layer may be amorphous carbon or a photoresist.","In various embodiments, the nanolaminate layer may be silicon oxide or titanium oxide.","In some embodiments, the thickness of the deposited nanolaminate layer is between about 15 Å and about 200 Å.","In certain embodiments, the nanolaminate layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.","In various embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.In some embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. In various embodiments, the metal nitride or metal oxide layer includes titanium oxide or silicon oxide.","The metal nitride or metal oxide layer may have etch selectivity to the core.","In certain embodiments, the metal nitride or metal oxide layer is deposited using PEALD by exposing the substrate to a metal-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or combinations thereof.","In some embodiments, the metal nitride or metal oxide layer is deposited at a temperature between about 50° C. and about 400° C. Another aspect involves a method of processing a semiconductor substrate by (a) exposing the substrate to a first titanium-containing precursor or a silicon-containing precursor; (b) exposing the substrate to a first oxidant; (c) initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2; (d) exposing the substrate to a second titanium-containing precursor; (e) exposing the substrate to a second oxidant; and (f) initiating a second plasma while the substrate is exposed to the second oxidant with a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.In some embodiments, (a) through (c) are processed at temperature between about 50° C. and 150° C. In some embodiments, (d) through (f) are processed at temperature between about 50° C. and 400° C. In some embodiments, (d) through (f) are processed at a higher temperature than (a) through (c) such that transitioning from (c) to (d) includes raising the substrate temperature by at least about 50° C., at least about 100° C., at least about 150° C., or at least about 200° C. The first titanium-containing precursor and the second titanium-containing precursor may be the same precursor, e.g., TDMAT.","In some embodiments, the first oxidant may be the same as the second oxidant (e.g., nitrous oxide, oxygen, carbon dioxide or combinations thereof).","In some embodiments, it may be advantageous to use a different oxidant or mixture.","In some embodiments, the substrate includes amorphous carbon.","In some embodiments, the amorphous carbon is patterned.","In various embodiments, the method also includes after initiating the second plasma, planarizing the substrate to expose the amorphous carbon, and selectively etching the amorphous carbon to form a mask.","Another aspect involves a method of patterning a semiconductor substrate by, prior to depositing a conformal film on a core layer, depositing a nanolaminate protective layer on a patterned core layer; depositing a conformal film on the nanolaminate protective layer; planarizing the conformal film to expose the core; and selectively etching the core to form a mask.","In certain embodiments, the core layer includes amorphous carbon.","In various embodiments, the nanolaminate protective layer includes silicon oxide or titanium oxide.","In certain embodiments, the thickness of the nanolaminate protective layer is between about 15 Å and about 200 Å.","In many embodiments, the nanolaminate protective layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a first plasma while the substrate is exposed to the oxidant.","In some embodiments, the nanolaminate protective layer is deposited at a temperature less than about 100° C. In various embodiments, the nanolaminate protective layer is deposited at a temperature between about 50° C. and about 150° C. and the first plasma is initiated at a HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.In some embodiments, the titanium oxide layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a second plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.Another aspect involves an apparatus for processing a semiconductor substrate including one or more process chambers; one or more gas inlets into the process chambers and associated flow-control hardware; a HFRF generator; and a controller having at least one processor and a memory, such that the at least one processer and the memory are communicatively connected with one another, the at least one processor is at least operatively connected with the flow-control hardware and HFRF generator, and the memory stores computer-executable instructions for: exposing the substrate to a metal-containing precursor; exposing the substrate to a first oxidant; initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power of between about 12.5 W and 125 W; exposing the substrate to a titanium-containing precursor; exposing the substrate to a second oxidant; and initiating a second plasma while the substrate is exposed to the second oxidant with HFRF power of at least about 125 W. These and other aspects are described further below with reference to the drawings.","BRIEF DESCRIPTION OF THE DRAWINGS FIGS.","1-11 are schematic depictions of an integration scheme in accordance with disclosed embodiments.","FIGS.","12-18 are schematic depictions of an integration scheme in accordance with disclosed embodiments.","FIG.","19 is a process flow diagram of a method in accordance with disclosed embodiments.","FIGS.","20A and 20B are process flow diagrams of methods in accordance with disclosed embodiments.","FIG.","21 is an illustration of a reaction chamber for practicing methods in accordance with disclosed embodiments.","FIG.","22 is an illustration of a multi-station apparatus that may be used for performing operations in accordance with disclosed embodiments.","FIGS.","23A-23C are images of deposited films from experiments in performing methods in accordance with disclosed embodiments.","DETAILED DESCRIPTION In the following description, numerous specific details are set forth to provide a thorough understanding of the presented embodiments.","The disclosed embodiments may be practiced without some or all of these specific details.","In other instances, well-known process operations have not been described in detail to not unnecessarily obscure the disclosed embodiments.","While the disclosed embodiments will be described in conjunction with the specific embodiments, it will be understood that it is not intended to limit the disclosed embodiments.","Fabrication of semiconductor devices typically involves depositing one or more thin films in an integrated manufacturing process and may include patterning steps.","Multiple patterning techniques are used to fabricate advanced integrated circuits, such as those with smaller features or higher aspect ratios, or down to 2× or 1× nm nodes.","The term “1×” node means a process node between 10 nm and 19 nm and the term “2×” node means a process node between 20 nm and 29 nm.","An example of multiple patterning is self-aligned double patterning, which produces double the number of features of a pattern formed by conventional lithography.","As the devices become smaller, narrower half-pitch features may be attained using advanced multiple patterning techniques, such as quadruple patterning, or “quad patterning.” An example of a quad patterning scheme is provided in FIGS.","1-11.FIG.","1 provides a schematic illustration of an example of various layers that may be included in a multi-layer stack, such as on a wafer suitable for semiconductor processing.","The multi-layer stack in FIG.","1 includes a first core layer formed into first cores (also referred to as first mandrels) 103, which may be lithographically defined in a previous process, on top of a hardmask 104.Hardmask 104 may be on top of a second core layer 105, which is itself deposited on layer 107.Layer 107 may include a hardmask layer 107a, a cap layer 107b, and a mask layer 107c, which may be used as a mask to pattern a subsequent target layer 150.Barrier layers, cap layers, or etch stop layers may be between the mask layer 107c and target layer 150.One of ordinary skill in the art will appreciate that there may be one or more layers deposited between any of the above described layers, and the target layer 150 may include one or more additional layers.","The first core layer (and thus first cores 103) may be highly etch selective to other materials in the stack, such as silicon and/or silicon-based oxides or nitrides, for example, and may be transparent.","The first core layer may be a photoresist or may be made of amorphous carbon material or amorphous silicon material.","In some embodiments, the first core layer may be deposited on top of hardmask 104 by a deposition technique, such as plasma-enhanced chemical vapor deposition (PECVD), and the deposition technique may involve generating a plasma in the deposition chamber from deposition gases including a hydrocarbon precursor.","The hydrocarbon precursor may be defined by the formula CxHy, where x is an integer between 2 and 10, and y is an integer between 2 and 24.Examples include methane (CH4), acetylene (C2H2), ethylene (C2H4), propylene (C3H6), butane (C4H10), cyclohexane (C6H12), benzene (C6H6), and toluene (C7H8).","A dual radio frequency (RF) plasma source including a high frequency (HF) power and a low frequency (LF) power may be used.","Alternatively a single RF plasma source may be used.","Typically such a source will be a HFRF source.","Under the first core layer formed into first cores 103 is a second core layer 105.Between the first core layer and the second core layer 105 may be a hardmask 104.The hardmask 104 may have high etch selectivity relative to first core layer and second core layer 105 so as not to etch second core layer 105 while first core layer is patterned.","The second core layer 105 may be made of amorphous carbon material or amorphous silicon material.","Methods of deposition and deposition precursors may be any of those described above with respect to first core layer.","Once patterned, the second core layer 105 is formed into second cores (also referred to as second mandrels) 105′ (shown in FIG.","5) and may be used to etch a mask in a subsequent layer, such as mask layer 107c, which may then be used to pattern the target layer 150.In certain embodiments, the mask layer 107c may be made of amorphous carbon material or amorphous silicon material.","In quadruple patterning schemes, such as that depicted in FIGS.","1-11, the mask layer 107c may be the quadruple pattern of a photoresist pattern such that one feature in a photoresist is patterned and transferred to form four features in the target layer 150.Between the second core layer 105 and target layer 150 may be other layers, such as a hardmask layer 107a, or cap layer 107b, or a mask layer 107c to be used to pattern the target layer 150.The target layer 150 may be the layer ultimately to be patterned.","The target layer 150 may be a semiconductor, dielectric or other layer and may be made of silicon (Si), silicon oxide (SiO2), silicon nitride (SiN), or titanium nitride (TiN), for example.","The target layer 150 may be deposited by atomic layer deposition (ALD), plasma-enhanced ALD (PEALD), chemical vapor deposition (CVD), or other suitable deposition techniques.","In one example, the compositions and thicknesses of a quad patterning stack such as the one shown in FIG.","1 may be the following: 400 Å amorphous carbon first cores 103, 150 Å tetraethylorthosilicate (TEOS) hardmask layer 104, 350 Å amorphous carbon second core layer 105, 150 Å TEOS hardmask layer 107a, 100 Å amorphous silicon cap layer 107b, 300 Å amorphous carbon mask layer 107c, 200 Å titanium nitride barrier layer (not shown), and 300 Å TEOS hardmask layer (not shown), all on a silicon target layer or substrate 150.In one example, the following may be deposited on top of the 400 Å amorphous carbon first core layer in order prior to lithographic patterning to define the first core layer as depicted in the example of FIG.","1: 100 Å-150 Å SiON etch stop layer, 300 Å bottom anti-reflective coating (BARC) layer, and 1000 Å photoresist first core layer.","In FIG.","2, a conformal film 109 is deposited over the first cores 103.The conformal film 109 may also be referred to as a “spacer” and may be deposited to conform to the shape of the pattern on the multi-layer stack to make an evenly distributed layer over the pattern.","As described further below, the conformal film 109 may be formed into multiple individual spacers, each of which abuts a sidewall of the first cores 103.The conformal film 109 has a high etch selectivity to the core.","For example, the conformal film 109 may have an etch selectivity greater than 3:1 relative to an amorphous carbon layer.","In some embodiments, conformal film 109 has an etch selectivity greater than 15:1 relative to poly-silicon in halide etch chemistry.","The conformal film 109 may be made of dielectric material, such as SiO2.The conformal film 109 may also be an oxide, such as titanium oxide (TiO2), or may be silicon nitride (SiN).","In some embodiments, the conformal film 109 is made of denser material to withstand more “passes” of patterning and may be deposited by ALD, PEALD, or conformal film deposition (CFD) methods as described briefly below.","ALD processes use surface-mediated deposition reactions to deposit films on a layer-by-layer basis.","In one example ALD process, a substrate surface, including a population of surface active sites, is exposed to a gas phase distribution of a first film precursor (P1).","Some molecules of P1 may form a condensed phase atop the substrate surface, including chemisorbed species and physisorbed molecules of P1.The reactor is then evacuated to remove gas phase and physisorbed P1 so that only chemisorbed species remain.","A second film precursor (P2) is then introduced to the reactor so that some molecules of P2 adsorb to the substrate surface.","The reactor may again be evacuated, this time to remove unbound P2.Subsequently, thermal energy provided to the substrate activates surface reactions between adsorbed molecules of P1 and P2, forming a film layer.","Finally, the reactor is evacuated to remove reaction by-products and possibly unreacted P1 and P2, ending the ALD cycle.","Additional ALD cycles may be included to build film thickness.","In an example of a PEALD process, a plasma is initiated while the second film precursor P2 is introduced to the reactor to activate the reaction between P1 and P2.CFD may be used to deposit the conformal film 109.Generally, CFD does not rely on complete purges of one or more reactants prior to reaction to form the film.","For example, there may be one or more reactants present in the vapor phase when a plasma (or other activation energy) is struck.","Accordingly, one or more of the process steps described in an ALD process may be shortened or eliminated in an example CFD process.","Further, in some embodiments, plasma activation of deposition reactions may result in lower deposition temperatures than thermally-activated reactions, potentially reducing the thermal budget of an integrated process.","For context, a short description of CFD is provided.","The concept of a CFD cycle is relevant to the discussion of various embodiments herein.","As with ALD processes, generally a cycle is the minimum set of operations required to perform a surface deposition reaction one time.","The result of one cycle is production of at least a partial film layer on a substrate surface.","Typically, a CFD cycle will include only those steps necessary to deliver and adsorb each reactant to the substrate surface, and then react those adsorbed reactants to form the partial layer of film.","The cycle may include certain ancillary steps such as sweeping one or more of the reactants or byproducts and/or treating the partial film as deposited.","Generally, a cycle contains only one instance of a unique sequence of operations.","As an example, a cycle may include the following operations: (i) delivery/adsorption of reactant A, (ii) delivery/adsorption of reactant B, (iii) sweep B out of the reaction chamber, and (iv) apply plasma to drive a surface reaction of A and B to form the partial film layer on the surface.","As used herein, the term PEALD includes CFD processes.","The following conditions are examples of conditions suitable depositing a silicon oxide conformal film 109 by a CFD process.","Deposition may occur at a temperature between about 50° C. and about 400° C., at a pressure between about 0.5 Torr and about 10 Torr, and an RF power for four stations between about 100 W and 10 kW.","RF activation frequency can vary from about 13.56 MHz to 40 MHz for various embodiments.","For a silicon oxide conformal film 109, process gases that may be used include, as a silicon source, a silicon amide (e.g., BTBAS, BDEAS (bis-di-ethyl aminosilane) or DIPAS (di-isopropyl aminosilane), and, as an oxygen source, oxygen or nitrous oxide or carbon dioxide, separately or together, diluted with an inert carrier gas, for example argon or nitrogen.","Process gas flow rates may be as follows: for (liquid) silicon precursor (e.g., BTBAS, BDEAS, and DIPAS), between about 1 sccm and 3 sccm, for example BTBAS at about 2.5 sccm; for oxygen precursor (O2, N2O), between about 5000 sccm and 10,000 sccm, for example N2O at 5000 sccm; and for the carrier gas (Ar or N2), between about 0 sccm and 10,000 sccm, for example about 5000 sccm Ar.","In FIG.","3, the conformal film 109 is etched back or planarized to expose the first cores 103.In various embodiments, the conformal film 109 may be planarized through a multi-step process.","In one example, the conformal film 109 may be etched back by first flowing about 10 sccm to about 100 sccm of chlorine (Cl2), then about 10 sccm to about 100 sccm of methane (CH4), then about 10 sccm to about 100 sccm of nitrogen (N2) for about 30 seconds.","In some embodiments, the conformal film 109 may be etched at a temperature between about 10° C. and about 20° C. and at a pressure between about 2 mTorr and about 20 mTorr for a time of about 30 seconds.","In some embodiments, the substrate may be etched at a temperature between about 40° C. and about 60° C. and at a pressure between about 5 mTorr and about 100 mTorr.","In many embodiments, an anisotropic plasma etch is performed to expose the core and define the structure of the spacers 109′ from the conformal film 109.In FIG.","4, the first cores 103 are stripped or etched, leaving free-standing spacers 109′ on the substrate.","If the first core layer is a photoresist, the first cores 103 may be etched by flowing oxygen (O2) at a flow rate between about 100 sccm and about 200 sccm at a temperature between about 40° C. and about 60° C. in a pressure between about 5 mTorr and about 20 mTorr.","If the first core layer is made of amorphous carbon material, the first cores 103 may be stripped or etched using an ashing method.","An ashing method may be dependent on chemical reactions for material removal, rather than directional movement of energetic ions.","For example, any surface that is exposed to the process gas used in an ashing operation may experience material removal due to the exposure, so the amorphous carbon material used in the first cores 103 may have high etch selectivity to the spacers 109′ such that the spacers 109′ are not etched while the first cores 103 are ashed.","Additionally, in contrast to some chemical etching processes, ashing operations may produce a reaction product that is completely in the gas phase.","Ashing operations for carbon films may, for example, utilize dissociated hydrogen (H2) or oxygen (O2) as a process gas, which may react with carbon films to form such gas-phase reaction byproducts.","In some embodiments, the remaining spacers 109′ may be shaped for subsequent processing using various etch conditions.","In FIG.","5, the second core layer 105 is etched down using the spacers 109′ as a mask, thereby transferring the pattern to form second cores 105′.","The second core layer 105 may be etched at a temperature between about 50° C. and about 70° C. in a pressure between about 5 mTorr and about 100 mTorr using chemistry suitable for etching the second core layer 105 but not the spacers 109′.","The second core layer 105 is thus highly etch selective to the spacers 109′.","The second core layer 105 may be an amorphous carbon layer, or amorphous silicon layer.","Above the second core layer 105 may be a cap layer 104, which may be a silicon anti-reflective coating, or PECVD dielectric layer, or spin-on glass.","In FIG.","6, the spacers 109′ and the cap layer 104 are etched or otherwise removed, leaving the patterned second cores 105′.","In some embodiments, the spacers 109′ may be removed at a temperature between about 10° C. and about 20° C. and at a pressure between about 2 mTorr and about 20 mTorr for a time of about 30 seconds.","In some embodiments, the substrate may be etched at a temperature between about 40° C. and about 60° C. and at a pressure between about 5 mTorr and about 100 mTorr.","In many embodiments, an anisotropic plasma etch is performed.","In one example, the spacers 109′ are etched by first flowing about 10 sccm to about 100 sccm of chlorine (Cl2), then about 10 sccm to about 100 sccm of methane (CH4), then about 10 sccm to about 100 sccm of nitrogen (N2) for about 30 seconds.","In FIG.","7, a second conformal film 119 is deposited over the patterned second cores 105′.","In many embodiments, the second conformal film 119 may be a layer of titanium oxide, which may be deposited by PEALD methods.","In FIG.","8, the second conformal film 119 is etched or planarized to expose the second cores 105′.","Conditions and methods may be any of those discussed above with respect to FIG.","3.In FIG.","9, the second cores 105′ is etched or removed, leaving free-standing second spacers 119′.","Conditions and methods may be any of those discussed above with respect to FIG.","4.In FIG.","10, the mask layer 107c is etched down using the second spacers 119′ as a mask, thereby transferring the pattern from the second spacers 119′ to form a patterned mask 107c′.","Mask layer 107c may be highly etch selective to the second conformal film 119, and may be etched by any method discussed above with respect to FIG.","5, depending on the chemistry of the mask layer 107c.","In FIG.","11, the second spacers 119′ are removed, along with etch stop layer 107a and cap layer 107b, leaving the patterned mask 107c′.","Conditions and methods for removing the second spacers 119′ may be any of those discussed above with respect to FIG.","6.The mask 107c′ may then be used to pattern subsequent layers, such as target layer 150.The result of process steps depicted in FIGS.","1 through 11 is a quad-patterning scheme such that a single lithographically defined feature (such as a first core 103 in FIG.","1) results in four smaller features on the substrate.","Quad patterning schemes may be used to form features with a half-pitch as small as 10 nm, or between 10 nm and 20 nm half-pitch, which cannot be achieved by current double patterning schemes.","Due to the nature of forming the smaller features, the material used for the second conformal film 119 may be of higher quality relative to conformal films used in spacers of wider cores so as to maintain robustness and prevent buckling when it is exposed to harsh conditions in subsequent patterning steps.","Higher quality conformal film material may have near-ideal stoichiometry, such as if the conformal film is titanium oxide, the higher quality titanium oxide conformal film may have near ideal Ti:O stoichiometry, for example 1:2, and low carbon content.","Higher quality conformal films may be deposited by ALD, which may perform a complete conversion from the oxidation half-reaction, thereby forming near ideal stoichiometry.","Thus, higher quality conformal film material may then have a low etch rate and high etch selectivity, and also being infinitely selective against oxides and nitrides.","These films may also have higher modulus, such as greater than about 150 MPa, which contributes to improved mechanical stability of the conformal film as a spacer, thereby improving critical dimension uniformity (CDU).","The higher quality conformal film material disclosed herein may also be dense to withstand subsequent integration steps.","Provided herein are methods of depositing thin, conformal nanolaminate protective layers.","Also provided are methods of forming high quality films that may be used as spacers, with the methods including deposition of a nanolaminate layer.","The nanolaminate layers can improve spacer robustness while protecting the underlying core layer from degradation during deposition of the conformal film.","Deposition of high quality films, such as high quality titanium oxide, directly on a core layer may result in degradation or consumption of the core due to harsh conditions during deposition of the spacer, thereby harming the underlying patterned core.","For example, during deposition of the high quality conformal film, a patterned core layer may be exposed to oxygen radicals, such as those produced from a N2O/O2 sequential plasma with a high HFRF power of at least about 1000 W. Due to the higher power, more oxygen radicals are formed, which increases radical bombardment on the core layer and subsequent degradation the pattern of the core.","Nitrides may be able to withstand such bombardment if used as a cap over the core layer, but since nitrides are not selective to certain core materials, nitrides are not suitable.","After a conformal film is deposited, the substrate may then be planarized to expose the core and remove the core, but since the core has been consumed or degraded, the resulting width between spacers may be diminished, which results in an irregular pattern in the semiconductor substrate.","Rather than using lower quality conformal films to prevent degradation of the core, the methods disclosed herein enable high quality spacer materials.","Nanolaminate protective layers may be less dense than conformal film due to the lower HFRF power used during deposition.","As such nanolaminate protective layers may be deposited at a minimum thickness that adequately protects the core.","Minimizing the nanolaminate protective layer may facilitate subsequent integration.","Nanolaminate protective layers may protect an underlying layer to the extent that a higher quality conformal film may be deposited over it.","Core consumption and degradation thereby decreases and the core can withstand harsher conditions during deposition of the high quality conformal film.","In subsequent patterning steps, the high quality conformal film can withstand other harsh conditions and still maintain its strong robustness as a free-standing structure.","The nanolaminate protective layers may also prevent spacer leaning and enable critical dimension variability, by maintaining the integrity of the core geometry and providing mechanical support to the free-standing spacer structures, thereby enhancing the ability to form finer features at lower half-pitch in semiconductor processing.","An example of a method of using a nanolaminate protective layer may begin by providing a multi-stack semiconductor substrate with a lithographically defined or patterned first core layer, such as the one discussed above with respect to FIG.","1.In some embodiments, a nanolaminate protective layer may be deposited on the first cores 103 prior to depositing a conformal film 109 as described in embodiments below with respect to FIG.","13.In various embodiments, a conformal film 109 may be deposited over the first cores 103, such as in FIG.","2.After the conformal film 109 is planarized, such as shown in FIG.","3, the first cores 103 may be etched or removed to reveal the remaining spacers 109′, such as shown in FIG.","4.A second core layer 105 may be etched down using the spacers 109′ as a mask to thereby transfer the pattern to form the second cores 105′ such as shown in FIG.","5.The spacers 109′ may be removed to reveal patterned second cores 105′ such as shown in FIG.","12.The second core layer 105 may be an amorphous carbon layer, or an amorphous silicon layer.","In FIG.","13, a nanolaminate protective layer 111 may be deposited conformally over the second cores 105′.","Examples of thicknesses of the nanolaminate layer 111 are between about 15 Å and about 200 Å thick, between about 15 Å and about 100 Å thick, or between about 15 Å and about 50 Å thick.","Note that the thickness depicted in FIG.","13 is exaggerated for the purposes of the illustration and as an example only.","In some embodiments, the nanolaminate layer 111 may include a stack, which may have two or more sublayers (not shown).","For example, the stack may be a bilayer.","In some embodiments the sublayers have the same composition, and in some embodiments, the sublayers have different compositions.","In some embodiments, the nanolaminate layer 111 is one layer.","In one example, the nanolaminate layer 111 is one layer of silicon oxide.","In another example, the nanolaminate layer 111 is one layer of titanium oxide.","In one example of a bilayer nanolaminate layer 111, the upper layer is silicon oxide, and the lower layer is titanium oxide.","In another example of a bilayer nanolaminate layer 111, the upper layer is titanium oxide and the lower layer is silicon oxide.","The nanolaminate layer 111 may also be less dense than the material deposited in a conformal film due to the lower HFRF power which may be used to deposit the nanolaminate layer 111.In some embodiments, the nanolaminate layer 111 may be an ALD oxide, such as silicon oxide (SiO2) or titanium oxide (TiO2) and referred to as “soft” ALD oxide.","The thickness of the nanolaminate layer 111 may be taken into account when configuring processing conditions for the patterning scheme and deciding the pattern to be etched.","In various embodiments, the nanolaminate layer 111 is deposited by conformal film deposition (CFD) or PEALD.","In FIG.","14, the second conformal film 129 is deposited over the nanolaminate layer 111.In certain embodiments, the second conformal film 129 is a high quality titanium oxide film, such as a titanium oxide layer with a low wet etch rate and high dry etch selectivity with infinite selectivity against oxides such as silicon oxide (SiO2) and nitrides such as silicon nitride (SiN).","For example, the second conformal film 129 may have an etch selectivity greater than 3:1 relative to an amorphous carbon layer.","In some embodiments, second conformal film 129 has an etch selectivity greater than 15:1 relative to a poly silicon layer in halide etch chemistry.","In one example, a nanolaminate layer 111 deposited to a thickness of about 15 Å may be sufficient to protect second cores 105′ from deposition of about 110 Å of the second conformal film 129.In various embodiments, the second conformal film 129 is deposited by CFD or PEALD.","In some embodiments the second conformal film 129 is denser than the nanolaminate layer 111.In FIG.","15, the substrate is planarized to expose the second cores 105′ with nanolaminate layer 111 sidewalls and yield sidewall second spacers 129′.","The conditions for the planarization may be any of those described above with respect to FIG.","3.In FIG.","16, the second cores 105′ are etched and removed.","Conditions and methods may be any of those discussed above with respect to FIG.","9.In some embodiments, a small portion of the nanolaminate layer 111 may be etched due to the nature of the etching step.","In some embodiments, the nanolaminate layer 111 is sufficiently etch selective and is not etched while the second cores 105′ are removed.","Note the second spacers 129′ are sitting on a thin layer of nanolaminate layer 111 with a thin nanolaminate layer 111 on its sidewall, which may thereby reinforce its stability and prevent leaning.","Still further, in some embodiments, the nanolaminate material may be completely removed with the second cores 105′.","As noted above, in some embodiments, the thickness of the nanolaminate layer 111 and how much of it will be removed may be taken into account when planning the patterning scheme to arrive at the desired dimension.","However, in some embodiments, the thickness of the nanolaminate layer 111 may be within the tolerance of the patterned dimensions, and may not need to be accounted for.","In FIG.","17, the mask layer 107c is etched down using the second spacers 129′ as a mask.","Due to the increased stability and robustness of the higher quality second spacers 129′, this operation may be more easily and more efficiently completed to form fine, stable features with high aspect ratios.","In FIG.","18, the nanolaminate layer 111 and second spacers 129′ are etched or removed to reveal the resulting patterned mask 107c′.","Conditions and methods may be any of those described above with respect to FIG.","5.The patterned mask 107c′ may then be used to pattern a subsequent layer, which can be used to pattern the target layer 150.In some embodiments, the patterned mask 107c′ may be used to pattern the target layer 150.FIG.","19 is a process flow diagram of steps of a method in accordance with various embodiments.","Cycle and exposure times described herein may depend on the apparatus and platform used and one of ordinary skill in the art may adjust cycle and exposure times accordingly.","In operation 1901, a substrate may be exposed to a first precursor, such as a titanium-containing precursor or silicon-containing precursor.","In some embodiments, the substrate includes a core layer.","In various embodiments, the core layer is amorphous carbon, amorphous silicon, or a photoresist.","In some embodiments, the core layer is lithographically defined or patterned.","In a certain embodiment, the substrate includes a patterned amorphous carbon layer.","Examples of a titanium-containing precursor include tetrakis(dimethylamino)titanium (TDMAT), tetraethoxytitanium, tetrakis-dimethyl-amido titanium, titanium isopropoxide, titanium tetraisopropoxide, and titanium tetrachloride.","A silicon-containing precursor may be, for example, a silane, a halosilane or an aminosilane.","A silane contains hydrogen and/or carbon groups, but does not contain a halogen.","Examples of silanes are silane (SiH4), disilane (Si2H6), and organo silanes such as methylsilane, ethylsilane, isopropylsilane, t-butylsilane, dimethylsilane, diethylsilane, di-t-butylsilane, allylsilane, sec-butylsilane, thexylsilane, isoamylsilane, t-butyldisilane, di-t-butyldisilane, tetra-ethyl-ortho-silicate (also known as tetra-ethoxy-silane or TEOS) and the like.","A halosilane contains at least one halogen group and may or may not contain hydrogens and/or carbon groups.","Examples of halosilanes are iodosilanes, bromosilanes, chlorosilanes and fluorosilanes.","Although halosilanes, particularly fluorosilanes, may form reactive halide species that can etch silicon materials, in certain embodiments described herein, the silicon-containing reactant is not present when a plasma is struck.","Specific chlorosilanes are tetrachlorosilane (SiCl4), trichlorosilane (HSiCl3), dichlorosilane (H2SiCl2), monochlorosilane (ClSiH3), chloroallylsilane, chloromethylsilane, dichloromethylsilane, chlorodimethylsilane, chloroethylsilane, t-butylchlorosilane, di-t-butylchlorosilane, chloroisopropylsilane, chloro-sec-butylsilane, t-butyldimethylchlorosilane, thexyldimethylchlorosilane, and the like.","An aminosilane includes at least one nitrogen atom bonded to a silicon atom, but may also contain hydrogens, oxygens, halogens and carbons.","Examples of aminosilanes are mono-, di-, tri- and tetra-aminosilane (H3Si(NH2)4, H2Si(NH2)2, HSi(NH2)3 and Si(NH2)4, respectively), as well as substituted mono-, di-, tri- and tetra-aminosilanes, for example, t-butylaminosilane, methylaminosilane, tert-butylsilanamine, bis(tertiarybutylamino)silane (SiH2(NHC(CH3)3)2 (BTBAS), tert-butyl silylcarbamate, SiH(CH3)—(N(CH3)2)2, SiHCl—(N(CH3)2)2, (Si(CH3)2NH)3 and the like.","A further example of an aminosilane is trisilylamine (N(SiH3)3).","After operation 1901, the deposition chamber may be purged in a sweep phase with an injector purge or a pump away step.","Generally, a sweep phase removes or purges one of the vapor phase reactant from a reaction chamber and typically occurs only after delivery of such reactant is completed.","In other words, that reactant is no longer delivered to the reaction chamber during the sweep phase.","However, the reactant remains adsorbed on the substrate surface during the sweep phase.","Typically, the sweep serves to remove any residual vapor phase reactant in the chamber after the reactant is adsorbed on the substrate surface to the desired level.","A sweep phase may also remove weakly adsorbed species (e.g., certain precursor ligands or reaction by-products) from the substrate surface.","In ALD, the sweep phase has been viewed as necessary to prevent gas phase interaction of two reactants or interaction of one reactant with a thermal, plasma or other driving force for the surface reaction.","In general, and unless otherwise specified herein, a sweep/purge phase may be accomplished by (i) evacuating a reaction chamber, and/or (ii) flowing gas not containing the species to be swept out through the reaction chamber.","In the case of (ii), such gas may be, for example, an inert gas.","In operation 1903, the substrate may be exposed to a second precursor or an oxidant.","In some embodiments, the oxidant is nitrous oxide (N2O) or oxygen (O2) or carbon dioxide (CO2) or a mixture or combinations thereof.","In some embodiments, the oxidizer may be a mixture of oxygen (O2) and a weak oxidizer such as N2O, CO, CO2, NO, NO2, SO, SO2, CxHyOz and/or H2O.","In other implementations, the oxidation reactant may be entirely a weak oxidizer.","Alternatively, the oxidation reactant may include O3.In some embodiments, the oxidation reactant is about 0-50% O2 and about 50-100% weak oxidizer.","In some cases, one of the reactants may be delivered continuously (e.g., even during delivery of other reactants and/or during plasma exposure).","For example, an oxidizing reactant may be delivered continuously.","The continuously flowing reactant may be delivered to the reaction chamber in conjunction with a carrier gas such as argon.","In some cases, the delivery of the continuously flowing reactants to reaction chamber is controlled by using divert valve/inlet valve toggling.","Gas flow changes may be diverted or co-flowed.","In one example, a continuously flowing reactant is periodically diverted from the reaction chamber such that it is only delivered to the reaction chamber at certain periods.","The continuously flowing gas may be diverted to an outlet/dump using appropriate valves.","For instance, an oxidizing reactant may flow continuously, but only be delivered to the reaction chamber periodically.","When the oxidizing reactant is not being delivered to the reaction chamber, it may be diverted to an outlet, recycle system, etc.","In operation 1905, a plasma may be initiated with a low HFRF power while the substrate is exposed to the oxidant.","In some embodiments, the low HFRF power per area of the wafer may be between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2 where mm2 represents the unit for surface area of the wafer.","Plasma power may be scaled linearly with wafer surface area.","For example, a low HFRF power may be between about 12.5 W to about 125 W per station for a 300 mm wafer, or between about 28 W and about 280 W for a 450 mm wafer.","The deposition temperature may be between about 50° C. and about 150° C. After operation 1905, the deposition chamber may be purged again.","These steps may be repeated until the desired thickness of the film is deposited.","In some embodiments, operation 1905 may occur at a low temperature, such as a temperature less than about 100° C. with an HFRF power while exposing a 300 mm substrate to the oxidant between about 50 W and about 500 W in a four-station tool, the power being the total power applied to the four-station tool.","In operation 1907, the substrate may be exposed to a titanium-containing precursor.","Examples of titanium-containing precursors may be any of those described with respect to operation 1901.As an example, the substrate may be exposed to TDMAT for about 2 seconds, which may be described as a “dose.” After operation 1907, the deposition chamber may be purged with an injector purge or pump away step.","As an example, the purge may last about 10 seconds.","In operation 1909, the substrate may be exposed to another precursor or an oxidant.","In many embodiments, the oxidant is nitrous oxide (N2O) or oxygen (O2) or carbon dioxide (CO2) or a mixture thereof.","As an example, operation 1909 may be about 30 seconds, such that for the first 25 seconds, no oxidant is flowed and only a carrier gas or inert gas is flowed, and an oxidant is flowed starting after the 25 seconds and is kept on through the next operation.","Examples of carrier gases include argon (Ar) and nitrogen (N2).","The flow rate of these carrier gases may be between about 0 sccm and about 10,000 sccm.","In operation 1911, a plasma may be initiated with high HFRF power while the substrate is exposed to the oxidant.","In many embodiments, the HFRF power may be between about 125 W and about 1500 W per station for 300 mm wafers.","As an example, HFRF power may be about 625 W per station.","The plasma may be initiated for a time between about 0.25 seconds and about 3 seconds, or about 0.5 seconds.","Operations 1907 through 1911 may occur at a temperature between about 50° C. and about 400° C., or between about 50° C. and 200° C., or about 150° C. and at a pressure between about 3 Torr and about 3.5 Torr.","After operation 1911, the plasma may be turned off and the chamber may be purged or pumped to base.","Example purge gases for use after operations 1901, 1903, 1905, 1907, 1909, and 1911 may be argon (Ar) or nitrogen (N2) or any other suitable purge gas.","In some embodiments, the density of the film deposited in operations 1901 through 1905 may be less dense than the film deposited in operations 1907 through 1911.According to various embodiments, operations 1901 through 1905 may be performed at a lower temperature, and/or lower RF power, and/or shorter RF time, and/or lower pressure, and/or with a weaker oxidant than operations 1907 through 1911.These deposition conditions may help prevent damage to the underlying substrate while producing an operable device.","FIG.","20A provides a process flow diagram of a method of using nanolaminate layers in accordance with various embodiments.","In operation 2001, a core layer may be deposited, such as those described with respect to FIG.","1.The core layer may be an amorphous carbon layer, or amorphous silicon layer, or may be a photoresist.","In some embodiments, the core layer is patterned.","In operation 2003, a nanolaminate layer is deposited on the core layer.","The nanolaminate layer may be deposited by CFD or PEALD methods.","The nanolaminate layer may be deposited using operations 1901-1905 with respect to FIG.","19 above.","In some embodiments the nanolaminate layer may be silicon oxide (SiO2) or titanium oxide (TiO2).","The thickness of the deposited nanolaminate layer may be between about 15 Å and about 200 Å, or between about 15 Å and about 100 Å.","In operation 2005, a metal nitride or metal oxide layer may be deposited on the nanolaminate layer.","The metal nitride or metal oxide layer may be deposited using operations 1907 through operation 1911 with respect to FIG.","19 above.","In some embodiments, the metal nitride or metal oxide layer is a silicon oxide or titanium oxide layer.","In some embodiments, the metal nitride or metal oxide layer is a high quality titanium oxide layer.","In various embodiments, the metal nitride or metal oxide layer has a high etch selectivity to the core.","In many embodiments, the metal nitride or metal oxide layer is denser than the nanolaminate layer.","FIG.","20B is a process flow diagram of an example of a method of using a nanolaminate layer in accordance with various embodiments.","In operation 2011, a thin nanolaminate layer is deposited on a substrate.","A nanolaminate layer may be any of those discussed above with respect to FIGS.","13 and 20A.","The nanolaminate layer may be deposited using operations 1901-1905 with respect to FIG.","19 above.","In operation 2013, a titanium oxide layer may be deposited on the nanolaminate layer.","An example of a titanium oxide layer deposited on a nanolaminate layer is described above with respect to FIG.","14.The titanium oxide layer may be deposited using operations 1907 through operation 1911 with respect to FIG.","19 above.","Apparatus Deposition techniques provided herein may be implemented in a plasma enhanced chemical vapor deposition (PECVD) reactor or a conformal film deposition (CFD) reactor.","Such a reactor may take many forms, and may be part of an apparatus that includes one or more chambers or “reactors” (sometimes including multiple stations) that may each house one or more wafers and may be configured to perform various wafer processing operations.","The one or more chambers may maintain the wafer in a defined position or positions (with or without motion within that position, e.g., rotation, vibration, or other agitation).","In one implementation, a wafer undergoing film deposition may be transferred from one station to another within a reactor chamber during the process.","In other implementations, the wafer may be transferred from chamber to chamber within the apparatus to perform different operations, such as etching operations or lithography operations.","The full film deposition may occur entirely at a single station or any fraction of the total film thickness for any deposition step.","While in process, each wafer may be held in place by a pedestal, wafer chuck, and/or other wafer-holding apparatus.","For certain operations in which the wafer is to be heated, the apparatus may include a heater, such as a heating plate.","A Vector™ (e.g., C3 Vector) or Sequel™ (e.g., C2 Sequel) reactor, produced by Lam Research Corp. of Fremont, Calif., are both examples of suitable reactors that may be used to implement the techniques described herein.","FIG.","21 provides a simple block diagram depicting various reactor components arranged for implementing methods described herein.","As shown, a reactor 2100 includes a process chamber 2124 that encloses other components of the reactor and serves to contain a plasma generated by a capacitive-discharge type system including a showerhead 2114 working in conjunction with a grounded heater block 2120.A high frequency (HF) radio frequency (RF) generator 2104 and a low frequency (LF) RF generator 2102 may be connected to a matching network 2106 and to the showerhead 2114.The power and frequency supplied by matching network 2106 may be sufficient to generate a plasma from process gases supplied to the process chamber 2124.For example, the matching network 2106 may provide 50 W to 500 W of HFRF power.","In some examples, the matching network 2106 may provide 100 W to 5000 W of HFRF power and 100 W to 5000 W of LFRF power total energy.","In a typical process, the HFRF component may generally be between 5 MHz to 60 MHz, e.g., 13.56 MHz.","In operations where there is an LF component, the LF component may be from about 100 kHz to 2 MHz, e.g., 430 kHz.","Within the reactor, a wafer pedestal 2118 may support a substrate 2116.The wafer pedestal 2118 may include a chuck, a fork, or lift pins (not shown) to hold and transfer the substrate during and between the deposition and/or plasma treatment reactions.","The chuck may be an electrostatic chuck, a mechanical chuck, or various other types of chuck as are available for use in the industry and/or for research.","Various process gases may be introduced via inlet 2112.Multiple source gas lines 2110 are connected to manifold 2108.The gases may be premixed or not.","Appropriate valving and mass flow control mechanisms may be employed to ensure that the correct process gases are delivered during the deposition and plasma treatment phases of the process.","In the case where a chemical precursor(s) is delivered in liquid form, liquid flow control mechanisms may be employed.","Such liquids may then be vaporized and mixed with process gases during transportation in a manifold heated above the vaporization point of the chemical precursor supplied in liquid form before reaching the deposition chamber.","Process gases may exit chamber 2124 via an outlet 2122.A vacuum pump, e.g., a one or two stage mechanical dry pump and/or turbomolecular pump 2140, may be used to draw process gases out of the process chamber 2124 and to maintain a suitably low pressure within the process chamber 2124 by using a closed-loop-controlled flow restriction device, such as a throttle valve or a pendulum valve.","As discussed above, the techniques for deposition discussed herein may be implemented on a multi-station or single station tool.","In specific implementations, a 300 mm Lam Vector™ tool having a 4-station deposition scheme or a 200 mm Sequel™ tool having a 6-station deposition scheme may be used.","In some implementations, tools for processing 450 mm wafers may be used.","In various implementations, the wafers may be indexed after every deposition and/or post-deposition plasma treatment, or may be indexed after etching steps if the etching chambers or stations are also part of the same tool, or multiple depositions and treatments may be conducted at a single station before indexing the wafer.","In some embodiments, an apparatus may be provided that is configured to perform the techniques described herein.","A suitable apparatus may include hardware for performing various process operations as well as a system controller 2130 having instructions for controlling process operations in accordance with the disclosed embodiments.","The system controller 2130 will typically include one or more memory devices and one or more processors communicatively connected with various process control equipment, e.g., valves, RF generators, wafer handling systems, etc., and configured to execute the instructions so that the apparatus will perform a technique in accordance with the disclosed embodiments, e.g., a technique such as that provided in the deposition steps of FIG.","19.Machine-readable media containing instructions for controlling process operations in accordance with the present disclosure may be coupled to the system controller 2130.The controller 2130 may be communicatively connected with various hardware devices, e.g., mass flow controllers, valves, RF generators, vacuum pumps, etc.","to facilitate control of the various process parameters that are associated with the deposition operations as described herein.","In some embodiments, a system controller 2130 may control all of the activities of the reactor 2100.The system controller 2130 may execute system control software stored in a mass storage device, loaded into a memory device, and executed on a processor.","The system control software may include instructions for controlling the timing of gas flows, wafer movement, RF generator activation, etc., as well as instructions for controlling the mixture of gases, the chamber and/or station pressure, the chamber and/or station temperature, the wafer temperature, the target power levels, the RF power levels, the substrate pedestal, chuck, and/or susceptor position, and other parameters of a particular process performed by the reactor apparatus 2100.The system control software may be configured in any suitable way.","For example, various process tool component subroutines or control objects may be written to control operation of the process tool components necessary to carry out various process tool processes.","The system control software may be coded in any suitable computer readable programming language.","The system controller 2130 may typically include one or more memory devices and one or more processors configured to execute the instructions so that the apparatus will perform a technique in accordance with the present disclosure.","Machine-readable media containing instructions for controlling process operations in accordance with disclosed embodiments may be coupled to the system controller 2130.The method and apparatus described herein may be used in conjunction with lithographic patterning tools or processes such as those described below for fabrication or manufacture of semiconductor devices, displays, LEDs, photovoltaic panels, and the like.","Typically, though not necessarily, such tools/processes will be used or conducted together in a common fabrication facility.","Lithographic patterning of a film typically includes some or all of the following steps, each step performed with a number of possible tools: (1) application of photoresist on a workpiece, i.e., substrate or multi-layer stack as provided in disclosed embodiments, using a spin-on or spray-on tool; (2) curing a photoresist using a hot plate or furnace or UV curing tool; (3) exposing the photoresist to visible or UV or x-ray light with a tool such as a wafer stepper; (4) developing the resist so as to selectively remove resist and thereby pattern it using a tool such as a wet bench; (5) transferred the resist pattern into an underlying film or workpiece, such as an amorphous carbon layer, by using a dry or plasma-assisted etching tool such as those described below; and (6) removing the resist using a tool such as an RF or microwave plasma resist stripper.","In one implementation, one or more gap features on a wafer are filled with a carbon film using a technique as described herein.","The carbon film may then be used, for example, for one of the purposes described herein.","Further the implementation may include one or more of steps (1) through (6) described above.","One or more process stations may be included in a multi-station processing tool.","FIG.","22 shows a schematic view of an embodiment of a multi-station processing tool 2200 with an inbound load lock 2202 and an outbound load lock 2204, either or both of which may include a remote plasma source.","A robot 2206, at atmospheric pressure, is configured to move wafers from a cassette loaded through a pod 2208 into inbound load lock 2202 via an atmospheric port 2210.A wafer is placed by the robot 2206 on a pedestal 2212 in the inbound load lock 2202, the atmospheric port 2210 is closed, and the load lock is pumped down.","Where the inbound load lock 2202 includes a remote plasma source, the wafer may be exposed to a remote plasma treatment in the load lock prior to being introduced into a processing chamber 2214.Further, the wafer also may be heated in the inbound load lock 2202 as well, for example, to remove moisture and adsorbed gases.","Next, a chamber transport port 2216 to processing chamber 2214 is opened, and another robot (not shown) places the wafer into the reactor on a pedestal of a first station shown in the reactor for processing.","While the embodiment depicted includes load locks, it will be appreciated that, in some embodiments, direct entry of a wafer into a process station may be provided.","The depicted processing chamber 2214 includes four process stations, numbered from 1 to 4 in the embodiment shown in FIG.","22.Each station has a heated pedestal (shown at 2218 for station 1), and gas line inlets.","It will be appreciated that in some embodiments, each process station may have different or multiple purposes.","For example, in some embodiments, a process station may be switchable between a CFD and PECVD process mode.","Additionally or alternatively, in some embodiments, processing chamber 2214 may include one or more matched pairs of CFD and PECVD process stations.","While the depicted processing chamber 2214 includes four stations, it will be understood that a processing chamber according to the present disclosure may have any suitable number of stations.","For example, in some embodiments, a processing chamber may have five or more stations, while in other embodiments a processing chamber may have three or fewer stations.","FIG.","22 also depicts an embodiment of a wafer handling system 2290 for transferring wafers within processing chamber 2214.In some embodiments, wafer handling system 2290 may transfer wafers between various process stations and/or between a process station and a load lock.","It will be appreciated that any suitable wafer handling system may be employed.","Non-limiting examples include wafer carousels and wafer handling robots.","FIG.","22 also depicts an embodiment of a system controller 2250 employed to control process conditions and hardware states of process tool 2200.System controller 2250 may include one or more memory devices 2256, one or more mass storage devices 2254, and one or more processors 2252.Processor 2252 may include a CPU or computer, analog and/or digital input/output connections, stepper motor controller boards, etc.","In some embodiments, system controller 2250 controls all of the activities of process tool 2200.System controller 2250 executes system control software 2258 stored in mass storage device 2254, loaded into memory device 2256, and executed on processor 2252.Alternatively, the control logic may be hard coded in the controller 2250.Applications Specific Integrated Circuits, Programmable Logic Devices (e.g., field-programmable gate arrays, or FPGAs) and the like may be used for these purposes.","In the following discussion, wherever “software” or “code” is used, functionally comparable hard coded logic may be used in its place.","System control software 2258 may include instructions for controlling the timing, mixture of gases, chamber and/or station pressure, chamber and/or station temperature, wafer temperature, target power levels, RF power levels, RF exposure time, substrate pedestal, chuck and/or susceptor position, and other parameters of a particular process performed by process tool 2200.System control software 2258 may be configured in any suitable way.","For example, various process tool component subroutines or control objects may be written to control operation of the process tool components necessary to carry out various process tool processes.","System control software 2258 may be coded in any suitable computer readable programming language.","In some embodiments, system control software 2258 may include input/output control (IOC) sequencing instructions for controlling the various parameters described above.","For example, each phase of a CFD process may include one or more instructions for execution by system controller 2250.The instructions for setting process conditions for a CFD process phase may be included in a corresponding CFD recipe phase.","In some embodiments, the CFD recipe phases may be sequentially arranged, so that all instructions for a CFD process phase are executed concurrently with that process phase.","Other computer software and/or programs stored on mass storage device 2254 and/or memory device 2256 associated with system controller 2250 may be employed in some embodiments.","Examples of programs or sections of programs for this purpose include a substrate positioning program, a process gas control program, a pressure control program, a heater control program, and a plasma control program.","A substrate positioning program may include program code for process tool components that are used to load the substrate onto pedestal 2218 and to control the spacing between the substrate and other parts of process tool 2200.A process gas control program may include code for controlling gas composition and flow rates and optionally for flowing gas into one or more process stations prior to deposition in order to stabilize the pressure in the process station.","In some embodiments, the controller includes instructions for depositing a nanolaminate protective layer on a core layer, and depositing a conformal layer over the protective layer.","A pressure control program may include code for controlling the pressure in the process station by regulating, for example, a throttle valve in the exhaust system of the process station, a gas flow into the process station, etc.","In some embodiments, the controller includes instructions for depositing a nanolaminate protective layer on a core layer, and depositing a conformal layer over the protective layer.","A heater control program may include code for controlling the current to a heating unit that is used to heat the substrate.","Alternatively, the heater control program may control delivery of a heat transfer gas (such as helium) to the substrate.","In certain implementations, the controller includes instructions for depositing a nanolaminate protective layer at a first temperature, and a conformal layer over the protective layer at a second temperature, where the second temperature is higher than the first temperature.","A plasma control program may include code for setting RF power levels and exposure times in one or more process stations in accordance with the embodiments herein.","In some embodiments, the controller includes instructions for depositing a nanolaminate protective layer at a first RF power level and RF duration, and depositing a conformal layer over the protective layer at a second RF power level and RF duration.","The second RF power level and/or the second RF duration may be higher/longer than the first RF power level/duration.","In some embodiments, there may be a user interface associated with system controller 2250.The user interface may include a display screen, graphical software displays of the apparatus and/or process conditions, and user input devices such as pointing devices, keyboards, touch screens, microphones, etc.","In some embodiments, parameters adjusted by system controller 2250 may relate to process conditions.","Non-limiting examples include process gas composition and flow rates, temperature, pressure, plasma conditions (such as RF bias power levels and exposure times), etc.","These parameters may be provided to the user in the form of a recipe, which may be entered utilizing the user interface.","Signals for monitoring the process may be provided by analog and/or digital input connections of system controller 2250 from various process tool sensors.","The signals for controlling the process may be output on the analog and digital output connections of process tool 2200.Non-limiting examples of process tool sensors that may be monitored include mass flow controllers, pressure sensors (such as manometers), thermocouples, etc.","Appropriately programmed feedback and control algorithms may be used with data from these sensors to maintain process conditions.","System controller 2250 may provide program instructions for implementing the above-described deposition processes.","The program instructions may control a variety of process parameters, such as DC power level, RF bias power level, pressure, temperature, etc.","The instructions may control the parameters to operate in-situ deposition of film stacks according to various embodiments described herein.","The system controller will typically include one or more memory devices and one or more processors configured to execute the instructions so that the apparatus will perform a method in accordance with the disclosed embodiments.","Machine-readable, non-transitory media containing instructions for controlling process operations in accordance with the disclosed embodiments may be coupled to the system controller.","EXPERIMENTAL Experiment 1 Experiments were conducted to compare deposited spacer or conformal films on unprotected cores and those deposited on cores protected by a nanolaminate protective layer.","In the first trial, a substrate with a patterned core layer made of amorphous carbon was provided.","High quality titanium oxide was deposited directly on the core layer by a plasma enhanced atomic layer deposition (PEALD) or conformal film deposition (CFD) method.","The chamber pressure was about 3 Torr and at a temperature about 150° C. The substrate was exposed to the first precursor, TDMAT, for 2 seconds, followed by a 10 second purge.","The substrate was then exposed to a mixture of oxidants N2O/O2 in a 30 second exposure where the first 25 seconds involved flowing only the carrier gas N2 (at a flow rate of up to 9500 sccm) and in the last five seconds, the N2O/O2 flow was turned on and stayed on until the plasma was initiated for 0.5 seconds.","The plasma was initiated with a high frequency radio frequency (HFRF) power of 625 W per station, or 2500 W for four stations.","The N2O/O2 flow and plasma were turned off at the same time after the 0.5 second plasma exposure, and lastly the chamber was pumped to base to purge the chamber.","An image of the deposited conformal film and the underlying core layer is shown in FIG.","23A.","The degraded core layer 2304a is shown underneath the titanium oxide (TiO2) conformal film layer 2302a.","In the second trial, a substrate with a patterned core layer made of amorphous carbon was also provided.","A silicon oxide (SiO2) nanolaminate protective layer was deposited on the core layer by PEALD.","Deposition chamber temperature was 50° C. and pressure of the chamber was 1.8 Torr.","The substrate was exposed to a silicon-containing precursor 0.2 seconds, followed by a 0.2 second purge.","The substrate was then exposed to a mixture of oxidants N2O/O2 in a 0.3 second exposure.","A plasma was initiated for the four-station chamber at 1000 W, or about 500 W per station.","The N2O/O2 flow and plasma were turned off and the chamber was purged.","Subsequently, the substrate was exposed to TDMAT for 2 seconds, followed by a 10 second purge.","Following the purge, the substrate was exposed to oxidants N2O/O2 in a 30 second exposure such that the mixture flowed only in the last 5 seconds and after the 30 seconds, continued to flow for 0.5 seconds while plasma was initiated for the 0.5 seconds at 625 W per station, or 2500 W for four stations.","After both the plasma and the oxidants N2O/O2 flow were turned off, the chamber was again purged.","An image of the deposited conformal film, nanolaminate layer, and underlying core layer is shown in FIG.","23B.","As shown, the deposited conformal film 2302b was deposited on top of a nanolaminate layer 2306 which is so thin that it is indistinguishable from the conformal film and core layer it is adjacent to.","Note that compared to FIG.","23A, the core mandrels 2304b have very little degradation or consumption.","In the third trial, a substrate with a patterned core layer made of amorphous carbon was also provided.","A titanium oxide (TiO2) nanolaminate protective layer was deposited on the core layer by PEALD.","Deposition chamber temperature was 150° C. and pressure of the chamber was 3.0 Torr.","The substrate was exposed to TDMAT for 2 seconds, followed by a 10 second purge.","The substrate was then exposed to a mixture of oxidants N2O/O2 in a 30 second exposure such that the mixture flowed only in the last 5 seconds and after the 30 seconds, continued to flow for 0.5 seconds while a plasma was initiated for the four-station chamber at 1000 W, or about 500 W per station.","The N2O/O2 flow and plasma were turned off and the chamber was purged.","Subsequently, the substrate was exposed to TDMAT for 2 seconds, followed by a 10 second purge.","Following the purge, the substrate was exposed to oxidants N2O/O2 in a 30 second exposure such that the mixture flowed only in the last 5 seconds and after the 30 seconds, continued to flow for 0.5 seconds while plasma was initiated for the 0.5 seconds at 625 W per station, or 2500 W for four stations.","After both the plasma and the oxidants N2O/O2 flow were turned off, the chamber was again purged.","An image of the deposited conformal film, nanolaminate layer, and underlying core layer is shown in FIG.","23C.","As shown, the deposited conformal film 2302c was deposited on top of a nanolaminate layer 2308 which is so also thin that it is indistinguishable from the conformal film and core layer it is adjacent to.","Note that the core mandrels 2304c have very little degradation or consumption.","Experiment 2 Another series of experiments were conducted using the same conditions as those described with respect to the three trials above, but for blanket substrates with no features.","In each trial, the thickness of the amorphous carbon layer was measured, then the spacer was deposited and the spacer thickness was measured, and lastly the thickness of the remaining amorphous carbon layer after spacer deposition was measured.","The carbon consumption was calculated by subtracting the thickness after spacer deposition from the thickness before spacer deposition.","The results of this series of experiments are shown in Table 1.TABLE 1 Carbon Consumption and Nanolaminate Layers Trial 1 Trial 2 Trial 3 Nanolaminate Composition None SiO2 TiO2 Deposition Power 500 W 500 W Deposition Temperature 50° C. 150° C. Thickness Deposited (TEM) 1.44 nm Spacer Thickness Deposited (TEM) 5.9 nm 4.7 nm Amorphous Thickness Before Spacer Deposition 43.886 nm 44.1 nm 45.0 nm Carbon Thickness After Spacer Deposition 28.36 nm 35.3 nm 36.4 nm Carbon Consumption 15.4 nm 8 nm 8.6 nm As shown in the table, presence of the nanolaminate layer reduced carbon consumption substantially.","Without the nanolaminate layer, carbon consumption was 15.4 nm, whereas for both the SiO2 and TiO2 nanolaminate layers, carbon consumption was only about 8 nm.","Thus, depositing a nanolaminate layer over an amorphous carbon layer, particularly patterned amorphous carbon layer, protects the amorphous carbon layer when the spacer is deposited and higher quality films may be deposited for spacer deposition as a result.","CONCLUSION Although the foregoing embodiments have been described in some detail for purposes of clarity of understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims.","It should be noted that there are many alternative ways of implementing the processes, systems and apparatus of the present embodiments.","Accordingly, the present embodiments are to be considered as illustrative and not restrictive, and the embodiments are not to be limited to the details given herein."]],"string":"[\n [\n \"SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING\",\n \"Methods for depositing nanolaminate protective layers over a core layer to enable deposition of high quality conformal films over the core layer for use in advanced multiple patterning schemes are provided.\",\n \"In certain embodiments, the methods involve depositing a thin silicon oxide or titanium oxide film using plasma-based atomic layer deposition techniques with a low high frequency radio frequency (HFRF) plasma power, followed by depositing a conformal titanium oxide film or spacer with a high HFRF plasma power.\"\n ],\n [\n \"1.A method of processing a substrate, the method comprising: depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer, wherein the nanolaminate layer comprises a stack comprising two or more sublayers, and wherein the nanolaminate layer comprises silicon oxide or titanium oxide.\",\n \"2.The method of claim 1, wherein the core layer is a patterned layer.\",\n \"3.The method of claim 1, wherein the core layer comprises amorphous carbon or a photoresist.\",\n \"4.\",\n \"(canceled) 5.The method of claim 1, wherein each of the more than one layer of the nanolaminate layer is deposited using plasma enhanced atomic layer deposition (PEALD) by: exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.\",\n \"6.The method of claim 1, wherein the metal nitride or metal oxide layer comprises titanium oxide or silicon oxide.\",\n \"7.The method of claim 1, wherein the metal nitride or metal oxide layer has etch selectivity to the core layer.\",\n \"8.A method of processing a substrate, the method comprising: depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer, wherein the metal nitride or metal oxide layer is deposited using a metal-containing precursor by plasma enhance atomic layer deposition (PEALD), wherein the nanolaminate layer comprises a stack comprising two or more sublayers.\",\n \"9-11.\",\n \"(canceled) 12.The method of claim 8, wherein the metal-containing precursor is a titanium-containing precursor or a silicon-containing precursor and the PEALD is performed by exposing the substrate to the titanium-containing precursor or the silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.\",\n \"13.The method of claim 12, wherein the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.14.The method of claim 12, wherein the nanolaminate layer is deposited at a temperature less than about 100° C. 15.A method of patterning a semiconductor substrate, the method comprising: prior to depositing a conformal film on a core layer, depositing a nanolaminate protective layer on a patterned core layer; depositing a conformal film on the nanolaminate protective layer; planarizing the conformal film to expose the patterned core layer; and selectively etching the patterned core layer to form a mask.\",\n \"16.The method of claim 15, wherein the patterned core layer comprises amorphous carbon.\",\n \"17.The method of claim 15, wherein the nanolaminate protective layer comprises silicon oxide or titanium oxide.\",\n \"18.\",\n \"(canceled) 19.The method of claim 15, wherein the nanolaminate protective layer is deposited using plasma enhanced atomic layer deposition (PEALD) by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a first plasma while the substrate is exposed to the oxidant.\",\n \"20.The method of claim 19, wherein the nanolaminate protective layer is deposited at a temperature less than about 100° C. 21.The method of claim 19, wherein the nanolaminate protective layer is deposited at a temperature between about 50° C. and about 150° C. and the first plasma is initiated at a HFRF power per square millimeter of substrate area between about 1.768×10-4 per mm2 and about 1.768×10-3 per mm2.22.The method of claim 19, wherein the conformal film is deposited using PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a second plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.23.\",\n \"(canceled) 24.The method of claim 8, wherein the metal nitride or metal oxide layer deposited using the metal-containing precursor by PEALD is performed by exposing the substrate to the metal-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.25.The method of claim 1, wherein the each of the two or more sublayers of the nanolaminate layer comprises silicon oxide or titanium oxide.\",\n \"26.The method of claim 8, wherein the two or more sublayers have different compositions.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Fabrication of advanced integrated circuits often involve patterning of 1× nm half-pitch features in high volume manufacturing of semiconductors.\",\n \"Multiple patterning techniques may enable feature size scaling based on lithographic techniques such as 193 nm immersion lithography.\",\n \"Self-aligned double patterning is an example of a multiple patterning technique.\",\n \"Extensions of order multiple patterning techniques to 11 nm half pitch and below present challenges.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>Provided herein are methods of processing semiconductor substrates to enable deposition of high quality conformal films for use in multiple patterning integration schemes.\",\n \"One aspect involves a method of processing a semiconductor substrate by depositing a nanolaminate layer on the substrate and depositing a titanium oxide layer on the nanolaminate layer.\",\n \"The nanolaminate layer may have a thickness between about 15 Å and about 200 Å and may have a density lower than the density of the titanium oxide layer.\",\n \"In various embodiments, the method also includes depositing an amorphous carbon layer.\",\n \"In some embodiments, the amorphous carbon layer is patterned.\",\n \"In various embodiments, the nanolaminate layer includes a stack that includes two or more sublayers.\",\n \"In some embodiments, the two or more sublayers include silicon oxide, or titanium oxide, or combinations thereof.\",\n \"In certain embodiments, the stack includes only two sublayers.\",\n \"In some embodiments, the nanolaminate layer includes a first sublayer of silicon oxide and a second sublayer of titanium oxide.\",\n \"In various embodiments, the nanolaminate layer is silicon oxide or titanium oxide.\",\n \"In certain embodiments, the nanolaminate layer is deposited using a plasma-based process such as plasma-enhanced atomic layer deposition (PEALD) by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.\",\n \"In certain embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with a high frequency radio frequency (HFRF) power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 .\",\n \"In certain embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. An example of a titanium-containing precursor that may be used with the methods disclosed herein is tetrakis(dimethylamino)titanium (TDMAT).\",\n \"An example of a silicon-containing precursor is bis(tertiarybutylamino)silane (SiH 2 (NHC(CH 3 ) 3 ) 2 (BTBAS).\",\n \"In various embodiments, the titanium oxide layer is deposited by PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .\",\n \"Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or a combination thereof.\",\n \"The titanium oxide layer may be deposited at a temperature between about 50° C. and about 400° C. in some embodiments.\",\n \"Another aspect involves a method of processing a semiconductor substrate by depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer.\",\n \"In some embodiments, the core layer is patterned.\",\n \"In certain embodiments, the core layer may be amorphous carbon or a photoresist.\",\n \"In various embodiments, the nanolaminate layer may be silicon oxide or titanium oxide.\",\n \"In some embodiments, the thickness of the deposited nanolaminate layer is between about 15 Å and about 200 Å.\",\n \"In certain embodiments, the nanolaminate layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.\",\n \"In various embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with HFRF power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 .\",\n \"In some embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. In various embodiments, the metal nitride or metal oxide layer includes titanium oxide or silicon oxide.\",\n \"The metal nitride or metal oxide layer may have etch selectivity to the core.\",\n \"In certain embodiments, the metal nitride or metal oxide layer is deposited using PEALD by exposing the substrate to a metal-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .\",\n \"Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or combinations thereof.\",\n \"In some embodiments, the metal nitride or metal oxide layer is deposited at a temperature between about 50° C. and about 400° C. Another aspect involves a method of processing a semiconductor substrate by (a) exposing the substrate to a first titanium-containing precursor or a silicon-containing precursor; (b) exposing the substrate to a first oxidant; (c) initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 ; (d) exposing the substrate to a second titanium-containing precursor; (e) exposing the substrate to a second oxidant; and (f) initiating a second plasma while the substrate is exposed to the second oxidant with a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .\",\n \"In some embodiments, (a) through (c) are processed at temperature between about 50° C. and 150° C. In some embodiments, (d) through (f) are processed at temperature between about 50° C. and 400° C. In some embodiments, (d) through (f) are processed at a higher temperature than (a) through (c) such that transitioning from (c) to (d) includes raising the substrate temperature by at least about 50° C., at least about 100° C., at least about 150° C., or at least about 200° C. The first titanium-containing precursor and the second titanium-containing precursor may be the same precursor, e.g., TDMAT.\",\n \"In some embodiments, the first oxidant may be the same as the second oxidant (e.g., nitrous oxide, oxygen, carbon dioxide or combinations thereof).\",\n \"In some embodiments, it may be advantageous to use a different oxidant or mixture.\",\n \"In some embodiments, the substrate includes amorphous carbon.\",\n \"In some embodiments, the amorphous carbon is patterned.\",\n \"In various embodiments, the method also includes after initiating the second plasma, planarizing the substrate to expose the amorphous carbon, and selectively etching the amorphous carbon to form a mask.\",\n \"Another aspect involves a method of patterning a semiconductor substrate by, prior to depositing a conformal film on a core layer, depositing a nanolaminate protective layer on a patterned core layer; depositing a conformal film on the nanolaminate protective layer; planarizing the conformal film to expose the core; and selectively etching the core to form a mask.\",\n \"In certain embodiments, the core layer includes amorphous carbon.\",\n \"In various embodiments, the nanolaminate protective layer includes silicon oxide or titanium oxide.\",\n \"In certain embodiments, the thickness of the nanolaminate protective layer is between about 15 Å and about 200 Å.\",\n \"In many embodiments, the nanolaminate protective layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a first plasma while the substrate is exposed to the oxidant.\",\n \"In some embodiments, the nanolaminate protective layer is deposited at a temperature less than about 100° C. In various embodiments, the nanolaminate protective layer is deposited at a temperature between about 50° C. and about 150° C. and the first plasma is initiated at a HFRF power per square millimeter of substrate area between about 1.768×10 −4 W per mm 2 and about 1.768×10 −3 W per mm 2 .\",\n \"In some embodiments, the titanium oxide layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a second plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10 −3 W per mm 2 .\",\n \"Another aspect involves an apparatus for processing a semiconductor substrate including one or more process chambers; one or more gas inlets into the process chambers and associated flow-control hardware; a HFRF generator; and a controller having at least one processor and a memory, such that the at least one processer and the memory are communicatively connected with one another, the at least one processor is at least operatively connected with the flow-control hardware and HFRF generator, and the memory stores computer-executable instructions for: exposing the substrate to a metal-containing precursor; exposing the substrate to a first oxidant; initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power of between about 12.5 W and 125 W; exposing the substrate to a titanium-containing precursor; exposing the substrate to a second oxidant; and initiating a second plasma while the substrate is exposed to the second oxidant with HFRF power of at least about 125 W. These and other aspects are described further below with reference to the drawings.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/177,108, filed on Jun.\",\n \"8, 2016, and titled “SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING,” which is a division of U.S. patent application Ser.\",\n \"No.\",\n \"14/194,324, filed on Feb. 28, 2014, and titled “SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING,” which is a continuation-in-part of U.S. patent application Ser.\",\n \"No.\",\n \"14/074,617 (now U.S. Pat.\",\n \"No.\",\n \"9,287,113), filed Nov. 7, 2013, issued Mar.\",\n \"15, 2016, and titled “METHODS FOR DEPOSITING FILMS ON SENSITIVE SUBSTRATES,” which are incorporated by reference herein in their entireties and for all purposes.\",\n \"BACKGROUND Fabrication of advanced integrated circuits often involve patterning of 1× nm half-pitch features in high volume manufacturing of semiconductors.\",\n \"Multiple patterning techniques may enable feature size scaling based on lithographic techniques such as 193 nm immersion lithography.\",\n \"Self-aligned double patterning is an example of a multiple patterning technique.\",\n \"Extensions of order multiple patterning techniques to 11 nm half pitch and below present challenges.\",\n \"SUMMARY Provided herein are methods of processing semiconductor substrates to enable deposition of high quality conformal films for use in multiple patterning integration schemes.\",\n \"One aspect involves a method of processing a semiconductor substrate by depositing a nanolaminate layer on the substrate and depositing a titanium oxide layer on the nanolaminate layer.\",\n \"The nanolaminate layer may have a thickness between about 15 Å and about 200 Å and may have a density lower than the density of the titanium oxide layer.\",\n \"In various embodiments, the method also includes depositing an amorphous carbon layer.\",\n \"In some embodiments, the amorphous carbon layer is patterned.\",\n \"In various embodiments, the nanolaminate layer includes a stack that includes two or more sublayers.\",\n \"In some embodiments, the two or more sublayers include silicon oxide, or titanium oxide, or combinations thereof.\",\n \"In certain embodiments, the stack includes only two sublayers.\",\n \"In some embodiments, the nanolaminate layer includes a first sublayer of silicon oxide and a second sublayer of titanium oxide.\",\n \"In various embodiments, the nanolaminate layer is silicon oxide or titanium oxide.\",\n \"In certain embodiments, the nanolaminate layer is deposited using a plasma-based process such as plasma-enhanced atomic layer deposition (PEALD) by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.\",\n \"In certain embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with a high frequency radio frequency (HFRF) power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.In certain embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. An example of a titanium-containing precursor that may be used with the methods disclosed herein is tetrakis(dimethylamino)titanium (TDMAT).\",\n \"An example of a silicon-containing precursor is bis(tertiarybutylamino)silane (SiH2(NHC(CH3)3)2 (BTBAS).\",\n \"In various embodiments, the titanium oxide layer is deposited by PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or a combination thereof.\",\n \"The titanium oxide layer may be deposited at a temperature between about 50° C. and about 400° C. in some embodiments.\",\n \"Another aspect involves a method of processing a semiconductor substrate by depositing a core layer; depositing a nanolaminate layer on the core layer; and depositing a metal nitride or metal oxide layer on the nanolaminate layer.\",\n \"In some embodiments, the core layer is patterned.\",\n \"In certain embodiments, the core layer may be amorphous carbon or a photoresist.\",\n \"In various embodiments, the nanolaminate layer may be silicon oxide or titanium oxide.\",\n \"In some embodiments, the thickness of the deposited nanolaminate layer is between about 15 Å and about 200 Å.\",\n \"In certain embodiments, the nanolaminate layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant.\",\n \"In various embodiments, the nanolaminate layer is deposited at a temperature between about 50° C. and about 150° C. and the plasma is initiated with HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.In some embodiments, the nanolaminate layer is deposited at a temperature less than about 100° C. In various embodiments, the metal nitride or metal oxide layer includes titanium oxide or silicon oxide.\",\n \"The metal nitride or metal oxide layer may have etch selectivity to the core.\",\n \"In certain embodiments, the metal nitride or metal oxide layer is deposited using PEALD by exposing the substrate to a metal-containing precursor; exposing the substrate to an oxidant; and initiating a plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.Examples of oxidants include nitrous oxide, oxygen, carbon dioxide or combinations thereof.\",\n \"In some embodiments, the metal nitride or metal oxide layer is deposited at a temperature between about 50° C. and about 400° C. Another aspect involves a method of processing a semiconductor substrate by (a) exposing the substrate to a first titanium-containing precursor or a silicon-containing precursor; (b) exposing the substrate to a first oxidant; (c) initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2; (d) exposing the substrate to a second titanium-containing precursor; (e) exposing the substrate to a second oxidant; and (f) initiating a second plasma while the substrate is exposed to the second oxidant with a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.In some embodiments, (a) through (c) are processed at temperature between about 50° C. and 150° C. In some embodiments, (d) through (f) are processed at temperature between about 50° C. and 400° C. In some embodiments, (d) through (f) are processed at a higher temperature than (a) through (c) such that transitioning from (c) to (d) includes raising the substrate temperature by at least about 50° C., at least about 100° C., at least about 150° C., or at least about 200° C. The first titanium-containing precursor and the second titanium-containing precursor may be the same precursor, e.g., TDMAT.\",\n \"In some embodiments, the first oxidant may be the same as the second oxidant (e.g., nitrous oxide, oxygen, carbon dioxide or combinations thereof).\",\n \"In some embodiments, it may be advantageous to use a different oxidant or mixture.\",\n \"In some embodiments, the substrate includes amorphous carbon.\",\n \"In some embodiments, the amorphous carbon is patterned.\",\n \"In various embodiments, the method also includes after initiating the second plasma, planarizing the substrate to expose the amorphous carbon, and selectively etching the amorphous carbon to form a mask.\",\n \"Another aspect involves a method of patterning a semiconductor substrate by, prior to depositing a conformal film on a core layer, depositing a nanolaminate protective layer on a patterned core layer; depositing a conformal film on the nanolaminate protective layer; planarizing the conformal film to expose the core; and selectively etching the core to form a mask.\",\n \"In certain embodiments, the core layer includes amorphous carbon.\",\n \"In various embodiments, the nanolaminate protective layer includes silicon oxide or titanium oxide.\",\n \"In certain embodiments, the thickness of the nanolaminate protective layer is between about 15 Å and about 200 Å.\",\n \"In many embodiments, the nanolaminate protective layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor or a silicon-containing precursor; exposing the substrate to an oxidant; and initiating a first plasma while the substrate is exposed to the oxidant.\",\n \"In some embodiments, the nanolaminate protective layer is deposited at a temperature less than about 100° C. In various embodiments, the nanolaminate protective layer is deposited at a temperature between about 50° C. and about 150° C. and the first plasma is initiated at a HFRF power per square millimeter of substrate area between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2.In some embodiments, the titanium oxide layer is deposited using PEALD by exposing the substrate to a titanium-containing precursor; exposing the substrate to an oxidant; and initiating a second plasma while the substrate is exposed to the oxidant at a HFRF power per square millimeter of substrate area of at least about 1.768×10−3 W per mm2.Another aspect involves an apparatus for processing a semiconductor substrate including one or more process chambers; one or more gas inlets into the process chambers and associated flow-control hardware; a HFRF generator; and a controller having at least one processor and a memory, such that the at least one processer and the memory are communicatively connected with one another, the at least one processor is at least operatively connected with the flow-control hardware and HFRF generator, and the memory stores computer-executable instructions for: exposing the substrate to a metal-containing precursor; exposing the substrate to a first oxidant; initiating a first plasma while the substrate is exposed to the first oxidant with a HFRF power of between about 12.5 W and 125 W; exposing the substrate to a titanium-containing precursor; exposing the substrate to a second oxidant; and initiating a second plasma while the substrate is exposed to the second oxidant with HFRF power of at least about 125 W. These and other aspects are described further below with reference to the drawings.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIGS.\",\n \"1-11 are schematic depictions of an integration scheme in accordance with disclosed embodiments.\",\n \"FIGS.\",\n \"12-18 are schematic depictions of an integration scheme in accordance with disclosed embodiments.\",\n \"FIG.\",\n \"19 is a process flow diagram of a method in accordance with disclosed embodiments.\",\n \"FIGS.\",\n \"20A and 20B are process flow diagrams of methods in accordance with disclosed embodiments.\",\n \"FIG.\",\n \"21 is an illustration of a reaction chamber for practicing methods in accordance with disclosed embodiments.\",\n \"FIG.\",\n \"22 is an illustration of a multi-station apparatus that may be used for performing operations in accordance with disclosed embodiments.\",\n \"FIGS.\",\n \"23A-23C are images of deposited films from experiments in performing methods in accordance with disclosed embodiments.\",\n \"DETAILED DESCRIPTION In the following description, numerous specific details are set forth to provide a thorough understanding of the presented embodiments.\",\n \"The disclosed embodiments may be practiced without some or all of these specific details.\",\n \"In other instances, well-known process operations have not been described in detail to not unnecessarily obscure the disclosed embodiments.\",\n \"While the disclosed embodiments will be described in conjunction with the specific embodiments, it will be understood that it is not intended to limit the disclosed embodiments.\",\n \"Fabrication of semiconductor devices typically involves depositing one or more thin films in an integrated manufacturing process and may include patterning steps.\",\n \"Multiple patterning techniques are used to fabricate advanced integrated circuits, such as those with smaller features or higher aspect ratios, or down to 2× or 1× nm nodes.\",\n \"The term “1×” node means a process node between 10 nm and 19 nm and the term “2×” node means a process node between 20 nm and 29 nm.\",\n \"An example of multiple patterning is self-aligned double patterning, which produces double the number of features of a pattern formed by conventional lithography.\",\n \"As the devices become smaller, narrower half-pitch features may be attained using advanced multiple patterning techniques, such as quadruple patterning, or “quad patterning.” An example of a quad patterning scheme is provided in FIGS.\",\n \"1-11.FIG.\",\n \"1 provides a schematic illustration of an example of various layers that may be included in a multi-layer stack, such as on a wafer suitable for semiconductor processing.\",\n \"The multi-layer stack in FIG.\",\n \"1 includes a first core layer formed into first cores (also referred to as first mandrels) 103, which may be lithographically defined in a previous process, on top of a hardmask 104.Hardmask 104 may be on top of a second core layer 105, which is itself deposited on layer 107.Layer 107 may include a hardmask layer 107a, a cap layer 107b, and a mask layer 107c, which may be used as a mask to pattern a subsequent target layer 150.Barrier layers, cap layers, or etch stop layers may be between the mask layer 107c and target layer 150.One of ordinary skill in the art will appreciate that there may be one or more layers deposited between any of the above described layers, and the target layer 150 may include one or more additional layers.\",\n \"The first core layer (and thus first cores 103) may be highly etch selective to other materials in the stack, such as silicon and/or silicon-based oxides or nitrides, for example, and may be transparent.\",\n \"The first core layer may be a photoresist or may be made of amorphous carbon material or amorphous silicon material.\",\n \"In some embodiments, the first core layer may be deposited on top of hardmask 104 by a deposition technique, such as plasma-enhanced chemical vapor deposition (PECVD), and the deposition technique may involve generating a plasma in the deposition chamber from deposition gases including a hydrocarbon precursor.\",\n \"The hydrocarbon precursor may be defined by the formula CxHy, where x is an integer between 2 and 10, and y is an integer between 2 and 24.Examples include methane (CH4), acetylene (C2H2), ethylene (C2H4), propylene (C3H6), butane (C4H10), cyclohexane (C6H12), benzene (C6H6), and toluene (C7H8).\",\n \"A dual radio frequency (RF) plasma source including a high frequency (HF) power and a low frequency (LF) power may be used.\",\n \"Alternatively a single RF plasma source may be used.\",\n \"Typically such a source will be a HFRF source.\",\n \"Under the first core layer formed into first cores 103 is a second core layer 105.Between the first core layer and the second core layer 105 may be a hardmask 104.The hardmask 104 may have high etch selectivity relative to first core layer and second core layer 105 so as not to etch second core layer 105 while first core layer is patterned.\",\n \"The second core layer 105 may be made of amorphous carbon material or amorphous silicon material.\",\n \"Methods of deposition and deposition precursors may be any of those described above with respect to first core layer.\",\n \"Once patterned, the second core layer 105 is formed into second cores (also referred to as second mandrels) 105′ (shown in FIG.\",\n \"5) and may be used to etch a mask in a subsequent layer, such as mask layer 107c, which may then be used to pattern the target layer 150.In certain embodiments, the mask layer 107c may be made of amorphous carbon material or amorphous silicon material.\",\n \"In quadruple patterning schemes, such as that depicted in FIGS.\",\n \"1-11, the mask layer 107c may be the quadruple pattern of a photoresist pattern such that one feature in a photoresist is patterned and transferred to form four features in the target layer 150.Between the second core layer 105 and target layer 150 may be other layers, such as a hardmask layer 107a, or cap layer 107b, or a mask layer 107c to be used to pattern the target layer 150.The target layer 150 may be the layer ultimately to be patterned.\",\n \"The target layer 150 may be a semiconductor, dielectric or other layer and may be made of silicon (Si), silicon oxide (SiO2), silicon nitride (SiN), or titanium nitride (TiN), for example.\",\n \"The target layer 150 may be deposited by atomic layer deposition (ALD), plasma-enhanced ALD (PEALD), chemical vapor deposition (CVD), or other suitable deposition techniques.\",\n \"In one example, the compositions and thicknesses of a quad patterning stack such as the one shown in FIG.\",\n \"1 may be the following: 400 Å amorphous carbon first cores 103, 150 Å tetraethylorthosilicate (TEOS) hardmask layer 104, 350 Å amorphous carbon second core layer 105, 150 Å TEOS hardmask layer 107a, 100 Å amorphous silicon cap layer 107b, 300 Å amorphous carbon mask layer 107c, 200 Å titanium nitride barrier layer (not shown), and 300 Å TEOS hardmask layer (not shown), all on a silicon target layer or substrate 150.In one example, the following may be deposited on top of the 400 Å amorphous carbon first core layer in order prior to lithographic patterning to define the first core layer as depicted in the example of FIG.\",\n \"1: 100 Å-150 Å SiON etch stop layer, 300 Å bottom anti-reflective coating (BARC) layer, and 1000 Å photoresist first core layer.\",\n \"In FIG.\",\n \"2, a conformal film 109 is deposited over the first cores 103.The conformal film 109 may also be referred to as a “spacer” and may be deposited to conform to the shape of the pattern on the multi-layer stack to make an evenly distributed layer over the pattern.\",\n \"As described further below, the conformal film 109 may be formed into multiple individual spacers, each of which abuts a sidewall of the first cores 103.The conformal film 109 has a high etch selectivity to the core.\",\n \"For example, the conformal film 109 may have an etch selectivity greater than 3:1 relative to an amorphous carbon layer.\",\n \"In some embodiments, conformal film 109 has an etch selectivity greater than 15:1 relative to poly-silicon in halide etch chemistry.\",\n \"The conformal film 109 may be made of dielectric material, such as SiO2.The conformal film 109 may also be an oxide, such as titanium oxide (TiO2), or may be silicon nitride (SiN).\",\n \"In some embodiments, the conformal film 109 is made of denser material to withstand more “passes” of patterning and may be deposited by ALD, PEALD, or conformal film deposition (CFD) methods as described briefly below.\",\n \"ALD processes use surface-mediated deposition reactions to deposit films on a layer-by-layer basis.\",\n \"In one example ALD process, a substrate surface, including a population of surface active sites, is exposed to a gas phase distribution of a first film precursor (P1).\",\n \"Some molecules of P1 may form a condensed phase atop the substrate surface, including chemisorbed species and physisorbed molecules of P1.The reactor is then evacuated to remove gas phase and physisorbed P1 so that only chemisorbed species remain.\",\n \"A second film precursor (P2) is then introduced to the reactor so that some molecules of P2 adsorb to the substrate surface.\",\n \"The reactor may again be evacuated, this time to remove unbound P2.Subsequently, thermal energy provided to the substrate activates surface reactions between adsorbed molecules of P1 and P2, forming a film layer.\",\n \"Finally, the reactor is evacuated to remove reaction by-products and possibly unreacted P1 and P2, ending the ALD cycle.\",\n \"Additional ALD cycles may be included to build film thickness.\",\n \"In an example of a PEALD process, a plasma is initiated while the second film precursor P2 is introduced to the reactor to activate the reaction between P1 and P2.CFD may be used to deposit the conformal film 109.Generally, CFD does not rely on complete purges of one or more reactants prior to reaction to form the film.\",\n \"For example, there may be one or more reactants present in the vapor phase when a plasma (or other activation energy) is struck.\",\n \"Accordingly, one or more of the process steps described in an ALD process may be shortened or eliminated in an example CFD process.\",\n \"Further, in some embodiments, plasma activation of deposition reactions may result in lower deposition temperatures than thermally-activated reactions, potentially reducing the thermal budget of an integrated process.\",\n \"For context, a short description of CFD is provided.\",\n \"The concept of a CFD cycle is relevant to the discussion of various embodiments herein.\",\n \"As with ALD processes, generally a cycle is the minimum set of operations required to perform a surface deposition reaction one time.\",\n \"The result of one cycle is production of at least a partial film layer on a substrate surface.\",\n \"Typically, a CFD cycle will include only those steps necessary to deliver and adsorb each reactant to the substrate surface, and then react those adsorbed reactants to form the partial layer of film.\",\n \"The cycle may include certain ancillary steps such as sweeping one or more of the reactants or byproducts and/or treating the partial film as deposited.\",\n \"Generally, a cycle contains only one instance of a unique sequence of operations.\",\n \"As an example, a cycle may include the following operations: (i) delivery/adsorption of reactant A, (ii) delivery/adsorption of reactant B, (iii) sweep B out of the reaction chamber, and (iv) apply plasma to drive a surface reaction of A and B to form the partial film layer on the surface.\",\n \"As used herein, the term PEALD includes CFD processes.\",\n \"The following conditions are examples of conditions suitable depositing a silicon oxide conformal film 109 by a CFD process.\",\n \"Deposition may occur at a temperature between about 50° C. and about 400° C., at a pressure between about 0.5 Torr and about 10 Torr, and an RF power for four stations between about 100 W and 10 kW.\",\n \"RF activation frequency can vary from about 13.56 MHz to 40 MHz for various embodiments.\",\n \"For a silicon oxide conformal film 109, process gases that may be used include, as a silicon source, a silicon amide (e.g., BTBAS, BDEAS (bis-di-ethyl aminosilane) or DIPAS (di-isopropyl aminosilane), and, as an oxygen source, oxygen or nitrous oxide or carbon dioxide, separately or together, diluted with an inert carrier gas, for example argon or nitrogen.\",\n \"Process gas flow rates may be as follows: for (liquid) silicon precursor (e.g., BTBAS, BDEAS, and DIPAS), between about 1 sccm and 3 sccm, for example BTBAS at about 2.5 sccm; for oxygen precursor (O2, N2O), between about 5000 sccm and 10,000 sccm, for example N2O at 5000 sccm; and for the carrier gas (Ar or N2), between about 0 sccm and 10,000 sccm, for example about 5000 sccm Ar.\",\n \"In FIG.\",\n \"3, the conformal film 109 is etched back or planarized to expose the first cores 103.In various embodiments, the conformal film 109 may be planarized through a multi-step process.\",\n \"In one example, the conformal film 109 may be etched back by first flowing about 10 sccm to about 100 sccm of chlorine (Cl2), then about 10 sccm to about 100 sccm of methane (CH4), then about 10 sccm to about 100 sccm of nitrogen (N2) for about 30 seconds.\",\n \"In some embodiments, the conformal film 109 may be etched at a temperature between about 10° C. and about 20° C. and at a pressure between about 2 mTorr and about 20 mTorr for a time of about 30 seconds.\",\n \"In some embodiments, the substrate may be etched at a temperature between about 40° C. and about 60° C. and at a pressure between about 5 mTorr and about 100 mTorr.\",\n \"In many embodiments, an anisotropic plasma etch is performed to expose the core and define the structure of the spacers 109′ from the conformal film 109.In FIG.\",\n \"4, the first cores 103 are stripped or etched, leaving free-standing spacers 109′ on the substrate.\",\n \"If the first core layer is a photoresist, the first cores 103 may be etched by flowing oxygen (O2) at a flow rate between about 100 sccm and about 200 sccm at a temperature between about 40° C. and about 60° C. in a pressure between about 5 mTorr and about 20 mTorr.\",\n \"If the first core layer is made of amorphous carbon material, the first cores 103 may be stripped or etched using an ashing method.\",\n \"An ashing method may be dependent on chemical reactions for material removal, rather than directional movement of energetic ions.\",\n \"For example, any surface that is exposed to the process gas used in an ashing operation may experience material removal due to the exposure, so the amorphous carbon material used in the first cores 103 may have high etch selectivity to the spacers 109′ such that the spacers 109′ are not etched while the first cores 103 are ashed.\",\n \"Additionally, in contrast to some chemical etching processes, ashing operations may produce a reaction product that is completely in the gas phase.\",\n \"Ashing operations for carbon films may, for example, utilize dissociated hydrogen (H2) or oxygen (O2) as a process gas, which may react with carbon films to form such gas-phase reaction byproducts.\",\n \"In some embodiments, the remaining spacers 109′ may be shaped for subsequent processing using various etch conditions.\",\n \"In FIG.\",\n \"5, the second core layer 105 is etched down using the spacers 109′ as a mask, thereby transferring the pattern to form second cores 105′.\",\n \"The second core layer 105 may be etched at a temperature between about 50° C. and about 70° C. in a pressure between about 5 mTorr and about 100 mTorr using chemistry suitable for etching the second core layer 105 but not the spacers 109′.\",\n \"The second core layer 105 is thus highly etch selective to the spacers 109′.\",\n \"The second core layer 105 may be an amorphous carbon layer, or amorphous silicon layer.\",\n \"Above the second core layer 105 may be a cap layer 104, which may be a silicon anti-reflective coating, or PECVD dielectric layer, or spin-on glass.\",\n \"In FIG.\",\n \"6, the spacers 109′ and the cap layer 104 are etched or otherwise removed, leaving the patterned second cores 105′.\",\n \"In some embodiments, the spacers 109′ may be removed at a temperature between about 10° C. and about 20° C. and at a pressure between about 2 mTorr and about 20 mTorr for a time of about 30 seconds.\",\n \"In some embodiments, the substrate may be etched at a temperature between about 40° C. and about 60° C. and at a pressure between about 5 mTorr and about 100 mTorr.\",\n \"In many embodiments, an anisotropic plasma etch is performed.\",\n \"In one example, the spacers 109′ are etched by first flowing about 10 sccm to about 100 sccm of chlorine (Cl2), then about 10 sccm to about 100 sccm of methane (CH4), then about 10 sccm to about 100 sccm of nitrogen (N2) for about 30 seconds.\",\n \"In FIG.\",\n \"7, a second conformal film 119 is deposited over the patterned second cores 105′.\",\n \"In many embodiments, the second conformal film 119 may be a layer of titanium oxide, which may be deposited by PEALD methods.\",\n \"In FIG.\",\n \"8, the second conformal film 119 is etched or planarized to expose the second cores 105′.\",\n \"Conditions and methods may be any of those discussed above with respect to FIG.\",\n \"3.In FIG.\",\n \"9, the second cores 105′ is etched or removed, leaving free-standing second spacers 119′.\",\n \"Conditions and methods may be any of those discussed above with respect to FIG.\",\n \"4.In FIG.\",\n \"10, the mask layer 107c is etched down using the second spacers 119′ as a mask, thereby transferring the pattern from the second spacers 119′ to form a patterned mask 107c′.\",\n \"Mask layer 107c may be highly etch selective to the second conformal film 119, and may be etched by any method discussed above with respect to FIG.\",\n \"5, depending on the chemistry of the mask layer 107c.\",\n \"In FIG.\",\n \"11, the second spacers 119′ are removed, along with etch stop layer 107a and cap layer 107b, leaving the patterned mask 107c′.\",\n \"Conditions and methods for removing the second spacers 119′ may be any of those discussed above with respect to FIG.\",\n \"6.The mask 107c′ may then be used to pattern subsequent layers, such as target layer 150.The result of process steps depicted in FIGS.\",\n \"1 through 11 is a quad-patterning scheme such that a single lithographically defined feature (such as a first core 103 in FIG.\",\n \"1) results in four smaller features on the substrate.\",\n \"Quad patterning schemes may be used to form features with a half-pitch as small as 10 nm, or between 10 nm and 20 nm half-pitch, which cannot be achieved by current double patterning schemes.\",\n \"Due to the nature of forming the smaller features, the material used for the second conformal film 119 may be of higher quality relative to conformal films used in spacers of wider cores so as to maintain robustness and prevent buckling when it is exposed to harsh conditions in subsequent patterning steps.\",\n \"Higher quality conformal film material may have near-ideal stoichiometry, such as if the conformal film is titanium oxide, the higher quality titanium oxide conformal film may have near ideal Ti:O stoichiometry, for example 1:2, and low carbon content.\",\n \"Higher quality conformal films may be deposited by ALD, which may perform a complete conversion from the oxidation half-reaction, thereby forming near ideal stoichiometry.\",\n \"Thus, higher quality conformal film material may then have a low etch rate and high etch selectivity, and also being infinitely selective against oxides and nitrides.\",\n \"These films may also have higher modulus, such as greater than about 150 MPa, which contributes to improved mechanical stability of the conformal film as a spacer, thereby improving critical dimension uniformity (CDU).\",\n \"The higher quality conformal film material disclosed herein may also be dense to withstand subsequent integration steps.\",\n \"Provided herein are methods of depositing thin, conformal nanolaminate protective layers.\",\n \"Also provided are methods of forming high quality films that may be used as spacers, with the methods including deposition of a nanolaminate layer.\",\n \"The nanolaminate layers can improve spacer robustness while protecting the underlying core layer from degradation during deposition of the conformal film.\",\n \"Deposition of high quality films, such as high quality titanium oxide, directly on a core layer may result in degradation or consumption of the core due to harsh conditions during deposition of the spacer, thereby harming the underlying patterned core.\",\n \"For example, during deposition of the high quality conformal film, a patterned core layer may be exposed to oxygen radicals, such as those produced from a N2O/O2 sequential plasma with a high HFRF power of at least about 1000 W. Due to the higher power, more oxygen radicals are formed, which increases radical bombardment on the core layer and subsequent degradation the pattern of the core.\",\n \"Nitrides may be able to withstand such bombardment if used as a cap over the core layer, but since nitrides are not selective to certain core materials, nitrides are not suitable.\",\n \"After a conformal film is deposited, the substrate may then be planarized to expose the core and remove the core, but since the core has been consumed or degraded, the resulting width between spacers may be diminished, which results in an irregular pattern in the semiconductor substrate.\",\n \"Rather than using lower quality conformal films to prevent degradation of the core, the methods disclosed herein enable high quality spacer materials.\",\n \"Nanolaminate protective layers may be less dense than conformal film due to the lower HFRF power used during deposition.\",\n \"As such nanolaminate protective layers may be deposited at a minimum thickness that adequately protects the core.\",\n \"Minimizing the nanolaminate protective layer may facilitate subsequent integration.\",\n \"Nanolaminate protective layers may protect an underlying layer to the extent that a higher quality conformal film may be deposited over it.\",\n \"Core consumption and degradation thereby decreases and the core can withstand harsher conditions during deposition of the high quality conformal film.\",\n \"In subsequent patterning steps, the high quality conformal film can withstand other harsh conditions and still maintain its strong robustness as a free-standing structure.\",\n \"The nanolaminate protective layers may also prevent spacer leaning and enable critical dimension variability, by maintaining the integrity of the core geometry and providing mechanical support to the free-standing spacer structures, thereby enhancing the ability to form finer features at lower half-pitch in semiconductor processing.\",\n \"An example of a method of using a nanolaminate protective layer may begin by providing a multi-stack semiconductor substrate with a lithographically defined or patterned first core layer, such as the one discussed above with respect to FIG.\",\n \"1.In some embodiments, a nanolaminate protective layer may be deposited on the first cores 103 prior to depositing a conformal film 109 as described in embodiments below with respect to FIG.\",\n \"13.In various embodiments, a conformal film 109 may be deposited over the first cores 103, such as in FIG.\",\n \"2.After the conformal film 109 is planarized, such as shown in FIG.\",\n \"3, the first cores 103 may be etched or removed to reveal the remaining spacers 109′, such as shown in FIG.\",\n \"4.A second core layer 105 may be etched down using the spacers 109′ as a mask to thereby transfer the pattern to form the second cores 105′ such as shown in FIG.\",\n \"5.The spacers 109′ may be removed to reveal patterned second cores 105′ such as shown in FIG.\",\n \"12.The second core layer 105 may be an amorphous carbon layer, or an amorphous silicon layer.\",\n \"In FIG.\",\n \"13, a nanolaminate protective layer 111 may be deposited conformally over the second cores 105′.\",\n \"Examples of thicknesses of the nanolaminate layer 111 are between about 15 Å and about 200 Å thick, between about 15 Å and about 100 Å thick, or between about 15 Å and about 50 Å thick.\",\n \"Note that the thickness depicted in FIG.\",\n \"13 is exaggerated for the purposes of the illustration and as an example only.\",\n \"In some embodiments, the nanolaminate layer 111 may include a stack, which may have two or more sublayers (not shown).\",\n \"For example, the stack may be a bilayer.\",\n \"In some embodiments the sublayers have the same composition, and in some embodiments, the sublayers have different compositions.\",\n \"In some embodiments, the nanolaminate layer 111 is one layer.\",\n \"In one example, the nanolaminate layer 111 is one layer of silicon oxide.\",\n \"In another example, the nanolaminate layer 111 is one layer of titanium oxide.\",\n \"In one example of a bilayer nanolaminate layer 111, the upper layer is silicon oxide, and the lower layer is titanium oxide.\",\n \"In another example of a bilayer nanolaminate layer 111, the upper layer is titanium oxide and the lower layer is silicon oxide.\",\n \"The nanolaminate layer 111 may also be less dense than the material deposited in a conformal film due to the lower HFRF power which may be used to deposit the nanolaminate layer 111.In some embodiments, the nanolaminate layer 111 may be an ALD oxide, such as silicon oxide (SiO2) or titanium oxide (TiO2) and referred to as “soft” ALD oxide.\",\n \"The thickness of the nanolaminate layer 111 may be taken into account when configuring processing conditions for the patterning scheme and deciding the pattern to be etched.\",\n \"In various embodiments, the nanolaminate layer 111 is deposited by conformal film deposition (CFD) or PEALD.\",\n \"In FIG.\",\n \"14, the second conformal film 129 is deposited over the nanolaminate layer 111.In certain embodiments, the second conformal film 129 is a high quality titanium oxide film, such as a titanium oxide layer with a low wet etch rate and high dry etch selectivity with infinite selectivity against oxides such as silicon oxide (SiO2) and nitrides such as silicon nitride (SiN).\",\n \"For example, the second conformal film 129 may have an etch selectivity greater than 3:1 relative to an amorphous carbon layer.\",\n \"In some embodiments, second conformal film 129 has an etch selectivity greater than 15:1 relative to a poly silicon layer in halide etch chemistry.\",\n \"In one example, a nanolaminate layer 111 deposited to a thickness of about 15 Å may be sufficient to protect second cores 105′ from deposition of about 110 Å of the second conformal film 129.In various embodiments, the second conformal film 129 is deposited by CFD or PEALD.\",\n \"In some embodiments the second conformal film 129 is denser than the nanolaminate layer 111.In FIG.\",\n \"15, the substrate is planarized to expose the second cores 105′ with nanolaminate layer 111 sidewalls and yield sidewall second spacers 129′.\",\n \"The conditions for the planarization may be any of those described above with respect to FIG.\",\n \"3.In FIG.\",\n \"16, the second cores 105′ are etched and removed.\",\n \"Conditions and methods may be any of those discussed above with respect to FIG.\",\n \"9.In some embodiments, a small portion of the nanolaminate layer 111 may be etched due to the nature of the etching step.\",\n \"In some embodiments, the nanolaminate layer 111 is sufficiently etch selective and is not etched while the second cores 105′ are removed.\",\n \"Note the second spacers 129′ are sitting on a thin layer of nanolaminate layer 111 with a thin nanolaminate layer 111 on its sidewall, which may thereby reinforce its stability and prevent leaning.\",\n \"Still further, in some embodiments, the nanolaminate material may be completely removed with the second cores 105′.\",\n \"As noted above, in some embodiments, the thickness of the nanolaminate layer 111 and how much of it will be removed may be taken into account when planning the patterning scheme to arrive at the desired dimension.\",\n \"However, in some embodiments, the thickness of the nanolaminate layer 111 may be within the tolerance of the patterned dimensions, and may not need to be accounted for.\",\n \"In FIG.\",\n \"17, the mask layer 107c is etched down using the second spacers 129′ as a mask.\",\n \"Due to the increased stability and robustness of the higher quality second spacers 129′, this operation may be more easily and more efficiently completed to form fine, stable features with high aspect ratios.\",\n \"In FIG.\",\n \"18, the nanolaminate layer 111 and second spacers 129′ are etched or removed to reveal the resulting patterned mask 107c′.\",\n \"Conditions and methods may be any of those described above with respect to FIG.\",\n \"5.The patterned mask 107c′ may then be used to pattern a subsequent layer, which can be used to pattern the target layer 150.In some embodiments, the patterned mask 107c′ may be used to pattern the target layer 150.FIG.\",\n \"19 is a process flow diagram of steps of a method in accordance with various embodiments.\",\n \"Cycle and exposure times described herein may depend on the apparatus and platform used and one of ordinary skill in the art may adjust cycle and exposure times accordingly.\",\n \"In operation 1901, a substrate may be exposed to a first precursor, such as a titanium-containing precursor or silicon-containing precursor.\",\n \"In some embodiments, the substrate includes a core layer.\",\n \"In various embodiments, the core layer is amorphous carbon, amorphous silicon, or a photoresist.\",\n \"In some embodiments, the core layer is lithographically defined or patterned.\",\n \"In a certain embodiment, the substrate includes a patterned amorphous carbon layer.\",\n \"Examples of a titanium-containing precursor include tetrakis(dimethylamino)titanium (TDMAT), tetraethoxytitanium, tetrakis-dimethyl-amido titanium, titanium isopropoxide, titanium tetraisopropoxide, and titanium tetrachloride.\",\n \"A silicon-containing precursor may be, for example, a silane, a halosilane or an aminosilane.\",\n \"A silane contains hydrogen and/or carbon groups, but does not contain a halogen.\",\n \"Examples of silanes are silane (SiH4), disilane (Si2H6), and organo silanes such as methylsilane, ethylsilane, isopropylsilane, t-butylsilane, dimethylsilane, diethylsilane, di-t-butylsilane, allylsilane, sec-butylsilane, thexylsilane, isoamylsilane, t-butyldisilane, di-t-butyldisilane, tetra-ethyl-ortho-silicate (also known as tetra-ethoxy-silane or TEOS) and the like.\",\n \"A halosilane contains at least one halogen group and may or may not contain hydrogens and/or carbon groups.\",\n \"Examples of halosilanes are iodosilanes, bromosilanes, chlorosilanes and fluorosilanes.\",\n \"Although halosilanes, particularly fluorosilanes, may form reactive halide species that can etch silicon materials, in certain embodiments described herein, the silicon-containing reactant is not present when a plasma is struck.\",\n \"Specific chlorosilanes are tetrachlorosilane (SiCl4), trichlorosilane (HSiCl3), dichlorosilane (H2SiCl2), monochlorosilane (ClSiH3), chloroallylsilane, chloromethylsilane, dichloromethylsilane, chlorodimethylsilane, chloroethylsilane, t-butylchlorosilane, di-t-butylchlorosilane, chloroisopropylsilane, chloro-sec-butylsilane, t-butyldimethylchlorosilane, thexyldimethylchlorosilane, and the like.\",\n \"An aminosilane includes at least one nitrogen atom bonded to a silicon atom, but may also contain hydrogens, oxygens, halogens and carbons.\",\n \"Examples of aminosilanes are mono-, di-, tri- and tetra-aminosilane (H3Si(NH2)4, H2Si(NH2)2, HSi(NH2)3 and Si(NH2)4, respectively), as well as substituted mono-, di-, tri- and tetra-aminosilanes, for example, t-butylaminosilane, methylaminosilane, tert-butylsilanamine, bis(tertiarybutylamino)silane (SiH2(NHC(CH3)3)2 (BTBAS), tert-butyl silylcarbamate, SiH(CH3)—(N(CH3)2)2, SiHCl—(N(CH3)2)2, (Si(CH3)2NH)3 and the like.\",\n \"A further example of an aminosilane is trisilylamine (N(SiH3)3).\",\n \"After operation 1901, the deposition chamber may be purged in a sweep phase with an injector purge or a pump away step.\",\n \"Generally, a sweep phase removes or purges one of the vapor phase reactant from a reaction chamber and typically occurs only after delivery of such reactant is completed.\",\n \"In other words, that reactant is no longer delivered to the reaction chamber during the sweep phase.\",\n \"However, the reactant remains adsorbed on the substrate surface during the sweep phase.\",\n \"Typically, the sweep serves to remove any residual vapor phase reactant in the chamber after the reactant is adsorbed on the substrate surface to the desired level.\",\n \"A sweep phase may also remove weakly adsorbed species (e.g., certain precursor ligands or reaction by-products) from the substrate surface.\",\n \"In ALD, the sweep phase has been viewed as necessary to prevent gas phase interaction of two reactants or interaction of one reactant with a thermal, plasma or other driving force for the surface reaction.\",\n \"In general, and unless otherwise specified herein, a sweep/purge phase may be accomplished by (i) evacuating a reaction chamber, and/or (ii) flowing gas not containing the species to be swept out through the reaction chamber.\",\n \"In the case of (ii), such gas may be, for example, an inert gas.\",\n \"In operation 1903, the substrate may be exposed to a second precursor or an oxidant.\",\n \"In some embodiments, the oxidant is nitrous oxide (N2O) or oxygen (O2) or carbon dioxide (CO2) or a mixture or combinations thereof.\",\n \"In some embodiments, the oxidizer may be a mixture of oxygen (O2) and a weak oxidizer such as N2O, CO, CO2, NO, NO2, SO, SO2, CxHyOz and/or H2O.\",\n \"In other implementations, the oxidation reactant may be entirely a weak oxidizer.\",\n \"Alternatively, the oxidation reactant may include O3.In some embodiments, the oxidation reactant is about 0-50% O2 and about 50-100% weak oxidizer.\",\n \"In some cases, one of the reactants may be delivered continuously (e.g., even during delivery of other reactants and/or during plasma exposure).\",\n \"For example, an oxidizing reactant may be delivered continuously.\",\n \"The continuously flowing reactant may be delivered to the reaction chamber in conjunction with a carrier gas such as argon.\",\n \"In some cases, the delivery of the continuously flowing reactants to reaction chamber is controlled by using divert valve/inlet valve toggling.\",\n \"Gas flow changes may be diverted or co-flowed.\",\n \"In one example, a continuously flowing reactant is periodically diverted from the reaction chamber such that it is only delivered to the reaction chamber at certain periods.\",\n \"The continuously flowing gas may be diverted to an outlet/dump using appropriate valves.\",\n \"For instance, an oxidizing reactant may flow continuously, but only be delivered to the reaction chamber periodically.\",\n \"When the oxidizing reactant is not being delivered to the reaction chamber, it may be diverted to an outlet, recycle system, etc.\",\n \"In operation 1905, a plasma may be initiated with a low HFRF power while the substrate is exposed to the oxidant.\",\n \"In some embodiments, the low HFRF power per area of the wafer may be between about 1.768×10−4 W per mm2 and about 1.768×10−3 W per mm2 where mm2 represents the unit for surface area of the wafer.\",\n \"Plasma power may be scaled linearly with wafer surface area.\",\n \"For example, a low HFRF power may be between about 12.5 W to about 125 W per station for a 300 mm wafer, or between about 28 W and about 280 W for a 450 mm wafer.\",\n \"The deposition temperature may be between about 50° C. and about 150° C. After operation 1905, the deposition chamber may be purged again.\",\n \"These steps may be repeated until the desired thickness of the film is deposited.\",\n \"In some embodiments, operation 1905 may occur at a low temperature, such as a temperature less than about 100° C. with an HFRF power while exposing a 300 mm substrate to the oxidant between about 50 W and about 500 W in a four-station tool, the power being the total power applied to the four-station tool.\",\n \"In operation 1907, the substrate may be exposed to a titanium-containing precursor.\",\n \"Examples of titanium-containing precursors may be any of those described with respect to operation 1901.As an example, the substrate may be exposed to TDMAT for about 2 seconds, which may be described as a “dose.” After operation 1907, the deposition chamber may be purged with an injector purge or pump away step.\",\n \"As an example, the purge may last about 10 seconds.\",\n \"In operation 1909, the substrate may be exposed to another precursor or an oxidant.\",\n \"In many embodiments, the oxidant is nitrous oxide (N2O) or oxygen (O2) or carbon dioxide (CO2) or a mixture thereof.\",\n \"As an example, operation 1909 may be about 30 seconds, such that for the first 25 seconds, no oxidant is flowed and only a carrier gas or inert gas is flowed, and an oxidant is flowed starting after the 25 seconds and is kept on through the next operation.\",\n \"Examples of carrier gases include argon (Ar) and nitrogen (N2).\",\n \"The flow rate of these carrier gases may be between about 0 sccm and about 10,000 sccm.\",\n \"In operation 1911, a plasma may be initiated with high HFRF power while the substrate is exposed to the oxidant.\",\n \"In many embodiments, the HFRF power may be between about 125 W and about 1500 W per station for 300 mm wafers.\",\n \"As an example, HFRF power may be about 625 W per station.\",\n \"The plasma may be initiated for a time between about 0.25 seconds and about 3 seconds, or about 0.5 seconds.\",\n \"Operations 1907 through 1911 may occur at a temperature between about 50° C. and about 400° C., or between about 50° C. and 200° C., or about 150° C. and at a pressure between about 3 Torr and about 3.5 Torr.\",\n \"After operation 1911, the plasma may be turned off and the chamber may be purged or pumped to base.\",\n \"Example purge gases for use after operations 1901, 1903, 1905, 1907, 1909, and 1911 may be argon (Ar) or nitrogen (N2) or any other suitable purge gas.\",\n \"In some embodiments, the density of the film deposited in operations 1901 through 1905 may be less dense than the film deposited in operations 1907 through 1911.According to various embodiments, operations 1901 through 1905 may be performed at a lower temperature, and/or lower RF power, and/or shorter RF time, and/or lower pressure, and/or with a weaker oxidant than operations 1907 through 1911.These deposition conditions may help prevent damage to the underlying substrate while producing an operable device.\",\n \"FIG.\",\n \"20A provides a process flow diagram of a method of using nanolaminate layers in accordance with various embodiments.\",\n \"In operation 2001, a core layer may be deposited, such as those described with respect to FIG.\",\n \"1.The core layer may be an amorphous carbon layer, or amorphous silicon layer, or may be a photoresist.\",\n \"In some embodiments, the core layer is patterned.\",\n \"In operation 2003, a nanolaminate layer is deposited on the core layer.\",\n \"The nanolaminate layer may be deposited by CFD or PEALD methods.\",\n \"The nanolaminate layer may be deposited using operations 1901-1905 with respect to FIG.\",\n \"19 above.\",\n \"In some embodiments the nanolaminate layer may be silicon oxide (SiO2) or titanium oxide (TiO2).\",\n \"The thickness of the deposited nanolaminate layer may be between about 15 Å and about 200 Å, or between about 15 Å and about 100 Å.\",\n \"In operation 2005, a metal nitride or metal oxide layer may be deposited on the nanolaminate layer.\",\n \"The metal nitride or metal oxide layer may be deposited using operations 1907 through operation 1911 with respect to FIG.\",\n \"19 above.\",\n \"In some embodiments, the metal nitride or metal oxide layer is a silicon oxide or titanium oxide layer.\",\n \"In some embodiments, the metal nitride or metal oxide layer is a high quality titanium oxide layer.\",\n \"In various embodiments, the metal nitride or metal oxide layer has a high etch selectivity to the core.\",\n \"In many embodiments, the metal nitride or metal oxide layer is denser than the nanolaminate layer.\",\n \"FIG.\",\n \"20B is a process flow diagram of an example of a method of using a nanolaminate layer in accordance with various embodiments.\",\n \"In operation 2011, a thin nanolaminate layer is deposited on a substrate.\",\n \"A nanolaminate layer may be any of those discussed above with respect to FIGS.\",\n \"13 and 20A.\",\n \"The nanolaminate layer may be deposited using operations 1901-1905 with respect to FIG.\",\n \"19 above.\",\n \"In operation 2013, a titanium oxide layer may be deposited on the nanolaminate layer.\",\n \"An example of a titanium oxide layer deposited on a nanolaminate layer is described above with respect to FIG.\",\n \"14.The titanium oxide layer may be deposited using operations 1907 through operation 1911 with respect to FIG.\",\n \"19 above.\",\n \"Apparatus Deposition techniques provided herein may be implemented in a plasma enhanced chemical vapor deposition (PECVD) reactor or a conformal film deposition (CFD) reactor.\",\n \"Such a reactor may take many forms, and may be part of an apparatus that includes one or more chambers or “reactors” (sometimes including multiple stations) that may each house one or more wafers and may be configured to perform various wafer processing operations.\",\n \"The one or more chambers may maintain the wafer in a defined position or positions (with or without motion within that position, e.g., rotation, vibration, or other agitation).\",\n \"In one implementation, a wafer undergoing film deposition may be transferred from one station to another within a reactor chamber during the process.\",\n \"In other implementations, the wafer may be transferred from chamber to chamber within the apparatus to perform different operations, such as etching operations or lithography operations.\",\n \"The full film deposition may occur entirely at a single station or any fraction of the total film thickness for any deposition step.\",\n \"While in process, each wafer may be held in place by a pedestal, wafer chuck, and/or other wafer-holding apparatus.\",\n \"For certain operations in which the wafer is to be heated, the apparatus may include a heater, such as a heating plate.\",\n \"A Vector™ (e.g., C3 Vector) or Sequel™ (e.g., C2 Sequel) reactor, produced by Lam Research Corp. of Fremont, Calif., are both examples of suitable reactors that may be used to implement the techniques described herein.\",\n \"FIG.\",\n \"21 provides a simple block diagram depicting various reactor components arranged for implementing methods described herein.\",\n \"As shown, a reactor 2100 includes a process chamber 2124 that encloses other components of the reactor and serves to contain a plasma generated by a capacitive-discharge type system including a showerhead 2114 working in conjunction with a grounded heater block 2120.A high frequency (HF) radio frequency (RF) generator 2104 and a low frequency (LF) RF generator 2102 may be connected to a matching network 2106 and to the showerhead 2114.The power and frequency supplied by matching network 2106 may be sufficient to generate a plasma from process gases supplied to the process chamber 2124.For example, the matching network 2106 may provide 50 W to 500 W of HFRF power.\",\n \"In some examples, the matching network 2106 may provide 100 W to 5000 W of HFRF power and 100 W to 5000 W of LFRF power total energy.\",\n \"In a typical process, the HFRF component may generally be between 5 MHz to 60 MHz, e.g., 13.56 MHz.\",\n \"In operations where there is an LF component, the LF component may be from about 100 kHz to 2 MHz, e.g., 430 kHz.\",\n \"Within the reactor, a wafer pedestal 2118 may support a substrate 2116.The wafer pedestal 2118 may include a chuck, a fork, or lift pins (not shown) to hold and transfer the substrate during and between the deposition and/or plasma treatment reactions.\",\n \"The chuck may be an electrostatic chuck, a mechanical chuck, or various other types of chuck as are available for use in the industry and/or for research.\",\n \"Various process gases may be introduced via inlet 2112.Multiple source gas lines 2110 are connected to manifold 2108.The gases may be premixed or not.\",\n \"Appropriate valving and mass flow control mechanisms may be employed to ensure that the correct process gases are delivered during the deposition and plasma treatment phases of the process.\",\n \"In the case where a chemical precursor(s) is delivered in liquid form, liquid flow control mechanisms may be employed.\",\n \"Such liquids may then be vaporized and mixed with process gases during transportation in a manifold heated above the vaporization point of the chemical precursor supplied in liquid form before reaching the deposition chamber.\",\n \"Process gases may exit chamber 2124 via an outlet 2122.A vacuum pump, e.g., a one or two stage mechanical dry pump and/or turbomolecular pump 2140, may be used to draw process gases out of the process chamber 2124 and to maintain a suitably low pressure within the process chamber 2124 by using a closed-loop-controlled flow restriction device, such as a throttle valve or a pendulum valve.\",\n \"As discussed above, the techniques for deposition discussed herein may be implemented on a multi-station or single station tool.\",\n \"In specific implementations, a 300 mm Lam Vector™ tool having a 4-station deposition scheme or a 200 mm Sequel™ tool having a 6-station deposition scheme may be used.\",\n \"In some implementations, tools for processing 450 mm wafers may be used.\",\n \"In various implementations, the wafers may be indexed after every deposition and/or post-deposition plasma treatment, or may be indexed after etching steps if the etching chambers or stations are also part of the same tool, or multiple depositions and treatments may be conducted at a single station before indexing the wafer.\",\n \"In some embodiments, an apparatus may be provided that is configured to perform the techniques described herein.\",\n \"A suitable apparatus may include hardware for performing various process operations as well as a system controller 2130 having instructions for controlling process operations in accordance with the disclosed embodiments.\",\n \"The system controller 2130 will typically include one or more memory devices and one or more processors communicatively connected with various process control equipment, e.g., valves, RF generators, wafer handling systems, etc., and configured to execute the instructions so that the apparatus will perform a technique in accordance with the disclosed embodiments, e.g., a technique such as that provided in the deposition steps of FIG.\",\n \"19.Machine-readable media containing instructions for controlling process operations in accordance with the present disclosure may be coupled to the system controller 2130.The controller 2130 may be communicatively connected with various hardware devices, e.g., mass flow controllers, valves, RF generators, vacuum pumps, etc.\",\n \"to facilitate control of the various process parameters that are associated with the deposition operations as described herein.\",\n \"In some embodiments, a system controller 2130 may control all of the activities of the reactor 2100.The system controller 2130 may execute system control software stored in a mass storage device, loaded into a memory device, and executed on a processor.\",\n \"The system control software may include instructions for controlling the timing of gas flows, wafer movement, RF generator activation, etc., as well as instructions for controlling the mixture of gases, the chamber and/or station pressure, the chamber and/or station temperature, the wafer temperature, the target power levels, the RF power levels, the substrate pedestal, chuck, and/or susceptor position, and other parameters of a particular process performed by the reactor apparatus 2100.The system control software may be configured in any suitable way.\",\n \"For example, various process tool component subroutines or control objects may be written to control operation of the process tool components necessary to carry out various process tool processes.\",\n \"The system control software may be coded in any suitable computer readable programming language.\",\n \"The system controller 2130 may typically include one or more memory devices and one or more processors configured to execute the instructions so that the apparatus will perform a technique in accordance with the present disclosure.\",\n \"Machine-readable media containing instructions for controlling process operations in accordance with disclosed embodiments may be coupled to the system controller 2130.The method and apparatus described herein may be used in conjunction with lithographic patterning tools or processes such as those described below for fabrication or manufacture of semiconductor devices, displays, LEDs, photovoltaic panels, and the like.\",\n \"Typically, though not necessarily, such tools/processes will be used or conducted together in a common fabrication facility.\",\n \"Lithographic patterning of a film typically includes some or all of the following steps, each step performed with a number of possible tools: (1) application of photoresist on a workpiece, i.e., substrate or multi-layer stack as provided in disclosed embodiments, using a spin-on or spray-on tool; (2) curing a photoresist using a hot plate or furnace or UV curing tool; (3) exposing the photoresist to visible or UV or x-ray light with a tool such as a wafer stepper; (4) developing the resist so as to selectively remove resist and thereby pattern it using a tool such as a wet bench; (5) transferred the resist pattern into an underlying film or workpiece, such as an amorphous carbon layer, by using a dry or plasma-assisted etching tool such as those described below; and (6) removing the resist using a tool such as an RF or microwave plasma resist stripper.\",\n \"In one implementation, one or more gap features on a wafer are filled with a carbon film using a technique as described herein.\",\n \"The carbon film may then be used, for example, for one of the purposes described herein.\",\n \"Further the implementation may include one or more of steps (1) through (6) described above.\",\n \"One or more process stations may be included in a multi-station processing tool.\",\n \"FIG.\",\n \"22 shows a schematic view of an embodiment of a multi-station processing tool 2200 with an inbound load lock 2202 and an outbound load lock 2204, either or both of which may include a remote plasma source.\",\n \"A robot 2206, at atmospheric pressure, is configured to move wafers from a cassette loaded through a pod 2208 into inbound load lock 2202 via an atmospheric port 2210.A wafer is placed by the robot 2206 on a pedestal 2212 in the inbound load lock 2202, the atmospheric port 2210 is closed, and the load lock is pumped down.\",\n \"Where the inbound load lock 2202 includes a remote plasma source, the wafer may be exposed to a remote plasma treatment in the load lock prior to being introduced into a processing chamber 2214.Further, the wafer also may be heated in the inbound load lock 2202 as well, for example, to remove moisture and adsorbed gases.\",\n \"Next, a chamber transport port 2216 to processing chamber 2214 is opened, and another robot (not shown) places the wafer into the reactor on a pedestal of a first station shown in the reactor for processing.\",\n \"While the embodiment depicted includes load locks, it will be appreciated that, in some embodiments, direct entry of a wafer into a process station may be provided.\",\n \"The depicted processing chamber 2214 includes four process stations, numbered from 1 to 4 in the embodiment shown in FIG.\",\n \"22.Each station has a heated pedestal (shown at 2218 for station 1), and gas line inlets.\",\n \"It will be appreciated that in some embodiments, each process station may have different or multiple purposes.\",\n \"For example, in some embodiments, a process station may be switchable between a CFD and PECVD process mode.\",\n \"Additionally or alternatively, in some embodiments, processing chamber 2214 may include one or more matched pairs of CFD and PECVD process stations.\",\n \"While the depicted processing chamber 2214 includes four stations, it will be understood that a processing chamber according to the present disclosure may have any suitable number of stations.\",\n \"For example, in some embodiments, a processing chamber may have five or more stations, while in other embodiments a processing chamber may have three or fewer stations.\",\n \"FIG.\",\n \"22 also depicts an embodiment of a wafer handling system 2290 for transferring wafers within processing chamber 2214.In some embodiments, wafer handling system 2290 may transfer wafers between various process stations and/or between a process station and a load lock.\",\n \"It will be appreciated that any suitable wafer handling system may be employed.\",\n \"Non-limiting examples include wafer carousels and wafer handling robots.\",\n \"FIG.\",\n \"22 also depicts an embodiment of a system controller 2250 employed to control process conditions and hardware states of process tool 2200.System controller 2250 may include one or more memory devices 2256, one or more mass storage devices 2254, and one or more processors 2252.Processor 2252 may include a CPU or computer, analog and/or digital input/output connections, stepper motor controller boards, etc.\",\n \"In some embodiments, system controller 2250 controls all of the activities of process tool 2200.System controller 2250 executes system control software 2258 stored in mass storage device 2254, loaded into memory device 2256, and executed on processor 2252.Alternatively, the control logic may be hard coded in the controller 2250.Applications Specific Integrated Circuits, Programmable Logic Devices (e.g., field-programmable gate arrays, or FPGAs) and the like may be used for these purposes.\",\n \"In the following discussion, wherever “software” or “code” is used, functionally comparable hard coded logic may be used in its place.\",\n \"System control software 2258 may include instructions for controlling the timing, mixture of gases, chamber and/or station pressure, chamber and/or station temperature, wafer temperature, target power levels, RF power levels, RF exposure time, substrate pedestal, chuck and/or susceptor position, and other parameters of a particular process performed by process tool 2200.System control software 2258 may be configured in any suitable way.\",\n \"For example, various process tool component subroutines or control objects may be written to control operation of the process tool components necessary to carry out various process tool processes.\",\n \"System control software 2258 may be coded in any suitable computer readable programming language.\",\n \"In some embodiments, system control software 2258 may include input/output control (IOC) sequencing instructions for controlling the various parameters described above.\",\n \"For example, each phase of a CFD process may include one or more instructions for execution by system controller 2250.The instructions for setting process conditions for a CFD process phase may be included in a corresponding CFD recipe phase.\",\n \"In some embodiments, the CFD recipe phases may be sequentially arranged, so that all instructions for a CFD process phase are executed concurrently with that process phase.\",\n \"Other computer software and/or programs stored on mass storage device 2254 and/or memory device 2256 associated with system controller 2250 may be employed in some embodiments.\",\n \"Examples of programs or sections of programs for this purpose include a substrate positioning program, a process gas control program, a pressure control program, a heater control program, and a plasma control program.\",\n \"A substrate positioning program may include program code for process tool components that are used to load the substrate onto pedestal 2218 and to control the spacing between the substrate and other parts of process tool 2200.A process gas control program may include code for controlling gas composition and flow rates and optionally for flowing gas into one or more process stations prior to deposition in order to stabilize the pressure in the process station.\",\n \"In some embodiments, the controller includes instructions for depositing a nanolaminate protective layer on a core layer, and depositing a conformal layer over the protective layer.\",\n \"A pressure control program may include code for controlling the pressure in the process station by regulating, for example, a throttle valve in the exhaust system of the process station, a gas flow into the process station, etc.\",\n \"In some embodiments, the controller includes instructions for depositing a nanolaminate protective layer on a core layer, and depositing a conformal layer over the protective layer.\",\n \"A heater control program may include code for controlling the current to a heating unit that is used to heat the substrate.\",\n \"Alternatively, the heater control program may control delivery of a heat transfer gas (such as helium) to the substrate.\",\n \"In certain implementations, the controller includes instructions for depositing a nanolaminate protective layer at a first temperature, and a conformal layer over the protective layer at a second temperature, where the second temperature is higher than the first temperature.\",\n \"A plasma control program may include code for setting RF power levels and exposure times in one or more process stations in accordance with the embodiments herein.\",\n \"In some embodiments, the controller includes instructions for depositing a nanolaminate protective layer at a first RF power level and RF duration, and depositing a conformal layer over the protective layer at a second RF power level and RF duration.\",\n \"The second RF power level and/or the second RF duration may be higher/longer than the first RF power level/duration.\",\n \"In some embodiments, there may be a user interface associated with system controller 2250.The user interface may include a display screen, graphical software displays of the apparatus and/or process conditions, and user input devices such as pointing devices, keyboards, touch screens, microphones, etc.\",\n \"In some embodiments, parameters adjusted by system controller 2250 may relate to process conditions.\",\n \"Non-limiting examples include process gas composition and flow rates, temperature, pressure, plasma conditions (such as RF bias power levels and exposure times), etc.\",\n \"These parameters may be provided to the user in the form of a recipe, which may be entered utilizing the user interface.\",\n \"Signals for monitoring the process may be provided by analog and/or digital input connections of system controller 2250 from various process tool sensors.\",\n \"The signals for controlling the process may be output on the analog and digital output connections of process tool 2200.Non-limiting examples of process tool sensors that may be monitored include mass flow controllers, pressure sensors (such as manometers), thermocouples, etc.\",\n \"Appropriately programmed feedback and control algorithms may be used with data from these sensors to maintain process conditions.\",\n \"System controller 2250 may provide program instructions for implementing the above-described deposition processes.\",\n \"The program instructions may control a variety of process parameters, such as DC power level, RF bias power level, pressure, temperature, etc.\",\n \"The instructions may control the parameters to operate in-situ deposition of film stacks according to various embodiments described herein.\",\n \"The system controller will typically include one or more memory devices and one or more processors configured to execute the instructions so that the apparatus will perform a method in accordance with the disclosed embodiments.\",\n \"Machine-readable, non-transitory media containing instructions for controlling process operations in accordance with the disclosed embodiments may be coupled to the system controller.\",\n \"EXPERIMENTAL Experiment 1 Experiments were conducted to compare deposited spacer or conformal films on unprotected cores and those deposited on cores protected by a nanolaminate protective layer.\",\n \"In the first trial, a substrate with a patterned core layer made of amorphous carbon was provided.\",\n \"High quality titanium oxide was deposited directly on the core layer by a plasma enhanced atomic layer deposition (PEALD) or conformal film deposition (CFD) method.\",\n \"The chamber pressure was about 3 Torr and at a temperature about 150° C. The substrate was exposed to the first precursor, TDMAT, for 2 seconds, followed by a 10 second purge.\",\n \"The substrate was then exposed to a mixture of oxidants N2O/O2 in a 30 second exposure where the first 25 seconds involved flowing only the carrier gas N2 (at a flow rate of up to 9500 sccm) and in the last five seconds, the N2O/O2 flow was turned on and stayed on until the plasma was initiated for 0.5 seconds.\",\n \"The plasma was initiated with a high frequency radio frequency (HFRF) power of 625 W per station, or 2500 W for four stations.\",\n \"The N2O/O2 flow and plasma were turned off at the same time after the 0.5 second plasma exposure, and lastly the chamber was pumped to base to purge the chamber.\",\n \"An image of the deposited conformal film and the underlying core layer is shown in FIG.\",\n \"23A.\",\n \"The degraded core layer 2304a is shown underneath the titanium oxide (TiO2) conformal film layer 2302a.\",\n \"In the second trial, a substrate with a patterned core layer made of amorphous carbon was also provided.\",\n \"A silicon oxide (SiO2) nanolaminate protective layer was deposited on the core layer by PEALD.\",\n \"Deposition chamber temperature was 50° C. and pressure of the chamber was 1.8 Torr.\",\n \"The substrate was exposed to a silicon-containing precursor 0.2 seconds, followed by a 0.2 second purge.\",\n \"The substrate was then exposed to a mixture of oxidants N2O/O2 in a 0.3 second exposure.\",\n \"A plasma was initiated for the four-station chamber at 1000 W, or about 500 W per station.\",\n \"The N2O/O2 flow and plasma were turned off and the chamber was purged.\",\n \"Subsequently, the substrate was exposed to TDMAT for 2 seconds, followed by a 10 second purge.\",\n \"Following the purge, the substrate was exposed to oxidants N2O/O2 in a 30 second exposure such that the mixture flowed only in the last 5 seconds and after the 30 seconds, continued to flow for 0.5 seconds while plasma was initiated for the 0.5 seconds at 625 W per station, or 2500 W for four stations.\",\n \"After both the plasma and the oxidants N2O/O2 flow were turned off, the chamber was again purged.\",\n \"An image of the deposited conformal film, nanolaminate layer, and underlying core layer is shown in FIG.\",\n \"23B.\",\n \"As shown, the deposited conformal film 2302b was deposited on top of a nanolaminate layer 2306 which is so thin that it is indistinguishable from the conformal film and core layer it is adjacent to.\",\n \"Note that compared to FIG.\",\n \"23A, the core mandrels 2304b have very little degradation or consumption.\",\n \"In the third trial, a substrate with a patterned core layer made of amorphous carbon was also provided.\",\n \"A titanium oxide (TiO2) nanolaminate protective layer was deposited on the core layer by PEALD.\",\n \"Deposition chamber temperature was 150° C. and pressure of the chamber was 3.0 Torr.\",\n \"The substrate was exposed to TDMAT for 2 seconds, followed by a 10 second purge.\",\n \"The substrate was then exposed to a mixture of oxidants N2O/O2 in a 30 second exposure such that the mixture flowed only in the last 5 seconds and after the 30 seconds, continued to flow for 0.5 seconds while a plasma was initiated for the four-station chamber at 1000 W, or about 500 W per station.\",\n \"The N2O/O2 flow and plasma were turned off and the chamber was purged.\",\n \"Subsequently, the substrate was exposed to TDMAT for 2 seconds, followed by a 10 second purge.\",\n \"Following the purge, the substrate was exposed to oxidants N2O/O2 in a 30 second exposure such that the mixture flowed only in the last 5 seconds and after the 30 seconds, continued to flow for 0.5 seconds while plasma was initiated for the 0.5 seconds at 625 W per station, or 2500 W for four stations.\",\n \"After both the plasma and the oxidants N2O/O2 flow were turned off, the chamber was again purged.\",\n \"An image of the deposited conformal film, nanolaminate layer, and underlying core layer is shown in FIG.\",\n \"23C.\",\n \"As shown, the deposited conformal film 2302c was deposited on top of a nanolaminate layer 2308 which is so also thin that it is indistinguishable from the conformal film and core layer it is adjacent to.\",\n \"Note that the core mandrels 2304c have very little degradation or consumption.\",\n \"Experiment 2 Another series of experiments were conducted using the same conditions as those described with respect to the three trials above, but for blanket substrates with no features.\",\n \"In each trial, the thickness of the amorphous carbon layer was measured, then the spacer was deposited and the spacer thickness was measured, and lastly the thickness of the remaining amorphous carbon layer after spacer deposition was measured.\",\n \"The carbon consumption was calculated by subtracting the thickness after spacer deposition from the thickness before spacer deposition.\",\n \"The results of this series of experiments are shown in Table 1.TABLE 1 Carbon Consumption and Nanolaminate Layers Trial 1 Trial 2 Trial 3 Nanolaminate Composition None SiO2 TiO2 Deposition Power 500 W 500 W Deposition Temperature 50° C. 150° C. Thickness Deposited (TEM) 1.44 nm Spacer Thickness Deposited (TEM) 5.9 nm 4.7 nm Amorphous Thickness Before Spacer Deposition 43.886 nm 44.1 nm 45.0 nm Carbon Thickness After Spacer Deposition 28.36 nm 35.3 nm 36.4 nm Carbon Consumption 15.4 nm 8 nm 8.6 nm As shown in the table, presence of the nanolaminate layer reduced carbon consumption substantially.\",\n \"Without the nanolaminate layer, carbon consumption was 15.4 nm, whereas for both the SiO2 and TiO2 nanolaminate layers, carbon consumption was only about 8 nm.\",\n \"Thus, depositing a nanolaminate layer over an amorphous carbon layer, particularly patterned amorphous carbon layer, protects the amorphous carbon layer when the spacer is deposited and higher quality films may be deposited for spacer deposition as a result.\",\n \"CONCLUSION Although the foregoing embodiments have been described in some detail for purposes of clarity of understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims.\",\n \"It should be noted that there are many alternative ways of implementing the processes, systems and apparatus of the present embodiments.\",\n \"Accordingly, the present embodiments are to be considered as illustrative and not restrictive, and the embodiments are not to be limited to the details given herein.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874766"}}},{"rowIdx":4494692,"cells":{"text":{"kind":"list like","value":[["PYRIDINE COMPOUNDS","The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity.","The present invention provides a compound represented by the formula (I): wherein R1 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R2 and R3 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R4 and R5 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R6 represents a hydrogen atom or the like, each R7 may be the same or different and may each represent an optionally substituted C1-6 alkoxy group or the like, X represents —CH═, —C(—R7)═, or —N═, and m represents 1 to 4, or a pharmacologically acceptable salt thereof."],["1.A method for the treatment of a disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by formula (I): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AB, a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different groups selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R2 and R3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group AC, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AB, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AE), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R4 and R5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AG), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), R6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), or a cyano group, X represents —CH═, —C(—R7)═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent AB: a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; AC: a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; AD: a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; AE: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AF: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; AG: a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AH: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and AJ: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof.","2.The method according to claim 1, wherein the disease or condition is pseudoxanthoma elasticum (PXE).","3.The method according to claim 1, wherein the subject is a human.","4.The method of claim 1, wherein the compound is represented by formula (Ia): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R2 and R3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R7)═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof.","5.The method of claim 4, wherein R1 is hydrogen atom.","6.The method of claim 4, wherein R2 and R3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.","7.The method of claim 4, wherein each substituent R7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro.","8.The method of claim 1, wherein the pharmacologically acceptable salt is sodium salt.","9.The method of claim 1, wherein the pharmacologically acceptable salt is potassium salt.","10.A method for inhibiting TNAP activity in a subject, comprising administering to a subject an effective amount of a compound represented by formula (I): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AB, a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different groups selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R2 and R3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group AC, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AB, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AE), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R4 and R5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AG), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), R6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), or a cyano group, X represents —CH═, —C(—R7)═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent AB: a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; AC: a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; AD: a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; AE: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AF: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; AG: a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AH: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and AJ: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof.","11.The method according to claim 10, wherein the subject is a human.","12.The method of claim 10, wherein the compound is represented by formula (Ia): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R2 and R3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R7)═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof.","13.The method of claim 12, wherein R1 is hydrogen atom.","14.The method of claim 12, wherein R2 and R3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.","15.The method of claim 12, wherein each substituent R7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro.","16.The method of claim 10, wherein the pharmacologically acceptable salt is sodium salt.","17.The method of claim 10, wherein the pharmacologically acceptable salt is potassium salt."],["<SOH> FIELD OF THE INVENTION <EOH>The present invention relates to a novel pyridine compound or a pharmacologically acceptable salt thereof which has excellent tissue non-specific alkaline phosphatase (hereinafter, referred to as TNAP) inhibitory activity.","The present invention also relates to a therapeutic agent and/or prophylactic agent (preferably a therapeutic agent) for pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient.","The present invention further relates to a composition for the treatment or prophylaxis of the aforementioned diseases, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient, use of the compound or the pharmacologically acceptable salt thereof for manufacturing a pharmaceutical for the treatment or prophylaxis of the disease, and a method for the treatment or prophylaxis of the disease, comprising administering a pharmacologically effective amount of the compound or the pharmacologically acceptable salt thereof to a mammal (preferably a human)."],["<SOH> SUMMARY OF THE INVENTION <EOH>The present inventors have conducted diligent studies and consequently found that a compound represented by the formula (I) mentioned later has excellent TNAP inhibitory activity based on its specific chemical structure, further has excellent properties in terms of the physicochemical properties (e.g., stability) of a pharmaceutical, and serves as a safe and useful pharmaceutical as a prophylactic or therapeutic agent for a pathological condition or a disease associated with ectopic calcification.","On the basis of these findings, the present invention has been completed.","Specifically, the compound of the present invention has excellent properties in terms of TNAP inhibitory activity, solubility, cell membrane permeability, oral absorbability, concentration in blood, metabolic stability, tissue penetration, bioavailability (hereinafter, also referred to as BA), in vitro activity, in vivo activity, ex vivo activity, quick onset of drug efficacy, persistence of drug efficacy, physical stability, drug interaction, safety (e.g., cardiotoxicity or hepatotoxicity), etc., and is useful as a pharmaceutical [particularly, a pharmaceutical for the treatment or prophylaxis (preferably treatment) of pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification].","The present invention provides: (1) a compound represented by the following general formula (I): wherein R 1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group A B , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group A B , a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group A B , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group A B , a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R 2 and R 3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group A C , a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group A B , a C6-10 aryl group optionally substituted by one or two groups selected from substituent group A B , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group A B , a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group A D , a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group A D , a C6-10 aryl group optionally substituted by one group selected from substituent group A D , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group A D , an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group A D , a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group A D , a C6-10 aryl group optionally substituted by one group selected from substituent group A D , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group A D , an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A E ), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A F ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group A F ), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A F ), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R 2 and R 3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R 4 and R 5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A G ), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), R 6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R 6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R 7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A H ), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A H ), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group A J ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A J ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group A J ), or a cyano group, X represents —CH═, —C(—R 7 )═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent A B : a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; A C : a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; A D : a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; A E : a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; A F : a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; A G : a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; A H : a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and A J : a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof; (2) a compound represented by the following general formula (Ia): wherein R 1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R 2 and R 3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R 2 and R 3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R 7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R 7 )═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof; (3) a compound according to the above (2), wherein R 1 is hydrogen atom; (4) a compound according to the above (2), wherein R 2 and R 3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R 2 and R 3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring; (5) a compound according to the above (2), wherein each substituent R 7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro; (6) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-fluoro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; and pharmacologically acceptable salts thereof; (7) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; 5-chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 2,5-dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; and pharmacologically acceptable salts thereof; (8) a compound according to the above (1), where the compound is 5-fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (9) a compound according to the above (1), where the compound is 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (10) a compound according to the above (1), where the compound is 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (11) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is sodium salt; (12) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is potassium salt; (13) a pharmaceutical composition comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (14) the pharmaceutical composition according to the above (13), wherein the pharmaceutical composition is intended for the treatment or prophylaxis of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), or aortic stenosis; (15) a TNAP inhibitor comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (16) a method for the treatment or prophylaxis of a disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis, comprising administering a therapeutically effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to a subject in need thereof; (17) a method according to (16), wherein the disease or condition is pseudoxanthoma elasticum (PXE); (18) a method for inhibiting TNAP in a subject, comprising administering an effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to the subject; (19) a method according to the above (16) to (18), wherein the subject is a human; (20) use of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for the manufacturing a pharmaceutical composition; (21) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis; and (22) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of pseudoxanthoma elastic (PXE).","In the present invention, the “C1-6 alkyl group” refers to a linear or branched alkyl group having 1 to 6 carbon atoms.","Examples thereof can include methyl, ethyl, n-propyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, and 2-ethylbutyl groups.","For R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , or A B , the C1-6 alkyl group is preferably an alkyl group having 1 to 3 carbon atoms, most preferably an ethyl or methyl group.","In the present invention, the “C1-6 alkylcarbonyl group” refers to the aforementioned “C1-6 alkyl group” bonded to a carbonyl group.","Examples thereof can include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, s-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, 2-methylbutylcarbonyl, neopentylcarbonyl, 1-ethylpropylcarbonyl, n-hexylcarbonyl, isohexylcarbonyl, 4-methylpentylcarbonyl, 3-methylpentylcarbonyl, 2-methylpentylcarbonyl, 1-methylpentylcarbonyl, 3,3-dimethylbutylcarbonyl, 2,2-dimethylbutylcarbonyl, 1,1-dimethylbutylcarbonyl, 1,2-dimethylbutylcarbonyl, 1,3-dimethylbutylcarbonyl, 2,3-dimethylbutylcarbonyl, and 2-ethylbutylcarbonyl groups.","For R 1 , R 2 , or R 3 , the C1-6 alkylcarbonyl group is preferably an alkylcarbonyl group having 1 to 3 carbon atoms, most preferably a methylcarbonyl group.","In the present invention, the “C3-8 cycloalkyl group” refers to a 3- to 8-membered saturated cyclic hydrocarbon group.","Examples thereof can include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.","For R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , A E , A F , A H , or A J , the C3-8 cycloalkyl group is preferably a 3- to 6-membered saturated cyclic hydrocarbon group, more preferably a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group.","In the present invention, the “C6-10 aryl group” refers to an aromatic hydrocarbon group having 6 to 10 carbon atoms.","Examples thereof can include phenyl, indenyl, and naphthyl groups.","For R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , A C , A E , A F , A H , or A J , the C6-10 aryl group is preferably a phenyl group.","In the present invention, the “C1-6 alkoxy group” refers to the aforementioned “C1-6 alkyl group” bonded to an oxygen atom.","Examples thereof can include linear or branched alkoxy groups each having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, tert-butoxy, n-pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, n-hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, and 2,3-dimethylbutoxy.","For R 1 , R 2 , R 3 , R 7 , A B , A D , A E , A F , A G , A H , or A J , the C1-6 alkoxy group is preferably a methoxy or ethoxy group.","In the present invention, the “C1-6 alkoxycarbonyl group” refers to the aforementioned “C1-6 alkoxy group” bonded to a carbonyl group.","Examples thereof can include linear or branched alkoxycarbonyl groups each having 1 to 6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, tert-butoxycarbonyl, n-pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, n-hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, and 2,3-dimethylbutoxycarbonyl.","For R 1 , R 2 , R 3 , R 7 , A H , or A J , the C1-6 alkoxycarbonyl group is preferably a methoxycarbonyl or ethoxycarbonyl group.","In the present invention, the “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 4- to 7-membered saturated heterocyclic group containing one or two atoms of nitrogen, oxygen, and sulfur.","Examples thereof can include oxetanyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolyl groups.","In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.","Examples thereof can include morpholinylcarbonyl, thiomorpholinylcarbonyl, pyrrolidinylcarbonyl, pyrrolinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, tetrahydrofuranylcarbonyl, tetrahydropyranylcarbonyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyl groups.","In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to an oxygen atom.","Examples thereof can include morpholinylcarbonyloxy, thiomorpholinylcarbonyloxy, pyrrolidinylcarbonyloxy, pyrrolinylcarbonyloxy, piperidinylcarbonyloxy, piperazinylcarbonyloxy, tetrahydrofuranylcarbonyloxy, tetrahydropyranylcarbonyloxy, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyloxy groups.","In the present invention, the “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 3- to 10-membered heterocyclic group containing one to four atoms of nitrogen, oxygen, and sulfur.","Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and aromatic heterocyclic groups such as furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl.","The “3- to 10-membered heterocyclic group” may be condensed with an additional cyclic group.","Examples thereof can include benzofuranyl, chromenyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, isoindolinyl, 2,3-dihydro-1-benzofuranyl, 3,4-dihydro-1H-isochromenyl, 1,2,3,4-tetrahydroquinolinyl, and 1,2,3,4-tetrahydroisoquinolinyl groups.","In the present invention, the “3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.","Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and carbonyl groups of aromatic heterocyclic groups such as furylcarbonyl, thienylcarbonyl, pyrrolylcarbonyl, azepinylcarbonyl, pyrazolylcarbonyl, imidazolylcarbonyl, oxazolylcarbonyl, oxadiazolylcarbonyl, isoxazolylcarbonyl, thiazolylcarbonyl, isothiazolylcarbonyl, 1,2,3-oxadiazolylcarbonyl, triazolylcarbonyl, tetrazolylcarbonyl, thiadiazolylcarbonyl, pyranylcarbonyl, pyridylcarbonyl, pyridazinylcarbonyl, pyrimidinylcarbonyl, and pyrazinylcarbonyl groups.","In the present invention, the “3- to 10-membered heterocyclylaminocarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group via an amino group.","Examples thereof can include aminocarbonyl groups of aromatic heterocyclic groups such as furylaminocarbonyl, thienylaminocarbonyl, pyrrolylaminocarbonyl, azepinylaminocarbonyl, pyrazolylaminocarbonyl, imidazolylaminocarbonyl, oxazolylaminocarbonyl, oxadiazolylaminocarbonyl, isoxazolylaminocarbonyl, thiazolylaminocarbonyl, isothiazolylaminocarbonyl, 1,2,3-oxadiazolylaminocarbonyl, triazolylaminocarbonyl, tetrazolylaminocarbonyl, thiadiazolylaminocarbonyl, pyranylaminocarbonyl, pyridylaminocarbonyl, pyridazinylaminocarbonyl, pyrimidinylaminocarbonyl, and pyrazinylaminocarbonyl groups.","In the present invention, the “halogeno group” refers to a fluoro, chloro, bromo, or iodo group.","For R 1 , R 2 , R 3 , R 7 , A B , A C , A D , A E , A F , A G , A H , or A J , the halogeno group is preferably a fluoro, chloro, or bromo group.","Preferably, R 1 of the present invention is a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur.","Preferably, R 2 and R 3 of the present invention are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R 2 and R 3 are bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.","Preferably, each of R 4 and R 5 of the present invention is a hydrogen atom.","Preferably, R 6 of the present invention is a hydrogen atom.","Preferably, each R 7 of the present invention, which may be the same or different, represents a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group.","The compound represented by the general formula (I) of the present invention can form a salt with a base.","Such a salt with a base is included in the scope of the present invention.","Examples of the salt with a base can include: alkali metal salts such as lithium salt, sodium salt, potassium salt, and cesium salt; alkaline earth metal salts such as magnesium salt, calcium salt, and barium salt; inorganic nitrogen compound salts such as ammonium salt and hydrazine salt; primary amine salts such as methylamine salt, ethylamine salt, n-propylamine salt, isopropylamine salt, n-butylamine salt, 2-butylamine salt, isobutylamine salt, and tert-butylamine salt; secondary amine salts such as dimethylamine salt, diethylamine salt, diisopropylamine salt, pyrrolidine salt, piperidine salt, and morpholine salt; tertiary amine salts such as triethylamine salt and N-methylmorpholine salt; and aromatic amine salts such as pyridine salt, 4-(N,N-dimethylamino)pyridine salt, imidazole salt, and 1-methylimidazole salt.","The salt is preferably an alkali metal salt, most preferably sodium salt or potassium salt.","The compound represented by the general formula (I) of the present invention can form any ratio of a salt with a base.","The respective salts with bases or mixtures thereof are included in the scope of the present invention.","The compound represented by the general formula (I) of the present invention can form an acid-addition salt, depending on its substituent.","Such an acid-addition salt is included in the scope of the present invention.","The compound represented by the general formula (I) of the present invention can form any ratio of an acid-addition salt, depending on its substituent.","The respective acid-addition salts (e.g., monoacid salt and hemi-acid salt) or mixtures thereof are included in the salt of the present invention.","The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an anhydrate, a hydrate, or a solvate.","The respective forms or mixtures thereof are included in the scope of the present invention.","When the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof has at least one asymmetric center, carbon-carbon double bond, axial chirality, tautomerism, or the like, optical isomers (including enantiomers and diastereomers), geometric isomers, rotational isomers, and tautomers may exist.","These isomers and mixtures thereof are represented by a single formula such as the formula (I).","The present invention encompasses these isomers and mixtures (including racemates) thereof at any ratio.","The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an isotopic compound by the replacement of one or more atoms constituting the compound or the salt with isotopes at nonnatural ratios.","The isotopes can be radioactive or nonradioactive.","Examples thereof include deuterium ( 2 H; D), tritium ( 3 H; T), carbon-14 ( 14 C), and iodine-125 ( 125 I).","The radioactive or nonradioactive isotopic compound may be used as a pharmaceutical for the treatment or prophylaxis of a disease, a reagent for research (e.g., a reagent for assay), a diagnostic agent (e.g., a diagnostic imaging agent), or the like.","The present invention encompasses these radioactive or nonradioactive isotopic compounds.","The compound represented by the general formula (I) of the present invention can be produced by, for example, the following method: In the structural formulas of the compounds in the method A and the description below, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , m, and X are as defined in the formula (I); L 1 represents a nitro group, a halogeno group, or an amino group and is preferably a nitro group or a bromo group; and L 2 represents a halogeno group and is preferably a chloro group.","When a compound serving as a reactive substrate in the reaction of each step in the method A has a group inhibiting the reaction of interest, such as an amino group, a hydroxy group, or a carboxyl group, an appropriate protective group may be introduced to the functional group and the introduced protective group may be removed, if necessary.","Such a protective group is not particularly limited as long as the protective group is one usually used.","The protective group can be a protective group described in, for example, T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc.","The reactions for the introduction and removal of these protective groups can be carried out according to routine methods such as methods described in the literature.","The solvent for use in the reaction of each step in the method A is not particularly limited as long as the solvent partially dissolves starting materials without inhibiting the reaction.","The solvent is selected from, for example, the following solvent group: aliphatic hydrocarbons such as hexane, pentane, heptane, petroleum ether, and cyclohexane; aromatic hydrocarbons such as toluene, benzene, and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, cyclopentylmethyl ether, t-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone; esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate; nitriles such as acetonitrile, propionitrile, butyronitrile, and isobutyronitrile; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, and 2-methyl-2-propanol; amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N,N′-dimethylpropyleneurea, and hexamethylphosphortriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; water; and mixtures thereof.","The acid for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the acid does not inhibit the reaction.","The acid is selected from the following acid group: inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, and nitric acid; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; and organic sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid.","The base for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the base does not inhibit the reaction.","The base is selected from the following base group: alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate; alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and barium hydroxide; alkali metal phosphates such as sodium phosphate and potassium phosphate; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; alkali metal amides such as lithium amide, sodium amide, and potassium amide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; lithium amides such as lithium diisopropylamide (LDA), lithium cyclohexylisopropylamide, and lithium tetramethylpiperazide; alkali metal silylamides such as lithium bistrimethylsilylamide, sodium bistrimethylsilylamide, and potassium bistrimethylsilylamide; alkyllithiums such as methyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium; alkyl magnesium halides such as methyl magnesium chloride, methyl magnesium bromide, methyl magnesium iodide, ethyl magnesium chloride, ethyl magnesium bromide, isopropyl magnesium chloride, isopropyl magnesium bromide, and isobutyl magnesium chloride; and organic amines such as triethylamine, tributylamine, diisopropylethylamine, diethylamine, diisopropylamine, N-methylpiperidine, N-methylmorpholine, N-ethylmorpholine, pyridine, picoline, 2,6-lutidine, 4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO), and 1,8-diazabicyclo[5,4,0]-7-undecene (DBU).","In the reaction of each step in the method A mentioned below, the reaction temperature differs depending on solvents, starting materials, reagents, etc., and the reaction time differs depending on solvents, starting materials, reagents, etc.","After the completion of the reaction of each step in the method A mentioned below, the compound of interest of each step is isolated from the reaction mixture according to a routine method.","The compound of interest is obtained, for example, by: (i) if necessary, filtering off insoluble matter such as a catalyst; (ii) adding water and a water-immiscible solvent (e.g., methylene chloride, chloroform, diethyl ether, ethyl acetate, or toluene) to the reaction mixture to extract the compound of interest; (iii) washing the organic layer with water, followed by drying using a desiccant such as anhydrous sodium sulfate or anhydrous magnesium sulfate; and (iv) distilling off the solvent.","The obtained compound of interest can be further purified, if necessary, by a routine method, for example, recrystallization, reprecipitation, or silica gel column chromatography.","Alternatively, the compound of interest of each step may be used directly in the next reaction without being purified.","In the reaction of each step in the method A mentioned below, optical isomers can be resolved by resolution using a chiral column.","Hereinafter, the reaction of each step in the method A will be described."],["CROSS-REFERENCES TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser.","No.","15/481,151, filed Apr.","6, 2017, which is a continuation of Ser.","No.","15/314,887, filed Nov. 29, 2016, which is the national stage of International Application No.","PCT/US2016/041345, filed Jul.","7, 2006, which claims the benefit of U.S.","Provisional Application No.","62/190,145, filed Jul.","8, 2015, which applications are expressly incorporated herein by reference in their entirety.","FIELD OF THE INVENTION The present invention relates to a novel pyridine compound or a pharmacologically acceptable salt thereof which has excellent tissue non-specific alkaline phosphatase (hereinafter, referred to as TNAP) inhibitory activity.","The present invention also relates to a therapeutic agent and/or prophylactic agent (preferably a therapeutic agent) for pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient.","The present invention further relates to a composition for the treatment or prophylaxis of the aforementioned diseases, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient, use of the compound or the pharmacologically acceptable salt thereof for manufacturing a pharmaceutical for the treatment or prophylaxis of the disease, and a method for the treatment or prophylaxis of the disease, comprising administering a pharmacologically effective amount of the compound or the pharmacologically acceptable salt thereof to a mammal (preferably a human).","DESCRIPTION OF THE RELATED ART In vivo calcification is strictly regulated by the balance of activation between osteoblasts and osteoclasts, phosphorus and calcium concentrations in plasma, and parathyroid hormone or vitamin D secreted in order to maintain the homeostasis of these concentrations (Non Patent Literature 1).","Ectopic calcification is found in diseases, for example, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, and peritoneal calcification.","In these pathological conditions, calcification in tissues (blood vessels, soft tissues, etc.)","that are usually not calcified is caused by the failure of the regulatory mechanism mentioned above, and is known to bring about significantly reduced quality of life (QOL) due to the limitation of activity and an increased cardiovascular risk (Non Patent Literatures 2 and 3).","No existing therapeutic agent is effective for ectopic calcification.","Thus, there are very high unmet medical needs for this disease (Non Patent Literature 4).","TNAP, one of alkaline phosphatases, includes membrane-bound and secretory forms.","TNAP is expressed in the bone, the liver, and the kidney and highly expressed particularly in the matrix vesicles of chondrocytes and osteoblasts.","This enzyme is known to play an important role in in vivo calcification via the degradation of pyrophosphate, which is an endogenous anti-calcification factor (Non Patent Literature 5).","A large number of reports show the increased expression level or elevated activity of TNAP at lesion sites of ectopic calcification, and ectopic calcification also occurs in mice which overexpress human TNAP, suggesting the importance of TNAP for ectopic calcification (Non Patent Literatures 6 and 7).","Thus, the inhibition of TNAP is considered to elevate pyrophosphate concentrations in blood and in tissues and suppress ectopic calcification (Non Patent Literature 8).","Some compounds are known to have TNAP inhibitory activity (see e.g., Patent Literatures 1 and 2 and, Non Patent Literatures 9 to 12).","Among them, compounds partially having a common skeleton are disclosed.","Nonetheless, a compound having a 7-membered ring condensed with a pyridine ring has not yet been disclosed.","PATENT LITERATURE [Patent Literature 1] International Publication No.","WO 2009/017863 (PCT/US2008/063106) [Patent Literature 2] International Publication No.","WO 2013/126608 (U.S. Patent Publication No.","2015-0011551) NON PATENT LITERATURE [Non Patent Literature 1] J.","Bone Miner Res, 2006, vol.","24, p. 176-181 [Non Patent Literature 2] Clin.","Kidery.","J., 2014, vol.","7, p. 167-173 [Non Patent Literature 3] Eur.","Heart.","J., 2014, vol.","35, p.","1515-1525.","[Non Patent Literature 4] Int.","J. Nephrol.","Renovasc.","Dis., 2014, vol.","7, p. 161-168 [Non Patent Literature 5] J. Histochem.","Cytochem., 2002, vol.","50, p. 333-340 [Non Patent Literature 6] J.","Am.","Soc.","Nephrol., 2004, vol.","15, p. 1392-1401 [Non Patent Literature 7] J.","Bone Miner Res, 2013, vol.","7, p. 1587-1598 [Non Patent Literature 8] J.","Bone Miner Res, 2007, vol.","22, p. 1700-1710 [Non Patent Literature 9] Bioorg.","Med.","Chem.","Lett., 2009, vol.","19, p. 222-225 [Non Patent Literature 10] J. Med.","Chem., 2009, vol.","52, p. 6919-6925 [Non Patent Literature 11] Bioorg.","Med.","Chem., 2013, vol.","21, p. 7981-7897 [Non Patent Literature 12] J.","Bone Miner Res, 2015, vol.","30, p. 824-836 SUMMARY OF THE INVENTION The present inventors have conducted diligent studies and consequently found that a compound represented by the formula (I) mentioned later has excellent TNAP inhibitory activity based on its specific chemical structure, further has excellent properties in terms of the physicochemical properties (e.g., stability) of a pharmaceutical, and serves as a safe and useful pharmaceutical as a prophylactic or therapeutic agent for a pathological condition or a disease associated with ectopic calcification.","On the basis of these findings, the present invention has been completed.","Specifically, the compound of the present invention has excellent properties in terms of TNAP inhibitory activity, solubility, cell membrane permeability, oral absorbability, concentration in blood, metabolic stability, tissue penetration, bioavailability (hereinafter, also referred to as BA), in vitro activity, in vivo activity, ex vivo activity, quick onset of drug efficacy, persistence of drug efficacy, physical stability, drug interaction, safety (e.g., cardiotoxicity or hepatotoxicity), etc., and is useful as a pharmaceutical [particularly, a pharmaceutical for the treatment or prophylaxis (preferably treatment) of pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification].","The present invention provides: (1) a compound represented by the following general formula (I): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AB, a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R2 and R3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group AC, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AB, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AE), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R4 and R5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AG), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), R6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), or a cyano group, X represents —CH═, —C(—R7)═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent AB: a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; AC: a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; AD: a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; AE: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AF: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; AG: a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AH: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and AJ: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof; (2) a compound represented by the following general formula (Ia): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R2 and R3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R7)═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof; (3) a compound according to the above (2), wherein R1 is hydrogen atom; (4) a compound according to the above (2), wherein R2 and R3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring; (5) a compound according to the above (2), wherein each substituent R7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro; (6) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-fluoro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; and pharmacologically acceptable salts thereof; (7) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; 5-chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 2,5-dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; and pharmacologically acceptable salts thereof; (8) a compound according to the above (1), where the compound is 5-fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (9) a compound according to the above (1), where the compound is 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (10) a compound according to the above (1), where the compound is 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (11) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is sodium salt; (12) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is potassium salt; (13) a pharmaceutical composition comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (14) the pharmaceutical composition according to the above (13), wherein the pharmaceutical composition is intended for the treatment or prophylaxis of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), or aortic stenosis; (15) a TNAP inhibitor comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (16) a method for the treatment or prophylaxis of a disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis, comprising administering a therapeutically effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to a subject in need thereof; (17) a method according to (16), wherein the disease or condition is pseudoxanthoma elasticum (PXE); (18) a method for inhibiting TNAP in a subject, comprising administering an effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to the subject; (19) a method according to the above (16) to (18), wherein the subject is a human; (20) use of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for the manufacturing a pharmaceutical composition; (21) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis; and (22) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of pseudoxanthoma elastic (PXE).","In the present invention, the “C1-6 alkyl group” refers to a linear or branched alkyl group having 1 to 6 carbon atoms.","Examples thereof can include methyl, ethyl, n-propyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, and 2-ethylbutyl groups.","For R1, R2, R3, R4, R5, R6, R7, or AB, the C1-6 alkyl group is preferably an alkyl group having 1 to 3 carbon atoms, most preferably an ethyl or methyl group.","In the present invention, the “C1-6 alkylcarbonyl group” refers to the aforementioned “C1-6 alkyl group” bonded to a carbonyl group.","Examples thereof can include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, s-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, 2-methylbutylcarbonyl, neopentylcarbonyl, 1-ethylpropylcarbonyl, n-hexylcarbonyl, isohexylcarbonyl, 4-methylpentylcarbonyl, 3-methylpentylcarbonyl, 2-methylpentylcarbonyl, 1-methylpentylcarbonyl, 3,3-dimethylbutylcarbonyl, 2,2-dimethylbutylcarbonyl, 1,1-dimethylbutylcarbonyl, 1,2-dimethylbutylcarbonyl, 1,3-dimethylbutylcarbonyl, 2,3-dimethylbutylcarbonyl, and 2-ethylbutylcarbonyl groups.","For R1, R2, or R3, the C1-6 alkylcarbonyl group is preferably an alkylcarbonyl group having 1 to 3 carbon atoms, most preferably a methylcarbonyl group.","In the present invention, the “C3-8 cycloalkyl group” refers to a 3- to 8-membered saturated cyclic hydrocarbon group.","Examples thereof can include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.","For R1, R2, R3, R4, R5, R7, AE, AF, AH, or AJ, the C3-8 cycloalkyl group is preferably a 3- to 6-membered saturated cyclic hydrocarbon group, more preferably a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group.","In the present invention, the “C6-10 aryl group” refers to an aromatic hydrocarbon group having 6 to 10 carbon atoms.","Examples thereof can include phenyl, indenyl, and naphthyl groups.","For R1, R2, R3, R4, R5, R7, AC, AE, AF, AH, or AJ, the C6-10 aryl group is preferably a phenyl group.","In the present invention, the “C1-6 alkoxy group” refers to the aforementioned “C1-6 alkyl group” bonded to an oxygen atom.","Examples thereof can include linear or branched alkoxy groups each having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, tert-butoxy, n-pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, n-hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, and 2,3-dimethylbutoxy.","For R1, R2, R3, R7, AB, AD, AE, AF, AG, AH, or AJ, the C1-6 alkoxy group is preferably a methoxy or ethoxy group.","In the present invention, the “C1-6 alkoxycarbonyl group” refers to the aforementioned “C1-6 alkoxy group” bonded to a carbonyl group.","Examples thereof can include linear or branched alkoxycarbonyl groups each having 1 to 6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, tert-butoxycarbonyl, n-pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, n-hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, and 2,3-dimethylbutoxycarbonyl.","For R1, R2, R3, R7, AH, or AJ, the C1-6 alkoxycarbonyl group is preferably a methoxycarbonyl or ethoxycarbonyl group.","In the present invention, the “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 4- to 7-membered saturated heterocyclic group containing one or two atoms of nitrogen, oxygen, and sulfur.","Examples thereof can include oxetanyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolyl groups.","In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.","Examples thereof can include morpholinylcarbonyl, thiomorpholinylcarbonyl, pyrrolidinylcarbonyl, pyrrolinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, tetrahydrofuranylcarbonyl, tetrahydropyranylcarbonyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyl groups.","In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to an oxygen atom.","Examples thereof can include morpholinylcarbonyloxy, thiomorpholinylcarbonyloxy, pyrrolidinylcarbonyloxy, pyrrolinylcarbonyloxy, piperidinylcarbonyloxy, piperazinylcarbonyloxy, tetrahydrofuranylcarbonyloxy, tetrahydropyranylcarbonyloxy, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyloxy groups.","In the present invention, the “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 3- to 10-membered heterocyclic group containing one to four atoms of nitrogen, oxygen, and sulfur.","Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and aromatic heterocyclic groups such as furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl.","The “3- to 10-membered heterocyclic group” may be condensed with an additional cyclic group.","Examples thereof can include benzofuranyl, chromenyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, isoindolinyl, 2,3-dihydro-1-benzofuranyl, 3,4-dihydro-1H-isochromenyl, 1,2,3,4-tetrahydroquinolinyl, and 1,2,3,4-tetrahydroisoquinolinyl groups.","In the present invention, the “3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.","Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and carbonyl groups of aromatic heterocyclic groups such as furylcarbonyl, thienylcarbonyl, pyrrolylcarbonyl, azepinylcarbonyl, pyrazolylcarbonyl, imidazolylcarbonyl, oxazolylcarbonyl, oxadiazolylcarbonyl, isoxazolylcarbonyl, thiazolylcarbonyl, isothiazolylcarbonyl, 1,2,3-oxadiazolylcarbonyl, triazolylcarbonyl, tetrazolylcarbonyl, thiadiazolylcarbonyl, pyranylcarbonyl, pyridylcarbonyl, pyridazinylcarbonyl, pyrimidinylcarbonyl, and pyrazinylcarbonyl groups.","In the present invention, the “3- to 10-membered heterocyclylaminocarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group via an amino group.","Examples thereof can include aminocarbonyl groups of aromatic heterocyclic groups such as furylaminocarbonyl, thienylaminocarbonyl, pyrrolylaminocarbonyl, azepinylaminocarbonyl, pyrazolylaminocarbonyl, imidazolylaminocarbonyl, oxazolylaminocarbonyl, oxadiazolylaminocarbonyl, isoxazolylaminocarbonyl, thiazolylaminocarbonyl, isothiazolylaminocarbonyl, 1,2,3-oxadiazolylaminocarbonyl, triazolylaminocarbonyl, tetrazolylaminocarbonyl, thiadiazolylaminocarbonyl, pyranylaminocarbonyl, pyridylaminocarbonyl, pyridazinylaminocarbonyl, pyrimidinylaminocarbonyl, and pyrazinylaminocarbonyl groups.","In the present invention, the “halogeno group” refers to a fluoro, chloro, bromo, or iodo group.","For R1, R2, R3, R7, AB, AC, AD, AE, AF, AG, AH, or AJ, the halogeno group is preferably a fluoro, chloro, or bromo group.","Preferably, R1 of the present invention is a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur.","Preferably, R2 and R3 of the present invention are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.","Preferably, each of R4 and R5 of the present invention is a hydrogen atom.","Preferably, R6 of the present invention is a hydrogen atom.","Preferably, each R7 of the present invention, which may be the same or different, represents a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group.","The compound represented by the general formula (I) of the present invention can form a salt with a base.","Such a salt with a base is included in the scope of the present invention.","Examples of the salt with a base can include: alkali metal salts such as lithium salt, sodium salt, potassium salt, and cesium salt; alkaline earth metal salts such as magnesium salt, calcium salt, and barium salt; inorganic nitrogen compound salts such as ammonium salt and hydrazine salt; primary amine salts such as methylamine salt, ethylamine salt, n-propylamine salt, isopropylamine salt, n-butylamine salt, 2-butylamine salt, isobutylamine salt, and tert-butylamine salt; secondary amine salts such as dimethylamine salt, diethylamine salt, diisopropylamine salt, pyrrolidine salt, piperidine salt, and morpholine salt; tertiary amine salts such as triethylamine salt and N-methylmorpholine salt; and aromatic amine salts such as pyridine salt, 4-(N,N-dimethylamino)pyridine salt, imidazole salt, and 1-methylimidazole salt.","The salt is preferably an alkali metal salt, most preferably sodium salt or potassium salt.","The compound represented by the general formula (I) of the present invention can form any ratio of a salt with a base.","The respective salts with bases or mixtures thereof are included in the scope of the present invention.","The compound represented by the general formula (I) of the present invention can form an acid-addition salt, depending on its substituent.","Such an acid-addition salt is included in the scope of the present invention.","The compound represented by the general formula (I) of the present invention can form any ratio of an acid-addition salt, depending on its substituent.","The respective acid-addition salts (e.g., monoacid salt and hemi-acid salt) or mixtures thereof are included in the salt of the present invention.","The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an anhydrate, a hydrate, or a solvate.","The respective forms or mixtures thereof are included in the scope of the present invention.","When the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof has at least one asymmetric center, carbon-carbon double bond, axial chirality, tautomerism, or the like, optical isomers (including enantiomers and diastereomers), geometric isomers, rotational isomers, and tautomers may exist.","These isomers and mixtures thereof are represented by a single formula such as the formula (I).","The present invention encompasses these isomers and mixtures (including racemates) thereof at any ratio.","The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an isotopic compound by the replacement of one or more atoms constituting the compound or the salt with isotopes at nonnatural ratios.","The isotopes can be radioactive or nonradioactive.","Examples thereof include deuterium (2H; D), tritium (3H; T), carbon-14 (14C), and iodine-125 (125I).","The radioactive or nonradioactive isotopic compound may be used as a pharmaceutical for the treatment or prophylaxis of a disease, a reagent for research (e.g., a reagent for assay), a diagnostic agent (e.g., a diagnostic imaging agent), or the like.","The present invention encompasses these radioactive or nonradioactive isotopic compounds.","The compound represented by the general formula (I) of the present invention can be produced by, for example, the following method: In the structural formulas of the compounds in the method A and the description below, R1, R2, R3, R4, R5, R6, R7, m, and X are as defined in the formula (I); L1 represents a nitro group, a halogeno group, or an amino group and is preferably a nitro group or a bromo group; and L2 represents a halogeno group and is preferably a chloro group.","When a compound serving as a reactive substrate in the reaction of each step in the method A has a group inhibiting the reaction of interest, such as an amino group, a hydroxy group, or a carboxyl group, an appropriate protective group may be introduced to the functional group and the introduced protective group may be removed, if necessary.","Such a protective group is not particularly limited as long as the protective group is one usually used.","The protective group can be a protective group described in, for example, T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc.","The reactions for the introduction and removal of these protective groups can be carried out according to routine methods such as methods described in the literature.","The solvent for use in the reaction of each step in the method A is not particularly limited as long as the solvent partially dissolves starting materials without inhibiting the reaction.","The solvent is selected from, for example, the following solvent group: aliphatic hydrocarbons such as hexane, pentane, heptane, petroleum ether, and cyclohexane; aromatic hydrocarbons such as toluene, benzene, and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, cyclopentylmethyl ether, t-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone; esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate; nitriles such as acetonitrile, propionitrile, butyronitrile, and isobutyronitrile; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, and 2-methyl-2-propanol; amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N,N′-dimethylpropyleneurea, and hexamethylphosphortriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; water; and mixtures thereof.","The acid for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the acid does not inhibit the reaction.","The acid is selected from the following acid group: inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, and nitric acid; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; and organic sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid.","The base for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the base does not inhibit the reaction.","The base is selected from the following base group: alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate; alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and barium hydroxide; alkali metal phosphates such as sodium phosphate and potassium phosphate; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; alkali metal amides such as lithium amide, sodium amide, and potassium amide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; lithium amides such as lithium diisopropylamide (LDA), lithium cyclohexylisopropylamide, and lithium tetramethylpiperazide; alkali metal silylamides such as lithium bistrimethylsilylamide, sodium bistrimethylsilylamide, and potassium bistrimethylsilylamide; alkyllithiums such as methyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium; alkyl magnesium halides such as methyl magnesium chloride, methyl magnesium bromide, methyl magnesium iodide, ethyl magnesium chloride, ethyl magnesium bromide, isopropyl magnesium chloride, isopropyl magnesium bromide, and isobutyl magnesium chloride; and organic amines such as triethylamine, tributylamine, diisopropylethylamine, diethylamine, diisopropylamine, N-methylpiperidine, N-methylmorpholine, N-ethylmorpholine, pyridine, picoline, 2,6-lutidine, 4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO), and 1,8-diazabicyclo[5,4,0]-7-undecene (DBU).","In the reaction of each step in the method A mentioned below, the reaction temperature differs depending on solvents, starting materials, reagents, etc., and the reaction time differs depending on solvents, starting materials, reagents, etc.","After the completion of the reaction of each step in the method A mentioned below, the compound of interest of each step is isolated from the reaction mixture according to a routine method.","The compound of interest is obtained, for example, by: (i) if necessary, filtering off insoluble matter such as a catalyst; (ii) adding water and a water-immiscible solvent (e.g., methylene chloride, chloroform, diethyl ether, ethyl acetate, or toluene) to the reaction mixture to extract the compound of interest; (iii) washing the organic layer with water, followed by drying using a desiccant such as anhydrous sodium sulfate or anhydrous magnesium sulfate; and (iv) distilling off the solvent.","The obtained compound of interest can be further purified, if necessary, by a routine method, for example, recrystallization, reprecipitation, or silica gel column chromatography.","Alternatively, the compound of interest of each step may be used directly in the next reaction without being purified.","In the reaction of each step in the method A mentioned below, optical isomers can be resolved by resolution using a chiral column.","Hereinafter, the reaction of each step in the method A will be described.","(Step A-1) Step A-1 is the step of condensing compound (1) with compound (2) to produce compound (3).","The compound (2) is known in the art or is easily obtained from a compound known in the art.","The method for condensing a carboxylic acid with an amine differs depending on the type of the carboxylic acid and can be generally carried out by a method well known in the techniques of organic synthetic chemistry, for example, a method described in Comprehensive Organic Transformations (Second Edition, 1999, John Wiley & Sons, Inc., pp.","1929-1930, 1941-1949, and 1953-1954).","A preferred method involves converting the carboxylic acid to a corresponding acid halide, which is then condensed with a corresponding amine.","Thus, step A-1 comprises: (step A-1a): the step of reacting compound (1) with a halogenating agent; and (step A-1b): the step of reacting the compound obtained in the step A-1a with compound (2) in the presence of a base.","(Step A-1a) Examples of the halogenating agent used can include: thionyl chloride, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, phosphorus tribromide, phosphorus pentabromide, oxalyl chloride, carbon tetrachloride-triphenylphosphine, hexachloroethane-triphenylphosphine, N-chlorosuccinimide-triphenylphosphine, carbon tetrabromide-triphenylphosphine, and N-bromosuccinimide-triphenylphosphine; and combinations of these halogenating agents with additives such as N,N-dimethylformamide.","The halogenating agent is preferably a combination of thionyl chloride with an additive or a combination of oxalyl chloride with an additive, more preferably a combination of oxalyl chloride with N,N-dimethylformamide.","Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, and esters.","The solvent is preferably a halogenated hydrocarbon or an ether, more preferably methylene chloride or tetrahydrofuran.","The reaction temperature is preferably 0° C. to 100° C., more preferably room temperature.","The reaction time is preferably 15 minutes to 6 hours.","(Step A-1b) Examples of the base used can include alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, lithium amides, alkali metal silylamides, alkyllithiums, and organic amines.","The base is preferably an organic amine, more preferably triethylamine or diisopropylethylamine.","Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, esters, and amides.","The solvent is preferably an ether or an amide, more preferably tetrahydrofuran or N,N-dimethylformamide.","The reaction temperature is preferably −78° C. to 100° C., more preferably −20° C. to room temperature.","The reaction time is preferably 15 minutes to 24 hours.","(Step A-2) Step A-2 is the step of intramolecularly cyclizing the compound (3) obtained in the step A-1b in the presence of a base to produce compound (4).","The compound (4) of interest of this step can also be converted, if necessary, to another compound (4) of interest through deprotection reaction.","Alternatively, the compound (4) of interest of this step can also be converted, if necessary, to another compound (4) of interest through modification reaction on the nitrogen atom of the amide group.","Examples of the base used can include alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal alkoxides, lithium amides, alkali metal silylamides, and organic amines.","The base is preferably an alkali metal hydride, an alkali metal carbonate, an alkali metal silylamide, or an organic amine, more preferably sodium bistrimethylsilylamide, sodium hydride, potassium carbonate, or cesium carbonate.","Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, and amides.","The solvent is preferably an ether, a nitrile, or an amide, more preferably tetrahydrofuran, acetonitrile, or N,N-dimethylformamide.","The reaction temperature is preferably −78° C. to 100° C. The reaction time is preferably 15 minutes to 24 hours.","The reaction for converting the compound (4) of interest obtained in this step to another compound (4) of interest by the removal of the protective group differs depending on the type of the protective group and can be generally carried out according to a routine method such as a method well known in the techniques of organic synthetic chemistry, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc.","The reaction for converting the compound (4) of interest obtained in this step to another compound (4) of interest through modification on the nitrogen atom of the amide group is not particularly limited as long as the reaction does not influence the other parts of the compound.","This reaction can be carried out by, for example, a method described in Comprehensive Organic Transformations (Second Edition, 1999, John Wiley & Sons, Inc., pp.","1978-1982).","(Step A-3) Step A-3 is the step of reacting the compound (4) obtained in the step A-2 with compound (5) in the presence of a base to produce compound (I).","The compound (5) is known in the art or is easily obtained from a compound known in the art.","The compound (I) of interest of this step can also be converted, if necessary, to another compound (I) of interest through deprotection reaction.","The reaction for converting the obtained compound (I) of interest to another compound (I) of interest by the removal of the protective group is not particularly limited as long as the reaction does not influence the other parts of the compound.","This reaction can be carried out according to a routine method, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc. Hereinafter, this step is referred to as step A-3-1 when L1 is a nitro group, as step A-3-2 when L1 is an amino group, and as step A-3-3 when L1 is a halogeno group.","(Step A-3-1) When L1 is a nitro group, step A-3-1 comprises: (step A-3-1a): the step of selectively reducing the nitro group of the compound obtained in the step A-2 into an amino group; and (step A-3-1b): the step of reacting the compound obtained in the step A-3-1a with compound (5) in the presence of a base to produce compound (I).","(Step A-3-1a) The method for selectively reducing the nitro group is not particularly limited as long as the method does not influence the other parts of the compound.","This method can be generally carried out by a method well known in the techniques of organic synthetic chemistry, for example, a method described in Comprehensive Organic Transformations (Second Edition, 1999, John Wiley & Sons, Inc., pp.","821-828).","The method is preferably a catalytic reduction method or a method using a combination of a reducing agent and an additive.","Examples of the metal catalyst for use in the catalytic reduction method can include: palladium catalysts such as palladium on carbon, palladium black, palladium hydroxide on carbon, and palladium on barium sulfate; platinum catalysts such as platinum oxide and platinum black, platinum on carbon; rhodium catalysts such as rhodium on aluminum oxide and chlorotris(triphenylphosphine)rhodium (I); and nickel catalysts such as Raney nickel.","The metal catalyst is preferably a palladium catalyst, more preferably 10% palladium on carbon.","The hydrogen pressure in the catalytic reduction method is preferably 1 to 10 atm, more preferably 1 atm.","The solvent for use in the catalytic reduction method is not particularly limited as long as the solvent is inert to this reaction.","Examples thereof can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, amides, and mixtures thereof.","The solvent is preferably an alcohol, an ether, an amide, or a mixture thereof, more preferably methanol or a mixture of tetrahydrofuran and ethanol.","The reaction temperature in the catalytic reduction method is preferably room temperature to 60° C. The reaction time in the catalytic reduction method is preferably 1 hour to 24 hours.","The combination of the reagents for use in the reaction using the combination of the reducing agent and the additive is preferably a combination of sodium borohydride and nickel(II) chloride hexahydrate, a combination of zinc powder and acetic acid, a combination of iron powder and acetic acid, or a combination of tin(II) chloride and hydrochloric acid, more preferably a combination of sodium borohydride and nickel(II) chloride hexahydrate.","The solvent for use in the reaction using the combination of the reducing agent and the additive is preferably a mixture of an alcohol and an ether, more preferably a mixture of tetrahydrofuran and methanol.","The reaction temperature in the reaction using the combination of the reducing agent and the additive is preferably 0° C. to room temperature.","The reaction time in the reaction using the combination of the reducing agent and the additive is preferably 5 minutes to 2 hours.","(Step A-3-1b) Examples of the base used can include alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, alkali metal hydroxides, alkali metal alkoxides, lithium amides, alkali metal silylamides, and organic amines.","The base is preferably an organic amine, more preferably pyridine.","Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, esters, nitriles, ketones, and amides.","Alternatively, the solvent may not be used.","Preferably, the solvent is not used.","The reaction temperature is preferably 0° C. to 100° C., more preferably room temperature to 80° C. The reaction time is preferably 15 minutes to 24 hours, more preferably 30 minutes to 3 hours.","The reaction for converting the obtained compound (I) of interest obtained in this step to another compound (I) of interest by the removal of the protective group is not particularly limited as long as the reaction does not influence the other parts of the compound.","This reaction can be carried out according to a routine method, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc. (Step A-3-2) When L1 is an amino group, the compound (I) can be produced according to the step A-3-1b.","(Step A-3-3) When L1 is a halogeno group, step A-3-3 comprises: (step A-3-3a): the step of converting the bromo group of the compound produced in the step A-2 to a N-Boc amide group using a metal catalyst in the presence of a base; (step A-3-3b): the step of deprotecting the N-Boc group of the compound obtained in the step A-3-3a to form an amino group; and (step A-3-3c): the step of reacting the compound obtained in the step A-3-3b with compound (5) in the presence of a base to produce compound (I).","(Step A-3-3a) The method for converting the bromo group on the aromatic ring to a N-Boc amide group is not particularly limited as long as the method does not influence the other parts of the compound.","This method can be carried out according to a method well known in the techniques of organic synthetic chemistry, for example, a method described in A. P. Dishington, P. D. Johnson, J. G. Kettle, Tetrahedron Letters, 45, 3733 (2004) or S. Bhagwanth, A. G. Waterson, G. M. Adjabeng, K. R. Hornberger, Journal of Organic Chemistry, 74, 4634 (2009).","The metal catalyst used is preferably a combination of tris(dibenzylideneacetone)dipalladium(0) chloroform complex and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos™) or a combination of tris(dibenzylideneacetone)dipalladium(0) chloroform complex and di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (tBuXPhos™).","The base used is preferably an alkali metal carbonate, an alkali metal phosphate, or an alkali metal alkoxide, more preferably potassium carbonate, cesium carbonate, potassium phosphate, or sodium tert-butoxide.","Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, amides, and mixtures thereof.","The solvent is preferably an aromatic hydrocarbon, an ether, a nitrile, or an amide, more preferably toluene, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide.","The reaction temperature is preferably room temperature to 100° C. The reaction time is preferably 1 hour to 48 hours.","(Step A-3-3b) The method for deprotecting the N-Boc group is not particularly limited as long as the method does not influence the other parts of the compound.","This method can be carried out according to a routine method, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc., pp.","725-735.","(Step A-3-3c) The compound (I) can be produced according to the step A-3-1b.","When L1 is a bromo group, the compound (I) can also be produced through the reaction of the compound (4) with the following compound (6): using a metal catalyst in the presence of a base.","The method for converting the bromo group on the aromatic ring to a benzenesulfonamide group is not particularly limited as long as the method does not influence the other parts of the compound.","This method can be carried out according to a method well known in the techniques of organic synthetic chemistry, for example, a method described in X. Wang, A. Guram, M. Ronk, J. E. Milne, J. S. Tedrow, M. M. Faul, Tetrahedron Letters, 53, 7 (2012), W. Deng, L. Liu, C. Zhang, M. Liu, Q.-X.","Guo, Tetrahedron Letters, 46, 7295 (2005), or D. K. Luci, J.","B. Jameson, A. Yasgar, G. Diaz, N. Joshi, A. Kantz, K. Markham, S. Perry, N. Kuhn, J. Yeung, E. H. Kerns, L. Schultz, M. Holinstat, J. Nadler, D. A. Taylor-Fishwick, A. Jadhav, A. Simeonov, T. R. Holman, D. J. Maloney, Journal of Medicinal Chemistry, 57, 495 (2014).","The metal catalyst used is preferably a combination of copper(I) iodide and N-methyl-2-(methylamino)ethylamine.","The base used is preferably an alkali metal carbonate, an alkali metal phosphate, or an alkali metal alkoxide, more preferably potassium carbonate or cesium carbonate.","Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, amides, and mixtures thereof.","The solvent is preferably an aromatic hydrocarbon, an ether, a nitrile, or an amide, more preferably xylene, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide.","The reaction temperature is preferably room temperature to 100° C. The reaction time is preferably 1 hour to 48 hours.","When the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof is used as a pharmaceutical, the compound or the salt can be administered alone (i.e., as a bulk) or can be administered orally as an appropriate pharmaceutically acceptable preparation such as a tablet, a capsule, granules, a powder, or a syrup or parenterally as an appropriate pharmaceutically acceptable preparation such as an injection, a suppository, or a patch (preferably orally).","These preparations are produced by well-known methods using additives such as excipients, binders, disintegrants, lubricants, emulsifiers, stabilizers, corrigents, diluents, solvents for injections, oleaginous bases, and water-soluble bases.","Examples of the excipients can include organic excipients and inorganic excipients.","Examples of the organic excipients can include: sugar derivatives such as lactose, saccharose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, and internally cross-linked carboxymethylcellulose sodium; gum arabic; dextran; and pullulan.","Examples of the inorganic excipients can include: light anhydrous silicic acid and silicate derivatives such as synthetic aluminum silicate and calcium silicate; phosphates such as calcium phosphate; and sulfates such as calcium sulfates.","Examples of the binders can include: the excipients listed above; gelatin; polyvinylpyrrolidone; and polyethylene glycol.","Examples of the disintegrants can include: the excipients listed above; chemically modified starch or cellulose derivatives such as croscarmellose sodium and carboxymethyl starch sodium; and cross-linked polyvinylpyrrolidone.","Examples of the lubricants can include: talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as bees wax and spermaceti; boric acid; glycol; D,L-leucine; carboxylic acids such as fumaric acid and adipic acid; carboxylic acid sodium salts such as sodium benzoate; sulfates such as sodium sulfate; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; and the starch derivatives listed as the excipients.","Examples of the emulsifiers can include: colloidal clay such as bentonite and veegum; anionic surfactants such as sodium lauryl sulfate and calcium stearate; cationic surfactants such as benzalkonium chloride; and nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, and sucrose fatty acid ester.","Examples of the stabilizers can include: p-hydroxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; and sorbic acid.","Examples of the corrigents can include sweeteners, acidulants, and flavors usually used.","Examples of the diluents can include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid esters.","Examples of the solvents for injections can include water, ethanol, and glycerin.","Examples of the oleaginous bases can include cacao butter, laurin butter, coconut oil, palm kernel oil, camellia oil, liquid paraffin, white petrolatum, purified lanoline, glycerin monostearate, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, sucrose fatty acid ester, stearyl alcohol, and cetanol.","Examples of the water-soluble bases can include glycerin, polyethylene glycol, ethanol, and purified water.","The dose of the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof serving as an active ingredient differs depending on the symptoms and age of a patient, etc.","The single dose thereof is 0.001 mg/kg (preferably 0.01 mg/kg) as the lower limit and 10 mg/kg (preferably 1 mg/kg) as the upper limit for oral administration and 0.001 mg/kg (preferably 0.01 mg/kg) as the lower limit and 10 mg/kg (preferably 1 mg/kg) as the upper limit for parenteral administration and can be administered once to six times a day according to the symptoms.","The compound of the present invention can be used in combination with any of various therapeutic or prophylactic agents for the aforementioned disease for which the compound of the present invention is probably effective.","In this combined use, the compound of the present invention and the agent may be administered simultaneously, separately but continuously, or at the desired time interval.","The preparations to be administered simultaneously may be formulated as a combination drug or formulated as separate preparations.","The pyridine compound or the pharmacologically acceptable salt thereof, which is the compound of the present invention, has an excellent TNAP inhibitory effect and is useful as a therapeutic or prophylactic agent for pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), arterial calcification due to deficiency of CD73 (ACDC), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, or peritoneal calcification.","Moreover, the compound of the present invention has low toxicity and excellent safety and as such, is very useful as a pharmaceutical.","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in more detail with reference to Examples, etc.","However, the scope of the present invention is not intended to be limited by them.","The chemical structural formulas described in Examples represent the chemical structures of corresponding compounds in a free form.","Elution in column chromatography in Examples was carried out under observation by thin layer chromatography (TLC).","In the TLC observation, silica gel 60F254 manufactured by Merck KGaA was used as a TLC plate; a solvent used as an eluting solvent in column chromatography was used as a developing solvent; and a UV detector or a chromogenic method using a coloring agent (e.g., a ninhydrin coloring solution, an anisaldehyde coloring solution, an ammonium phosphomolybdate coloring solution, a cerium ammonium nitrate (CAM) coloring solution, or an alkaline permanganate coloring solution) was used as a detection method.","Silica gel SK-85 (230-400 mesh) also manufactured by Merck KGaA, silica gel 60 N (40-50 μm) manufactured by Kanto Chemical Co., Inc., or Chromatorex NH (200-350 mesh) manufactured by Fuji Silysia Chemical Ltd. was used as silica gel for columns.","In addition to general column chromatography, an automatic chromatography apparatus (Purif-α2 or Purif-espoir2) manufactured by Shoko Scientific Co., Ltd., an automatic chromatography apparatus (W-Prep 2XY) manufactured by Yamazen Corp., an automatic chromatography apparatus (Isolera One) manufactured by Biotage Japan Ltd., or an automatic chromatography apparatus (CombiFlash Rf) manufactured by Teledyne Isco, Inc. was appropriately used.","The eluting solvent was determined on the basis of the TLC observation.","In Examples, nuclear magnetic resonance (1H NMR) spectra were indicated by chemical shift δ values (ppm) determined with tetramethylsilane as a standard.","Splitting patterns were indicated by s for singlet, d for doublet, t for triplet, q for quartet, m for multiplet, and br for broad.","Mass spectrometry (hereinafter, referred to as MS) was conducted by the electron ionization (EI), electron spray ionization (ESI), atmospheric pressure chemical ionization (APCI), electron spray atmospheric pressure chemical ionization (ES/APCI), or fast atom bombardment (FAB) method.","In each step of Examples, the adjustment of a reaction solution and reaction were carried out at room temperature unless the temperature is otherwise specified.","EXAMPLES (Example 1) 5-Chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (1a) 2-Chloro-N-(2-hydroxyethyl)-N-methyl-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (500 mg, 2.47 mmol) in methylene chloride (10 mL), oxalyl chloride (0.28 mL, 3.3 mmol) and N,N-dimethylformamide (0.05 mL, 0.64 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 2 hours.","The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.","To a solution of 2-(methylamino)ethanol (0.197 mL, 2.47 mmol) and N,N-diisopropylethylamine (0.84 mL, 4.9 mmol) in tetrahydrofuran (5 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (5 mL) was added over 10 minutes under ice cooling, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (494.3 mg, yield: 77%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.30-9.22 (1H, m), 8.58-8.46 (1H, m), 4.00-3.68 (4H, m), 3.24-2.99 (3H, m).","(1b) 4-Methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a suspension of 2-chloro-N-(2-hydroxyethyl)-N-methyl-5-nitropyridine-3-carboxamide (259.2 mg, 1.00 mmol) obtained in Example (1a) in tetrahydrofuran (50 mL), sodium hydride (63% content, 68.8 mg, 1.81 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 22 hours.","The reaction mixture was cooled in an ice water bath.","A 1 N aqueous sodium hydroxide solution (10 mL) was added thereto, and the mixture was stirred at room temperature for 20 minutes.","The reaction mixture was diluted by addition of ethyl acetate, and the organic layer was separated and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure to obtain the title compound (173.3 mg, yield: 78%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.35 (1H, d, J=3.0 Hz), 9.23 (1H, d, J=3.0 Hz), 4.76-4.70 (2H, m), 3.83-3.73 (2H, m), 3.27 (3H, s).","(1c) 7-Amino-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a mixture of 4-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (173.3 mg, 0.78 mmol) obtained in Example (1b) in tetrahydrofuran (5 L) and methanol (5 mL), nickel(II) chloride hexahydrate (386 mg, 1.62 mmol) was added.","Subsequently, the mixture was cooled in an ice water bath.","Sodium borohydride (122 mg, 3.22 mmol) was added thereto over 10 minutes, and then, the mixture was stirred at room temperature for 30 minutes.","The reaction mixture was diluted by addition of acetone and a saturated aqueous solution of sodium bicarbonate, further Celite 545® (approximately 0.6 g) was added thereto, and the mixture was stirred at room temperature for 30 minutes.","The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure.","The residue was purified by reverse-phase silica gel column chromatography (Chromatorex ODS 100-200 mesh 50 mL, water/methanol=100/0-70/30) to obtain the title compound (96.4 mg, yield: 64%).","1H NMR spectrum (CD3OD, 400 MHz) δ: 7.77 (1H, d, J=3.0 Hz), 7.47 (1H, d, J=3.0 Hz), 4.44 (2H, t, J=5.2 Hz), 3.61 (2H, t, J=5.2 Hz), 3.19 (3H, s).","(1d) 5-Chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a mixture of 7-amino-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (40.0 mg, 0.21 mmol) obtained in Example (1c) and pyridine (1.0 mL, 12.4 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (56.5 mg, 0.23 mmol) was added, and the mixture was stirred at 80° C. for 2 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-80/20).","The obtained solid was suspended by the addition of diisopropyl ether (1 mL), and then, the solid was collected by filtration and dried to obtain the title compound (31.9 mg, yield: 39%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.28 (1H, d, J=2.4 Hz), 8.08 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.02-6.98 (2H, m), 4.53 (2H, t, J=4.6 Hz), 4.08 (3H, s), 3.64 (2H, t, J=4.3 Hz), 3.19 (3H, s).","MS spectrum (ES/APCI+): 398 (M+H), 400 (M+2+H).","(Example 2) 5-Fluoro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a mixture of 7-amino-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (96.4 mg, 0.50 mmol) obtained in Example (1c) and pyridine (2.0 mL, 24.9 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (124.4 mg, 0.56 mmol) was added, and the mixture was stirred at 80° C. for 70 minutes in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15).","The obtained solid was suspended by the addition of diisopropyl ether (1 mL), and then, the solid was collected by filtration and dried to obtain the title compound (145.4 mg, yield: 76%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.27 (1H, d, J=2.4 Hz), 8.08 (1H, d, J=3.0 Hz), 7.50 (1H, dd, J=7.3, 3.0 Hz), 7.25-7.20 (1H, m), 7.07 (1H, s), 7.02 (1H, dd, J=9.1, 4.3 Hz), 4.52 (2H, t, J=4.6 Hz), 4.06 (3H, s), 3.63 (2H, t, J=4.6 Hz), 3.19 (3H, s).","MS spectrum (ES/APCI+): 382 (M+H).","(Example 3) 5-Chloro-N-(4-ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide (3a) 4-Ethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (288 mg, yield for 2 steps: 49%) was obtained by production according to Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (502 mg, 2.47 mmol) and 2-(ethylamino)ethanol (223 mg, 2.50 mmol) as starting materials.","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.34 (1H, d, J=3.0 Hz), 9.22 (1H, d, J=3.0 Hz), 4.71-4.69 (2H, m), 3.76-3.74 (2H, m), 3.69 (2H, q, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz).","(3b) 7-Amino-4-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of 4-ethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (288 mg, 1.22 mmol) obtained in Example (3a) and 10% palladium carbon (water content: 54.6%, 31 mg) in methanol (15 mL) was stirred at room temperature for 5 hours at normal pressure under the hydrogen atmosphere.","Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.","The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (247 mg, yield: 98%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.88 (1H, d, J=3.0 Hz), 7.60 (1H, d, J=3.0 Hz), 4.47 (2H, t, J=4.9 Hz), 3.68-3.63 (4H, m), 3.55 (2H, t, J=4.9 Hz), 1.25 (3H, t, J=7.3 Hz).","(3c) 5-Chloro-N-(4-ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide The title compound (222 mg, yield: 90%) was obtained by production according to Example (1d) using 7-amino-4-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (124 mg, 0.60 mmol) obtained in Example (3b) and 5-chloro-2-methoxybenzenesulfonyl chloride (159 mg, 0.66 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.26 (1H, d, J=2.4 Hz), 8.07 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.05-6.98 (2H, m), 4.52 (2H, t, J=4.3 Hz), 4.08 (3H, s), 3.65-3.59 (4H, m), 1.22 (3H, t, J=7.0 Hz).","MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).","(Example 4) N-(4-Ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-5-fluoro-2-methoxybenzenesulfonamide The title compound (206 mg, yield: 88%) was obtained by production according to the method described in Example (1d) using 7-amino-4-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (123 mg, 0.59 mmol) obtained in Example (3b) and 5-fluoro-2-methoxybenzenesulfonyl chloride (150 mg, 0.67 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.26 (1H, d, J=3.0 Hz), 8.08 (1H, d, J=2.4 Hz), 7.50 (1H, dd, J=7.6, 3.3 Hz), 7.25-7.21 (1H, m), 7.10-7.07 (1H, m), 7.02 (1H, dd, J=9.1, 3.6 Hz), 4.51 (2H, t, J=4.6 Hz), 4.06 (3H, s), 3.65-3.58 (4H, m), 1.22 (3H, t, J=7.3 Hz).","MS spectrum (ES/APCI+): 396 (M+H).","(Example 5) 5-Chloro-2-methoxy-N-[5-oxo-4-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (5a) 5-Chloro-2-methoxybenzenesulfonamide To a solution of 5-chloro-2-methoxybenzenesulfonyl chloride (3 g, 12.4 mmol) in tetrahydrofuran (20 mL), a 28% aqueous ammonia solution (20 mL, 295 mmol) was added, and the mixture was stirred at room temperature for 19 hours.","The reaction mixture was diluted by addition of 1 N hydrochloric acid, followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure to obtain the title compound (2.74 g, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.91 (1H, d, J=3.0 Hz), 7.56-7.46 (1H, m), 7.00 (1H, d, J=8.5 Hz), 5.06 (2H, br s), 4.02 (3H, s).","(5b) 5-Bromo-2-chloro-N-(2-hydroxyethyl)-N-(propan-2-yl)pyridine-3-carboxamide The title compound (1.20 g, yield: 88%) was obtained by production according to the method described in Example (1a) using 5-bromo-2-chloropyridine-3-carboxylic acid (1.00 g, 4.22 mmol) and 2-(propan-2-ylamino)ethanol (481 mg, 4.66 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.51-8.46 (1H, m), 7.82-7.73 (1H, m), 3.96-3.85 (2H, m), 3.72-3.54 (3H, m), 3.31-3.25 (1H, m), 1.38-1.09 (6H, m).","(5c) 7-Bromo-4-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of 5-bromo-2-chloro-N-(2-hydroxyethyl)-N-(propan-2-yl)pyridine-3-carboxamide (600 mg, 1.87 mmol) obtained in Example (5b) in N,N-dimethylformamide (20 mL), sodium hydride (63% content, 141 mg, 3.70 mmol) was added under ice cooling, and the mixture was stirred at 80° C. for 3 hours and 20 minutes in an oil bath.","The reaction mixture was cooled and diluted by addition of a saturated aqueous solution of sodium chloride, followed by extraction with ethyl acetate.","The organic layer was washed with a 5% aqueous sodium chloride solution three times and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (hexane/ethyl acetate=100/0-0/100) to obtain the title compound (142 mg, yield: 27%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.48-8.47 (1H, m), 8.43-8.42 (1H, m), 5.06-4.99 (1H, m), 4.52 (2H, t, J=4.6 Hz), 3.52 (2H, t, J=4.6 Hz), 1.21 (6H, d, J=6.7 Hz).","(5d) 5-Chloro-2-methoxy-N-[5-oxo-4-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide A mixture of 7-bromo-4-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (142 mg, 0.50 mmol) obtained in Example (5c), 5-chloro-2-methoxybenzenesulfonamide (114 mg, 0.51 mmol) obtained in Example (5a), potassium carbonate (145 mg, 1.05 mmol), N,N′-dimethylethylene-1,2-diamine (0.27 mL, 2.5 mmol), and copper(I) iodide (48.8 mg, 0.26 mmol) in acetonitrile (5 mL) was heated to reflux for 6 hours and 30 minutes in an oil bath.","The reaction mixture was cooled, diluted by addition of 1 N hydrochloric acid, and then stirred at room temperature for 30 minutes.","The reaction mixture was filtered through pad of Celite 545®, and the filtrate was subjected to extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15).","The obtained solid was suspended by the addition of diisopropyl ether, and then, the solid was collected by filtration and dried to obtain the title compound (44.4 mg, yield: 21%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.25 (1H, d, J=2.4 Hz), 8.03 (1H, d, J=2.4 Hz), 7.75 (1H, d, J=3.0 Hz), 7.48 (1H, dd, J=8.8, 2.7 Hz), 7.02-6.98 (2H, m), 5.02-4.95 (1H, m), 4.47 (2H, t, J=4.6 Hz), 4.08 (3H, s), 3.48 (2H, t, J=4.6 Hz), 1.19 (6H, d, J=6.7 Hz).","MS spectrum (ES/APCI+): 426 (M+H), 428 (M+2+H).","(Example 6) 5-Chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (6a) 4-(2-Hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (318 mg, yield for 2 steps: 51%) was obtained by production according to the method described in Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (501 mg, 2.47 mmol) and 2,2-iminodiethanol (257 mg, 2.44 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.24 (1H, d, J=2.4 Hz), 8.56 (1H, d, J=2.4 Hz), 4.23-4.14 (1H, m), 4.06-3.96 (1H, m), 3.90-3.82 (2H, m), 3.73-3.59 (2H, m), 3.44-3.32 (1H, m), 3.06-3.00 (1H, m), 2.53-2.47 (1H, m).","(6b) 7-Amino-4-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (125 mg, yield: 90%) was obtained by production according to the method described in Example (3c) using 4-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (158 mg, 0.62 mmol) obtained in Example (6a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.90 (1H, d, J=3.0 Hz), 7.58 (1H, d, J=3.0 Hz), 4.52 (2H, t, J=4.9 Hz), 3.92-3.88 (2H, m), 3.81-3.78 (2H, m), 3.68-3.65 (3H, m).","(6c) 5-Chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (199 mg, yield: 83%) was obtained by production according to Example (1d) using 7-amino-4-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (125 mg, 0.56 mmol) obtained in Example (6b) and 5-chloro-2-methoxybenzenesulfonyl chloride (150 mg, 0.62 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.34 (1H, s), 8.08 (1H, d, J=3.0 Hz), 7.94 (1H, d, J=3.0 Hz), 7.70-7.62 (2H, m), 7.26 (1H, dd, J=10.9, 2.4 Hz), 4.82-4.79 (1H, m), 4.44 (2H, t, J=4.6 Hz), 3.87 (3H, s), 3.63 (2H, t, J=4.6 Hz), 3.59-3.51 (4H, m).","MS spectrum (ES/APCI+): 428 (M+H), 430 (M+2+H).","(Example 7) 5-Chloro-2-methoxy-N-[4-(2-methoxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (7a) 4-(2-Methoxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of 4-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (158 mg, 0.62 mmol) obtained in Example (6a) in tetrahydrofuran (4 mL), methyl iodide (0.062 mL, 1.0 mmol) and sodium hydride (63%, 32 mg, 0.84 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 4 hours.","To the mixture, methyl iodide (0.1 mL, 1.6 mmol) and sodium hydride (63%, 80 mg, 2.1 mmol) were further added, and the mixture was stirred at room temperature for 20 hours.","Methyl iodide (0.1 mL, 1.6 mmol) and sodium hydride (63%, 60 mg, 1.6 mmol) were further added thereto, and the mixture was stirred at room temperature for 7 hours and 30 minutes.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium chloride, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (76.7 mg, yield: 46%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.30 (1H, d, J=3.0 Hz), 9.23 (1H, d, J=3.0 Hz), 4.72 (2H, t, J=3.9 Hz), 3.87-3.84 (2H, m), 3.81 (2H, t, J=4.9 Hz), 3.65 (2H, t, J=4.9 Hz), 3.37 (3H, s).","(7b) 7-Amino-4-(2-methoxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (65.3 mg, yield: 96%) was obtained by production according to the method described in Example (3c) using 4-(2-methoxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (76.7 mg, 0.29 mmol) obtained in Example (7a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.88 (1H, d, J=3.0 Hz), 7.58 (1H, d, J=3.0 Hz), 4.49 (2H, t, J=5.2 Hz), 3.78 (2H, t, J=4.9 Hz), 3.67-3.61 (6H, m), 3.37 (3H, s).","(7c) 5-Chloro-2-methoxy-N-[4-(2-methoxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (86.9 mg, yield: 72%) was obtained by production according to Example (1d) using 7-amino-4-(2-methoxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (65.3 mg, 0.28 mmol) obtained in Example (7b) and 5-chloro-2-methoxybenzenesulfonyl chloride (81.5 mg, 0.34 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.25 (1H, d, J=2.4 Hz), 8.07 (1H, d, J=2.4 Hz), 7.75 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.15-7.11 (1H, m), 7.00 (1H, d, J=8.5 Hz), 4.56-4.52 (2H, m), 4.06 (3H, s), 3.76-3.70 (4H, m), 3.61 (2H, t, J=4.9 Hz), 3.35 (3H, s).","MS spectrum (ES/APCI+): 442 (M+H), 444 (M+2+H).","(Example 8) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (8a) 2-[(2,4-Dimethoxybenzyl)amino]ethanol To a mixture of 2,4-dimethoxybenzaldehyde (16.20 g, 97.5 mmol) and 2-aminoethanol (5.98 g, 97.9 mmol) in methanol (120 mL), anhydrous sodium sulfate (6.23 g, 43.9 mmol) was added, and the mixture was stirred at room temperature for 20 hours.","Subsequently, to the mixture, sodium borohydride (1.84 g, 48.6 mmol) was added over 15 minutes, and the mixture was stirred at 22° C. for 30 minutes.","To the reaction mixture, acetic acid (2.8 mL, 49 mmol) was added, and the mixture was stirred for 10 minutes and concentrated into approximately ½ of the amount under reduced pressure.","The concentrated mixture was diluted by addition of water and a saturated aqueous solution of sodium bicarbonate, followed by extraction with methylene chloride.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, n-hexane (100 mL) and ethyl acetate (4 mL) were added, and the precipitated solid was collected by filtration, washed with n-hexane, and then dried to obtain the title compound (18.44 g, yield: 90%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.12 (1H, d, J=8.2 Hz), 6.47-6.42 (2H, m), 3.82 (3H, s), 3.80 (3H, s), 3.74 (2H, S), 3.65-3.63 (2H, m), 2.76-2.74 (2H, m).","(8b) 2-Chloro-N-(2,4-dimethoxybenzyl)-N-(2-hydroxyethyl)-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (4.91 g, 24.2 mmol) and oxalyl chloride (2.6 mL, 30 mmol) in methylene chloride (120 mL), N,N-dimethylformamide (0.10 mL, 1.3 mmol) was added at room temperature, and the mixture was stirred at the same temperature as above for 30 minutes.","The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.","To a solution of 2-[(2,4-dimethoxybenzyl)amino]ethanol (5.11 g, 24.2 mmol) obtained in Example (8a) and N,N-diisopropylethylamine (8.25 mL, 48.5 mmol) in tetrahydrofuran (50 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (70 mL) was added over 20 minutes under ice cooling, and the reaction mixture was stirred at the same temperature as above for 90 minutes.","To the reaction mixture, water (0.05 mL) was added, and then, the mixture was concentrated under reduced pressure.","The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and anhydrous magnesium sulfate and charcoal were added thereto.","After filtration through pad of Celite 545 ®, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether (50 mL) and ethyl acetate (10 mL) were added to precipitate a solid.","The suspension was stirred at room temperature for 30 minutes.","The precipitated solid was collected by filtration, washed with a mixed solvent of diisopropyl ether/ethyl acetate=5/1, and then dried to obtain the title compound (8.30 g, yield: 87%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.24 (0.8H, d, J=2.7 Hz), 9.21 (0.2H, d, J=2.7 Hz), 8.57 (0.2H, d, J=2.7 Hz), 8.44 (0.8H, d, J=2.7 Hz), 7.38 (0.2H, d, J=8.2 Hz), 6.99 (0.8H, d, J=8.2 Hz), 6.54-6.48 (0.4H, m), 6.45-6.40 (1.6H, m), 5.13 (0.2H, d, J=14.9 Hz), 4.53 (0.2H, d, J=14.9 Hz), 4.38-3.54 (10.8H, m), 3.24-3.19 (0.4H, t, J=5.1 Hz), 2.42 (0.4H, t, J=5.1 Hz).","(8c) 4-(2,4-Dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (ca.","1.9 mol/L, 14.4 mL, 27.4 mmol) was diluted with tetrahydrofuran (450 mL).","A solution of 2-chloro-N-(2,4-dimethoxybenzyl)-N-(2-hydroxyethyl)-5-nitropyridine-3-carboxamide (7.22 g, 18.2 mmol) obtained in Example (8b) in tetrahydrofuran (450 mL) was added thereto over 70 minutes under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes and further stirred at room temperature for 30 minutes.","To the reaction mixture, a saturated aqueous solution of ammonium chloride (100 mL) was added, and then, the reaction mixture was concentrated into approximately ⅕ of the amount under reduced pressure.","The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate twice.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane/methylene chloride=1/1/1-3/2/2).","To the obtained solid, diisopropyl ether (20 mL) and ethyl acetate (10 mL) were added, and the suspension was stirred at room temperature for overnight.","The precipitated solid was collected by filtration, washed with a mixed solvent of diisopropyl ether/ethyl acetate=2/1, and then dried to obtain the title compound (4.18 g, yield: 64%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.34 (1H, d, J=2.7 Hz), 9.20 (1H, d, J=2.7 Hz), 7.34-7.32 (1H, m), 6.50-6.48 (2H, m), 4.76 (2H, s), 4.53-4.51 (2H, m), 3.84 (3H, s), 3.81 (3H, s), 3.78-3.76 (2H, m).","(8d) 7-Amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of 4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (4.18 g, 11.6 mmol) obtained in Example (8c) and 10% palladium carbon (water content: 54.6%, 1.36 g) in tetrahydrofuran (110 mL) and ethanol (55 mL) was stirred at room temperature for 3 hours at normal pressure under the hydrogen atmosphere.","Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.","The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (3.93 g, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.86 (1H, d, J=3.1 Hz), 7.62 (1H, d, J=3.1 Hz), 7.31-7.28 (1H, m), 6.49-6.47 (2H, m), 4.75 (2H, s), 4.25 (2H, t, J=4.9 Hz), 3.82 (3H, s), 3.81 (3H, s), 3.64 (2H, br s), 3.55 (2H, t, J=4.9 Hz).","(8e) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (229 mg, 0.70 mmol) obtained in Example (8d) and pyridine (3.0 mL, 37.3 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (190 mg, 0.79 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (349 mg, yield: 94%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=3.0 Hz), 8.07 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.48 (1H, dd, J=8.8, 2.7 Hz), 7.30-7.22 (2H, m), 7.01 (1H, d, J=9.1 Hz), 6.49-6.46 (2H, m), 4.70 (2H, s), 4.32 (2H, t, J=4.6 Hz), 4.09 (3H, s), 3.81-3.80 (6H, m), 3.60 (2H, t, J=4.6 Hz).","MS spectrum (ES/APCI+): 534 (M+H), 536 (M+2+H).","(Example 9) 5-Chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of 5-chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (335 mg, 0.63 mmol) obtained in Example (8e) in chloroform (5 mL), anisole (0.136 mL, 1.25 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.165 mL, 1.88 mmol) were added at room temperature, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of chloroform and a saturated aqueous solution of sodium bicarbonate and stirred at room temperature for 10 minutes.","The organic layer was separated, and the aqueous layer was subjected to extraction with a mixed solvent of ethyl acetate/tetrahydrofuran=2/1 three times.","All the organic layers were combined and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration to obtain the title compound (154 mg, yield: 64%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, s), 8.53 (1H, br t, J=5.2 Hz), 8.11-8.08 (2H, m), 7.69-7.64 (2H, m), 7.26 (1H, d, J=8.5 Hz), 4.37-4.35 (2H, m), 3.88 (3H, s), 3.38-3.34 (2H, m).","MS spectrum (ES/APCI+): 384 (M+H), 386 (M+2+H).","(Example 10) 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (10a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (200 mg, 0.61 mmol) obtained in Example (8d) and pyridine (6 mL, 74.6 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (158 mg, 0.70 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the title compound (305 mg, yield: 97%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=2.4 Hz), 8.08 (1H, d, J=2.4 Hz), 7.52-7.49 (1H, m), 7.26-7.20 (2H, m), 7.04-7.00 (1H, m), 6.95 (1H, br s), 6.48-6.46 (2H, m), 4.70 (2H, s), 4.31 (2H, br t, J=4.3 Hz), 4.08 (3H, s), 3.81-3.80 (6H, m), 3.59 (2H, br t, J=4.3 Hz).","(10b) 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (305 mg, 0.59 mmol) obtained in Example (10a) in chloroform (5 mL), anisole (0.128 mL, 1.17 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.155 mL, 1.77 mmol) were added at room temperature, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of ethyl acetate and a saturated aqueous solution of sodium bicarbonate and stirred at room temperature for 1.5 hours.","The precipitated solid was collected by filtration to obtain the title compound (192 mg, yield: 89%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.28 (1H, s), 8.52 (1H, br t, J=4.9 Hz), 8.11-8.08 (2H, m), 7.51-7.46 (2H, m), 7.26-7.23 (1H, m), 4.36 (2H, t, J=4.3 Hz), 3.86 (3H, s), 3.40-3.35 (2H, m).","MS spectrum (ES/APCI+): 368 (M+H).","(Example 11) 2,5-Dimethoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (11a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (200 mg, 0.61 mmol) obtained in Example (8d) and pyridine (5 mL, 62 mmol), 2,5-dimethoxybenzenesulfonyl chloride (158 mg, 0.67 mmol) was added, and the mixture was stirred at 80° C. for 3 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (290 mg, yield: 90%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=3.0 Hz), 8.09-8.08 (1H, m), 7.30-7.25 (2H, m), 7.07-6.98 (3H, m), 6.48-6.45 (2H, m), 4.70 (2H, s), 4.30 (2H, t, J=4.6 Hz), 4.04 (3H, s), 3.81-3.79 (6H, m), 3.75 (3H, s), 3.58 (2H, t, J=4.6 Hz).","(11b) 2,5-Dimethoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a solution of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide (290 mg, 0.55 mmol) obtained in Example (11a) in chloroform (4 mL), anisole (0.12 mL, 1.1 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.15 mL, 1.7 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was neutralized by the addition of a saturated aqueous solution of sodium bicarbonate, followed by extraction with chloroform.","The organic layer was dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (144 mg, yield: 77%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.16 (1H, s), 8.51 (1H, t, J=5.2 Hz), 8.09 (2H, dd, J=10.3, 3.0 Hz), 7.21-7.12 (3H, m), 4.35 (2H, t, J=4.3 Hz), 3.81 (3H, s), 3.72 (3H, s), 3.39-3.34 (2H, m).","MS spectrum (ES/APCI+): 380 (M+H).","(Example 12) 2-Methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (12a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (150 mg, 0.46 mmol) obtained in Example (8d) and pyridine (4 mL, 50 mmol), 2-methoxybenzenesulfonyl chloride (104 mg, 0.50 mmol) was added, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (212 mg, yield: 93%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.23 (1H, d, J=2.4 Hz), 8.07-8.06 (1H, m), 7.79-7.77 (1H, m), 7.55-7.51 (1H, m), 7.30-7.24 (1H, m), 7.08-6.98 (2H, m), 6.92 (1H, s), 6.48-6.43 (2H, m), 4.69 (2H, s), 4.29 (2H, t, J=4.3 Hz), 4.09 (3H, s), 3.81-3.78 (6H, m), 3.56 (2H, t, J=4.6 Hz).","(12b) 2-Methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl)benzenesulfonamide To a suspension of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (212 mg, 0.43 mmol) obtained in Example (12a) in chloroform (4 mL), anisole (0.1 mL, 0.9 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.11 mL, 1.3 mmol) were added, and the mixture was stirred at room temperature for 3 hours.","The reaction mixture was neutralized by the addition of a saturated aqueous solution of sodium bicarbonate, followed by extraction with chloroform twice.","The organic layer was dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (55.2 mg, yield: 37%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.12 (1H, s), 8.52-8.48 (1H, m), 8.10-8.06 (2H, m), 7.70 (1H, dd, J=7.9, 1.8 Hz), 7.61-7.56 (1H, m), 7.20 (1H, d, J=8.5 Hz), 7.03 (1H, t, J=7.6 Hz), 4.34 (2H, t, J=4.3 Hz), 3.88 (3H, s), 3.37-3.31 (2H, m).","MS spectrum (ES/APCI+): 350 (M+H).","(Example 13) 5-Chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide (13a) 5-Chloro-2-(trifluoromethoxy)benzenesulfonyl chloride To chlorosulfonic acid (30.0 mL, 451 mmol), 4-chlorophenyl trifluoromethyl ether (2.60 mL, 18.1 mmol) was added, and the mixture was stirred at room temperature for 46 hours.","The reaction mixture was carefully poured into ice (approximately 300 mL), followed by extraction with methylene chloride twice.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/methylene chloride=1/1) to obtain the title compound (approximately 83% content, 4.67 g, yield: 73%) as a mixture containing positional isomers.","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (0.83H, d, J=2.7 Hz), 8.02 (0.17H, br d, J=2.7 Hz), 7.75 (0.83H, dd, J=8.8, 2.7 Hz), 7.71 (0.17H, d, J=8.6 Hz), 7.55-7.52 (0.17H, m), 7.50-7.47 (0.83H, m).","(13b) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (260 mg, 0.79 mmol) obtained in Example (8d) and pyridine (8 mL, 99 mmol), 5-chloro-2-(trifluoromethoxy)benzenesulfonyl chloride (approximately 83% content, 325 mg, 0.92 mmol) obtained in Example (13a) was added at room temperature, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (305 mg, yield: 66%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.29 (1H, d, J=3.0 Hz), 8.17 (1H, d, J=3.0 Hz), 7.90 (1H, d, J=3.0 Hz), 7.58-7.54 (1H, m), 7.38-7.27 (3H, m), 6.49-6.44 (2H, m), 4.73 (2H, s), 4.33 (2H, t, J=4.6 Hz), 3.81 (6H, s), 3.63-3.60 (2H, m).","(13c) 5-Chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide To a solution of 5-chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (305 mg, 0.52 mmol) obtained in Example (13b) and anisole (0.113 mL, 1.04 mmol) in chloroform (8 mL), trifluoroacetic acid (3 mL, 39 mmol) and trifluoromethanesulfonic acid (0.137 mL, 1.56 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2.5 hours.","To the reaction mixture, water was added, and the mixture was stirred at room temperature for 1 hour, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (171 mg, yield: 75%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.78 (1H, s), 8.58-8.53 (1H, m), 8.13-8.06 (2H, m), 7.91-7.85 (2H, m), 7.65-7.60 (1H, m), 4.39 (2H, t, J=4.3 Hz), 3.41-3.36 (2H, m).","MS spectrum (ES/APCI+): 438 (M+H), 440 (M+2+H).","(Example 14) 5-Chloro-N-(2,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide (14a) 2,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (280 mg, yield for 2 steps: 44%) was obtained by production according to Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (550 mg, 2.71 mmol) and 1-(methylamino)propan-2-ol (240 mg, 2.69 mmol) as starting materials.","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.23 (2H, s), 4.92-4.85 (1H, m), 3.69-3.56 (2H, m), 3.27 (3H, s), 1.24 (3H, d, J=12.8 Hz).","(14b) 7-Amino-2,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (200 mg, yield: 82%) was obtained by production according to the method described in Example (1c) using 2,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (280 mg, 1.18 mmol) obtained in Example (14a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.87 (1H, d, J=3.0 Hz), 7.50 (1H, d, J=3.0 Hz), 4.77-4.70 (1H, m), 4.00-3.91 (1H, m), 3.65 (2H, br s), 3.49-3.44 (1H, m), 3.35-3.27 (1H, m), 3.23 (3H, s), 1.43 (5H, d, J=6.7 Hz).","(14c) 5-Chloro-N-(2,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide The title compound (90 mg, yield: 46%) was obtained by production according to Example (1d) using 7-amino-2,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (99 mg, 0.48 mmol) obtained in Example (14b) and 5-chloro-2-methoxybenzenesulfonyl chloride (132.5 mg, 0.55 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.39 (1H, s), 8.08 (1H, d, J=3.0 Hz), 7.82 (1H, d, J=3.0 Hz), 7.69-7.66 (2H, m), 7.28-7.23 (1H, m), 4.73-4.67 (1H, m), 3.86 (3H, s), 3.55-3.49 (1H, m), 3.40-3.29 (2H, m), 3.07 (3H, s), 1.26 (4H, d, J=6.1 Hz).","MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).","(Example 15) N-(2,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-5-fluoro-2-methoxybenzenesulfonamide The title compound (104 mg, yield: 55%) was obtained by production according to Example (1d) using 7-amino-2,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (99 mg, 0.48 mmol) obtained in Example (14b) and 5-fluoro-2-methoxybenzenesulfonyl chloride (114 mg, 0.51 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.38 (1H, s), 8.08 (1H, d, J=2.4 Hz), 7.82-7.81 (1H, m), 7.53-7.47 (2H, m), 7.24 (1H, dd, J=8.5, 4.3 Hz), 4.72-4.67 (1H, m), 3.85 (3H, s), 3.54-3.48 (1H, m), 3.39-3.30 (1H, m), 3.07 (3H, s), 1.25 (3H, d, J=6.1 Hz).","MS spectrum (ES/APCI+): 396 (M+H).","(Example 16) 5-Chloro-N-(3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide (16a) 3,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (234 mg, yield for 2 steps: 37%) was obtained by production according to the method described in Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (550 mg, 2.71 mmol) and 2-(methylamino)propan-1-ol (240 mg, 2.69 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.59 (1H, d, J=3.0 Hz), 9.23-9.20 (1H, m), 4.70 (1H, dd, J=13.1, 5.2 Hz), 4.47 (1H, d, J=12.8 Hz), 3.84-3.76 (1H, m), 3.25 (3H, s), 1.36 (4H, d, J=7.3 Hz).","(16b) 7-Amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (168 mg, yield: 82%) was obtained by production according to the method described in Example (1c) using 3,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (234 mg, 0.99 mmol) obtained in Example (16a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.00 (1H, d, J=3.0 Hz), 7.88 (1H, d, J=3.0 Hz), 4.44 (1H, dd, J=12.5, 6.4 Hz), 4.28-4.23 (1H, m), 3.81-3.71 (1H, m), 3.60 (2H, br s), 3.18 (3H, s), 1.32 (3H, d, J=6.7 Hz).","(16c) 5-Chloro-N-(3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide The title compound (73 mg, yield: 44%) was obtained by production according to Example (1d) using 7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (84 mg, 0.41 mmol) obtained in Example (16b) and 5-chloro-2-methoxybenzenesulfonyl chloride (111 mg, 0.46 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.36-8.32 (2H, m), 7.74 (1H, d, J=3.1 Hz), 7.46 (1H, dd, J=8.9, 2.7 Hz), 7.06 (1H, br s), 7.00 (1H, d, J=8.5 Hz), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.26 (1H, d, J=12.8 Hz), 4.08 (3H, s), 3.73-3.67 (1H, m), 3.17 (3H, s), 1.30 (3H, d, J=6.7 Hz).","MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).","(Example 17) N-(3,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-5-fluoro-2-methoxybenzenesulfonamide The title compound (78 mg, yield: 50%) was obtained by production according to Example (1d) using 7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (83 mg, 0.40 mmol) obtained in Example (16b) and 5-fluoro-2-methoxybenzenesulfonyl chloride (104 mg, 0.46 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.36-8.31 (2H, m), 7.49 (1H, dd, J=7.6, 3.4 Hz), 7.24-7.20 (1H, m), 7.08 (1H, br s), 7.02 (1H, dd, J=9.2, 4.3 Hz), 4.51 (1H, dd, J=12.5, 5.2 Hz), 4.25 (1H, d, J=12.8 Hz), 4.08 (3H, s), 3.73-3.66 (1H, m), 3.16 (3H, s), 1.29 (3H, d, J=7.3 Hz).","MS spectrum (ES/APCI+): 396 (M+H).","(Example 18) 5-Chloro-N-[(3S)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (18a) (2S)-2-[(2,4-Dimethoxybenzyl)amino]propan-1-ol The title compound (2.98 g, yield: 99%) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (2.22 g, 13.4 mmol) and (2S)-2-aminopropan-1-ol (1 g, 13.3 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.13 (1H, d, J=7.9 Hz), 6.50-6.42 (2H, m), 3.85-3.79 (7H, m), 3.77-3.60 (3H, m), 3.26 (1H, dd, J=10.6, 6.4 Hz), 2.84-2.76 (1H, m), 1.06 (3H, d, J=6.7 Hz).","(18b) (3S)-4-(2,4-Dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (781.8 mg, yield for 2 steps: 60%) was obtained by production according to the method described in Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (700 mg, 3.46 mmol) and (2S)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol (785 mg, 3.49 mmol) obtained in Example (18a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.62-9.61 (1H, m), 9.20 (1H, d, J=3.0 Hz), 7.33 (1H, d, J=8.5 Hz), 6.50-6.47 (2H, m), 4.95 (1H, d, J=14.6 Hz), 4.65-4.55 (2H, m), 4.31 (1H, d, J=12.8 Hz), 4.04-3.97 (1H, m), 3.84 (3H, s), 3.81 (3H, s), 1.23 (3H, d, J=6.7 Hz).","(18c) (3S)-3-Methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of (3S)-4-(2,4-dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (450 mg, 1.21 mmol) obtained in Example (18b) and anisole (0.2 mL, 1.8 mmol) in chloroform (5 mL), trifluoroacetic acid (3 mL, 39 mmol) and trifluoromethanesulfonic acid (0.2 mL, 2.3 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of chloroform, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (228 mg, yield: 85%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.49-9.47 (1H, m), 9.26-9.24 (1H, m), 6.49 (1H, br s), 4.60 (1H, d, J=12.1 Hz), 4.47-4.40 (1H, m), 4.02-3.94 (1H, m), 1.42-1.39 (3H, m).","(18d) (3S)-3,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of (3S)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (228 mg, 1.02 mmol) obtained in Example (18c) in N,N-dimethylformamide (5 mL), sodium hydride (63% content, 53 mg, 1.39 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 20 minutes.","Subsequently, the mixture was cooled in an ice water bath.","Methyl iodide (0.127 mL, 2.04 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour and 45 minutes.","The reaction mixture was diluted by addition of ethyl acetate, washed with a 5% aqueous sodium chloride solution three times, and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (160 mg, yield: 66%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.59 (1H, d, J=3.0 Hz), 9.22-9.21 (1H, m), 4.70 (1H, dd, J=12.8, 5.5 Hz), 4.47 (1H, d, J=12.8 Hz), 3.84-3.77 (1H, m), 3.25 (3H, s), 1.36 (3H, d, J=7.3 Hz).","(18e) (3S)-7-Amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (175 mg, yield: quantitative) was obtained by production according to the method described in Example (3c) using (3S)-3,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (160 mg, 0.67 mmol) obtained in Example (18d).","1H NMR spectrum (CD3OD, 400 MHz) δ: 7.87-7.85 (1H, m), 7.79-7.78 (1H, m), 5.47-5.44 (1H, m), 4.45-4.39 (1H, m), 4.22 (1H, d, J=12.8 Hz), 3.92-3.84 (2H, m), 3.15 (3H, s), 1.32-1.23 (3H, m).","(18f) 5-Chloro-N-[(3S)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (87 mg, yield: 63%) was obtained by production according to Example (1d) using (3S)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1, 4]oxazepin-5(2H)-one (69 mg, 0.34 mmol) obtained in Example (18e) and 5-chloro-2-methoxybenzenesulfonyl chloride (91 mg, 0.38 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.34 (2H, dd, J=12.1, 2.4 Hz), 7.74 (1H, d, J=2.4 Hz), 7.46 (1H, dd, J=8.8, 2.7 Hz), 7.10 (1H, s), 7.00 (1H, d, J=9.1 Hz), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.26 (1H, d, J=12.8 Hz), 4.07 (3H, s), 3.74-3.66 (1H, m), 3.17 (3H, s), 1.30 (3H, d, J=7.3 Hz).","MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).","(Example 19) N-[(3S)-3,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide The title compound (81 mg, yield: 61%) was obtained by production according to Example (1d) using (3S)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (69 mg, 0.34 mmol) obtained in Example (18e) and 5-fluoro-2-methoxybenzenesulfonyl chloride (88 mg, 0.39 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.34 (2H, dd, J=14.9, 2.7 Hz), 7.49 (1H, dd, J=7.9, 3.0 Hz), 7.24-7.19 (1H, m), 7.08 (1H, s), 7.02 (1H, dd, J=9.1, 4.3 Hz), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.25 (1H, d, J=12.8 Hz), 4.07 (3H, s), 3.73-3.66 (1H, m), 3.16 (3H, s), 1.29 (3H, d, J=6.7 Hz).","MS spectrum (ES/APCI+): 396 (M+H).","(Example 20) 5-Chloro-N-[(3R)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (20a) (2R)-2-[(2,4-Dimethoxybenzyl)amino]propan-1-ol The title compound (3.10 g, yield: quantitative) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (2.25 g, 13.5 mmol) and (2R)-2-aminopropan-1-ol (1.02 g, 13.6 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.13 (1H, d, J=7.9 Hz), 6.50-6.42 (2H, m), 3.86-3.79 (7H, m), 3.77-3.61 (3H, m), 3.26 (1H, dd, J=10.6, 6.4 Hz), 2.84-2.76 (1H, m), 1.06 (3H, d, J=6.1 Hz).","(20b) (3R)-4-(2,4-Dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (783 mg, yield for 2 steps: 61%) was obtained using 2-chloro-5-nitropyridine-3-carboxylic acid (700 mg, 3.46 mmol) and (2R)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol (778 mg, 3.45 mmol) obtained in Example (20a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.62 (1H, d, J=3.0 Hz), 9.20 (1H, d, J=3.0 Hz), 7.33 (1H, d, J=8.5 Hz), 6.50-6.47 (2H, m), 4.95 (1H, d, J=14.0 Hz), 4.65-4.54 (2H, m), 4.31 (1H, d, J=13.4 Hz), 4.04-3.97 (1H, m), 3.84 (3H, s), 3.81 (3H, s), 1.23 (3H, d, J=7.3 Hz).","(20c) (3R)-3,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (120 mg, yield for 2 steps: 48%) was obtained by production according to the method described in Examples (18c) and (18d) using (3R)-4-(2,4-dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (390 mg, 1.04 mmol) obtained in Example (20b).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.59 (1H, d, J=2.4 Hz), 9.21 (1H, d, J=2.4 Hz), 4.70 (1H, dd, J=13.1, 5.2 Hz), 4.47 (1H, d, J=13.1 Hz), 3.84-3.77 (1H, m), 3.25 (3H, s), 1.36 (3H, d, J=6.7 Hz).","(20d) (3R)-7-Amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (87.9 mg, yield: 84%) was obtained by production according to the method described in Example (1c) using (3R)-3,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (120 mg, 0.51 mmol) obtained in Example (20c).","1H NMR spectrum (CD3OD, 400 MHz) δ: 7.86 (1H, d, J=3.0 Hz), 7.79 (1H, d, J=3.0 Hz), 4.42 (1H, dd, J=12.5, 7.0 Hz), 4.22 (1H, dd, J=12.5, 1.5 Hz), 3.93-3.86 (1H, m), 3.15 (3H, s), 1.27 (3H, d, J=6.7 Hz).","(20e) 5-Chloro-N-[(3R)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (82 mg, yield: 96%) was obtained by production according to Example (1d) using (3R)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (43 mg, 0.21 mmol) obtained in Example (20d) and 5-chloro-2-methoxybenzenesulfonyl chloride (58 mg, 0.24 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.33 (2H, dd, J=8.8, 2.7 Hz), 7.73 (1H, d, J=3.0 Hz), 7.46 (1H, dd, J=8.8, 2.7 Hz), 7.02-6.97 (2H, m), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.26 (1H, d, J=12.8 Hz), 4.09 (3H, s), 3.73-3.67 (1H, m), 3.16 (3H, s), 1.30 (3H, d, J=6.7 Hz).","MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).","(Example 21) N-[(3R)-3,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide The title compound (74 mg, yield: 90%) was obtained by production according to Example (1d) using (3R)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (43 mg, 0.21 mmol) obtained in Example (20d) and 5-fluoro-2-methoxybenzenesulfonyl chloride (56 mg, 0.25 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.33 (2H, dd, J=12.5, 2.7 Hz), 7.49 (1H, dd, J=7.3, 3.0 Hz), 7.24-7.19 (1H, m), 7.04-7.00 (2H, m), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.25 (1H, d, J=12.8 Hz), 4.08 (3H, s), 3.72-3.66 (1H, m), 3.16 (3H, s), 1.29 (3H, d, J=6.7 Hz).","MS spectrum (ES/APCI+): 396 (M+H).","(Example 22) 5-Chloro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (22a) (3S)-7-Amino-4-(2,4-dimethoxybenzyl)-3-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a mixture of (3S)-4-(2,4-dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (330 mg, 0.88 mmol) obtained in Example (18b) in tetrahydrofuran (4 mL) and methanol (4 mL), nickel(II) chloride hexahydrate (432 mg, 1.82 mmol) was added.","Subsequently, the mixture was cooled in an ice water bath.","Sodium borohydride (134 mg, 3.54 mmol) was added thereto over 10 minutes, and then, the mixture was stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of acetone, then Celite 545® (approximately 0.6 g) was added thereto, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was filtered, and the solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (303 mg, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.10 (1H, d, J=3.0 Hz), 7.89 (1H, d, J=3.0 Hz), 7.31-7.26 (1H, m), 6.49-6.44 (2H, m), 4.93 (1H, d, J=14.6 Hz), 4.57 (1H, d, J=14.6 Hz), 4.38 (1H, dd, J=12.8, 5.8 Hz), 4.12 (1H, d, J=12.8 Hz), 4.00-3.74 (7H, m), 3.57 (2H, br s), 1.21 (3H, d, J=7.3 Hz).","(22b) 5-Chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-4-(2,4-dimethoxybenzyl)-3-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (150 mg, 0.44 mmol) obtained in Example (22a) and pyridine (3 mL, 37 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (121 mg, 0.50 mmol) was added, and the mixture was stirred at 80° C. for 1 hour in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (200 mg, yield: 83%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.38 (1H, d, J=2.4 Hz), 8.31 (1H, d, J=2.4 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=9.1, 2.4 Hz), 7.21 (1H, d, J=9.1 Hz), 7.01 (1H, d, J=9.1 Hz), 6.92 (1H, s), 6.47-6.43 (2H, m), 4.91 (1H, d, J=15.2 Hz), 4.51-4.41 (2H, m), 4.15-4.11 (1H, m), 4.09 (3H, s), 3.85-3.80 (1H, m), 3.80-3.79 (6H, m), 1.17 (3H, d, J=6.7 Hz).","(22c) 5-Chloro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide To a solution of 5-chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (200 mg, 0.36 mmol) obtained in Example (22b) and anisole (0.1 mL, 0.9 mmol) in chloroform (3 mL), trifluoroacetic acid (1 mL, 13 mmol) and trifluoromethanesulfonic acid (0.1 mL, 1.1 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and then, the residue was diluted with chloroform, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (105 mg, yield: 72%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.31 (1H, d, J=3.0 Hz), 8.22 (1H, d, J=2.4 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=9.1, 2.4 Hz), 7.02-6.95 (2H, m), 6.10 (1H, br s), 4.41 (1H, d, J=12.1 Hz), 4.23 (1H, dd, J=12.8, 7.3 Hz), 4.08 (3H, s), 1.31 (3H, d, J=6.7 Hz).","MS spectrum (ES/APCI+): 398 (M+H), 400 (M+2+H).","(Example 23) 5-Fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (23a) N-[(3S)-4-(2,4-Dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-4-(2,4-dimethoxybenzyl)-3-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (150 mg, 0.44 mmol) obtained in Example (22a) and pyridine (3 mL, 37 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (120 mg, 0.53 mmol) was added, and the mixture was stirred at 80° C. for 2 hours and 20 minutes in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (189 mg, yield: 81%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.39 (1H, d, J=3.0 Hz), 8.30-8.29 (1H, m), 7.50 (1H, dd, J=7.9, 3.0 Hz), 7.31-7.20 (2H, m), 7.03 (1H, dd, J=9.1, 3.6 Hz), 6.95 (1H, br s), 6.46-6.44 (2H, m), 4.91 (1H, d, J=14.6 Hz), 4.49 (1H, d, J=14.6 Hz), 4.43 (1H, dd, J=12.8, 5.5 Hz), 4.16-4.11 (1H, m), 4.09 (3H, s), 3.84-3.79 (7H, m), 1.16 (3H, d, J=6.7 Hz).","(23b) 5-Fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide To a solution of N-[(3S)-4-(2,4-dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (189 mg, 0.35 mmol) obtained in Example (23a) and anisole (0.1 mL, 0.9 mmol) in chloroform (3 mL), trifluoroacetic acid (1 mL, 13 mmol) and trifluoromethanesulfonic acid (0.1 mL, 1.1 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and then, the residue was diluted with chloroform, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (73.1 mg, yield: 54%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.31 (1H, d, J=2.4 Hz), 8.23 (1H, d, J=2.4 Hz), 7.49 (1H, dd, J=7.6, 3.3 Hz), 7.25-7.20 (1H, m), 7.07-7.00 (2H, m), 6.14 (1H, br s), 4.41 (1H, d, J=11.5 Hz), 4.22 (1H, dd, J=12.8, 7.3 Hz), 4.07 (3H, s), 3.88-3.82 (1H, m), 1.30 (3H, d, J=7.3 Hz).","MS spectrum (ES/APCI+): 382 (M+H).","(Example 24) 5-Chloro-N-[(3S)-3-ethyl-4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (24a) (2S)-2-[(2,4-Dimethoxybenzyl)amino]butan-1-ol The title compound (2.54 g, yield: 97%) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (1.81 g, 10.9 mmol) and (2S)-2-aminobutan-1-ol (0.98 g, 11.0 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.12 (1H, d, J=8.5 Hz), 6.48-6.41 (2H, m), 3.83 (3H, s), 3.80 (3H, s), 3.71 (2H, s), 3.66 (1H, dd, J=10.3, 4.3 Hz), 3.31 (1H, dd, J=10.3, 6.1 Hz), 2.60-2.52 (1H, m), 1.54-1.38 (2H, m), 0.90 (3H, t, J=7.3 Hz).","(24b) (3S)-7-Bromo-4-(2,4-dimethoxybenzyl)-3-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (379 mg, yield for 2 steps: 78%) was obtained by production according to the method described in Examples (1a) and (1b) using 5-bromo-2-chloropyridine-3-carboxylic acid (500 mg, 2.11 mmol) and (2S)-2-[(2,4-dimethoxybenzyl)amino]butan-1-ol (506 mg, 2.11 mmol) obtained in Example (24a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.90 (1H, d, J=2.4 Hz), 8.38 (1H, d, J=2.4 Hz), 7.34-7.31 (1H, m), 6.49-6.46 (2H, m), 5.08 (1H, d, J=14.6 Hz), 4.62 (1H, dd, J=13.1, 5.2 Hz), 4.41 (1H, d, J=14.6 Hz), 4.11-4.09 (1H, m), 3.83 (3H, s), 3.81 (3H, s), 3.69-3.63 (1H, m), 1.62-1.52 (2H, m), 1.00 (3H, t, J=7.3 Hz).","(24c) (3S)-7-Bromo-3-ethyl-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (85.1 mg, yield for 2 steps: 66%) was obtained by production according to the method described in Examples (18c) and (18d) using (3S)-7-bromo-4-(2,4-dimethoxybenzyl)-3-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (189 mg, 0.45 mmol) obtained in Example (24b).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.86 (1H, d, J=2.4 Hz), 8.39 (1H, d, J=2.4 Hz), 4.72 (1H, dd, J=13.1, 5.2 Hz), 4.30 (1H, d, J=12.8 Hz), 3.48-3.41 (1H, m), 3.22 (3H, s), 1.72-1.64 (2H, m), 1.05 (3H, t, J=7.6 Hz).","(24d) 5-Chloro-N-[(3S)-3-ethyl-4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (63.2 mg, yield: 50%) was obtained by production according to the method described in Example (5d) using (3S)-7-bromo-3-ethyl-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (85.1 mg, 0.30 mmol) obtained in Example (24c) and 5-chloro-2-methoxybenzenesulfonamide (75.8 mg, 0.34 mmol) obtained in Example (5a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.39-8.31 (2H, m), 7.74 (1H, d, J=3.0 Hz), 7.46 (1H, dd, J=8.8, 2.7 Hz), 7.13 (1H, br s), 6.99 (1H, d, J=9.1 Hz), 4.67 (1H, dd, J=13.4, 5.5 Hz), 4.22 (1H, d, J=12.8 Hz), 4.07 (3H, s), 3.43-3.37 (1H, m), 3.19 (3H, s), 1.70-1.60 (2H, m), 1.02 (3H, t, J=7.3 Hz).","MS spectrum (ES/APCI+): 426 (M+H), 428 (M+2+H).","(Example 25) 5-Chloro-N-[(3S)-3-ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (133 mg, yield for 2 steps: 72%) was obtained by production according to the method described in Examples (5d) and (9) using (3S)-7-bromo-4-(2,4-dimethoxybenzyl)-3-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (189 mg, 0.45 mmol) obtained in Example (24b) and 5-chloro-2-methoxybenzenesulfonamide (104 mg, 0.47 mmol) obtained in Example (5a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.31 (1H, d, J=2.4 Hz), 8.25 (1H, d, J=3.0 Hz), 7.75 (1H, d, J=3.0 Hz), 7.47 (1H, dd, J=9.1, 2.4 Hz), 7.29-7.25 (1H, m), 7.00 (1H, d, J=9.1 Hz), 6.27 (1H, br s), 4.42 (1H, d, J=12.8 Hz), 4.33 (1H, dd, J=12.8, 6.7 Hz), 4.07 (3H, s), 3.59-3.53 (1H, m), 1.73-1.60 (2H, m), 1.05 (3H, t, J=7.3 Hz).","MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).","(Example 26) 5-Chloro-2-methoxy-N-[(3S)-5-oxo-3-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (26a) (2S)-2-[(2,4-Dimethoxybenzyl)amino]-3-methylbutan-1-ol The title compound (2.53 g, yield: 99%) was obtained by production according to the method described in Examples (8a) using 2,4-dimethoxybenzaldehyde (1.68 g, 10.9 mmol) and (2S)-2-amino-3-methylbutan-1-ol (1.04 g, 10.1 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.11 (1H, d, J=7.9 Hz), 6.50-6.42 (2H, m), 3.88-3.81 (7H, m), 3.71 (2H, d, J=4.3 Hz), 3.65 (1H, dd, J=10.3, 4.3 Hz), 3.35 (1H, dd, J=10.3, 6.7 Hz), 2.40-2.35 (1H, m), 1.84-1.73 (1H, m), 0.95 (3H, d, J=6.7 Hz), 0.89 (3H, d, J=6.7 Hz).","(26b) (3S)-7-Bromo-4-(2,4-dimethoxybenzyl)-3-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (1.43 g, yield for 2 steps: 77%) was obtained by production according to the method described in Examples (1a) and (1b) using 5-bromo-2-chloropyridine-3-carboxylic acid (1.00 g, 4.23 mmol) and (2S)-2-[(2,4-dimethoxybenzyl)amino]-3-methylbutan-1-ol (1.07 g, 4.22 mmol) obtained in Example (26a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.84 (1H, d, J=2.4 Hz), 8.37 (1H, d, J=2.4 Hz), 7.38-7.35 (1H, m), 6.50-6.43 (2H, m), 5.33 (1H, d, J=14.0 Hz), 4.66 (1H, dd, J=12.8, 5.5 Hz), 4.17-4.11 (1H, m), 4.00 (1H, d, J=12.8 Hz), 3.83 (3H, s), 3.81 (3H, s), 3.40 (1H, dd, J=10.9, 5.5 Hz), 1.85-1.78 (1H, m), 1.05 (3H, d, J=6.7 Hz), 1.02 (3H, d, J=6.7 Hz).","(26c) 5-Chloro-2-methoxy-N-[(3S)-5-oxo-3-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (186 mg, yield for 2 steps: 53%) was obtained by production according to the method described in Examples (5d) and (9) using (3S)-7-bromo-4-(2,4-dimethoxybenzyl)-3-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (355 mg, 0.82 mmol) obtained in Example (26b) and 5-chloro-2-methoxybenzenesulfonamide (199 mg, 0.90 mmol) obtained in Example (5a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.29 (2H, dd, J=16.4, 3.0 Hz), 7.75 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.10 (1H, s), 7.00 (1H, d, J=8.5 Hz), 6.36-6.33 (1H, m), 4.47-4.39 (2H, m), 4.07 (3H, s), 3.35-3.29 (1H, m), 1.95-1.88 (1H, m), 1.08-1.00 (6H, m).","MS spectrum (ES/APCI+): 426 (M+H), 428 (M+2+H).","(Example 27) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (27a) (2R)-3-(Benzyloxy)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol The title compound (4.18 g, yield: quantitative) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (2.00 g, 12.0 mmol) and (2R)-2-amino-3-(benzyloxy)propan-1-ol (2.18 g, 12.0 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.36-2.26 (5H, m), 7.12 (1H, d, J=7.8 Hz), 6.45-6.42 (2H, m), 4.46 (2H, s), 3.81-3.68 (9H, m), 3.52 (2H, d, J=5.9 Hz), 3.44 (1H, dd, J=11.0, 4.3 Hz), 2.95-2.90 (1H, m).","(27b) N-[(2R)-1-(Benzyloxy)-3-hydroxypropan-2-yl]-2-chloro-N-(2,4-dimethoxybenzyl)-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (1.21 g, 5.97 mmol) in methylene chloride (30 mL), oxalyl chloride (0.64 mL, 7.5 mmol) and N,N-dimethylformamide (0.024 mL, 0.31 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 30 minutes.","The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.","To a solution of (2R)-3-(benzyloxy)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol (1.98 g, 5.97 mmol) obtained in Example (27a) and N,N-diisopropylethylamine (2.05 mL, 12.1 mmol) in tetrahydrofuran (15 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (15 mL) was added over 10 minutes under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes.","To the reaction mixture, water (0.05 mL) was added, and then, the mixture was concentrated under reduced pressure.","The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/2-2/3) to obtain the title compound (2.74 g, yield: 89%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.21-9.18 (1H, m), 8.59-8.25 (1H, m), 7.58-6.98 (6H, m), 6.54-6.30 (2H, m), 4.97-2.83 (14H, m).","(27c) (3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (ca.","1.9 mol/L, 4.2 mL, 8.0 mmol) was diluted with tetrahydrofuran (130 mL).","A solution of N-[(2R)-1-(benzyloxy)-3-hydroxypropan-2-yl]-2-chloro-N-(2,4-dimethoxybenzyl)-5-nitropyridine-3-carboxamide (2.73 g, 5.29 mmol) obtained in Example (27b) in tetrahydrofuran (130 mL) was added thereto over 40 minutes under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes and further stirred at room temperature for 40 minutes.","To the reaction mixture, a saturated aqueous solution of ammonium chloride (50 mL) was added, and then, the mixture was concentrated into approximately ⅕ of the amount under reduced pressure.","The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate twice.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1) to obtain the title compound (1.93 g, yield: 76%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.53 (1H, d, J=3.1 Hz), 9.12 (1H, d, J=3.1 Hz), 7.35-7.19 (6H, m), 6.49-6.46 (2H, m), 5.06 (1H, d, J=14.1 Hz), 4.88 (1H, dd, J=12.9, 5.1 Hz), 4.52 (1H, d, J=14.1 Hz), 4.46 (1H, d, J=11.7 Hz), 4.40 (1H, d, J=11.7 Hz), 4.26 (1H, d, J=12.9 Hz), 4.16-4.10 (1H, m), 3.83 (6H, s) 3.56 (1H, dd, J=9.4, 7.4 Hz), 3.48 (1H, dd, J=9.4, 6.1 Hz).","(27d) (3S)-7-Amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of (3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (1.93 g, 4.03 mmol) obtained in Example (27c) and 10% palladium carbon (water content: 54.6%, 0.48 g) in tetrahydrofuran (26 mL) and ethanol (13 mL) was stirred at room temperature for 5 hours at normal pressure under the hydrogen atmosphere.","Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.","The solvent in the filtrate was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=1/0-20/1) to obtain the title compound (1.57 g, yield: 87%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (1H, d, J=3.1 Hz), 7.87 (1H, d, J=3.1 Hz), 7.35-7.26 (6H, m), 6.46-6.44 (2H, m), 5.09 (1H, d, J=14.9 Hz), 4.67 (1H, dd, J=12.7, 5.3 Hz), 4.53-4.42 (3H, m), 4.08-3.97 (2H, m), 3.80 (6H, s), 3.63 (1H, dd, J=9.6, 7.2 Hz), 3.56-3.47 (3H, m).","(27e) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (226 mg, 0.50 mmol) obtained in Example (27d) and pyridine (0.81 mL, 37.3 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (134 mg, 0.55 mmol) was added, and the mixture was stirred at 80° C. for 30 minutes in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) to obtain the title compound (323 mg, yield: 98%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.36 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.74 (1H, d, J=2.7 Hz), 7.46 (1H, dd, J=9.0, 2.7 Hz), 7.34-7.21 (6H, m), 7.00 (1H, d, J=9.0 Hz), 6.90 (1H, br s), 6.45-6.43 (2H, m), 5.04 (1H, d, J=14.5 Hz), 4.73 (1H, dd, J=12.9, 5.1 Hz), 4.49-4.39 (3H, m), 4.08-4.05 (4H, m), 4.01-3.97 (1H, m), 3.79 (3H, s), 3.77 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.43 (1H, dd, J=9.6, 6.5 Hz).","(27f) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-methoxybenzenesulfonamide (324 mg, 0.50 mmol) obtained in Example (27e) and anisole (0.17 mL, 1.6 mmol) in chloroform (2.5 mL), trifluoroacetic acid (0.76 mL, 9.9 mmol) and trifluoromethanesulfonic acid (0.13 mL, 1.5 mmol) were added, and the mixture was stirred at room temperature for 3 hours.","The reaction mixture was poured into a mixture of sodium bicarbonate (0.83 g, 9.9 mmol) and water (5 mL), and the mixture was stirred at room temperature for 30 minutes.","To the reaction mixture, sodium bicarbonate (0.13 g, 1.5 mmol) was further added, and then, the mixture was concentrated under reduced pressure.","The concentrated mixture was diluted by addition of tetrahydrofuran (5 mL).","2 N sulfuric acid (0.50 mL, 1.0 mmol) was added thereto, and the mixture was stirred at room temperature for 10 minutes.","To the reaction mixture, a 2 N aqueous sodium hydroxide solution (0.50 mL, 1.0 mmol) was added, and the mixture was concentrated under reduced pressure.","To the concentrated mixture, a saturated aqueous solution of sodium chloride was added, and the mixture was washed with ethyl acetate.","The aqueous layer was rendered acidic by the addition of 1 N hydrochloric acid, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1 twice.","The organic layer was dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (162 mg, yield: 79%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.35 (1H, br d, J=4.3 Hz), 8.24 (1H, d, J=3.1 Hz), 8.07 (1H, d, J=3.1 Hz), 7.68-7.64 (2H, m), 7.25 (1H, d, J=9.0 Hz), 5.04 (1H, t, J=5.5 Hz), 4.40-4.32 (2H, m), 3.87 (3H, s), 3.48-3.36 (3H, m).","MS spectrum (ES/APCI−): 412 (M−H), 414 (M+2−H).","(Example 28) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (28a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (310 mg, 0.69 mmol) obtained in Example (27d) and pyridine (1.1 mL, 13.7 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (171 mg, 0.76 mmol) was added, and the mixture was stirred at 80° C. for 30 minutes in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) to obtain the title compound (425 mg, yield: 97%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.37 (1H, d, J=2.7 Hz), 8.29 (1H, d, J=2.7 Hz), 7.49 (1H, dd, J=7.4, 3.1 Hz), 7.34-7.19 (7H, m), 7.02 (1H, dd, J=9.0, 3.9 Hz), 6.97 (1H, br s), 6.45-6.42 (2H, m), 5.03 (1H, d, J=14.5 Hz), 4.72 (1H, dd, J=12.7, 5.3 Hz), 4.48-4.39 (3H, m), 4.07-3.96 (5H, m), 3.79 (3H, s), 3.77 (3H, s), 3.54 (1H, dd, J=9.6, 7.4 Hz), 3.42 (1H, dd, J=9.6, 6.5 Hz).","(28b) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (213 mg, 0.33 mmol) obtained in Example (28a) and anisole (0.11 mL, 1.0 mmol) in chloroform (1.7 mL), trifluoroacetic acid (0.51 mL, 6.6 mmol) and trifluoromethanesulfonic acid (0.09 mL, 1.0 mmol) were added, and the mixture was stirred at room temperature for 4 hours.","The reaction mixture was poured into a mixture of sodium bicarbonate (0.65 g, 7.7 mmol) and water (3.4 mL), and the mixture was stirred at room temperature for 30 minutes.","The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of tetrahydrofuran (3.4 mL).","2 N sulfuric acid (0.34 mL, 0.68 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour.","To the reaction mixture, a 2 N aqueous sodium hydroxide solution (0.34 mL, 0.68 mmol) was added, and the mixture was concentrated under reduced pressure.","To the concentrated mixture, a saturated aqueous solution of sodium chloride was added, and the mixture was washed with ethyl acetate.","The aqueous layer was rendered acidic by the addition of 1 N hydrochloric acid, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1 twice.","The organic layer was dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (113 mg, yield: 85%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.27 (1H, br s), 8.34 (1H, br d, J=3.9 Hz), 8.24 (1H, d, J=2.7 Hz), 8.07 (1H, d, J=2.7 Hz), 7.51-7.47 (2H, m), 7.26-7.22 (1H, m), 5.04 (1H, t, J=5.5 Hz), 4.38-4.32 (2H, m), 3.86 (3H, s), 3.50-3.38 (3H, m).","MS spectrum (ES/APCI+): 398 (M+H).","(Example 29) 5-Bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (29a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-bromo-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (200 mg, 0.45 mmol) obtained in Example (27d) and pyridine (0.72 mL, 8.9 mmol), 5-bromo-2-methoxybenzenesulfonyl chloride (140 mg, 0.49 mmol) was added, and the mixture was stirred at 80° C. for 2 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (318 mg, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.37 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.87 (1H, d, J=2.0 Hz), 7.60 (1H, dd, J=8.6, 2.3 Hz), 7.33-7.21 (5H, m), 6.95 (2H, d, J=8.6 Hz), 6.44 (2H, d, J=6.7 Hz), 5.04 (1H, d, J=14.5 Hz), 4.73 (1H, dd, J=12.9, 5.1 Hz), 4.49-4.39 (3H, m), 4.08-4.05 (4H, m), 3.99 (1H, dd, J=12.3, 6.6 Hz), 3.79 (3H, s), 3.77 (3H, s), 3.55 (1H, t, J=8.6 Hz), 3.44 (1H, dd, J=9.4, 6.6 Hz).","(29b) 5-Bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-bromo-2-methoxybenzenesulfonamide (318 mg, 0.46 mmol) obtained in Example (29a) and anisole (0.15 mL, 1.4 mmol) in chloroform (2.5 mL), trifluoroacetic acid (0.7 mL, 9.1 mmol) and trifluoromethanesulfonic acid (0.12 mL, 1.4 mmol) were added, and the mixture was stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of water (5 mL) and tetrahydrofuran (2.5 mL) and stirred at room temperature for 1 hour.","To the reaction mixture, sodium bicarbonate (0.92 g, 10.9 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.","To the mixture, a 2 N aqueous sodium hydroxide solution (0.5 mL, 1.0 mmol) was added, and the mixture was washed with ethyl acetate.","To the aqueous layer, 2 N hydrochloric acid (0.75 mL, 1.5 mmol) was added, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1.The organic layer was dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (147 mg, yield: 71%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, s), 8.36 (1H, d, J=3.9 Hz), 8.23 (1H, d, J=2.7 Hz), 8.06 (1H, d, J=2.7 Hz), 7.80-7.76 (1H, m), 7.75 (1H, d, J=2.7 Hz), 7.19 (1H, d, J=9.4 Hz), 5.05 (1H, t, J=5.3 Hz), 4.37-4.35 (2H, m), 3.86 (3H, s), 3.50-3.38 (3H, m).","MS spectrum (ES/APCI+): 458 (M+H), 460 (M+2+H).","(Example 30) N-[(3S)-3-(Hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide (30a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (180 mg, 0.40 mmol) obtained in Example (27d) and pyridine (0.65 mL, 8.0 mmol), 2,5-dimethoxybenzenesulfonyl chloride (104 mg, 0.44 mmol) was added, and the mixture was stirred at 80° C. for 2 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (266 mg, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.42 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.33-7.21 (8H, m), 7.03 (1H, dd, J=9.0, 3.1 Hz), 6.98 (1H, d, J=9.0 Hz), 6.45-6.41 (2H, m), 5.03 (1H, d, J=14.5 Hz), 4.71 (1H, dd, J=12.7, 5.3 Hz), 4.47-4.38 (3H, m), 4.06-3.95 (5H, m), 3.79 (3H, s), 3.77 (3H, s), 3.73 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.42 (1H, dd, J=9.6, 6.5 Hz).","(30b) N-[(3S)-3-(Hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide (266 mg, 0.41 mmol) obtained in Example (30a) and anisole (0.13 mL, 1.2 mmol) in chloroform (2.5 mL), trifluoroacetic acid (0.63 mL, 8.2 mmol) and trifluoromethanesulfonic acid (0.11 mL, 1.2 mmol) were added, and the mixture was stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of water (5 mL) and tetrahydrofuran (2.5 mL) and stirred at room temperature for 1 hour.","To the reaction mixture, sodium bicarbonate (0.83 g, 9.8 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.","To the reaction mixture, a 2 N aqueous sodium hydroxide solution (0.5 mL, 1.0 mmol) was added, and the mixture was washed with ethyl acetate.","To the aqueous layer, 2 N hydrochloric acid (0.75 mL, 1.5 mmol) was added, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1.The organic layer was dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (74 mg, yield: 44%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.17 (1H, br s), 8.35 (1H, d, J=3.9 Hz), 8.25 (1H, d, J=2.7 Hz), 8.07 (1H, d, J=2.7 Hz), 7.21 (1H, d, J=2.7 Hz), 7.19-7.13 (2H, m), 4.36-4.32 (2H, m), 3.81 (3H, s), 3.72 (3H, s), 3.49-3.35 (3H, m).","MS spectrum (ES/APCI+): 410 (M+H).","(Example 31) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (31a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-(trifluoromethoxy)benzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (220 mg, 0.49 mmol) obtained in Example (27d) and pyridine (0.79 mL, 9.8 mmol), 5-chloro-2-(trifluoromethoxy)benzenesulfonyl chloride (approximately 83% content, 159 mg, 0.54 mmol) obtained in Example (13a) was added, and the mixture was stirred at 80° C. for 1 hour in an oil bath.","The reaction mixture was cooled and then diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-65/35) to obtain the title compound (239 mg, yield: 69%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.45 (1H, d, J=2.7 Hz), 8.28 (1H, d, J=2.7 Hz), 7.88 (1H, d, J=2.7 Hz), 7.56 (1H, dd, J=8.8, 2.5 Hz), 7.39-7.21 (7H, m), 6.99 (1H, br s), 6.46-6.42 (2H, m), 5.05 (1H, d, J=14.5 Hz), 4.75 (1H, dd, J=12.9, 5.1 Hz), 4.50-4.39 (3H, m), 4.10-4.00 (2H, m), 3.79 (3H, s), 3.78 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.44 (1H, dd, J=9.6, 6.5 Hz).","(31b) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-(trifluoromethoxy)benzenesulfonamide (234 mg, 0.33 mmol) obtained in Example (31a) and anisole (0.11 mL, 1.0 mmol) in chloroform (1.6 mL), trifluoroacetic acid (0.51 mL, 6.6 mmol) and trifluoromethanesulfonic acid (0.09 mL, 1.0 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was diluted by addition of water (3.2 mL) and tetrahydrofuran (1.6 mL) and stirred at room temperature for 1 hour.","To the reaction mixture, sodium bicarbonate (0.67 g, 7.9 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.","The reaction mixture was concentrated under reduced pressure.","To the concentrated mixture, a 2 N aqueous sodium hydroxide solution (0.33 mL, 0.66 mmol) was added, and the mixture was washed with ethyl acetate.","To the aqueous layer, 1 N hydrochloric acid (0.66 mL, 0.66 mmol) was added, followed by extraction with a mixed solvent of methylene chloride/isopropanol=4/1.The organic layer was dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (101 mg, yield: 65%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.77 (1H, br s), 8.41 (1H, br d, J=4.3 Hz), 8.21 (1H, d, J=2.7 Hz), 8.11 (1H, d, J=2.7 Hz), 7.91 (1H, d, J=2.7 Hz), 7.87 (1H, dd, J=8.8, 2.7 Hz), 7.64-7.60 (1H, m), 5.07 (1H, t, J=5.5 Hz), 4.43-4.34 (2H, m), 3.52-3.37 (3H, m).","MS spectrum (ESI+): 468 (M+H), 470 (M+2+H).","(Example 32) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (32a) 5-Fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride The title compound (approximately 50% content, 2.49 g, yield: 81%) was obtained as a mixture containing positional isomers by production according to the method described in Example (13a) using 4-fluorophenyl trifluoromethyl ether (2.00 g, 11.1 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.87-7.82 (1H, m), 7.65-7.60 (0 5H, m), 7.57-7.47 (1H, m), 7.42 (0 5H, t, J=9.0 Hz).","(32b) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (410 mg, 0.91 mmol) obtained in Example (27d) and pyridine (1.48 mL, 18.2 mmol), 5-fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride (approximately 50% content, 280 mg, 1.00 mmol) obtained in Example (32a) was added, and the mixture was stirred at 80° C. for 1 hour in an oil bath.","The reaction mixture was cooled and then diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-65/35) to obtain the title compound (265 mg, yield: 42%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.44 (1H, d, J=2.7 Hz), 8.27 (1H, d, J=2.7 Hz), 7.61 (1H, dd, J=7.4, 3.1 Hz), 7.45-7.40 (1H, m), 7.34-7.22 (7H, m), 7.01 (1H, br s), 6.46-6.42 (2H, m), 5.04 (1H, d, J=14.5 Hz), 4.74 (1H, dd, J=12.9, 5.1 Hz), 4.49-4.39 (3H, m), 4.10-3.99 (2H, m), 3.79 (3H, s), 3.78 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.43 (1H, dd, J=9.6, 6.3 Hz).","(32c) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide (258 mg, 0.37 mmol) obtained in Example (32b) and anisole (0.12 mL, 1.1 mmol) in chloroform (1.8 mL), trifluoroacetic acid (0.57 mL, 7.5 mmol) and trifluoromethanesulfonic acid (0.10 mL, 1.1 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was diluted by addition of water (3.6 mL) and tetrahydrofuran (1.8 mL) and stirred at room temperature for 1 hour.","To the reaction mixture, sodium bicarbonate (0.75 g, 9.0 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.","The reaction mixture was concentrated under reduced pressure.","To the concentrated mixture, a 2 N aqueous sodium hydroxide solution (0.37 mL, 0.74 mmol) was added, followed by extraction with ethyl acetate.","To the aqueous layer, 1 N hydrochloric acid (0.75 mL, 0.75 mmol) was added, followed by extraction with a mixed solvent of methylene chloride/isopropanol=4/1.The organic layer was dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (135 mg, yield: 80%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.77 (1H, br s), 8.40 (1H, br d, J=4.3 Hz), 8.21 (1H, d, J=2.7 Hz), 8.11 (1H, d, J=2.7 Hz), 7.76-7.72 (1H, m), 7.69-7.63 (2H, m), 5.07 (1H, t, J=5.3 Hz), 4.44-4.34 (2H, m), 3.54-3.37 (3H, m).","MS spectrum (ESI+): 452 (M+H).","(Example 33) 5-Chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (33a) (6S)—N-(2,4-Dimethoxybenzyl)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine To a solution of tert-butyl [(2S)-1,4-dihydroxybutan-2-yl]carbamate (2.00 g, 9.74 mmol) in methylene chloride (50 mL), imidazole (1.99 g, 11.5 mmol) and tert-butyl(chloro)diphenylsilane (5.89 g, 21.4 mmol) were added, and the mixture was stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-90/10) to obtain tert-butyl [(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]carbamate.","To tert-butyl [(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]carbamate thus obtained, trifluoroacetic acid (50 mL, 653 mmol) was added, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and the residue was neutralized by the addition of saturated sodium bicarbonate, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of (6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine.","To a solution of the crude product of (6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine thus obtained in methanol (9.35 mL), 2,4-dimethoxybenzaldehyde (2.11 g, 12.7 mmol) and triethylamine (9.56 mL, 69.2 mmol) were added, and the mixture was stirred at room temperature for 1 hour.","Subsequently, to the reaction mixture, anhydrous sodium sulfate (0.901 g, 6.34 mmol) was added, and the mixture was stirred at room temperature for 18 hours.","Subsequently, to the reaction mixture, sodium borohydride (0.24 g, 6.34 mmol) was added under ice cooling, and the reaction mixture was stirred at the same temperature as above for 1 hour.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-40/60) to obtain the title compound (8.08 g, yield for 3 steps: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.70-7.59 (8H, m), 7.45-7.30 (12H, m), 7.04 (1H, d, J=8.2 Hz), 6.51-6.35 (2H, m), 3.82 (3H, s), 3.81 (3H, s), 3.74-3.51 (6H, m), 2.90-2.75 (1H, m), 1.77-1.56 (2H, m).","(33b) (3S)-4-(2,4-Dimethoxybenzyl)-3-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (2.24 g, 11.04 mmol) in methylene chloride (110 mL), oxalyl chloride (1.42 mL, 16.6 mmol) and N,N-dimethylformamide (1.42 mL, 5.52 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 2 hours.","The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.","Subsequently, to a solution of (6S)—N-(2,4-dimethoxybenzyl)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine (8.08 g, 11.04 mmol) obtained in Example (33a) and N,N-diisopropylethylamine (3.85 mL, 22.1 mmol) in tetrahydrofuran (110 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (20 mL) was added under ice cooling, and the mixture was stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-80/20) to obtain 2-chloro-N-(2,4-dimethoxybenzyl)-5-nitro-N-[(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]pyridine-3-carboxamide (7.193 g, yield: 71%).","To a solution of 2-chloro-N-(2,4-dimethoxybenzyl)-5-nitro-N-[(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]pyridine-3-carboxamide (1.09 g, 1.19 mmol) thus obtained in tetrahydrofuran (15 mL), a solution of tetrabutylammonium fluoride in tetrahydrofuran (1 mol/L, 3.57 mL, 3.57 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 24 hours.","The reaction mixture was diluted by addition of a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (233 mg, yield: 49%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.58 (1H, d, J=2.5 Hz), 9.19 (1H, d, J=2.5 Hz), 7.37 (1H, d, J=8.2 Hz), 6.52-6.47 (2H, m), 5.12 (1H, d, J=14.3 Hz), 4.76 (1H, dd, J=12.9, 5.5 Hz), 4.48 (1H, d, J=14.3 Hz), 4.31-4.22 (2H, m), 3.84 (3H, s), 3.81 (3H, s), 3.79-3.67 (2H, m), 1.89-1.79 (1H, m), 1.75-1.65 (1H, m).","(33c) (3S)-7-Amino-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (60.0 mg, yield: quantitative) was obtained by production according to the method described in Example (3c) using (3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (64.0 mg, 0.16 mmol) obtained in Example (33b).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (1H, d, J=2.7 Hz), 7.86 (1H, d, J=2.7 Hz), 7.33-7.31 (1H, m), 6.48-6.46 (2H, m), 5.10 (1H, d, J=14.5 Hz), 4.54 (1H, dd, J=12.9, 5.5 Hz), 4.45 (1H, d, J=14.5 Hz), 4.08 (1H, d, J=12.9 Hz), 4.05-3.97 (1H, m), 3.82 (3H, s), 3.80 (3H, s), 3.76-3.49 (5H, m), 1.90-1.70 (2H, m).","(33d) 5-Chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (67 mg, yield: 72%) was obtained by production according to Example (1d) using (3S)-7-amino-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (60.0 mg, 0.16 mmol) obtained in Example (33c) and 5-chloro-2-methoxybenzenesulfonyl chloride (42.6 mg, 0.18 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.40 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.74 (1H, dd, J=3.7, 2.5 Hz), 7.49-7.43 (1H, m), 7.34-7.24 (1H, m), 7.00 (1H, dd, J=9.0, 3.9 Hz), 6.48-6.43 (2H, m), 5.08 (1H, dd, J=14.4, 3.6 Hz), 4.59 (1H, dt, J=12.7, 4.7 Hz), 4.41 (1H, dd, J=14.4, 3.6 Hz), 4.15-4.03 (8H, m), 3.80 (3H, s), 3.75-3.62 (2H, m), 1.85-1.58 (2H, m).","(33e) 5-Chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (42 mg, yield: 85%) was obtained by production according to the method described in Example (9) using 5-chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (67 mg, 0.12 mmol) obtained in Example (33d).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.48 (1H, d, J=5.9 Hz), 8.14 (1H, d, J=2.7 Hz), 8.08 (1H, d, J=2.7 Hz), 7.68 (1H, d, J=2.4 Hz), 7.65 (1H, dd, J=5.9, 2.4 Hz), 7.25 (1H, d, J=8.8 Hz), 4.32-4.29 (2H, m), 3.87 (3H, s), 3.63-3.40 (3H, m), 1.60-1.55 (2H, m).","MS spectrum (ES/APCI+): 428 (M+H), 430 (M+2+H).","(Example 34) 2-[(3S)-7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (34a) 2-[(3S)-4-(2,4-Dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide To a mixture of (3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (120 mg, 0.30 mmol) obtained in Example (33b) in acetonitrile (3 mL) and a phosphate buffer solution (pH 6.86) (2 mL), 2-azaadamantane-N-oxyl (45.3 mg, 0.030 mmol) and sodium chlorate (32.3 mg, 0.036 mmol) were added, subsequently an aqueous sodium hypochlorite solution (available chlorine concentration: >5%, 2.35 mL, 0.9 mmol) was added under ice cooling, and the mixture was stirred for 3 hours under ice cooling.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium thiosulfate and a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of [(3S)-4-(2,4-dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]acetic acid.","To a solution of the crude product of [(3S)-4-(2,4-dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]acetic acid thus obtained in N,N-dimethylformamide (10 mL), dimethylamine hydrochloride (36.3 mg, 0.45 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (114 mg, 0.59 mmol), 1-hydroxybenzotriazole monohydrate (91.0 mg, 0.59 mmol), and triethylamine (0.206 mL, 1.49 mmol) were added, and the mixture was stirred at room temperature for 17 hours.","The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (108 mg, yield for 2 steps: 82%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.62 (1H, d, J=2.7 Hz), 9.21 (1H, dd, J=4.9, 2.7 Hz), 7.44-7.36 (1H, m), 6.52-6.45 (2H, m), 5.00-4.90 (2H, m), 4.70-4.56 (2H, m), 4.28 (1H, d, J=12.5 Hz), 3.82 (3H, s), 3.80 (3H, s), 2.85 (3H, s), 2.82 (3H, s), 2.61 (1H, td, J=16.2, 9.4 Hz), 2.39 (1H, dq, J=16.2, 4.4 Hz).","(34b) 2-[(3S)-7-Amino-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide The title compound (90.0 mg, yield: 89%) was obtained by production according to the method described in Example (3c) using 2-[(3S)-4-(2,4-dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (108 mg, 0.24 mmol) obtained in Example (34a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.14 (1H, t, J=2.9 Hz), 7.90 (1H, t, J=3.5 Hz), 7.40-7.30 (1H, m), 6.50-6.43 (2H, m), 4.93 (1H, t, J=15.3 Hz), 4.70 (1H, dq, J=12.6, 2.5 Hz), 4.55 (1H, dd, J=14.5, 3.9 Hz), 4.52-4.45 (1H, m), 4.08 (1H, dd, J=12.6, 6.8 Hz), 3.91 (3H, s), 3.79 (3H, s), 2.92 (3H, s), 2.85 (3H, s), 2.76-2.64 (1H, m), 2.37 (1H, td, J=10.6, 5.5 Hz).","(34c) 2-[(3S)-7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N, N-dimethylacetamide The title compound (40 mg, yield: 30%) was obtained by production according to Example (1d) using 2-[(3S)-7-amino-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (90.0 mg, 0.22 mmol) obtained in Example (34b) and 5-chloro-2-methoxybenzenesulfonyl chloride (57.6 mg, 0.24 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.43 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.73 (1H, d, J=2.4 Hz), 7.46 (1H, dd, J=8.9, 2.7 Hz), 7.32-7.24 (1H, m), 7.01 (1H, dd, J=8.9, 2.4 Hz), 6.49-6.42 (2H, m), 4.91 (1H, d, J=14.1 Hz), 4.75 (1H, dd, J=12.7, 5.3 Hz), 4.56-4.46 (2H, m), 4.06 (3H, s), 3.91-3.83 (1H, m), 3.78 (3H, s), 3.78 (3H, s), 2.91 (3H, s), 2.79 (3H, s), 2.58 (1H, dd, J=16.0, 9.4 Hz), 2.31 (1H, dd, J=16.0, 4.7 Hz).","(34d) 2-[(3S)-7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide The title compound (12 mg, yield: 40%) was obtained by production according to the method described in Example (9) using 2-[(3S)-7-{[(5-chloro-2-methoxyphenyl)sulfonyl]amino}-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (40.0 mg, 0.065 mmol) obtained in Example (34c).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.32 (1H, br s), 8.19 (1H, d, J=2.7 Hz), 8.09 (1H, d, J=2.7 Hz), 7.68-7.65 (2H, m), 7.25 (1H, d, J=8.6 Hz), 4.40-4.28 (2H, m), 3.92-3.83 (4H, m), 3.80-3.74 (1H, m), 2.88 (3H, s), 2.82 (3H, s), 2.79-2.64 (2H, m).","MS spectrum (ES/APCI+): 469 (M+H), 471 (M+2+H).","(Example 35) 5-Chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (35a) {1-[(2,4-Dimethoxybenzyl)amino]cyclopropyl}methanol The title compound (1.90 g, yield: 91%) was obtained by production according to the method described in Example (8a) using (1-aminocyclopropyl)methanol (0.75 g, 0.24 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.14 (1H, d, J=8.2 Hz), 6.46-6.42 (2H, m), 3.83 (3H, s), 3.79 (3H, s), 3.74 (2H, s), 3.51 (2H, s), 3.48 (1H, s), 0.70-0.68 (2H, m), 0.52-0.49 (2H, m).","(35b) 2-Chloro-N-(2,4-dimethoxybenzyl)-N-[1-(hydroxymethyl)cyclopropyl]-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (1.587 g, 7.83 mmol) in methylene chloride (80 mL), oxalyl chloride (0.84 mL, 9.8 mmol) and N,N-dimethylformamide (0.30 mL, 3.92 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 2 hours.","The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.","To a solution of {1-[(2,4-dimethoxybenzyl)amino]cyclopropyl}methanol (1.859 g, 7.83 mmol) obtained in Example (35a) and N,N-diisopropylethylamine (2.73 mL, 15.7 mmol) in tetrahydrofuran (60 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (20 mL) was added under ice cooling, and the reaction mixture was stirred at room temperature for 30 minutes.","The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-40/60) to obtain the title compound (2.155 g, yield: 65%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.25 (0.14H, d, J=2.7 Hz), 9.19 (0.86H, d, J=2.7 Hz), 8.47 (0.14H, d, J=2.7 Hz), 7.06 (1H, br d, J=8.2 Hz), 6.43-6.36 (2H, m), 4.04-3.03 (11H, m), 1.28-1.23 (4H, m).","(35c) 4′-(2,4-Dimethoxybenzyl)-7′-nitrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one To a solution of 2-chloro-N-(2,4-dimethoxybenzyl)-N-[1-(hydroxymethyl)cyclopropyl]-5-nitropyridine-3-carboxamide (400 mg, 0.95 mmol) obtained in Example (35b) in N,N-dimethylformamide (47 mL), potassium carbonate (393 mg, 2.84 mmol) was added, and the mixture was stirred at room temperature for 22 hours and subsequently stirred at 50° C. for 2 hours and at 70° C. for 2 hours.","The reaction mixture was cooled, and insoluble matter was filtered off.","The residue was washed with ethyl acetate.","The filtrate and the washes were combined.","The solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-50/50) to obtain the title compound (238 mg, yield: 65%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.23-9.19 (1H, m), 9.11-9.08 (1H, m), 7.22 (1H, d, J=7.8 Hz), 6.49-6.45 (2H, m), 4.27-4.08 (3H, m), 3.92-3.74 (7H, m), 1.32-1.20 (2H, m), 0.97-0.87 (2H, m).","(35d) 7′-Amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one A mixture of 4′-(2,4-dimethoxybenzyl)-7′-nitrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (238 mg, 0.62 mmol) obtained in Example (35c) and 10% palladium carbon (water content: 54.6%, 100 mg) in tetrahydrofuran (30 mL), and methanol (30 mL) was stirred at room temperature for 3 hours at normal pressure under the hydrogen atmosphere.","Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.","The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (227 mg, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.84 (1H, d, J=2.2 Hz), 7.48 (1H, d, J=2.2 Hz), 7.20 (1H, d, J=8.2 Hz), 6.48-6.43 (2H, m), 4.70 (2H, br s), 3.82 (3H, s), 3.81 (3H, s), 3.69 (2H, s), 3.48 (2H, d, J=3.1 Hz), 0.93 (2H, br s), 0.63 (2H, br s).","(35e) 5-Chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide The title compound (80 mg, yield: 56%) was obtained by production according to the method described in Examples (1d) and (9) using 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (124 mg, 0.35 mmol) obtained in Example (35d) and 5-chloro-2-methoxybenzenesulfonyl chloride (92.5 mg, 0.38 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.84 (1H, s), 8.08 (1H, d, J=2.7 Hz), 7.94 (1H, d, J=2.7 Hz), 7.68-7.62 (2H, m), 7.25 (1H, d, J=8.6 Hz), 4.26 (2H, s), 3.87 (3H, s), 0.74 (4H, br s).","MS spectrum (ES/APCI+): 410 (M+H), 412 (M+2+H).","(Example 36) 5-Fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide The title compound (81 mg, yield for 2 steps: 71%) was obtained by production according to the method described in Examples (1d) and (9) using 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (103 mg, 0.29 mmol) obtained in Example (35d) and 5-fluoro-2-methoxybenzenesulfonyl chloride (71.6 mg, 0.32 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.27 (1H, br s), 8.83 (1H, s), 8.08 (1H, d, J=3.1 Hz), 7.95 (1H, d, J=3.1 Hz), 7.51-7.46 (2H, m), 7.26-7.22 (1H, m), 4.25 (2H, s), 3.86 (3H, s), 0.74 (4H, br s).","MS spectrum (ES/APCI+): 394 (M+H).","(Example 37) 5-Chloro-2-methoxy-N-(5-oxo-4-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (37a) 7-Nitro-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (324 mg, yield for 2 steps: 39%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (591 mg, 2.92 mmol) and 2-anilinoethanol (400 mg, 2.92 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.32 (1H, d, J=3.1 Hz), 9.28 (1H, d, J=3.1 Hz), 7.50-7.46 (2H, m), 7.39-7.35 (1H, m), 7.33-7.30 (2H, m), 4.87-4.85 (2H, m), 4.15-4.13 (2H, m).","(37b) 7-Amino-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (243 mg, yield: 84%) was obtained by production according to the method described in Example (3b) using 7-nitro-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (324 mg, 1.14 mmol) obtained in Example (37a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.93 (1H, d, J=3.1 Hz), 7.60 (1H, d, J=3.1 Hz), 7.46 (2H, t, J=7.6 Hz), 7.37-7.31 (3H, m), 4.58 (2H, t, J=5.1 Hz), 3.96 (2H, t, J=5.1 Hz), 3.69 (2H, br s).","(37c) 5-Chloro-2-methoxy-N-(5-oxo-4-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide The title compound (77 mg, yield: 71%) was obtained by production according to Example (1d) using 7-amino-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (60 mg, 0.24 mmol) obtained in Example (37b) and 5-chloro-2-methoxybenzenesulfonyl chloride (62 mg, 0.26 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.39 (1H, br s), 8.16 (1H, d, J=2.4 Hz), 7.98 (1H, d, J=2.4 Hz), 7.69-7.67 (2H, m), 7.44 (2H, t, J=7.3 Hz), 7.36 (2H, d, J=7.3 Hz), 7.32-7.25 (2H, m), 4.56 (2H, t, J=4.6 Hz), 3.95 (2H, t, J=4.6 Hz), 3.88 (3H, s).","MS spectrum (ES/APCI+): 460 (M+H), 462 (M+2+H).","(Example 38) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (38a) 7-Nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (1.24 g, yield: quantitative) was obtained by production according to Example (18c) using 4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (2.00 g, 5.57 mmol) obtained in Example (8c).","1H NMR spectrum (CD3OD, 400 MHz) δ: 9.30 (1H, d, J=2.7 Hz), 9.19 (1H, d, J=2.7 Hz), 4.70-4.69 (2H, m), 3.67-3.65 (2H, m).","(38b) 7-Nitro-4-(pyridin-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of 7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (100 mg, 0.48 mmol) obtained in Example (38a), 2-bromopyridine (90.6 mg, 0.57 mmol), tris(dibenzylideneacetone)dipalladium(0) (87.6 mg, 0.010 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (11.1 mg, 0.019 mmol), and cesium carbonate (0.312 g, 0.96 mmol) in dioxane (10 mL) was heated to reflux for 18 hours in an oil bath.","The reaction mixture was cooled.","The solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate/methanol=100/0/0-0/100/0-0/85/15) to obtain the title compound (41 mg, yield: 30%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.30 (1H, d, J=2.7 Hz), 9.25 (1H, d, J=2.7 Hz), 8.46-8.44 (1H, m), 8.06 (1H, d, J=8.2 Hz), 7.83-7.79 (1H, m), 7.22-7.19 (1H, m), 4.90 (2H, t, J=4.3 Hz), 4.57 (2H, t, J=4.3 Hz.","(38c) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (58 mg, yield for 2 steps: 88%) was obtained by production according to Examples (3b) and (1d) using 7-nitro-4-(pyridin-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (41.0 mg, 0.14 mmol) obtained in Example (38b) and 5-chloro-2-methoxybenzenesulfonyl chloride (35.2 mg, 0.15 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.45 (1H, br s), 8.47 (1H, d, J=3.9 Hz), 8.18 (1H, br s), 7.95-7.86 (3H, m), 7.70-7.67 (2H, m), 7.29-7.25 (2H, m), 4.53 (2H, br s), 4.30 (2H, br s), 3.88 (3H, s).","MS spectrum (ES/APCI+): 461 (M+H), 463 (M+2+H).","(Example 39) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (39a) 7-Nitro-4-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (104 mg, yield: 76%) was obtained by production according to the method described in Example (38b) using 7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (100 mg, 0.48 mmol) obtained in Example (38a) and 3-iodopyridine (118 mg, 0.57 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.34-9.30 (2H, m), 8.62-8.61 (2H, m), 7.74-7.71 (1H, m), 7.44 (1H, dd, J=8.0, 4.9 Hz), 4.89 (2H, t, J=4.1 Hz), 4.18 (2H, t, J=4.1 Hz).","(39b) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (13 mg, yield for 2 steps: 8%) was obtained by production according to the method described in Examples (3b) and (1d) using 7-nitro-4-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (104 mg, 0.36 mmol) obtained in Example (39a) and 5-chloro-2-methoxybenzenesulfonyl chloride (21.7 mg, 0.09 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.40 (1H, br s), 8.62 (1H, d, J=2.4 Hz), 8.50-8.49 (1H, m), 8.18 (1H, d, J=2.9 Hz), 8.01 (1H, d, J=2.9 Hz), 7.84 (1H, br d, J=8.3 Hz), 7.69-7.67 (2H, m), 7.49 (1H, dd, J=8.1, 4.6 Hz), 7.27-7.25 (1H, m), 4.59 (2H, t, J=4.1 Hz), 4.01 (2H, t, J=4.1 Hz), 3.88 (3H, s).","MS spectrum (ES/APCI+): 461 (M+H), 463 (M+2+H).","(Example 40) 5-Chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide (40a) 5-Chloro-2-(trifluoromethoxy)benzenesulfonyl chloride To a suspension of 5-chloro-2-(trifluoromethoxy)aniline (5.00 g, 23.6 mmol) and dibenzyl disulfide (4.66 g, 18.9 mmol) in acetonitrile (75 mL), Isoamyl nitrite (3.46 mL, 26.0 mmol) was slowly added at 60° C. in an oil bath, and the mixture was stirred at the same temperature as above for 2 hours.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-95/5) to prepare 2-(benzylsulfanyl)-4-chlorophenyl trifluoromethyl ether (3.86 g, yield: 51%).","To a mixture of the obtained 2-(benzylsulfanyl)-4-chlorophenyl trifluoromethyl ether (4.84 g, 15.2 mmol), acetic acid (4.5 mL) and water (3 mL) in acetonitrile (120 mL), 1,3-dichloro-5,5-dimethylhydantoin (5.98 g, 30.4 mmol) was added under ice cooling, and the mixture was stirred at the same temperature as above for 3 hours.","The mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate, extracted with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (hexane/ethyl acetate=100/0-85/15) to obtain the title compound (3.64 g, yield: 81%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (1H, d, J=2.3 Hz), 7.75 (1H, dd, J=9.0, 2.7 Hz), 7.50-7.47 (1H, m).","(40b) 5-Chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-(trifluoromethoxy)benzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (95.0 mg, 0.267 mmol) obtained in Example (35d) and pyridine (0.432 mL, 5.35 mmol), 5-chloro-2-(trifluoromethoxy)benzenesulfonyl chloride (86.8 mg, 0.294 mmol) in Example (40a) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the title compound (142 mg, yield: 87%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.23 (1H, d, J=2.7 Hz), 7.91 (1H, d, J=2.7 Hz), 7.87 (1H, d, J=2.7 Hz), 7.57 (1H, dd, J=8.8, 2.5 Hz), 7.39-7.35 (1H, m), 7.17 (1H, d, J=8.2 Hz), 6.46-6.44 (2H, m), 4.68 (1H, br s), 3.96 (1H, br s), 3.81 (3H, s), 3.80 (3H, s), 0.93 (2H, br s), 0.69 (2H, br s).","(40c) 5-Chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide To a solution of 5-chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-(trifluoromethoxy)benzenesulfonamide (142 mg, 0.231 mmol) obtained in Example (40b) in chloroform (8 mL), anisole (0.0504 mL, 0.463 mmol), trifluoroacetic acid (4 mL, 52 mmol) and trifluoromethanesulfonic acid (0.0609 mL, 0.694 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with ethyl acetate.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the title compound (84 mg, yield: 78%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.73 (1H, br s), 8.87 (1H, br s), 8.11 (1H, d, J=2.4 Hz), 7.93-7.86 (3H, m), 7.61 (1H, d, J=8.8 Hz), 4.30 (2H, br s), 0.80 (2H, br s), 0.77 (2H, br s).","MS spectrum (ES/APCI+): 464 (M+H), 466 (M+2+H).","(Example 41) 5-Fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide (41a) 5-Fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride The title compound (0.82 g, yield for 2 steps: 29%) was obtained by production according to the method described in Example (40a) using 5-fluoro-2-(trifluoromethoxy)aniline (2.00 g, 10.3 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ:7.84 (1H, dd, J=6.8, 2.9 Hz), 7.56-7.47 (2H, m).","(41b) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (100 mg, 0.281 mmol) obtained in Example (35d) and pyridine (0.453 mL, 5.63 mmol), 5-fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride (94.1 mg, 0.338 mmol) in Example (41a) was added at room temperature, and the mixture was stirred at 80° C. for 5 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (156 mg, yield: 93%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.27 (1H, d, J=2.7 Hz), 7.94 (1H, d, J=2.7 Hz), 7.63 (1H, dd, J=7.4, 3.1 Hz), 7.32-7.28 (2H, m), 7.16 (1H, d, J=8.2 Hz), 6.46-6.43 (2H, m), 4.69 (1H, br s), 3.95 (2H, br s), 3.81 (3H, s), 3.80 (3H, s), 0.92 (2H, br s), 0.69 (2H, br s).","(41c) 5-Fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide To a suspension of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide (156 mg, 0.261 mmol) obtained in Example (41b) in chloroform (5 mL), anisole (84.7 mg, 0.783 mmol), trifluoroacetic acid (0.40 mL, 5.2 mmol) and trifluoromethanesulfonic acid (0.0687 mL, 0.783 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hours.","To the mixture, an additional trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for further 2 hours.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with chloroform.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-95/5) to obtain the title compound (97 mg, yield: 83%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.75 (1H, br s), 8.88 (1H, br s), 8.11 (1H, d, J=2.7 Hz), 7.92 (1H, d, J=2.7 Hz), 7.75-7.66 (3H, m), 4.30 (2H, br s), 0.82-0.75 (4H, m).","MS spectrum (ES/APCI+): 448 (M+H).","(Example 42) 2-Ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (42a) 5-Fluoro-2-ethoxybenzenesulfonyl chloride The title compound (3.16 g, yield: 36%) was obtained by production according to the method described in Example (13a) using 1-ethoxy-4-fluorobenzene (5.11 g, 36.5 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.70 (1H, dd, J=7.4, 3.1 Hz), 7.41-7.36 (1H, m), 7.07 (1H, dd, J=9.4, 3.9 Hz), 4.26 (2H, q, J=6.8 Hz), 1.55 (3H, t, J=6.8 Hz).","(42b) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (100 mg, 0.281 mmol) obtained in Example (35d) and pyridine (0.453 mL, 5.63 mmol), 5-Fluoro-2-ethoxybenzenesulfonyl chloride (73.9 mg, 0.310 mmol) obtained in Example (42a) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (146 mg, yield: 93%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.20 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=7.4, 3.1 Hz), 7.23-7.14 (2H, m), 7.02-6.95 (2H, m), 6.46-6.43 (2H, m), 4.66 (1H, br s), 4.29 (2H, q, J=7.0 Hz), 3.92 (1H, br s), 3.80 (3H, s), 3.79 (3H, s), 1.58 (3H, t, J=7.0 Hz), 0.87 (2H, br s), 0.63 (2H, br s).","(42c) 2-Ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a suspension of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide (146 mg, 0.262 mmol) obtained in Example (42b) in chloroform (4 mL), anisole (0.0571 mL, 0.524 mmol), trifluoroacetic acid (2 mL, 26.1 mmol) and trifluoromethanesulfonic acid (0.0689 mL, 0.786 mmol) were added at room temperature, and the mixture was stirred at room temperature for 3 hours.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with chloroform.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain a crude solid.","To a suspension of the crude solid in ethanol (3 mL), a 1 N aqueous sodium hydroxide solution (0.40 mL) was added and the mixture was stirred at room temperature until dissolved.","The mixture was concentrated under reduced pressure, diluted by addition of water, and then filtered.","A 1 N hydrochloric acid (0.40 mL) was added to the filtrate, the precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (95 mg, yield: 89%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.15 (1H, s), 8.83 (1H, s), 8.09 (1H, d, J=2.7 Hz), 7.95 (1H, d, J=2.7 Hz), 7.52-7.44 (2H, m), 7.24 (1H, dd, J=9.0, 4.3 Hz), 4.26 (br 2H, s), 4.16 (2H, q, J=7.0 Hz), 1.26 (3H, t, J=7.0 Hz), 0.77-0.71 (4H, m).","MS spectrum (ES/APCI+): 408 (M+H).","(Example 43) 2,5-Dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (43a) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2,5-dimethoxybenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (90.0 mg, 0.253 mmol) obtained in Example (35d) and pyridine (0.408 mL, 5.06 mmol), 2,5-dimethoxybenzenesulfonyl chloride (65.9 mg, 0.279 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 3 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (143 mg, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.22 (1H, d, J=2.7 Hz), 7.88 (1H, br d, J=2.7 Hz), 7.37-7.28 (2H, m), 7.15 (1H, br d, J=8.6 Hz), 7.04 (1H, dd, J=9.0, 3.1 Hz), 6.97 (1H, d, J=9.0 Hz), 6.45-6.43 (2H, m), 4.66 (2H, br s), 3.99 (3H, s), 3.91 (2H, br s), 3.80 (3H, s), 3.79 (3H, s), 3.73 (3H, s), 0.86 (2H, br s), 0.61 (2H, br s).","(43b) 2,5-Dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a suspension of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1, 4]oxazepin]-7′-yl]-2,5-dimethoxybenzenesulfonamide (0.143 mg, 0.257 mmol) obtained in Example (43a) in chloroform (4 mL), anisole (0.0561 mL, 0.515 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.0678 mL, 0.772 mmol) were added under ice cooling, the mixture was stirred at the same temperature as above for 3 hours and subsequently stirred at room temperature for 2 hours.","The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with chloroform.","The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the crude solid.","To a suspension of the crude solid in ethanol (3 mL), a 1 N aqueous sodium hydroxide solution (1 mL) was added and the mixture was stirred at room temperature until dissolved.","The mixture was concentrated under reduce pressure, diluted by addition of ethyl acetate and water.","Most of the organic solvent was distillated off under reduce pressure, and then filtered.","A 1 N hydrochloric acid (1 mL) was added the filtrate, the precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (55 mg, yield: 53%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.17 (1H, br s), 8.83 (1H, br s), 8.07 (1H, d, J=2.7 Hz), 7.95 (1H, d, J=2.7 Hz), 7.20-7.15 (3H, m), 4.24 (2H, br s), 3.81 (3H, s), 3.71 (3H, s), 0.74 (4H, br s).","MS spectrum (ES/APCI+): 406 (M+H).","(Example 44) 5-Chloro-2-methoxy-N-[5-oxo-3-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (44a) 2-[(2,4-Dimethoxybenzyl)amino]-2-(pyridin-3-yl)ethanol The title compound (approximately 77% content, 0.9217 g, yield: 69%) as a mixture containing 2.5-dimethoxybenzylalcohol was obtained by production according to the method of Example (8a) using 2,4-dimethoxybenzaldehyde (627.6 mg, 3.78 mmol) and 2-amino-2-(pyridin-3-yl)ethanol (495.3 mg, 3.59 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.54-8.51 (1.32H, m), 7.70-7.68 (0.66H, m), 7.29-7.26 (0.66H, m), 7.17 (0.34H, d, J=8.2 Hz), 7.03-7.01 (0.66H, d, J=7.8 Hz), 6.48-6.40 (2H, m), 4.61 (0.68H, s), 3.85-3.79 (6.66H, m), 3.76-3.70 (1.32H, m), 3.56-3.52 (1.32H, m).","(44b) 4-(2,4-Dimethoxybenzyl)-7-nitro-3-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (283.2 mg, yield for 2 steps: 27%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (501.1 mg, 2.47 mmol) and 2-[(2,4-dimethoxybenzyl)amino]-2-(pyridin-3-yl)ethanol (approximately 77% content, 0.912 g, 2.44 mmol) obtained in Example (44a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.66 (1H, d, J=2.7 Hz), 9.10 (1H, d, J=2.7 Hz), 8.51 (1H, dd, J=4.7, 1.6 Hz), 8.42 (1H, br d, J=2.3 Hz), 7.42 (1H, d, J=8.2 Hz), 7.35-7.32 (1H, m), 7.21-7.17 (1H, m), 6.49 (1H, dd, J=8.2, 2.3 Hz), 6.40 (1H, d, J=2.3 Hz), 5.19 (1H, d, J=5.3 Hz), 5.10 (1H, d, J=14.5 Hz), 5.02 (1H, dd, J=13.1, 5.3 Hz), 4.56 (1H, d, J=13.3 Hz), 4.50 (1H, d, J=14.5 Hz), 3.80 (3H, s), 3.72 (3H, s).","(44c) 7-Amino-4-(2,4-dimethoxybenzyl)-3-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (270.0 mg, yield: quantitative) was obtained by production according to the method of Example (8d) using 4-(2,4-dimethoxybenzyl)-7-nitro-3-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (287.5 mg, 0.659 mmol) obtained in example (44b).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.48 (1H, dd, J=4.9, 1.6 Hz), 8.40 (1H, d, J=2.3 Hz), 8.20 (1H, d, J=2.7 Hz), 7.81 (1H, d, J=2.7 Hz), 7.39-7.35 (2H, m), 7.17 (1H, dd, J=8.0, 4.9 Hz), 6.47 (1H, dd, J=8.2, 2.3 Hz), 6.39 (1H, d, J=2.3 Hz), 5.10 (1H, d, J=14.5 Hz), 4.97 (1H, d, J=5.3 Hz), 4.75 (1H, dd, J=13.1, 5.3 Hz), 4.38-4.34 (2H, m), 3.80 (3H, s), 3.72 (3H, s), 3.60 (2H, br s).","(44d) 5-Chloro-2-methoxy-N-[5-oxo-3-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (191.0 mg, yield for 2 steps: 64%) was obtained by production according to the method described in Examples (1d) and (9) using 7-amino-4-(2,4-dimethoxybenzyl)-3-(pyridine-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (267.5 mg, 0.66 mmol) obtained in Example (44c) and 5-chloro-2-methoxybenzenesulfonyl chloride (166.7 mg, 0.69 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.33 (1H, br s), 8.93 (1H, br d, J=5.5 Hz), 8.48-8.46 (2H, m), 8.35 (1H, d, J=2.7 Hz), 8.04 (1H, d, J=2.7 Hz), 7.70-7.69 (2H, m), 7.60-7.57 (1H, m), 7.33 (1H, dd, J=7.8, 4.7 Hz), 7.26 (1H, d, J=9.0 Hz), 4.93 (1H, t, J=5.5 Hz), 4.78 (1H, dd, J=12.9, 5.5 Hz), 4.51 (1H, br d, J=12.9 Hz).","MS spectrum (ES/APCI+): 461 (M+H), 463 (M+2+H).","(Example 45) 7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepine-3-carboxamide (45a) O-Benzyl-N-[(benzyloxy)carbonyl]serine To a suspension of O-benzylserine (5.00 g, 25.6 mmol) in 1,4-dioxane (50 mL), a 2 N aqueous sodium hydroxide solution (26.8 mL, 53.8 mmol) was added, and the mixture was stirred at room temperature for 10 minutes.","Subsequently, to the mixture, benzyl chloroformate (3.82 mL, 26.9 mmol) was added, and the mixture was stirred at room temperature for 3 hours.","The reaction mixture was concentrated under reduce pressure, and diluted by addition of a 5 N hydrochloric acid (10.8 mL, 54.2 mmol), followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","To the residue, n-hexane (20 mL) and ethyl acetate (1 mL) were added, and the precipitated solid was collected by filtration, washed with n-hexane, and then dried to obtain the title compound (7.24 g, yield: 86%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.37-7.27 (10H, m), 5.64 (1H, br d, J=8.2 Hz), 5.15 (1H, br d, J=12.1 Hz), 5.11 (1H, br d, J=12.1 Hz), 4.57-4.53 (3H, m), 3.96 (1H, br dd, J=9.4, 3.1 Hz), 3.72 (1H, br dd, J=9.4, 3.3 Hz).","(45b) Benzyl [3-(benzyloxy)-1-(dimethylamino)-1-oxopropan-2-yl]carbamate To a solution of O-benzyl-N-[(benzyloxy)carbonyl]serine (1.50 g, 4.55 mmol) obtained in example (45a), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.06 g, 5.53 mmol) and 1-hydroxybenzotriazole (0.68 g, 5.0 mmol) in methylene chloride (22 mL), dimethylamine in tetrahydrofuran (2.0 mol/L, 5.5 mL, 11 mmol) was added under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes and subsequently at room temperature for 1 hour.","The mixture was diluted by addition of a 1 N hydrochloric acid (50 mL), followed by extraction with ethyl acetate.","The organic layer was washed with water, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate.","After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=2/1-1/0) to obtain the title compound (1.47 g, yield: 91%) 1H NMR spectrum (CDCl3, 400 MHz) δ: 7.35-7.26 (10H, m), 5.75 (1H, d, J=8.2 Hz), 5.10 (2H, br s), 4.95-4.90 (1H, m), 4.54 (1H, d, J=12.1 Hz), 4.49 (1H, d, J=12.1 Hz), 3.66 (1H, dd, J=9.4, 5.5 Hz), 3.59 (1H, dd, J=9.4, 7.0 Hz), 3.05 (3H, s), 2.97 (3H, s).","(45c) N,N-Dimethylserinamide A mixture of benzyl [3-(benzyloxy)-1-(dimethylamino)-1-oxopropan-2-yl]carbamate (1.46 g, 4.10 mmol) obtained in Example (45b) and 10% palladium carbon (water content: 54.6%, 0.28 g) in ethanol (41 mL) was stirred at room temperature for 1 hour at normal pressure under the hydrogen atmosphere.","Subsequently the mixture was stirred at 50° C. for 24 hours in an oil bath at normal pressure under the hydrogen atmosphere.","Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.","The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (approximately 70% content, 0.60 g, yield: 78%) as a mixture containing O-benzyl-N,N-dimethylserinamide 1H NMR spectrum (CDCl3, 400 MHz) δ: 7.36-7.29 (1H, m), 4.53 (0.4H, br s), 3.98 (0.2H, dd, J=7.0, 5.9 Hz), 3.77 (0.8H, dd, J=7.0, 4.7 Hz), 3.66 (0.8H, dd, J=10.9, 4.7 Hz), 3.57 (0.2H, dd, J=9.2, 5.9 Hz), 3.50-3.44 (1H, m), 3.10 (2.4H, s), 3.04 (0.6H, s), 2.98 (2.4H, s), 2.97 (0.6H, s).","(45d) N2-(2,4-Dimethoxybenzyl)-N,N-dimethylserinamide The title compound (0.76 g, yield: 85%) was obtained by production according to the method of Example (8a) using 2,4-dimethoxybenzaldehyde (0.68 g, 4.1 mmol) and N,N-dimethylserinamide (approximately 70% content, 0.60 g, 3.2 mmol) obtained in Example (45c).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.14 (1H, d, J=7.8 Hz), 6.44-6.41 (2H, m), 3.82 (3H, s), 3.80 (3H, s), 3.73-3.63 (3H, m) 3.59 (1H, dd, J=7.8, 4.7 Hz), 3.37 (1H, dd, J=10.2, 7.8 Hz), 2.99 (3H, s), 2.89 (3H, s).","(45e) 4-(2,4-Dimethoxybenzyl)-N,N-dimethyl-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-3-carboxamide The title compound (0.55 g, yield for 2 steps: 46%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (0.55 g, 2.7 mmol) and N2-(2,4-dimethoxybenzyl)-N,N-dimethylserinamide (0.76 g, 2.7 mmol) obtained in example (45d).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.73 (1H, d, J=2.7 Hz), 9.12 (1H, d, J=2.7 Hz), 7.37 (1H, d, J=8.2 Hz), 6.51-6.47 (2H, m), 5.04 (1H, d, J=14.5 Hz), 4.95-4.89 (2H, m), 4.43 (1H, d, J=14.5 Hz), 4.34 (1H, d, J=12.1 Hz), 3.83 (3H, s), 3.81 (3H, s), 3.04 (3H, s), 2.88 (3H, s).","(45f) 7-Amino-4-(2,4-dimethoxybenzyl)-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-3-carboxamide The title compound (342.7 mg, yield: 67%) was obtained by production according to the method of Example (8d) using 4-(2,4-dimethoxybenzyl)-N,N-dimethyl-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-3-carboxamide (552.0 mg, 1.24 mmol) obtained in Example (45e).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.19 (1H, d, J=2.7 Hz), 7.79 (1H, d, J=2.7 Hz), 7.35 (1H, d, J=8.2 Hz), 6.49-6.45 (2H, m), 5.09 (1H, d, J=14.5 Hz), 4.79-4.73 (2H, m), 4.31 (1H, d, J=14.5 Hz), 4.18-4.13 (1H, m), 3.81 (3H, s), 3.81 (3H, s), 3.55 (1H, br d, J=9.4 Hz), 3.00 (3H, s), 2.90 (3H, s).","(45g) 7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepine-3-carboxamide The title compound (261.1 mg, yield for 2 steps: 69%) was obtained by production according to the method described in Examples (1d) and (9) using 7-amino-4-(2,4-dimethoxybenzyl)-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepine-3-carboxamide (340.2 mg, 0.82 mmol) obtained in Example (45f) and 5-Chloro-2-methoxybenzenesulfonyl chloride (207.3 mg, 0.86 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.40 (1H, d, J=2.7 Hz), 8.14 (1H, d, J=2.7 Hz), 7.74 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=9.0, 2.7 Hz), 7.34 (1H, br s), 7.12 (1H, br s), 7.01 (1H, d, J=9.0 Hz), 4.72 (1H, br d, J=12.5 Hz), 4.56 (1H, br dd, J=6.6, 3.5 Hz), 4.27 (1H, dd, J=12.5, 6.6 Hz), 4.08 (3H, s), 3.11 (3H, s), 3.05 (3H, s).","MS spectrum (ES/APCI+): 455 (M+H), 457 (M+2+H).","Example 46 5-chloro-2-methoxy-N-[3-(morpholin-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (46a) 2-[(2,4-Dimethoxybenzyl)amino]-3-hydroxy-1-(morpholin-4-yl)propan-1-one The title compound (1.39 g, yield for 3 steps: 88%) was obtained by production according to the method described in Examples (45b), (45c) and (8a) using O-benzyl-N-[(benzyloxy)carbonyl]serine (1.50 g, 4.55 mmol) obtained in example (45a), morpholine (0.96 mL, 11 mmol) and 2,4-dimethoxybenzaldehyde (0.71 g, 4.3 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 7.11 (1H, d, J=8.2 Hz), 6.44-6.41 (2H, m), 3.82 (3H, s), 3.80 (3H, s), 3.75 (1H, d, J=12.9 Hz), 3.68-3.51 (9H, m), 3.44-3.39 (3H, m).","(46b) 4-(2,4-Dimethoxybenzyl)-3-(morpholin-4-ylcarbonyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (0.87 g, yield for 2 steps: 45%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (0.85 g, 4.2 mmol) and 2-[(2,4-dimethoxybenzyl)amino]-3-hydroxy-1-(morpholin-4-yl)propan-1-one (1.40 g, 4.3 mmol) obtained in Example (46a).","1H NMR spectrum (CDCl3, 400 MHz) δ: 9.75 (1H, d, J=2.7 Hz), 9.13 (1H, d, J=2.7 Hz), 7.33 (1H, d, J=8.2 Hz), 6.51-6.47 (2H, m), 4.99 (1H, d, J=14.1 Hz), 4.86-4.79 (2H, m), 4.53 (1H, d, J=14.1 Hz), 4.36 (1H, d, J=12.9 Hz), 3.83 (3H, s), 3.81 (3H, s), 3.74-3.29 (8H, m).","(46c) 5-Chloro-2-methoxy-N-[3-(morpholin-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (255.5 mg, yield for 3 steps: 28%) was obtained by production according to the method described in Examples (8d), (1d) and (9) using 4-(2,4-dimethoxybenzyl)-3-(morpholin-4-ylcarbonyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (0.87 g, 1.8 mmol) obtained in Example (46b) and 5-chloro-2-methoxybenzenesulfonyl chloride (0.32 g, 1.3 mmol).","1H NMR spectrum (CDCl3, 400 MHz) δ: 10.28 (1H, br s), 8.36 (1H, br d, J=5.5 Hz), 8.32 (1H, d, J=2.7 Hz), 8.03 (1H, d, J=2.7 Hz), 7.68-7.65 (2H, m), 7.26 (1H, d, J=8.6 Hz), 4.76 (1H, t, J=5.5 Hz), 4.62 (1H, dd, J=12.9, 5.5 Hz), 4.33 (1H, d, J=12.5 Hz), 3.88 (3H, s), 3.60-3.37 (8H, m).","MS spectrum (ES/APCI+): 497 (M+H), 499 (M+2+H).","(Example 47) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide (potassium salt of Example 9) (47a) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (1.31 g, 3.98 mmol) obtained in Example (8d) and pyridine (20 mL, 249 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (1.035 g, 4.29 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (2.17 g, yield: quantitative).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=3.0 Hz), 8.07 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.48 (1H, dd, J=8.8, 2.7 Hz), 7.30-7.22 (2H, m), 7.01 (1H, d, J=9.1 Hz), 6.49-6.46 (2H, m), 4.70 (2H, s), 4.32 (2H, t, J=4.6 Hz), 4.09 (3H, s), 3.81-3.80 (6H, m), 3.60 (2H, t, J=4.6 Hz).","(47b) 5-Chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of 5-chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (2.17 g, 4.06 mmol) obtained in Example (47a) in chloroform (30 mL), anisole (0.88 mL, 8.1 mmol), trifluoroacetic acid (15 mL, 195 mmol) and trifluoromethanesulfonic acid (0.73 mL, 8.3 mmol) were added at room temperature, and the mixture was stirred at room temperature for 1 hour.","The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of chloroform and a saturated aqueous solution of sodium bicarbonate.","The precipitated solid was collected by filtration.","An organic layer of the filtrate was separated, and dried over anhydrous sodium sulfate.","After filtration, the solvent was distilled off under reduced pressure.","The residue was combined with the above precipitated solid, diisopropyl ether was added thereto, and the suspension was stirred at room temperature for 1 hour.","The precipitated solid was collected by filtration, and then dried to obtain the title compound (1.2921 g, yield: 83%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.53 (1H, br t, J=5.2 Hz), 8.11-8.08 (2H, m), 7.69-7.64 (2H, m), 7.26 (1H, d, J=8.5 Hz), 4.37-4.35 (2H, m), 3.88 (3H, s), 3.38-3.34 (2H, m).","(47c) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide To a suspension of 5-chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (1.0921 g, 2.845 mmol) obtained in Example (47b) in ethanol (12 mL), a solution of 0.5 N potassium hydroxide in ethanol (5.68 mL, 2.85 mmol) was added at room temperature, and the mixture was stirred at room temperature for 1 hour.","The precipitated solid was collected by filtration, washed with ethanol and then dried to obtain the title compound (1.1065 g, yield: 92%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.19 (1H, br t, J=5.2 Hz), 7.70 (1H, br t, J=2.4 Hz), 7.65-7.61 (2H, m), 7.35-7.32 (1H, m), 6.99 (1H, d, J=9.1 Hz), 4.18 (2H, t, J=5.2 Hz), 3.70-3.62 (3H, m), 3.22 (2H, q, J=5.2 Hz).","(Example 48) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide (potassium salt of Example 10) (48a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (3.83 g, 11.2 mmol) obtained in Example (8d) and pyridine (18.1 mL, 223 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (2.76 g, 12.3 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 1 hour in an oil bath.","The reaction mixture was cooled to room temperature, diluted with water (90 mL) to precipitate a solid, and the suspension was stirred at room temperature for 1 hour.","The precipitated solid was collected by filtration, and washed with water to obtain the crude solid.","A suspension of the crude solid in ethanol (60 mL) was stirred at 80° C. for 1 hour in an oil bath.","After cooling, the suspension was stirred in an ice water bath for 30 minutes.","The precipitated solid was collected by filtration, washed with cold ethanol, and then dried to obtain the title compound (4.87 g, yield: 84%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.34 (1H, br s), 8.09 (1H, d, J=2.7 Hz), 7.97 (1H, t, J=2.7 Hz), 7.52-7.47 (2H, m), 7.26-7.23 (1H, m), 7.09 (1H, d, J=8.2 Hz), 6.58 (1H, d, J=2.7 Hz), 6.49 (1H, dd, J=8.2, 2.7 Hz), 4.57 (2H, s), 4.28 (2H, br t, J=4.7 Hz), 3.86 (3H, s), 3.77 (3H, s), 3.75 (3H, s), 3.53 (2H, br t, J=4.7 Hz).","(48b) 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (4.86 g, 9.39 mmol) obtained in Example (48a) and anisole (2.04 mL, 18.8 mmol) in chloroform (45 mL), trifluoroacetic acid (14.4 mL, 188 mmol) and trifluoromethanesulfonic acid (1.65 mL, 18.8 mmol) were added at room temperature, and the mixture was stirred at room temperature for 30 minutes.","The reaction mixture was carefully poured into a suspension of sodium bicarbonate (17.4 g, 207 mmol) in water (90 mL) at room temperature, and the mixture was stirred at room temperature for 10 minutes.","Most of the organic solvents were distilled off under reduced pressure, the concentrated mixture was diluted by addition of ethyl acetate (90 mL), a precipitated solid was collected by filtration, and washed with water and ethyl acetate to obtain the crude solid.","To a suspension of the crude solid in ethanol (50 mL), a 1 N aqueous solution of potassium hydroxide (10.3 mL, 10.3 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 minutes.","The reaction mixture was filtered, and the residue on the filter paper was washed with water and ethanol.","The filtrate and washings were combined, a 1 N hydrochloric acid (10.3 mL, 10.3 mmol) was added thereto, and the suspension was stirred in an ice water bath for 20 minutes.","The precipitated solid was collected by filtration, washed with cold ethanol, and then dried to obtain the slightly crude solid.","To a suspension of the slightly crude solid in ethanol (50 mL), a 1 N aqueous solution of potassium hydroxide (8.8 mL, 8.8 mmol) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes.","A 1 N hydrochloric acid (8.8 mL, 8.8 mmol) was added thereto, and the suspension was stirred at room temperature for 30 minutes.","The precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (2.16 g, yield: 63%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.28 (1H, br s), 8.52 (1H, br t, J=4.9 Hz), 8.11-8.08 (2H, m), 7.51-7.46 (2H, m), 7.26-7.23 (1H, m), 4.36 (2H, t, J=4.3 Hz), 3.86 (3H, s), 3.40-3.35 (2H, m).","(48c) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide To a suspension of 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (1.950 g, 5.308 mmol) obtained in example (48b) in a mixed solvent of ethanol (53.5 mL) and water (0.478 mL), a solution of 0.5 N potassium hydroxide in ethanol (11.15 mL, 5.574 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours.","The precipitated solid was collected by filtration, washed with ethanol and then dried to obtain the title compound (2.200 g, yield: quantitative).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.19 (1H, br t, J=5.2 Hz), 7.72 (1H, d, J=2.7 Hz), 7.63 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.16-7.11 (1H, m), 6.98 (1H, dd, J=9.0, 4.3 Hz), 4.18 (2H, t, J=5.2 Hz), 3.65 (3H, s), 3.23 (2H, q, J=5.2 Hz).","(Example 49) Sodium [(5-fluoro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl)azanide (sodium salt of Example 10) To a suspension of 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (101.9 mg, 0.277 mmol) obtained in example (48b) in ethanol (2.7 mL), a 2 N aqueous solution of sodium hydroxide (0.138 mL, 0.277 mmol) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes.","The precipitated solid was collected by filtration, washed with ethanol and then dried to obtain the title compound (98.4 mg, yield: 91%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.20 (1H, br t, J=5.1 Hz), 7.71 (1H, d, J=2.7 Hz), 7.62 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.16-7.11 (1H, m), 6.97 (1H, dd, J=9.0, 4.3 Hz), 4.17 (2H, t, J=5.1 Hz), 3.66 (3H, s), 3.22 (2H, q, J=5.1 Hz).","(Example 50) Potassium {[5-chloro-2-(trifluoromethoxy)phenyl]sulfonyl}(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide (potassium salt of Example 13) The title compound (85.2 mg, yield: 78%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide (100 mg, 0.228 mmol) obtained in example (13c) and a solution of 0.5 N potassium hydroxide in ethanol (0.478 mL, 0.240 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.22 (1H, br t, J=5.2 Hz), 7.78-7.73 (2H, m), 7.63-7.62 (1H, m), 7.53-7.51 (1H, m), 7.36-7.33 (1H, m), 4.19 (2H, t, J=5.2 Hz), 3.23 (2H, q, J=5.2 Hz).","(Example 51) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl][(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 27) The title compound (124.1 mg, yield: 94%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (121.3 mg, 0.293 mmol) obtained in Example (27f) and a solution of 0.5 N potassium hydroxide in ethanol (0.962 mL, 0.482 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.93 (1H, br s), 7.77 (1H, d, J=2.7 Hz), 7.70 (1H, d, J=2.7 Hz), 7.64 (1H, d, J=2.7 Hz), 7.34 (1H, dd, J=8.6, 2.7 Hz), 6.99 (1H, d, J=8.6 Hz), 4.92 (1H, br t, J=5.7 Hz), 4.20-4.12 (2H, m), 3.66 (3H, s), 3.46-3.41 (3H, m).","(Example 52) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl][(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 28) The title compound (78.7 mg, yield: 84%) was obtained by production according to the method described in Examples 47c using 5-fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (75.5 mg, 0.190 mmol) obtained in Example (28b) and a solution of 0.5 N potassium hydroxide in ethanol (0.386 mL, 0.194 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.92 (1H, br s), 7.77 (1H, br s), 7.71 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.16-7.11 (1H, m), 6.97 (1H, dd, J=9.0, 4.3 Hz), 4.91 (1H, t, J=5.5 Hz), 4.20-4.12 (2H, m), 3.65 (3H, s), 3.46-3.40 (3H, m).","(Example 53) Potassium [(5-bromo-2-methoxyphenyl)sulfonyl][(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 29) The title compound (92.7 mg, yield: 82%) was obtained by production according to the method described in Example (47c) using 5-bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (104.4 mg, 0.228 mmol) obtained in Example (29b) and a solution of 0.5 N potassium hydroxide in ethanol (0.451 mL, 0.228 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.93 (1H, br d, J=3.5 Hz), 7.78-7.75 (2H, m), 7.68 (1H, d, J=2.7 Hz), 7.44 (1H, dd, J=9.0, 2.7 Hz), 6.93 (1H, d, J=9.0 Hz), 4.92 (1H, t, J=5.5 Hz), 4.20-4.14 (2H, m), 3.63 (3H, s), 3.46-3.41 (3H, m).","(Example 54) Potassium {[5-chloro-2-(trifluoromethoxy)phenyl]sulfonyl}[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 31) The title compound (44 mg, yield: 58%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (70 mg, 0.15 mmol) obtained in Example (31b) and a solution of 0.5 N potassium hydroxide in ethanol (0.31 mL, 0.16 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.96 (1H, br d, J=3.5 Hz), 7.78 (1H, d, J=2.7 Hz), 7.77 (1H, d, J=2.7 Hz), 7.72 (1H, d, J=2.7 Hz), 7.51 (1H, dd, J=8.6, 2.7 Hz), 7.34-7.32 (1H, m), 4.95-4.92 (1H, m), 4.21-4.14 (2H, m), 3.43-3.39 (3H, m).","(Example 55) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 35) (55a) 5-Chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1, 4]oxazepin]-7′-yl]-2-methoxybenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (0.9040 g, 2.54 mmol) obtained in Example (35d) and pyridine (4.1 mL, 51 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (0.6450 g, 2.68 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 20 minutes in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was diluted with water, followed by extraction with ethyl acetate.","The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and anhydrous magnesium sulfate and charcoal were added thereto.","After filtration through pad of Celite 545®, the solvent was distilled off under reduced pressure.","To the residue, diisopropyl ether (7 mL) and ethyl acetate (7 mL) were added to precipitate a solid.","The suspension was stirred at room temperature for 30 minutes.","The precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (1.3007 g, yield: 92%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.20 (1H, d, J=2.7 Hz), 7.84 (1H, d, J=2.7 Hz), 7.73 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=9.0, 2.7 Hz), 7.16-7.14 (1H, m), 7.02-6.99 (2H, m), 6.46-6.43 (2H, m), 4.66 (2H, br s), 4.06 (3H, s), 3.93 (2H, br s), 3.81 (3H, s), 3.79 (3H, s), 0.88 (2H, br s), 0.64 (2H, br s).","(55b) 5-Chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a mixture of 5-chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-methoxybenzenesulfonamide (1.2938 g, 2.31 mmol) obtained in Example (55a) and anisole (0.51 mL, 4.7 mmol) in chloroform (11.5 mL), trifluoroacetic acid (3.60 mL, 47.0 mmol) and trifluoromethanesulfonic acid (0.41 mL, 4.7 mmol) were added under ice cooling, and the mixture was stirred at the same temperature as above for 3 hours and subsequently stirred at room temperature for 5 hours.","The reaction mixture was carefully poured into a suspension of sodium bicarbonate (3.88 g, 46.2 mmol) in water (11.5 mL) at room temperature, and the mixture was stirred at room temperature for 1 hour.","Most of the organic solvents were distilled off under reduced pressure, the concentrated mixture was diluted by addition of water (30 mL) and ethyl acetate (30 mL), a precipitated solid was collected by filtration, and washed with water and ethyl acetate to obtain the crude solid.","To a suspension of the crude solid in a mixed solvent of ethanol (11.5 mL) and water (11.5 mL), a 1 N aqueous solution of potassium hydroxide (3.45 mL, 3.48 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 minutes.","After filtration, a 2 N hydrochloric acid (1.74 mL, 3.49 mmol) was added to the filtrate, and the precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (0.6970 g, yield: 74%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.84 (1H, br s), 8.08 (1H, d, J=3.1 Hz), 7.95 (1H, d, J=3.1 Hz), 7.67 (1H, dd, J=9.0, 2.7 Hz), 7.63 (1H, d, J=2.7 Hz), 7.25 (1H, d, J=9.0 Hz), 4.26 (2H, s), 3.88 (3H, s), 0.75-0.73 (4H, m).","(55c) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide To a suspension of 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (40.0 mg, 0.098 mmol) obtained in Example (55b) in ethanol (2 mL), a solution of 0.5 N potassium hydroxide in ethanol (0.195 mL, 0.098 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours.","The mixture was concentrated under reduced pressure, acetone (1 mL) was added thereto, the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (42 mg, yield: 96%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.48 (1H, br s), 7.68 (1H, d, J=2.7 Hz), 7.61 (1H, d, J=2.7 Hz), 7.54 (1H, d, J=2.7 Hz), 7.32 (1H, dd, J=8.6, 2.7 Hz), 6.98 (1H, d, J=8.6 Hz), 4.07 (2H, s), 3.65 (3H, s), 0.68-0.60 (4H, m).","(Example 56) Sodium [(5-chloro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (sodium salt of Example 35) To a suspension of 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (95.2 mg, 0.232 mmol) obtained in Example (55b) in ethanol (2.3 mL), a 2 N aqueous solution of sodium hydroxide 0.116 mL, 0.233 mmol) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes.","The mixture was concentrated under reduced pressure, acetone (2.3 mL) was added thereto, the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (106.2 mg, yield: quantitative).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.49 (1H, br s), 7.69 (1H, d, J=2.7 Hz), 7.62 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.33 (1H, dd, J=8.6, 2.7 Hz), 6.99 (1H, d, J=8.6 Hz), 4.07 (2H, s), 3.67 (3H, s), 0.67-0.60 (4H, m).","(Example 57) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 36) The title compound (41 mg, yield: 94%) was obtained by production according to the method described in Example (47c) using 5-fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (40.0 mg, 0.102 mmol) obtained in Example 36 and a solution of 0.5 N potassium hydroxide in ethanol (0.203 mL, 0.102 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ:8.48 (1H, br s), 7.68 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.39 (1H, dd, J=9.0, 3.1 Hz), 7.15-7.10 (1H, m), 6.96 (1H, dd, J=9.0, 4.3 Hz), 4.06 (2H, br s), 3.64 (3H, br s), 0.66-0.61 (4H, m).","(Example 58) Potassium {[5-chloro-2-(trifluoromethoxy)phenyl]sulfonyl}(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 40) The title compound (63 mg, yield: 94%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide (62.0 mg, 0.134 mmol) obtained in Example (40c) and a solution of 0.5 N potassium hydroxide in ethanol (0.267 mL, 0.134 mmol).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.51 (1H, br s), 7.76-7.72 (2H, m), 7.56-7.51 (2H, m), 7.35 (1H, d, J=9.0 Hz), 4.08 (2H, br s), 0.65-0.63 (4H, m).","(Example 59) Potassium (2-ethoxy-5-fluorophenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 42) (59a) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (0.9073 g, 2.55 mmol) obtained in Example (35d) and pyridine (4.1 mL, 51 mmol), 5-fluoro-2-ethoxybenzenesulfonyl chloride (0.6401 g, 2.68 mmol) obtained in Example (42a) was added at room temperature, and the mixture was stirred at 80° C. for 20 minutes in an oil bath.","The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was diluted with water (50 mL) and ethyl acetate (50 mL), the aqueous layer was separated off, the organic layer was diluted with tetrahydrofuran (150 mL), and anhydrous magnesium sulfate and charcoal were added thereto.","After filtration through pad of Celite 545®, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate (14 mL) was added to precipitate a solid, and the suspension was stirred at room temperature for 1 hour.","The precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (1.2525 g, yield: 88%).","1H NMR spectrum (CDCl3, 400 MHz) δ: 8.20 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=7.4, 3.1 Hz), 7.23-7.14 (2H, m), 7.02-6.95 (2H, m), 6.46-6.43 (2H, m), 4.66 (2H, br s), 4.29 (2H, q, J=7.0 Hz), 3.92 (2H, br s), 3.80 (3H, s), 3.79 (3H, s), 1.58 (3H, t, J=7.0 Hz), 0.87 (2H, br s), 0.63 (2H, br s).","(59b) 2-Ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a mixture of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide (1.2658 g, 2.27 mmol) obtained in Example (59a) and anisole (0.50 mL, 4.6 mmol) in chloroform (11.5 mL), trifluoroacetic acid (3.45 mL, 45.1 mmol) and trifluoromethanesulfonic acid (0.40 mL, 4.0 mmol) were added under ice cooling, and the mixture was stirred at the same temperature as above for 30 minutes and subsequently stirred at room temperature for 5 hours.","The reaction mixture was carefully poured into a suspension of sodium bicarbonate (3.82 g, 45.5 mmol) in water (11.5 mL) at room temperature, isopropyl alcohol (5 mL) was added thereto, and the mixture was stirred at room temperature for 20 minutes.","Most of the organic solvents were distilled off under reduced pressure, the concentrated mixture was diluted by addition of water (50 mL) followed by extraction with a mixed solvent of ethyl acetate (100 mL) and tetrahydrofuran (50 mL).","The organic layer was washed with a saturated aqueous solution of sodium chloride, and anhydrous magnesium sulfate and charcoal were added thereto.","After filtration through pad of Celite 545®, the solvent was distilled off under reduced pressure.","To the residue, ethyl acetate (12 mL) was added to precipitate a solid, and the suspension was stirred at room temperature for 30 minutes.","The precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (0.7940 g, yield: 86%).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.15 (1H, s), 8.83 (1H, s), 8.09 (1H, d, J=2.7 Hz), 7.95 (1H, d, J=2.7 Hz), 7.52-7.44 (2H, m), 7.24 (1H, dd, J=9.0, 4.3 Hz), 4.26 (br 2H, s), 4.16 (2H, q, J=7.0 Hz), 1.26 (3H, t, J=7.0 Hz), 0.77-0.71 (4H, m).","(59c) Potassium [(2-ethoxy-5-fluorophenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide To a suspension of 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (70.0 mg, 0.172 mmol) obtained in example (59b) in ethanol (5 mL), a solution of 0.5 N potassium hydroxide in ethanol (0.343 mL, 0.172 mmol) was added at room temperature, and the mixture was stirred at room temperature for 3 hours.","The solvent was distillated off under reduce pressure to obtain the title compound (77 mg, yield: quantitative).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.45 (1H, br s), 7.70 (1H, d, J=2.7 Hz), 7.54 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.11-7.06 (1H, m), 6.95 (1H, dd, J=9.0, 4.3 Hz), 4.06 (2H, s), 3.93 (2H, q, J=6.9 Hz), 1.12 (3H, t, J=6.9 Hz), 0.67-0.59 (4H, m).","(Example 60) Sodium [(2-ethoxy-5-fluorophenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (sodium salt of Example 42) To a suspension of 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (97.3 mg, 0.239 mmol) obtained in example (59b) in ethanol (2.4 mL), a 2 N aqueous solution of sodium hydroxide (0.119 mL, 0.239 mmol) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes.","The mixture was concentrated under reduced pressure, acetone (2.4 mL) was added thereto, the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (104.1 mg, yield: quantitative).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.47 (1H, br s), 7.71 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.13-7.07 (1H, m), 6.96 (1H, dd, J=9.0, 4.3 Hz), 4.06 (2H, s), 3.94 (2H, q, J=7.0 Hz), 1.13 (3H, t, J=7.0 Hz), 0.66-0.59 (4H, m).","(Example 61) Potassium [(2,5-dimethoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 43) To a suspension of 2,5-dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (43.0 mg, 0.106 mmol) obtained in Example (43b) in ethanol (5 mL), a solution of 0.5 N potassium hydroxide in ethanol (0.211 mL, 0.106 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours.","The solvent was distilled off under reduce pressure to obtain the title compound (51 mg, yield: quantitative).","1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.47 (1H, br s), 7.68 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.29 (1H, d, J=3.1 Hz), 6.89 (1H, d, J=8.6 Hz), 6.84 (1H, dd, J=8.6, 3.1 Hz), 4.05 (2H, br s), 3.66 (3H, s), 3.63 (3H, s), 0.67-0.57 (4H, m).","Test Examples (Test Example 1) Inhibitory Test of TNAP Activity COS1 cells (DS Pharma Biomedical Co., Ltd.) were transfected with human TNAP (OriGene Technologies, Inc.) using Lipofectamine LTX & Plus reagent (Invitrogen Corp.).","On the next day, the medium was replaced with a fresh medium, and the cells were cultured in an incubator for 3 days.","After 3 days, the culture supernatant was collected and concentrated by centrifugation at 5000 G for 30 minutes using Amicon 14, 104 cut (Merck Millipore).","The concentrated culture supernatant was dialyzed against 5 L of 50 mM Tris/200 mM NaCl/1 mM MgCl2/20 μM ZnCl2 twice and used as an enzyme source (enzyme solution).","The substrate pNPP (ProteoChem Inc.) was adjusted to 3.1 mM with Milli-Q water, and a solution of each test compound dissolved in dimethyl sulfoxide (DMSO; Wako Pure Chemical Industries, Ltd.) by 6 serial dilutions at a 5-fold common ratio from 100 μM, or DMSO was added thereto at a final concentration of 1% by volume.","The enzyme solution adjusted to 2 μg/mL with an assay buffer (200 mM Tris/2 mM MgCl2/0.04 mM ZnCl2/0.01% Tween 20) was added in the same amount of the substrate solution and incubated at room temperature for 60 minutes.","Then, the absorbance (ABS: 405 nm) was measured using a microplate reader (model plus 384, Molecular Devices, LLC), and the concentration of produced p-nitrophenol was calculated.","The inhibition of human TNAP activity by the test compound was evaluated on the basis of the concentration IC50 at which each test compound suppressed 50% of p-nitrophenol production.","The results are shown in Table 1.TABLE 1 Example compound No.","IC50 (nM) 1 6.3 2 12.7 3 12.8 4 22.9 5 71.3 6 6.1 7 10.7 8 9.1 9 1.4 10 4.0 11 4.8 12 13.4 13 3.4 14 36.2 15 95.7 16 6.2 17 12.6 18 3.9 19 6.4 20 27.1 21 46.0 22 1.7 23 3.5 24 7.2 25 1.7 26 8.7 27 1.5 28 3.6 29 1.2 30 3.8 31 1.6 32 4.1 33 1.9 34 6.7 35 1.1 36 2.2 37 43.4 38 24.4 39 13.2 40 1.9 41 2.7 42 0.6 43 1.0 44 1.4 45 14.6 46 25.2 The compound of the present invention exhibits the excellent inhibition of human TNAP activity and is useful as a pharmaceutical agent for the treatment or prophylaxis of ectopic calcification.","(Test Example 2) Specific Inhibitory Test of TNAP Activity COS1 cells (DS Pharma Biomedical Co., Ltd.) were transfected with human IAP (small-intestinal alkaline phosphatase, purchased from OriGene Technologies, Inc.) or human PLAP (placental alkaline phosphatase, purchased from OriGene Technologies, Inc.) using Lipofectamine LTX & Plus reagent (Invitrogen Corp.).","On the next day, the medium was replaced with a fresh medium, and the cells were cultured in an incubator for 3 days.","After 3 days, the culture supernatant was collected and concentrated by centrifugation at 5000 G for 30 minutes using Amicon 14, 104 cut (Merck Millipore).","The concentrated culture supernatant was dialyzed against 5 L of 50 mM Tris/200 mM NaCl/1 mM MgCl2/20 μM ZnCl2 twice and used as an enzyme source (enzyme solution).","The substrate pNPP (ProteoChem Inc.) was adjusted to 3.1 mM with Milli-Q water, and a solution of each test compound dissolved in dimethyl sulfoxide (DMSO; Wako Pure Chemical Industries, Ltd.) by 6 serial dilutions at a 5-fold common ratio from 100 μM, or DMSO was added thereto at a final concentration of 1% by volume.","The enzyme solution of human IAP or human PLAP adjusted to 2 μg/mL with an assay buffer (200 mM Tris/2 mM MgCl2/0.04 mM ZnCl2/0.01% Tween 20) was added in the same amount of the substrate solution and incubated at room temperature for 60 minutes.","Then, the absorbance (ABS: 405 nm) was measured using a microplate reader (model plus 384, Molecular Devices, LLC), and the concentration of produced p-nitrophenol was calculated.","The inhibition of human IAP or PLAP activity by the test compound was evaluated on the basis of the concentration IC50 at which each test compound suppressed 50% of p-nitrophenol production.","The compound of the present invention exhibits the excellent specific inhibition of TNAP activity and is useful as a pharmaceutical drug for the treatment or prevention of ectopic calcification.","(Test Example 3) Inhibitory Test of Plasma TNAP Activity in B6 Mouse (Charles River Laboratories Japan, Inc.) After blood sampling from the tail vein using a heparin-treated hematocrit capillary tube (EM Meister Hematocrit Capillary Tube, AS ONE Corp.) (as the sample before compound administration), each test compound suspended in a 0.5% methylcellulose solution (powder purchased from Wako Pure Chemical Industries, Ltd. was adjusted to 0.5% with Otsuka distilled water) was administered orally to the mouse.","1, 2, 4, 6, and 24 hours after the administration, blood was collected from the tail vein using a heparin-treated hematocrit capillary tube to obtain a plasma sample.","The plasma sample was added to an assay buffer (1 M Tris, 1 M MgCl2, 20 mM ZnCl2, and water, pH 7.5), and the mixture was left standing for 5 minutes.","Then, the absorbance at 405 nm was measured and used as a blank.","The substrate pNPP was added to the plasma sample and incubated at room temperature for 180 minutes.","Then, the absorbance (ABS: 405 nm) was measured using a microplate reader (model plus 384, Molecular Devices, LLC), and the concentration of produced p-nitrophenol was calculated.","The blank was subtracted from all measurement values to calculate TNAP activity at each time point with the TNAP activity of the sample before compound administration defined as 100%.","The pharmaceutical effect of the test compound was evaluated by the average inhibition of plasma ALP (80-90% containing TNAP) activity for 6 hours from 0 hour to 6 hours after the administration of the test compound.","It was calculated according to the following expression: 100−((plasma ALP activity at 0 hr+plasma ALP activity at 1 hr)*½+(plasma ALP activity at 1 hr+plasma ALP activity at 2 hr)*½+(plasma ALP activity at 2 hr+plasma ALP activity at 4 hr)*2/2+(plasma ALP activity at 4 hr+plasma ALP activity at 6 hr)*2/2)/6.The results are shown in Table 2.TABLE 2 Plasma ALP inhibition Example compound No.","(6 h ave. inhibition %) 47 54.7 48 61.6 50 56.0 51 63.7 52 61.3 53 59.2 54 74.8 55 58.9 57 53.5 58 50.3 59 66.2 61 67.5 The compound of the present invention exhibits an excellent in vivo TNAP inhibitory effect and is useful as a pharmaceutical agent for the treatment or prophylaxis of ectopic calcification.","(Test Example 4) In Vivo Anti-Calcification Test in Vitamin D-Induced Calcification Model A DBA/2 mouse (male, 6 weeks old when used, Charles River Laboratories Japan, Inc.) was given powder feed (FR-2 powder feed, Funabashi Farm Co., Ltd.) containing each test compound.","3.75 mg/kg cholecalciferol (Sigma-Aldrich Corp.) was intraperitoneally administered for 3 days from the next day.","Seven days after the final cholecalciferol administration, the animal was sacrificed, and the thoracic aorta and the kidney were sampled.","The tissue samples were freeze-dried (FREEZE DRYER, FRD-50M, Iwaki Asahi Techno Glass Corp.).","Then, 10% formic acid (undiluted solution purchased from Kishida Chemical Co., Ltd. was adjusted to 10% with Milli-Q water) was added to each tissue sample, which was then homogenized using QIAGEN Retsch MM300 TissueLyser (Qiagen N.V.).","The homogenate was centrifuged, and the supernatant was used as a sample.","The calcium concentration in the sample was measured as absorbance (ABS 612 nm, Microplate reader, model plus 384, Molecular Devices, LLC) using Calcium assay kit (Wako Pure Chemical Industries, Ltd.) to calculate the amount of calcium in the tissue.","The compound of the present invention exhibits an excellent anti-calcification effect and is useful as a therapeutic agent for the treatment or prevention of ectopic calcification.","(Test Example 5) In Vivo Anti-Calcification Test in Nephrectomized Mouse A 5/6 nephrectomized DBA/2 mouse (male, 8 weeks old) was purchased from CLEA Japan, Inc.","This mouse was loaded with 1.2% high-phosphorus diet (Oriental Yeast Co., Ltd.).","Each test compound suspended in a 0.5% methylcellulose solution (powder purchased from Wako Pure Chemical Industries, Ltd. was adjusted to 0.5% with Otsuka distilled water) was administered orally twice daily for three months.","After three months, the animal was sacrificed, and the kidney was sampled.","The tissue sample was freeze-dried (FREEZE DRYER, FRD-50M, Iwaki Asahi Techno Glass Corp.).","Then, 10% formic acid (undiluted solution purchased from Kishida Chemical Co., Ltd. was adjusted to 10% with Milli-Q water) was added to the tissue sample, which was then homogenized using QIAGEN Retsch MM300 TissueLyser (Qiagen N.V.).","The homogenate was centrifuged, and the supernatant was used as a sample.","The calcium concentration in the sample was measured as absorbance (ABS 612 nm, Microplate reader, model plus 384, Molecular Devices, LLC) using Calcium assay kit (Wako Pure Chemical Industries, Ltd.) to calculate the amount of calcium in the tissue.","The compound of the present invention exhibits an excellent anti-calcification effect and is useful as a pharmaceutical drug for the treatment or prophylaxis of ectopic calcification.","(Test Example 6) Pharmacokinetic Test The pharmacokinetic test can be conducted according to a method well-known in the field of pharmacodynamics.","Each test compound was suspended in a 0.5% aqueous methylcellulose solution.","The obtained suspension was orally administered at a dose in an appropriate range (e.g., 0.01 mg/kg to 10 mg/kg) to an animal (e.g., a mouse, a rat, a dog, or a cynomolgus monkey) generally used in the pharmacokinetic test.","Also, the test compound was dissolved in saline.","The obtained solution was intravenously (e.g., through the tail vein, the cephalic vein, or the saphenous vein) administered at a dose in an appropriate range (e.g., 0.1 mg/kg to 10 mg/kg) to an animal (e.g., a mouse, a rat, a dog, or a cynomolgus monkey) generally used in the pharmacokinetic test.","After given times (e.g., 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours) from the administration, blood was collected from an appropriate blood collection site (e.g., the jugular vein, the cephalic vein, or the saphenous vein).","The obtained blood was centrifuged to prepare a plasma sample.","The concentration of the test compound contained in the plasma sample was measured by quantitative analysis using a liquid chromatography-mass spectrometer (LC-MS/MS).","The pharmacokinetics of the test compound were evaluated on the basis of maximum plasma concentration (Cmax), area under the plasma drug concentration-time curve (AUC), total clearance (CL), and bioavailability and analyzed using software (Phoenix, etc.).","Cmax represents the maximum plasma concentration of the orally administered test compound.","AUC was calculated according to the trapezium rule from the plasma concentrations of the test compound from the time when the test compound was administered up to the final time when the test compound was quantifiable.","The bioavailability was calculated according to the following expression: [(AUC after oral administration/Dose of the oral administration)/(AUC after intravenous administration/Dose of the intravenous administration)].","The compound of the present invention exhibits excellent pharmacokinetics (Cmax, AUC, CL, or bioavailability) and is useful as a pharmaceutical (particularly, a pharmaceutical for the treatment or prevention of ectopic calcification).","Preparation Examples (Preparation Example 1) Capsule Compound of Example 1 50 mg Lactose 128 mg Corn starch 70 mg Magnesium stearate 2 mg 250 mg A powder having the formulation mentioned above is mixed and sifted through a 60-mesh sieve.","Then, this powder is put in a gelatin capsule shell to prepare a capsule.","(Preparation Example 2) Tablet Compound of Example 1 50 mg Lactose 126 mg Corn starch 23 mg Magnesium stearate 1 mg 200 mg A powder having the formulation mentioned above is mixed, granulated using corn starch paste, and dried, followed by compression in a tableting machine to prepare tablets (200 mg each).","This tablet can be coated, if necessary.","The novel pyridine compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof has an excellent TNAP inhibitory effect and is useful as a pharmaceutical."]],"string":"[\n [\n \"PYRIDINE COMPOUNDS\",\n \"The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity.\",\n \"The present invention provides a compound represented by the formula (I): wherein R1 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R2 and R3 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R4 and R5 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R6 represents a hydrogen atom or the like, each R7 may be the same or different and may each represent an optionally substituted C1-6 alkoxy group or the like, X represents —CH═, —C(—R7)═, or —N═, and m represents 1 to 4, or a pharmacologically acceptable salt thereof.\"\n ],\n [\n \"1.A method for the treatment of a disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by formula (I): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AB, a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different groups selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R2 and R3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group AC, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AB, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AE), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R4 and R5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AG), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), R6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), or a cyano group, X represents —CH═, —C(—R7)═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent AB: a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; AC: a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; AD: a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; AE: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AF: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; AG: a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AH: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and AJ: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof.\",\n \"2.The method according to claim 1, wherein the disease or condition is pseudoxanthoma elasticum (PXE).\",\n \"3.The method according to claim 1, wherein the subject is a human.\",\n \"4.The method of claim 1, wherein the compound is represented by formula (Ia): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R2 and R3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R7)═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof.\",\n \"5.The method of claim 4, wherein R1 is hydrogen atom.\",\n \"6.The method of claim 4, wherein R2 and R3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.\",\n \"7.The method of claim 4, wherein each substituent R7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro.\",\n \"8.The method of claim 1, wherein the pharmacologically acceptable salt is sodium salt.\",\n \"9.The method of claim 1, wherein the pharmacologically acceptable salt is potassium salt.\",\n \"10.A method for inhibiting TNAP activity in a subject, comprising administering to a subject an effective amount of a compound represented by formula (I): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AB, a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different groups selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R2 and R3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group AC, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AB, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AE), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R4 and R5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AG), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), R6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), or a cyano group, X represents —CH═, —C(—R7)═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent AB: a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; AC: a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; AD: a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; AE: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AF: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; AG: a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AH: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and AJ: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof.\",\n \"11.The method according to claim 10, wherein the subject is a human.\",\n \"12.The method of claim 10, wherein the compound is represented by formula (Ia): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R2 and R3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R7)═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof.\",\n \"13.The method of claim 12, wherein R1 is hydrogen atom.\",\n \"14.The method of claim 12, wherein R2 and R3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.\",\n \"15.The method of claim 12, wherein each substituent R7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro.\",\n \"16.The method of claim 10, wherein the pharmacologically acceptable salt is sodium salt.\",\n \"17.The method of claim 10, wherein the pharmacologically acceptable salt is potassium salt.\"\n ],\n [\n \"<SOH> FIELD OF THE INVENTION <EOH>The present invention relates to a novel pyridine compound or a pharmacologically acceptable salt thereof which has excellent tissue non-specific alkaline phosphatase (hereinafter, referred to as TNAP) inhibitory activity.\",\n \"The present invention also relates to a therapeutic agent and/or prophylactic agent (preferably a therapeutic agent) for pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient.\",\n \"The present invention further relates to a composition for the treatment or prophylaxis of the aforementioned diseases, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient, use of the compound or the pharmacologically acceptable salt thereof for manufacturing a pharmaceutical for the treatment or prophylaxis of the disease, and a method for the treatment or prophylaxis of the disease, comprising administering a pharmacologically effective amount of the compound or the pharmacologically acceptable salt thereof to a mammal (preferably a human).\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>The present inventors have conducted diligent studies and consequently found that a compound represented by the formula (I) mentioned later has excellent TNAP inhibitory activity based on its specific chemical structure, further has excellent properties in terms of the physicochemical properties (e.g., stability) of a pharmaceutical, and serves as a safe and useful pharmaceutical as a prophylactic or therapeutic agent for a pathological condition or a disease associated with ectopic calcification.\",\n \"On the basis of these findings, the present invention has been completed.\",\n \"Specifically, the compound of the present invention has excellent properties in terms of TNAP inhibitory activity, solubility, cell membrane permeability, oral absorbability, concentration in blood, metabolic stability, tissue penetration, bioavailability (hereinafter, also referred to as BA), in vitro activity, in vivo activity, ex vivo activity, quick onset of drug efficacy, persistence of drug efficacy, physical stability, drug interaction, safety (e.g., cardiotoxicity or hepatotoxicity), etc., and is useful as a pharmaceutical [particularly, a pharmaceutical for the treatment or prophylaxis (preferably treatment) of pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification].\",\n \"The present invention provides: (1) a compound represented by the following general formula (I): wherein R 1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group A B , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group A B , a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group A B , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group A B , a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R 2 and R 3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group A C , a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group A B , a C6-10 aryl group optionally substituted by one or two groups selected from substituent group A B , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group A B , a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group A D , a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group A D , a C6-10 aryl group optionally substituted by one group selected from substituent group A D , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group A D , an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group A D , a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group A D , a C6-10 aryl group optionally substituted by one group selected from substituent group A D , a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group A D , an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A E ), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A F ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group A F ), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A F ), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A E and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R 2 and R 3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R 4 and R 5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A G ), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), R 6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R 6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R 7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A H ), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A H ), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group A G ), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group A J ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group A J ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group A J ), or a cyano group, X represents —CH═, —C(—R 7 )═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent A B : a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; A C : a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; A D : a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; A E : a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; A F : a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; A G : a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; A H : a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and A J : a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof; (2) a compound represented by the following general formula (Ia): wherein R 1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R 2 and R 3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R 2 and R 3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R 7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R 7 )═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof; (3) a compound according to the above (2), wherein R 1 is hydrogen atom; (4) a compound according to the above (2), wherein R 2 and R 3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R 2 and R 3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring; (5) a compound according to the above (2), wherein each substituent R 7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro; (6) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-fluoro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; and pharmacologically acceptable salts thereof; (7) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; 5-chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 2,5-dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; and pharmacologically acceptable salts thereof; (8) a compound according to the above (1), where the compound is 5-fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (9) a compound according to the above (1), where the compound is 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (10) a compound according to the above (1), where the compound is 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (11) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is sodium salt; (12) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is potassium salt; (13) a pharmaceutical composition comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (14) the pharmaceutical composition according to the above (13), wherein the pharmaceutical composition is intended for the treatment or prophylaxis of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), or aortic stenosis; (15) a TNAP inhibitor comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (16) a method for the treatment or prophylaxis of a disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis, comprising administering a therapeutically effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to a subject in need thereof; (17) a method according to (16), wherein the disease or condition is pseudoxanthoma elasticum (PXE); (18) a method for inhibiting TNAP in a subject, comprising administering an effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to the subject; (19) a method according to the above (16) to (18), wherein the subject is a human; (20) use of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for the manufacturing a pharmaceutical composition; (21) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis; and (22) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of pseudoxanthoma elastic (PXE).\",\n \"In the present invention, the “C1-6 alkyl group” refers to a linear or branched alkyl group having 1 to 6 carbon atoms.\",\n \"Examples thereof can include methyl, ethyl, n-propyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, and 2-ethylbutyl groups.\",\n \"For R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , or A B , the C1-6 alkyl group is preferably an alkyl group having 1 to 3 carbon atoms, most preferably an ethyl or methyl group.\",\n \"In the present invention, the “C1-6 alkylcarbonyl group” refers to the aforementioned “C1-6 alkyl group” bonded to a carbonyl group.\",\n \"Examples thereof can include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, s-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, 2-methylbutylcarbonyl, neopentylcarbonyl, 1-ethylpropylcarbonyl, n-hexylcarbonyl, isohexylcarbonyl, 4-methylpentylcarbonyl, 3-methylpentylcarbonyl, 2-methylpentylcarbonyl, 1-methylpentylcarbonyl, 3,3-dimethylbutylcarbonyl, 2,2-dimethylbutylcarbonyl, 1,1-dimethylbutylcarbonyl, 1,2-dimethylbutylcarbonyl, 1,3-dimethylbutylcarbonyl, 2,3-dimethylbutylcarbonyl, and 2-ethylbutylcarbonyl groups.\",\n \"For R 1 , R 2 , or R 3 , the C1-6 alkylcarbonyl group is preferably an alkylcarbonyl group having 1 to 3 carbon atoms, most preferably a methylcarbonyl group.\",\n \"In the present invention, the “C3-8 cycloalkyl group” refers to a 3- to 8-membered saturated cyclic hydrocarbon group.\",\n \"Examples thereof can include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.\",\n \"For R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , A E , A F , A H , or A J , the C3-8 cycloalkyl group is preferably a 3- to 6-membered saturated cyclic hydrocarbon group, more preferably a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group.\",\n \"In the present invention, the “C6-10 aryl group” refers to an aromatic hydrocarbon group having 6 to 10 carbon atoms.\",\n \"Examples thereof can include phenyl, indenyl, and naphthyl groups.\",\n \"For R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , A C , A E , A F , A H , or A J , the C6-10 aryl group is preferably a phenyl group.\",\n \"In the present invention, the “C1-6 alkoxy group” refers to the aforementioned “C1-6 alkyl group” bonded to an oxygen atom.\",\n \"Examples thereof can include linear or branched alkoxy groups each having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, tert-butoxy, n-pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, n-hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, and 2,3-dimethylbutoxy.\",\n \"For R 1 , R 2 , R 3 , R 7 , A B , A D , A E , A F , A G , A H , or A J , the C1-6 alkoxy group is preferably a methoxy or ethoxy group.\",\n \"In the present invention, the “C1-6 alkoxycarbonyl group” refers to the aforementioned “C1-6 alkoxy group” bonded to a carbonyl group.\",\n \"Examples thereof can include linear or branched alkoxycarbonyl groups each having 1 to 6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, tert-butoxycarbonyl, n-pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, n-hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, and 2,3-dimethylbutoxycarbonyl.\",\n \"For R 1 , R 2 , R 3 , R 7 , A H , or A J , the C1-6 alkoxycarbonyl group is preferably a methoxycarbonyl or ethoxycarbonyl group.\",\n \"In the present invention, the “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 4- to 7-membered saturated heterocyclic group containing one or two atoms of nitrogen, oxygen, and sulfur.\",\n \"Examples thereof can include oxetanyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolyl groups.\",\n \"In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.\",\n \"Examples thereof can include morpholinylcarbonyl, thiomorpholinylcarbonyl, pyrrolidinylcarbonyl, pyrrolinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, tetrahydrofuranylcarbonyl, tetrahydropyranylcarbonyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyl groups.\",\n \"In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to an oxygen atom.\",\n \"Examples thereof can include morpholinylcarbonyloxy, thiomorpholinylcarbonyloxy, pyrrolidinylcarbonyloxy, pyrrolinylcarbonyloxy, piperidinylcarbonyloxy, piperazinylcarbonyloxy, tetrahydrofuranylcarbonyloxy, tetrahydropyranylcarbonyloxy, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyloxy groups.\",\n \"In the present invention, the “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 3- to 10-membered heterocyclic group containing one to four atoms of nitrogen, oxygen, and sulfur.\",\n \"Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and aromatic heterocyclic groups such as furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl.\",\n \"The “3- to 10-membered heterocyclic group” may be condensed with an additional cyclic group.\",\n \"Examples thereof can include benzofuranyl, chromenyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, isoindolinyl, 2,3-dihydro-1-benzofuranyl, 3,4-dihydro-1H-isochromenyl, 1,2,3,4-tetrahydroquinolinyl, and 1,2,3,4-tetrahydroisoquinolinyl groups.\",\n \"In the present invention, the “3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.\",\n \"Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and carbonyl groups of aromatic heterocyclic groups such as furylcarbonyl, thienylcarbonyl, pyrrolylcarbonyl, azepinylcarbonyl, pyrazolylcarbonyl, imidazolylcarbonyl, oxazolylcarbonyl, oxadiazolylcarbonyl, isoxazolylcarbonyl, thiazolylcarbonyl, isothiazolylcarbonyl, 1,2,3-oxadiazolylcarbonyl, triazolylcarbonyl, tetrazolylcarbonyl, thiadiazolylcarbonyl, pyranylcarbonyl, pyridylcarbonyl, pyridazinylcarbonyl, pyrimidinylcarbonyl, and pyrazinylcarbonyl groups.\",\n \"In the present invention, the “3- to 10-membered heterocyclylaminocarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group via an amino group.\",\n \"Examples thereof can include aminocarbonyl groups of aromatic heterocyclic groups such as furylaminocarbonyl, thienylaminocarbonyl, pyrrolylaminocarbonyl, azepinylaminocarbonyl, pyrazolylaminocarbonyl, imidazolylaminocarbonyl, oxazolylaminocarbonyl, oxadiazolylaminocarbonyl, isoxazolylaminocarbonyl, thiazolylaminocarbonyl, isothiazolylaminocarbonyl, 1,2,3-oxadiazolylaminocarbonyl, triazolylaminocarbonyl, tetrazolylaminocarbonyl, thiadiazolylaminocarbonyl, pyranylaminocarbonyl, pyridylaminocarbonyl, pyridazinylaminocarbonyl, pyrimidinylaminocarbonyl, and pyrazinylaminocarbonyl groups.\",\n \"In the present invention, the “halogeno group” refers to a fluoro, chloro, bromo, or iodo group.\",\n \"For R 1 , R 2 , R 3 , R 7 , A B , A C , A D , A E , A F , A G , A H , or A J , the halogeno group is preferably a fluoro, chloro, or bromo group.\",\n \"Preferably, R 1 of the present invention is a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur.\",\n \"Preferably, R 2 and R 3 of the present invention are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R 2 and R 3 are bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.\",\n \"Preferably, each of R 4 and R 5 of the present invention is a hydrogen atom.\",\n \"Preferably, R 6 of the present invention is a hydrogen atom.\",\n \"Preferably, each R 7 of the present invention, which may be the same or different, represents a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group.\",\n \"The compound represented by the general formula (I) of the present invention can form a salt with a base.\",\n \"Such a salt with a base is included in the scope of the present invention.\",\n \"Examples of the salt with a base can include: alkali metal salts such as lithium salt, sodium salt, potassium salt, and cesium salt; alkaline earth metal salts such as magnesium salt, calcium salt, and barium salt; inorganic nitrogen compound salts such as ammonium salt and hydrazine salt; primary amine salts such as methylamine salt, ethylamine salt, n-propylamine salt, isopropylamine salt, n-butylamine salt, 2-butylamine salt, isobutylamine salt, and tert-butylamine salt; secondary amine salts such as dimethylamine salt, diethylamine salt, diisopropylamine salt, pyrrolidine salt, piperidine salt, and morpholine salt; tertiary amine salts such as triethylamine salt and N-methylmorpholine salt; and aromatic amine salts such as pyridine salt, 4-(N,N-dimethylamino)pyridine salt, imidazole salt, and 1-methylimidazole salt.\",\n \"The salt is preferably an alkali metal salt, most preferably sodium salt or potassium salt.\",\n \"The compound represented by the general formula (I) of the present invention can form any ratio of a salt with a base.\",\n \"The respective salts with bases or mixtures thereof are included in the scope of the present invention.\",\n \"The compound represented by the general formula (I) of the present invention can form an acid-addition salt, depending on its substituent.\",\n \"Such an acid-addition salt is included in the scope of the present invention.\",\n \"The compound represented by the general formula (I) of the present invention can form any ratio of an acid-addition salt, depending on its substituent.\",\n \"The respective acid-addition salts (e.g., monoacid salt and hemi-acid salt) or mixtures thereof are included in the salt of the present invention.\",\n \"The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an anhydrate, a hydrate, or a solvate.\",\n \"The respective forms or mixtures thereof are included in the scope of the present invention.\",\n \"When the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof has at least one asymmetric center, carbon-carbon double bond, axial chirality, tautomerism, or the like, optical isomers (including enantiomers and diastereomers), geometric isomers, rotational isomers, and tautomers may exist.\",\n \"These isomers and mixtures thereof are represented by a single formula such as the formula (I).\",\n \"The present invention encompasses these isomers and mixtures (including racemates) thereof at any ratio.\",\n \"The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an isotopic compound by the replacement of one or more atoms constituting the compound or the salt with isotopes at nonnatural ratios.\",\n \"The isotopes can be radioactive or nonradioactive.\",\n \"Examples thereof include deuterium ( 2 H; D), tritium ( 3 H; T), carbon-14 ( 14 C), and iodine-125 ( 125 I).\",\n \"The radioactive or nonradioactive isotopic compound may be used as a pharmaceutical for the treatment or prophylaxis of a disease, a reagent for research (e.g., a reagent for assay), a diagnostic agent (e.g., a diagnostic imaging agent), or the like.\",\n \"The present invention encompasses these radioactive or nonradioactive isotopic compounds.\",\n \"The compound represented by the general formula (I) of the present invention can be produced by, for example, the following method: In the structural formulas of the compounds in the method A and the description below, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , m, and X are as defined in the formula (I); L 1 represents a nitro group, a halogeno group, or an amino group and is preferably a nitro group or a bromo group; and L 2 represents a halogeno group and is preferably a chloro group.\",\n \"When a compound serving as a reactive substrate in the reaction of each step in the method A has a group inhibiting the reaction of interest, such as an amino group, a hydroxy group, or a carboxyl group, an appropriate protective group may be introduced to the functional group and the introduced protective group may be removed, if necessary.\",\n \"Such a protective group is not particularly limited as long as the protective group is one usually used.\",\n \"The protective group can be a protective group described in, for example, T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc.\",\n \"The reactions for the introduction and removal of these protective groups can be carried out according to routine methods such as methods described in the literature.\",\n \"The solvent for use in the reaction of each step in the method A is not particularly limited as long as the solvent partially dissolves starting materials without inhibiting the reaction.\",\n \"The solvent is selected from, for example, the following solvent group: aliphatic hydrocarbons such as hexane, pentane, heptane, petroleum ether, and cyclohexane; aromatic hydrocarbons such as toluene, benzene, and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, cyclopentylmethyl ether, t-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone; esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate; nitriles such as acetonitrile, propionitrile, butyronitrile, and isobutyronitrile; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, and 2-methyl-2-propanol; amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N,N′-dimethylpropyleneurea, and hexamethylphosphortriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; water; and mixtures thereof.\",\n \"The acid for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the acid does not inhibit the reaction.\",\n \"The acid is selected from the following acid group: inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, and nitric acid; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; and organic sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid.\",\n \"The base for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the base does not inhibit the reaction.\",\n \"The base is selected from the following base group: alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate; alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and barium hydroxide; alkali metal phosphates such as sodium phosphate and potassium phosphate; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; alkali metal amides such as lithium amide, sodium amide, and potassium amide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; lithium amides such as lithium diisopropylamide (LDA), lithium cyclohexylisopropylamide, and lithium tetramethylpiperazide; alkali metal silylamides such as lithium bistrimethylsilylamide, sodium bistrimethylsilylamide, and potassium bistrimethylsilylamide; alkyllithiums such as methyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium; alkyl magnesium halides such as methyl magnesium chloride, methyl magnesium bromide, methyl magnesium iodide, ethyl magnesium chloride, ethyl magnesium bromide, isopropyl magnesium chloride, isopropyl magnesium bromide, and isobutyl magnesium chloride; and organic amines such as triethylamine, tributylamine, diisopropylethylamine, diethylamine, diisopropylamine, N-methylpiperidine, N-methylmorpholine, N-ethylmorpholine, pyridine, picoline, 2,6-lutidine, 4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO), and 1,8-diazabicyclo[5,4,0]-7-undecene (DBU).\",\n \"In the reaction of each step in the method A mentioned below, the reaction temperature differs depending on solvents, starting materials, reagents, etc., and the reaction time differs depending on solvents, starting materials, reagents, etc.\",\n \"After the completion of the reaction of each step in the method A mentioned below, the compound of interest of each step is isolated from the reaction mixture according to a routine method.\",\n \"The compound of interest is obtained, for example, by: (i) if necessary, filtering off insoluble matter such as a catalyst; (ii) adding water and a water-immiscible solvent (e.g., methylene chloride, chloroform, diethyl ether, ethyl acetate, or toluene) to the reaction mixture to extract the compound of interest; (iii) washing the organic layer with water, followed by drying using a desiccant such as anhydrous sodium sulfate or anhydrous magnesium sulfate; and (iv) distilling off the solvent.\",\n \"The obtained compound of interest can be further purified, if necessary, by a routine method, for example, recrystallization, reprecipitation, or silica gel column chromatography.\",\n \"Alternatively, the compound of interest of each step may be used directly in the next reaction without being purified.\",\n \"In the reaction of each step in the method A mentioned below, optical isomers can be resolved by resolution using a chiral column.\",\n \"Hereinafter, the reaction of each step in the method A will be described.\"\n ],\n [\n \"CROSS-REFERENCES TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser.\",\n \"No.\",\n \"15/481,151, filed Apr.\",\n \"6, 2017, which is a continuation of Ser.\",\n \"No.\",\n \"15/314,887, filed Nov. 29, 2016, which is the national stage of International Application No.\",\n \"PCT/US2016/041345, filed Jul.\",\n \"7, 2006, which claims the benefit of U.S.\",\n \"Provisional Application No.\",\n \"62/190,145, filed Jul.\",\n \"8, 2015, which applications are expressly incorporated herein by reference in their entirety.\",\n \"FIELD OF THE INVENTION The present invention relates to a novel pyridine compound or a pharmacologically acceptable salt thereof which has excellent tissue non-specific alkaline phosphatase (hereinafter, referred to as TNAP) inhibitory activity.\",\n \"The present invention also relates to a therapeutic agent and/or prophylactic agent (preferably a therapeutic agent) for pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient.\",\n \"The present invention further relates to a composition for the treatment or prophylaxis of the aforementioned diseases, comprising the compound or the pharmacologically acceptable salt thereof as an active ingredient, use of the compound or the pharmacologically acceptable salt thereof for manufacturing a pharmaceutical for the treatment or prophylaxis of the disease, and a method for the treatment or prophylaxis of the disease, comprising administering a pharmacologically effective amount of the compound or the pharmacologically acceptable salt thereof to a mammal (preferably a human).\",\n \"DESCRIPTION OF THE RELATED ART In vivo calcification is strictly regulated by the balance of activation between osteoblasts and osteoclasts, phosphorus and calcium concentrations in plasma, and parathyroid hormone or vitamin D secreted in order to maintain the homeostasis of these concentrations (Non Patent Literature 1).\",\n \"Ectopic calcification is found in diseases, for example, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, and peritoneal calcification.\",\n \"In these pathological conditions, calcification in tissues (blood vessels, soft tissues, etc.)\",\n \"that are usually not calcified is caused by the failure of the regulatory mechanism mentioned above, and is known to bring about significantly reduced quality of life (QOL) due to the limitation of activity and an increased cardiovascular risk (Non Patent Literatures 2 and 3).\",\n \"No existing therapeutic agent is effective for ectopic calcification.\",\n \"Thus, there are very high unmet medical needs for this disease (Non Patent Literature 4).\",\n \"TNAP, one of alkaline phosphatases, includes membrane-bound and secretory forms.\",\n \"TNAP is expressed in the bone, the liver, and the kidney and highly expressed particularly in the matrix vesicles of chondrocytes and osteoblasts.\",\n \"This enzyme is known to play an important role in in vivo calcification via the degradation of pyrophosphate, which is an endogenous anti-calcification factor (Non Patent Literature 5).\",\n \"A large number of reports show the increased expression level or elevated activity of TNAP at lesion sites of ectopic calcification, and ectopic calcification also occurs in mice which overexpress human TNAP, suggesting the importance of TNAP for ectopic calcification (Non Patent Literatures 6 and 7).\",\n \"Thus, the inhibition of TNAP is considered to elevate pyrophosphate concentrations in blood and in tissues and suppress ectopic calcification (Non Patent Literature 8).\",\n \"Some compounds are known to have TNAP inhibitory activity (see e.g., Patent Literatures 1 and 2 and, Non Patent Literatures 9 to 12).\",\n \"Among them, compounds partially having a common skeleton are disclosed.\",\n \"Nonetheless, a compound having a 7-membered ring condensed with a pyridine ring has not yet been disclosed.\",\n \"PATENT LITERATURE [Patent Literature 1] International Publication No.\",\n \"WO 2009/017863 (PCT/US2008/063106) [Patent Literature 2] International Publication No.\",\n \"WO 2013/126608 (U.S. Patent Publication No.\",\n \"2015-0011551) NON PATENT LITERATURE [Non Patent Literature 1] J.\",\n \"Bone Miner Res, 2006, vol.\",\n \"24, p. 176-181 [Non Patent Literature 2] Clin.\",\n \"Kidery.\",\n \"J., 2014, vol.\",\n \"7, p. 167-173 [Non Patent Literature 3] Eur.\",\n \"Heart.\",\n \"J., 2014, vol.\",\n \"35, p.\",\n \"1515-1525.\",\n \"[Non Patent Literature 4] Int.\",\n \"J. Nephrol.\",\n \"Renovasc.\",\n \"Dis., 2014, vol.\",\n \"7, p. 161-168 [Non Patent Literature 5] J. Histochem.\",\n \"Cytochem., 2002, vol.\",\n \"50, p. 333-340 [Non Patent Literature 6] J.\",\n \"Am.\",\n \"Soc.\",\n \"Nephrol., 2004, vol.\",\n \"15, p. 1392-1401 [Non Patent Literature 7] J.\",\n \"Bone Miner Res, 2013, vol.\",\n \"7, p. 1587-1598 [Non Patent Literature 8] J.\",\n \"Bone Miner Res, 2007, vol.\",\n \"22, p. 1700-1710 [Non Patent Literature 9] Bioorg.\",\n \"Med.\",\n \"Chem.\",\n \"Lett., 2009, vol.\",\n \"19, p. 222-225 [Non Patent Literature 10] J. Med.\",\n \"Chem., 2009, vol.\",\n \"52, p. 6919-6925 [Non Patent Literature 11] Bioorg.\",\n \"Med.\",\n \"Chem., 2013, vol.\",\n \"21, p. 7981-7897 [Non Patent Literature 12] J.\",\n \"Bone Miner Res, 2015, vol.\",\n \"30, p. 824-836 SUMMARY OF THE INVENTION The present inventors have conducted diligent studies and consequently found that a compound represented by the formula (I) mentioned later has excellent TNAP inhibitory activity based on its specific chemical structure, further has excellent properties in terms of the physicochemical properties (e.g., stability) of a pharmaceutical, and serves as a safe and useful pharmaceutical as a prophylactic or therapeutic agent for a pathological condition or a disease associated with ectopic calcification.\",\n \"On the basis of these findings, the present invention has been completed.\",\n \"Specifically, the compound of the present invention has excellent properties in terms of TNAP inhibitory activity, solubility, cell membrane permeability, oral absorbability, concentration in blood, metabolic stability, tissue penetration, bioavailability (hereinafter, also referred to as BA), in vitro activity, in vivo activity, ex vivo activity, quick onset of drug efficacy, persistence of drug efficacy, physical stability, drug interaction, safety (e.g., cardiotoxicity or hepatotoxicity), etc., and is useful as a pharmaceutical [particularly, a pharmaceutical for the treatment or prophylaxis (preferably treatment) of pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), ossification of ligamentum flavum, arterial calcification due to deficiency of CD73 (ACDC), calcification of joints and arteries (CALJA), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, idiopathic basal ganglia calcification (IBGC), heterotopic ossification (HO), calcific aortic valve disease (aortic valve stenosis), calcific tendinitis, ossification of the posterior longitudinal ligament (OPLL) ossification of the anterior longitudinal ligament (OALL), diffuse idiopathic skeletal hyperostosis (DISH), meniscal calcification, or peritoneal calcification].\",\n \"The present invention provides: (1) a compound represented by the following general formula (I): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur), a C3-8 cycloalkyl group (wherein the cycloalkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one or two groups, which may be the same or different halogeno groups, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups, which may be the same or different halogeno groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group optionally substituted by one group selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AB, a carboxyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C3-8 cycloalkyl group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, an amino group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), R2 and R3 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one group selected from substituent group AC, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AB, a C6-10 aryl group optionally substituted by one or two groups selected from substituent group AB, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one or two groups selected from substituent group AB, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from the following substituents: a hydroxy group, a C1-6 alkoxy group optionally substituted by one to three groups, which may be the same or different halogeno groups, a C1-6 alkyl group optionally substituted by one group selected from substituent group AD, a C3-8 cycloalkyl group optionally substituted by one group selected from substituent group AD, a C6-10 aryl group optionally substituted by one group selected from substituent group AD, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur and optionally substituted by one group selected from substituent group AD, an amino group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a carboxyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an aminocarbonyloxy group optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups, a 4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group), a C1-6 alkylcarbonyl group (wherein the alkylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AE), a C6-10 arylcarbonyl group (wherein the arylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), a C6-10 arylaminocarbonyl group (wherein the arylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), a 4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylcarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AF), or a 3- to 10-membered heterocyclylaminocarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclylaminocarbonyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AE and a C1-6 halogenoalkyl group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring or to form a 4- to 6-membered saturated heterocyclic ring via one nitrogen or oxygen atom (wherein one nitrogen atom in the 4- to 6-membered saturated heterocyclic ring is optionally replaced with a hydrogen atom, a C1-6 alkyl group, a C1-6 alkylcarbonyl group, a C1-6 alkoxycarbonyl group), R4 and R5 are the same or different and each represent a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AG), a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), R6 represents a hydrogen atom, hydroxyl group or a C1-6 alkyl group (R6 is a carbon substituent of the pyridinyl ring, not a nitrogen substituent), each substituent R7 may be the same or different and may each represent a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AH), a halogeno group, a C6-10 aryl group (wherein the aryl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur (wherein the heterocyclyl group is optionally substituted by one or two groups, which may be the same or different, selected from substituent group AG), a hydroxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), a carboxyl group, a C1-6 alkoxycarbonyl group (wherein the alkoxycarbonyl group is optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups each optionally substituted by one to three groups, which may be the same or different, selected from substituent group AJ), or a cyano group, X represents —CH═, —C(—R7)═, or —N═, m represents an integer selected from 1 to 4, and the substituent groups represent AB: a hydroxy group, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one to three halogeno groups), a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups), a halogeno group, an amino group, and a cyano group; AC: a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, and a halogeno group; AD: a hydroxy group, a C1-6 alkoxy group, an amino group, a halogeno group, and a cyano group; AE: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AF: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a halogeno group, and a cyano group; AG: a hydroxy group, a C1-6 alkoxy group, an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; AH: a hydroxy group, a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), an amino group (wherein the amino group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group; and AJ: a C1-6 alkoxy group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, a carboxyl group, a C1-6 alkoxycarbonyl group, an aminocarbonyl group (wherein the aminocarbonyl group is optionally substituted by one or two groups, which may be the same or different C1-6 alkyl groups), a halogeno group, and a cyano group, or a pharmacologically acceptable salt thereof; (2) a compound represented by the following general formula (Ia): wherein R1 represents a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur, R2 and R3 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring, each substituent R7 may be the same or different and may represent a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group, X represents —CH═, —C(—R7)═, or —N═, and m represents an integer of 1 or 2, or a pharmacologically acceptable salt thereof; (3) a compound according to the above (2), wherein R1 is hydrogen atom; (4) a compound according to the above (2), wherein R2 and R3 are the same or different and each represent a hydrogen atom or the C1-6 alkyl groups of R2 and R3 are optionally bonded to each other to form a 3- to 6-membered saturated carbocyclic ring; (5) a compound according to the above (2), wherein each substituent R7 may be the same or different and may represent a methoxy group, ethoxy group, trifluoromethoxy group, fluoro or chloro; (6) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-fluoro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; 5-chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide; and pharmacologically acceptable salts thereof; (7) a compound according to the above (1) selected from the group consisting of: 5-chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide; 5-chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; 5-chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide; 2,5-dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide; and pharmacologically acceptable salts thereof; (8) a compound according to the above (1), where the compound is 5-fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (9) a compound according to the above (1), where the compound is 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (10) a compound according to the above (1), where the compound is 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide, or a pharmacologically acceptable salt thereof; (11) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is sodium salt; (12) a compound according to the above (1) to (10), wherein the pharmacologically acceptable salt is potassium salt; (13) a pharmaceutical composition comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (14) the pharmaceutical composition according to the above (13), wherein the pharmaceutical composition is intended for the treatment or prophylaxis of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), or aortic stenosis; (15) a TNAP inhibitor comprising a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof as an active ingredient; (16) a method for the treatment or prophylaxis of a disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis, comprising administering a therapeutically effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to a subject in need thereof; (17) a method according to (16), wherein the disease or condition is pseudoxanthoma elasticum (PXE); (18) a method for inhibiting TNAP in a subject, comprising administering an effective amount of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof to the subject; (19) a method according to the above (16) to (18), wherein the subject is a human; (20) use of a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for the manufacturing a pharmaceutical composition; (21) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of disease or condition selected from the group consisting of ectopic calcification, pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), calcification of joints and arteries (CALJA), vascular calcification in CKD/ESRD, calciphylaxis, ossification of posterior longitudinal ligaments (OPLL), ossification of yellow ligaments (OYLL), and aortic stenosis; and (22) a compound according to the above (1) to (10) or a pharmacologically acceptable salt thereof for use in the treatment of pseudoxanthoma elastic (PXE).\",\n \"In the present invention, the “C1-6 alkyl group” refers to a linear or branched alkyl group having 1 to 6 carbon atoms.\",\n \"Examples thereof can include methyl, ethyl, n-propyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, and 2-ethylbutyl groups.\",\n \"For R1, R2, R3, R4, R5, R6, R7, or AB, the C1-6 alkyl group is preferably an alkyl group having 1 to 3 carbon atoms, most preferably an ethyl or methyl group.\",\n \"In the present invention, the “C1-6 alkylcarbonyl group” refers to the aforementioned “C1-6 alkyl group” bonded to a carbonyl group.\",\n \"Examples thereof can include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, s-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, 2-methylbutylcarbonyl, neopentylcarbonyl, 1-ethylpropylcarbonyl, n-hexylcarbonyl, isohexylcarbonyl, 4-methylpentylcarbonyl, 3-methylpentylcarbonyl, 2-methylpentylcarbonyl, 1-methylpentylcarbonyl, 3,3-dimethylbutylcarbonyl, 2,2-dimethylbutylcarbonyl, 1,1-dimethylbutylcarbonyl, 1,2-dimethylbutylcarbonyl, 1,3-dimethylbutylcarbonyl, 2,3-dimethylbutylcarbonyl, and 2-ethylbutylcarbonyl groups.\",\n \"For R1, R2, or R3, the C1-6 alkylcarbonyl group is preferably an alkylcarbonyl group having 1 to 3 carbon atoms, most preferably a methylcarbonyl group.\",\n \"In the present invention, the “C3-8 cycloalkyl group” refers to a 3- to 8-membered saturated cyclic hydrocarbon group.\",\n \"Examples thereof can include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.\",\n \"For R1, R2, R3, R4, R5, R7, AE, AF, AH, or AJ, the C3-8 cycloalkyl group is preferably a 3- to 6-membered saturated cyclic hydrocarbon group, more preferably a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group.\",\n \"In the present invention, the “C6-10 aryl group” refers to an aromatic hydrocarbon group having 6 to 10 carbon atoms.\",\n \"Examples thereof can include phenyl, indenyl, and naphthyl groups.\",\n \"For R1, R2, R3, R4, R5, R7, AC, AE, AF, AH, or AJ, the C6-10 aryl group is preferably a phenyl group.\",\n \"In the present invention, the “C1-6 alkoxy group” refers to the aforementioned “C1-6 alkyl group” bonded to an oxygen atom.\",\n \"Examples thereof can include linear or branched alkoxy groups each having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, tert-butoxy, n-pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, n-hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, and 2,3-dimethylbutoxy.\",\n \"For R1, R2, R3, R7, AB, AD, AE, AF, AG, AH, or AJ, the C1-6 alkoxy group is preferably a methoxy or ethoxy group.\",\n \"In the present invention, the “C1-6 alkoxycarbonyl group” refers to the aforementioned “C1-6 alkoxy group” bonded to a carbonyl group.\",\n \"Examples thereof can include linear or branched alkoxycarbonyl groups each having 1 to 6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, tert-butoxycarbonyl, n-pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, n-hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, and 2,3-dimethylbutoxycarbonyl.\",\n \"For R1, R2, R3, R7, AH, or AJ, the C1-6 alkoxycarbonyl group is preferably a methoxycarbonyl or ethoxycarbonyl group.\",\n \"In the present invention, the “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 4- to 7-membered saturated heterocyclic group containing one or two atoms of nitrogen, oxygen, and sulfur.\",\n \"Examples thereof can include oxetanyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolyl groups.\",\n \"In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.\",\n \"Examples thereof can include morpholinylcarbonyl, thiomorpholinylcarbonyl, pyrrolidinylcarbonyl, pyrrolinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, tetrahydrofuranylcarbonyl, tetrahydropyranylcarbonyl, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyl groups.\",\n \"In the present invention, the “4- to 7-membered saturated heterocyclylcarbonyloxy group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to an oxygen atom.\",\n \"Examples thereof can include morpholinylcarbonyloxy, thiomorpholinylcarbonyloxy, pyrrolidinylcarbonyloxy, pyrrolinylcarbonyloxy, piperidinylcarbonyloxy, piperazinylcarbonyloxy, tetrahydrofuranylcarbonyloxy, tetrahydropyranylcarbonyloxy, and 5-oxo-4,5-dihydro-1,2,4-oxadiazolylcarbonyloxy groups.\",\n \"In the present invention, the “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to a 3- to 10-membered heterocyclic group containing one to four atoms of nitrogen, oxygen, and sulfur.\",\n \"Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered heterocyclyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and aromatic heterocyclic groups such as furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl.\",\n \"The “3- to 10-membered heterocyclic group” may be condensed with an additional cyclic group.\",\n \"Examples thereof can include benzofuranyl, chromenyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, isoindolinyl, 2,3-dihydro-1-benzofuranyl, 3,4-dihydro-1H-isochromenyl, 1,2,3,4-tetrahydroquinolinyl, and 1,2,3,4-tetrahydroisoquinolinyl groups.\",\n \"In the present invention, the “3- to 10-membered heterocyclylcarbonyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group.\",\n \"Examples thereof can include the groups listed as the examples of the aforementioned “4- to 7-membered saturated heterocyclylcarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur”, and carbonyl groups of aromatic heterocyclic groups such as furylcarbonyl, thienylcarbonyl, pyrrolylcarbonyl, azepinylcarbonyl, pyrazolylcarbonyl, imidazolylcarbonyl, oxazolylcarbonyl, oxadiazolylcarbonyl, isoxazolylcarbonyl, thiazolylcarbonyl, isothiazolylcarbonyl, 1,2,3-oxadiazolylcarbonyl, triazolylcarbonyl, tetrazolylcarbonyl, thiadiazolylcarbonyl, pyranylcarbonyl, pyridylcarbonyl, pyridazinylcarbonyl, pyrimidinylcarbonyl, and pyrazinylcarbonyl groups.\",\n \"In the present invention, the “3- to 10-membered heterocyclylaminocarbonyl group containing one or two heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” refers to the aforementioned “3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur” bonded to a carbonyl group via an amino group.\",\n \"Examples thereof can include aminocarbonyl groups of aromatic heterocyclic groups such as furylaminocarbonyl, thienylaminocarbonyl, pyrrolylaminocarbonyl, azepinylaminocarbonyl, pyrazolylaminocarbonyl, imidazolylaminocarbonyl, oxazolylaminocarbonyl, oxadiazolylaminocarbonyl, isoxazolylaminocarbonyl, thiazolylaminocarbonyl, isothiazolylaminocarbonyl, 1,2,3-oxadiazolylaminocarbonyl, triazolylaminocarbonyl, tetrazolylaminocarbonyl, thiadiazolylaminocarbonyl, pyranylaminocarbonyl, pyridylaminocarbonyl, pyridazinylaminocarbonyl, pyrimidinylaminocarbonyl, and pyrazinylaminocarbonyl groups.\",\n \"In the present invention, the “halogeno group” refers to a fluoro, chloro, bromo, or iodo group.\",\n \"For R1, R2, R3, R7, AB, AC, AD, AE, AF, AG, AH, or AJ, the halogeno group is preferably a fluoro, chloro, or bromo group.\",\n \"Preferably, R1 of the present invention is a hydrogen atom, a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group or C1-6 alkoxy group), a C6-10 aryl group, or a 3- to 10-membered heterocyclyl group containing one to four heteroatoms, which may be the same or different, selected from nitrogen, oxygen, and sulfur.\",\n \"Preferably, R2 and R3 of the present invention are the same or different and each represent a hydrogen atom or a C1-6 alkyl group (wherein the alkyl group is optionally substituted by one hydroxy group), or the C1-6 alkyl groups of R2 and R3 are bonded to each other to form a 3- to 6-membered saturated carbocyclic ring.\",\n \"Preferably, each of R4 and R5 of the present invention is a hydrogen atom.\",\n \"Preferably, R6 of the present invention is a hydrogen atom.\",\n \"Preferably, each R7 of the present invention, which may be the same or different, represents a C1-6 alkoxy group (wherein the alkoxy group is optionally substituted by one to three halogeno groups) or a halogeno group.\",\n \"The compound represented by the general formula (I) of the present invention can form a salt with a base.\",\n \"Such a salt with a base is included in the scope of the present invention.\",\n \"Examples of the salt with a base can include: alkali metal salts such as lithium salt, sodium salt, potassium salt, and cesium salt; alkaline earth metal salts such as magnesium salt, calcium salt, and barium salt; inorganic nitrogen compound salts such as ammonium salt and hydrazine salt; primary amine salts such as methylamine salt, ethylamine salt, n-propylamine salt, isopropylamine salt, n-butylamine salt, 2-butylamine salt, isobutylamine salt, and tert-butylamine salt; secondary amine salts such as dimethylamine salt, diethylamine salt, diisopropylamine salt, pyrrolidine salt, piperidine salt, and morpholine salt; tertiary amine salts such as triethylamine salt and N-methylmorpholine salt; and aromatic amine salts such as pyridine salt, 4-(N,N-dimethylamino)pyridine salt, imidazole salt, and 1-methylimidazole salt.\",\n \"The salt is preferably an alkali metal salt, most preferably sodium salt or potassium salt.\",\n \"The compound represented by the general formula (I) of the present invention can form any ratio of a salt with a base.\",\n \"The respective salts with bases or mixtures thereof are included in the scope of the present invention.\",\n \"The compound represented by the general formula (I) of the present invention can form an acid-addition salt, depending on its substituent.\",\n \"Such an acid-addition salt is included in the scope of the present invention.\",\n \"The compound represented by the general formula (I) of the present invention can form any ratio of an acid-addition salt, depending on its substituent.\",\n \"The respective acid-addition salts (e.g., monoacid salt and hemi-acid salt) or mixtures thereof are included in the salt of the present invention.\",\n \"The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an anhydrate, a hydrate, or a solvate.\",\n \"The respective forms or mixtures thereof are included in the scope of the present invention.\",\n \"When the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof has at least one asymmetric center, carbon-carbon double bond, axial chirality, tautomerism, or the like, optical isomers (including enantiomers and diastereomers), geometric isomers, rotational isomers, and tautomers may exist.\",\n \"These isomers and mixtures thereof are represented by a single formula such as the formula (I).\",\n \"The present invention encompasses these isomers and mixtures (including racemates) thereof at any ratio.\",\n \"The compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof can form an isotopic compound by the replacement of one or more atoms constituting the compound or the salt with isotopes at nonnatural ratios.\",\n \"The isotopes can be radioactive or nonradioactive.\",\n \"Examples thereof include deuterium (2H; D), tritium (3H; T), carbon-14 (14C), and iodine-125 (125I).\",\n \"The radioactive or nonradioactive isotopic compound may be used as a pharmaceutical for the treatment or prophylaxis of a disease, a reagent for research (e.g., a reagent for assay), a diagnostic agent (e.g., a diagnostic imaging agent), or the like.\",\n \"The present invention encompasses these radioactive or nonradioactive isotopic compounds.\",\n \"The compound represented by the general formula (I) of the present invention can be produced by, for example, the following method: In the structural formulas of the compounds in the method A and the description below, R1, R2, R3, R4, R5, R6, R7, m, and X are as defined in the formula (I); L1 represents a nitro group, a halogeno group, or an amino group and is preferably a nitro group or a bromo group; and L2 represents a halogeno group and is preferably a chloro group.\",\n \"When a compound serving as a reactive substrate in the reaction of each step in the method A has a group inhibiting the reaction of interest, such as an amino group, a hydroxy group, or a carboxyl group, an appropriate protective group may be introduced to the functional group and the introduced protective group may be removed, if necessary.\",\n \"Such a protective group is not particularly limited as long as the protective group is one usually used.\",\n \"The protective group can be a protective group described in, for example, T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc.\",\n \"The reactions for the introduction and removal of these protective groups can be carried out according to routine methods such as methods described in the literature.\",\n \"The solvent for use in the reaction of each step in the method A is not particularly limited as long as the solvent partially dissolves starting materials without inhibiting the reaction.\",\n \"The solvent is selected from, for example, the following solvent group: aliphatic hydrocarbons such as hexane, pentane, heptane, petroleum ether, and cyclohexane; aromatic hydrocarbons such as toluene, benzene, and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, cyclopentylmethyl ether, t-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone; esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate; nitriles such as acetonitrile, propionitrile, butyronitrile, and isobutyronitrile; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, and 2-methyl-2-propanol; amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N,N′-dimethylpropyleneurea, and hexamethylphosphortriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; water; and mixtures thereof.\",\n \"The acid for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the acid does not inhibit the reaction.\",\n \"The acid is selected from the following acid group: inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, and nitric acid; organic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, and pentafluoropropionic acid; and organic sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid.\",\n \"The base for use in the reaction of each step in the method A mentioned below is not particularly limited as long as the base does not inhibit the reaction.\",\n \"The base is selected from the following base group: alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate; alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and barium hydroxide; alkali metal phosphates such as sodium phosphate and potassium phosphate; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; alkali metal amides such as lithium amide, sodium amide, and potassium amide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; lithium amides such as lithium diisopropylamide (LDA), lithium cyclohexylisopropylamide, and lithium tetramethylpiperazide; alkali metal silylamides such as lithium bistrimethylsilylamide, sodium bistrimethylsilylamide, and potassium bistrimethylsilylamide; alkyllithiums such as methyllithium, n-butyllithium, sec-butyllithium, and tert-butyllithium; alkyl magnesium halides such as methyl magnesium chloride, methyl magnesium bromide, methyl magnesium iodide, ethyl magnesium chloride, ethyl magnesium bromide, isopropyl magnesium chloride, isopropyl magnesium bromide, and isobutyl magnesium chloride; and organic amines such as triethylamine, tributylamine, diisopropylethylamine, diethylamine, diisopropylamine, N-methylpiperidine, N-methylmorpholine, N-ethylmorpholine, pyridine, picoline, 2,6-lutidine, 4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO), and 1,8-diazabicyclo[5,4,0]-7-undecene (DBU).\",\n \"In the reaction of each step in the method A mentioned below, the reaction temperature differs depending on solvents, starting materials, reagents, etc., and the reaction time differs depending on solvents, starting materials, reagents, etc.\",\n \"After the completion of the reaction of each step in the method A mentioned below, the compound of interest of each step is isolated from the reaction mixture according to a routine method.\",\n \"The compound of interest is obtained, for example, by: (i) if necessary, filtering off insoluble matter such as a catalyst; (ii) adding water and a water-immiscible solvent (e.g., methylene chloride, chloroform, diethyl ether, ethyl acetate, or toluene) to the reaction mixture to extract the compound of interest; (iii) washing the organic layer with water, followed by drying using a desiccant such as anhydrous sodium sulfate or anhydrous magnesium sulfate; and (iv) distilling off the solvent.\",\n \"The obtained compound of interest can be further purified, if necessary, by a routine method, for example, recrystallization, reprecipitation, or silica gel column chromatography.\",\n \"Alternatively, the compound of interest of each step may be used directly in the next reaction without being purified.\",\n \"In the reaction of each step in the method A mentioned below, optical isomers can be resolved by resolution using a chiral column.\",\n \"Hereinafter, the reaction of each step in the method A will be described.\",\n \"(Step A-1) Step A-1 is the step of condensing compound (1) with compound (2) to produce compound (3).\",\n \"The compound (2) is known in the art or is easily obtained from a compound known in the art.\",\n \"The method for condensing a carboxylic acid with an amine differs depending on the type of the carboxylic acid and can be generally carried out by a method well known in the techniques of organic synthetic chemistry, for example, a method described in Comprehensive Organic Transformations (Second Edition, 1999, John Wiley & Sons, Inc., pp.\",\n \"1929-1930, 1941-1949, and 1953-1954).\",\n \"A preferred method involves converting the carboxylic acid to a corresponding acid halide, which is then condensed with a corresponding amine.\",\n \"Thus, step A-1 comprises: (step A-1a): the step of reacting compound (1) with a halogenating agent; and (step A-1b): the step of reacting the compound obtained in the step A-1a with compound (2) in the presence of a base.\",\n \"(Step A-1a) Examples of the halogenating agent used can include: thionyl chloride, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, phosphorus tribromide, phosphorus pentabromide, oxalyl chloride, carbon tetrachloride-triphenylphosphine, hexachloroethane-triphenylphosphine, N-chlorosuccinimide-triphenylphosphine, carbon tetrabromide-triphenylphosphine, and N-bromosuccinimide-triphenylphosphine; and combinations of these halogenating agents with additives such as N,N-dimethylformamide.\",\n \"The halogenating agent is preferably a combination of thionyl chloride with an additive or a combination of oxalyl chloride with an additive, more preferably a combination of oxalyl chloride with N,N-dimethylformamide.\",\n \"Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, and esters.\",\n \"The solvent is preferably a halogenated hydrocarbon or an ether, more preferably methylene chloride or tetrahydrofuran.\",\n \"The reaction temperature is preferably 0° C. to 100° C., more preferably room temperature.\",\n \"The reaction time is preferably 15 minutes to 6 hours.\",\n \"(Step A-1b) Examples of the base used can include alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, lithium amides, alkali metal silylamides, alkyllithiums, and organic amines.\",\n \"The base is preferably an organic amine, more preferably triethylamine or diisopropylethylamine.\",\n \"Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, esters, and amides.\",\n \"The solvent is preferably an ether or an amide, more preferably tetrahydrofuran or N,N-dimethylformamide.\",\n \"The reaction temperature is preferably −78° C. to 100° C., more preferably −20° C. to room temperature.\",\n \"The reaction time is preferably 15 minutes to 24 hours.\",\n \"(Step A-2) Step A-2 is the step of intramolecularly cyclizing the compound (3) obtained in the step A-1b in the presence of a base to produce compound (4).\",\n \"The compound (4) of interest of this step can also be converted, if necessary, to another compound (4) of interest through deprotection reaction.\",\n \"Alternatively, the compound (4) of interest of this step can also be converted, if necessary, to another compound (4) of interest through modification reaction on the nitrogen atom of the amide group.\",\n \"Examples of the base used can include alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal alkoxides, lithium amides, alkali metal silylamides, and organic amines.\",\n \"The base is preferably an alkali metal hydride, an alkali metal carbonate, an alkali metal silylamide, or an organic amine, more preferably sodium bistrimethylsilylamide, sodium hydride, potassium carbonate, or cesium carbonate.\",\n \"Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, and amides.\",\n \"The solvent is preferably an ether, a nitrile, or an amide, more preferably tetrahydrofuran, acetonitrile, or N,N-dimethylformamide.\",\n \"The reaction temperature is preferably −78° C. to 100° C. The reaction time is preferably 15 minutes to 24 hours.\",\n \"The reaction for converting the compound (4) of interest obtained in this step to another compound (4) of interest by the removal of the protective group differs depending on the type of the protective group and can be generally carried out according to a routine method such as a method well known in the techniques of organic synthetic chemistry, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc.\",\n \"The reaction for converting the compound (4) of interest obtained in this step to another compound (4) of interest through modification on the nitrogen atom of the amide group is not particularly limited as long as the reaction does not influence the other parts of the compound.\",\n \"This reaction can be carried out by, for example, a method described in Comprehensive Organic Transformations (Second Edition, 1999, John Wiley & Sons, Inc., pp.\",\n \"1978-1982).\",\n \"(Step A-3) Step A-3 is the step of reacting the compound (4) obtained in the step A-2 with compound (5) in the presence of a base to produce compound (I).\",\n \"The compound (5) is known in the art or is easily obtained from a compound known in the art.\",\n \"The compound (I) of interest of this step can also be converted, if necessary, to another compound (I) of interest through deprotection reaction.\",\n \"The reaction for converting the obtained compound (I) of interest to another compound (I) of interest by the removal of the protective group is not particularly limited as long as the reaction does not influence the other parts of the compound.\",\n \"This reaction can be carried out according to a routine method, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc. Hereinafter, this step is referred to as step A-3-1 when L1 is a nitro group, as step A-3-2 when L1 is an amino group, and as step A-3-3 when L1 is a halogeno group.\",\n \"(Step A-3-1) When L1 is a nitro group, step A-3-1 comprises: (step A-3-1a): the step of selectively reducing the nitro group of the compound obtained in the step A-2 into an amino group; and (step A-3-1b): the step of reacting the compound obtained in the step A-3-1a with compound (5) in the presence of a base to produce compound (I).\",\n \"(Step A-3-1a) The method for selectively reducing the nitro group is not particularly limited as long as the method does not influence the other parts of the compound.\",\n \"This method can be generally carried out by a method well known in the techniques of organic synthetic chemistry, for example, a method described in Comprehensive Organic Transformations (Second Edition, 1999, John Wiley & Sons, Inc., pp.\",\n \"821-828).\",\n \"The method is preferably a catalytic reduction method or a method using a combination of a reducing agent and an additive.\",\n \"Examples of the metal catalyst for use in the catalytic reduction method can include: palladium catalysts such as palladium on carbon, palladium black, palladium hydroxide on carbon, and palladium on barium sulfate; platinum catalysts such as platinum oxide and platinum black, platinum on carbon; rhodium catalysts such as rhodium on aluminum oxide and chlorotris(triphenylphosphine)rhodium (I); and nickel catalysts such as Raney nickel.\",\n \"The metal catalyst is preferably a palladium catalyst, more preferably 10% palladium on carbon.\",\n \"The hydrogen pressure in the catalytic reduction method is preferably 1 to 10 atm, more preferably 1 atm.\",\n \"The solvent for use in the catalytic reduction method is not particularly limited as long as the solvent is inert to this reaction.\",\n \"Examples thereof can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, amides, and mixtures thereof.\",\n \"The solvent is preferably an alcohol, an ether, an amide, or a mixture thereof, more preferably methanol or a mixture of tetrahydrofuran and ethanol.\",\n \"The reaction temperature in the catalytic reduction method is preferably room temperature to 60° C. The reaction time in the catalytic reduction method is preferably 1 hour to 24 hours.\",\n \"The combination of the reagents for use in the reaction using the combination of the reducing agent and the additive is preferably a combination of sodium borohydride and nickel(II) chloride hexahydrate, a combination of zinc powder and acetic acid, a combination of iron powder and acetic acid, or a combination of tin(II) chloride and hydrochloric acid, more preferably a combination of sodium borohydride and nickel(II) chloride hexahydrate.\",\n \"The solvent for use in the reaction using the combination of the reducing agent and the additive is preferably a mixture of an alcohol and an ether, more preferably a mixture of tetrahydrofuran and methanol.\",\n \"The reaction temperature in the reaction using the combination of the reducing agent and the additive is preferably 0° C. to room temperature.\",\n \"The reaction time in the reaction using the combination of the reducing agent and the additive is preferably 5 minutes to 2 hours.\",\n \"(Step A-3-1b) Examples of the base used can include alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, alkali metal hydroxides, alkali metal alkoxides, lithium amides, alkali metal silylamides, and organic amines.\",\n \"The base is preferably an organic amine, more preferably pyridine.\",\n \"Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, esters, nitriles, ketones, and amides.\",\n \"Alternatively, the solvent may not be used.\",\n \"Preferably, the solvent is not used.\",\n \"The reaction temperature is preferably 0° C. to 100° C., more preferably room temperature to 80° C. The reaction time is preferably 15 minutes to 24 hours, more preferably 30 minutes to 3 hours.\",\n \"The reaction for converting the obtained compound (I) of interest obtained in this step to another compound (I) of interest by the removal of the protective group is not particularly limited as long as the reaction does not influence the other parts of the compound.\",\n \"This reaction can be carried out according to a routine method, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc. (Step A-3-2) When L1 is an amino group, the compound (I) can be produced according to the step A-3-1b.\",\n \"(Step A-3-3) When L1 is a halogeno group, step A-3-3 comprises: (step A-3-3a): the step of converting the bromo group of the compound produced in the step A-2 to a N-Boc amide group using a metal catalyst in the presence of a base; (step A-3-3b): the step of deprotecting the N-Boc group of the compound obtained in the step A-3-3a to form an amino group; and (step A-3-3c): the step of reacting the compound obtained in the step A-3-3b with compound (5) in the presence of a base to produce compound (I).\",\n \"(Step A-3-3a) The method for converting the bromo group on the aromatic ring to a N-Boc amide group is not particularly limited as long as the method does not influence the other parts of the compound.\",\n \"This method can be carried out according to a method well known in the techniques of organic synthetic chemistry, for example, a method described in A. P. Dishington, P. D. Johnson, J. G. Kettle, Tetrahedron Letters, 45, 3733 (2004) or S. Bhagwanth, A. G. Waterson, G. M. Adjabeng, K. R. Hornberger, Journal of Organic Chemistry, 74, 4634 (2009).\",\n \"The metal catalyst used is preferably a combination of tris(dibenzylideneacetone)dipalladium(0) chloroform complex and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos™) or a combination of tris(dibenzylideneacetone)dipalladium(0) chloroform complex and di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (tBuXPhos™).\",\n \"The base used is preferably an alkali metal carbonate, an alkali metal phosphate, or an alkali metal alkoxide, more preferably potassium carbonate, cesium carbonate, potassium phosphate, or sodium tert-butoxide.\",\n \"Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, amides, and mixtures thereof.\",\n \"The solvent is preferably an aromatic hydrocarbon, an ether, a nitrile, or an amide, more preferably toluene, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide.\",\n \"The reaction temperature is preferably room temperature to 100° C. The reaction time is preferably 1 hour to 48 hours.\",\n \"(Step A-3-3b) The method for deprotecting the N-Boc group is not particularly limited as long as the method does not influence the other parts of the compound.\",\n \"This method can be carried out according to a routine method, for example, a method described in T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, Fourth Edition, 2007, John Wiley & Sons, Inc., pp.\",\n \"725-735.\",\n \"(Step A-3-3c) The compound (I) can be produced according to the step A-3-1b.\",\n \"When L1 is a bromo group, the compound (I) can also be produced through the reaction of the compound (4) with the following compound (6): using a metal catalyst in the presence of a base.\",\n \"The method for converting the bromo group on the aromatic ring to a benzenesulfonamide group is not particularly limited as long as the method does not influence the other parts of the compound.\",\n \"This method can be carried out according to a method well known in the techniques of organic synthetic chemistry, for example, a method described in X. Wang, A. Guram, M. Ronk, J. E. Milne, J. S. Tedrow, M. M. Faul, Tetrahedron Letters, 53, 7 (2012), W. Deng, L. Liu, C. Zhang, M. Liu, Q.-X.\",\n \"Guo, Tetrahedron Letters, 46, 7295 (2005), or D. K. Luci, J.\",\n \"B. Jameson, A. Yasgar, G. Diaz, N. Joshi, A. Kantz, K. Markham, S. Perry, N. Kuhn, J. Yeung, E. H. Kerns, L. Schultz, M. Holinstat, J. Nadler, D. A. Taylor-Fishwick, A. Jadhav, A. Simeonov, T. R. Holman, D. J. Maloney, Journal of Medicinal Chemistry, 57, 495 (2014).\",\n \"The metal catalyst used is preferably a combination of copper(I) iodide and N-methyl-2-(methylamino)ethylamine.\",\n \"The base used is preferably an alkali metal carbonate, an alkali metal phosphate, or an alkali metal alkoxide, more preferably potassium carbonate or cesium carbonate.\",\n \"Examples of the solvent used can include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, nitriles, ketones, amides, and mixtures thereof.\",\n \"The solvent is preferably an aromatic hydrocarbon, an ether, a nitrile, or an amide, more preferably xylene, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide.\",\n \"The reaction temperature is preferably room temperature to 100° C. The reaction time is preferably 1 hour to 48 hours.\",\n \"When the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof is used as a pharmaceutical, the compound or the salt can be administered alone (i.e., as a bulk) or can be administered orally as an appropriate pharmaceutically acceptable preparation such as a tablet, a capsule, granules, a powder, or a syrup or parenterally as an appropriate pharmaceutically acceptable preparation such as an injection, a suppository, or a patch (preferably orally).\",\n \"These preparations are produced by well-known methods using additives such as excipients, binders, disintegrants, lubricants, emulsifiers, stabilizers, corrigents, diluents, solvents for injections, oleaginous bases, and water-soluble bases.\",\n \"Examples of the excipients can include organic excipients and inorganic excipients.\",\n \"Examples of the organic excipients can include: sugar derivatives such as lactose, saccharose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, and internally cross-linked carboxymethylcellulose sodium; gum arabic; dextran; and pullulan.\",\n \"Examples of the inorganic excipients can include: light anhydrous silicic acid and silicate derivatives such as synthetic aluminum silicate and calcium silicate; phosphates such as calcium phosphate; and sulfates such as calcium sulfates.\",\n \"Examples of the binders can include: the excipients listed above; gelatin; polyvinylpyrrolidone; and polyethylene glycol.\",\n \"Examples of the disintegrants can include: the excipients listed above; chemically modified starch or cellulose derivatives such as croscarmellose sodium and carboxymethyl starch sodium; and cross-linked polyvinylpyrrolidone.\",\n \"Examples of the lubricants can include: talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as bees wax and spermaceti; boric acid; glycol; D,L-leucine; carboxylic acids such as fumaric acid and adipic acid; carboxylic acid sodium salts such as sodium benzoate; sulfates such as sodium sulfate; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; and the starch derivatives listed as the excipients.\",\n \"Examples of the emulsifiers can include: colloidal clay such as bentonite and veegum; anionic surfactants such as sodium lauryl sulfate and calcium stearate; cationic surfactants such as benzalkonium chloride; and nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, and sucrose fatty acid ester.\",\n \"Examples of the stabilizers can include: p-hydroxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; and sorbic acid.\",\n \"Examples of the corrigents can include sweeteners, acidulants, and flavors usually used.\",\n \"Examples of the diluents can include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid esters.\",\n \"Examples of the solvents for injections can include water, ethanol, and glycerin.\",\n \"Examples of the oleaginous bases can include cacao butter, laurin butter, coconut oil, palm kernel oil, camellia oil, liquid paraffin, white petrolatum, purified lanoline, glycerin monostearate, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, sucrose fatty acid ester, stearyl alcohol, and cetanol.\",\n \"Examples of the water-soluble bases can include glycerin, polyethylene glycol, ethanol, and purified water.\",\n \"The dose of the compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof serving as an active ingredient differs depending on the symptoms and age of a patient, etc.\",\n \"The single dose thereof is 0.001 mg/kg (preferably 0.01 mg/kg) as the lower limit and 10 mg/kg (preferably 1 mg/kg) as the upper limit for oral administration and 0.001 mg/kg (preferably 0.01 mg/kg) as the lower limit and 10 mg/kg (preferably 1 mg/kg) as the upper limit for parenteral administration and can be administered once to six times a day according to the symptoms.\",\n \"The compound of the present invention can be used in combination with any of various therapeutic or prophylactic agents for the aforementioned disease for which the compound of the present invention is probably effective.\",\n \"In this combined use, the compound of the present invention and the agent may be administered simultaneously, separately but continuously, or at the desired time interval.\",\n \"The preparations to be administered simultaneously may be formulated as a combination drug or formulated as separate preparations.\",\n \"The pyridine compound or the pharmacologically acceptable salt thereof, which is the compound of the present invention, has an excellent TNAP inhibitory effect and is useful as a therapeutic or prophylactic agent for pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), craniometaphyseal dysplasia (CMD), ossification of the yellow ligament (OYL), arterial calcification due to deficiency of CD73 (ACDC), arthrosis deformans, osteoarthritis, ankylosis of the joint, idiopathic infantile arterial calcification (IIAC), ankylosing spondylitis (AS), tumoral calcinosis (TC), progressive osseous heteroplasia (POH), Keutel syndrome, vascular calcification associated with chronic renal failure (including glomerulonephritis, IgA nephropathy, hypertensive nephropathy, and diabetic nephropathy) and secondary parathyroid hyperplasia, metastatic calcification, calciphylaxis, calcific tendinitis of the longus colli muscle, fibrodysplasia ossificans progressiva (FOP), calcific aortic stenosis, pericarditis calculosa, atherosclerotic vascular calcification, calcific uremic arteriopathy (CUA), Kawasaki disease, calcification due to obesity and aging, tibial arterial calcification, bone metastasis, prosthetic calcification, Paget's disease, or peritoneal calcification.\",\n \"Moreover, the compound of the present invention has low toxicity and excellent safety and as such, is very useful as a pharmaceutical.\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in more detail with reference to Examples, etc.\",\n \"However, the scope of the present invention is not intended to be limited by them.\",\n \"The chemical structural formulas described in Examples represent the chemical structures of corresponding compounds in a free form.\",\n \"Elution in column chromatography in Examples was carried out under observation by thin layer chromatography (TLC).\",\n \"In the TLC observation, silica gel 60F254 manufactured by Merck KGaA was used as a TLC plate; a solvent used as an eluting solvent in column chromatography was used as a developing solvent; and a UV detector or a chromogenic method using a coloring agent (e.g., a ninhydrin coloring solution, an anisaldehyde coloring solution, an ammonium phosphomolybdate coloring solution, a cerium ammonium nitrate (CAM) coloring solution, or an alkaline permanganate coloring solution) was used as a detection method.\",\n \"Silica gel SK-85 (230-400 mesh) also manufactured by Merck KGaA, silica gel 60 N (40-50 μm) manufactured by Kanto Chemical Co., Inc., or Chromatorex NH (200-350 mesh) manufactured by Fuji Silysia Chemical Ltd. was used as silica gel for columns.\",\n \"In addition to general column chromatography, an automatic chromatography apparatus (Purif-α2 or Purif-espoir2) manufactured by Shoko Scientific Co., Ltd., an automatic chromatography apparatus (W-Prep 2XY) manufactured by Yamazen Corp., an automatic chromatography apparatus (Isolera One) manufactured by Biotage Japan Ltd., or an automatic chromatography apparatus (CombiFlash Rf) manufactured by Teledyne Isco, Inc. was appropriately used.\",\n \"The eluting solvent was determined on the basis of the TLC observation.\",\n \"In Examples, nuclear magnetic resonance (1H NMR) spectra were indicated by chemical shift δ values (ppm) determined with tetramethylsilane as a standard.\",\n \"Splitting patterns were indicated by s for singlet, d for doublet, t for triplet, q for quartet, m for multiplet, and br for broad.\",\n \"Mass spectrometry (hereinafter, referred to as MS) was conducted by the electron ionization (EI), electron spray ionization (ESI), atmospheric pressure chemical ionization (APCI), electron spray atmospheric pressure chemical ionization (ES/APCI), or fast atom bombardment (FAB) method.\",\n \"In each step of Examples, the adjustment of a reaction solution and reaction were carried out at room temperature unless the temperature is otherwise specified.\",\n \"EXAMPLES (Example 1) 5-Chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (1a) 2-Chloro-N-(2-hydroxyethyl)-N-methyl-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (500 mg, 2.47 mmol) in methylene chloride (10 mL), oxalyl chloride (0.28 mL, 3.3 mmol) and N,N-dimethylformamide (0.05 mL, 0.64 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 2 hours.\",\n \"The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.\",\n \"To a solution of 2-(methylamino)ethanol (0.197 mL, 2.47 mmol) and N,N-diisopropylethylamine (0.84 mL, 4.9 mmol) in tetrahydrofuran (5 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (5 mL) was added over 10 minutes under ice cooling, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (494.3 mg, yield: 77%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.30-9.22 (1H, m), 8.58-8.46 (1H, m), 4.00-3.68 (4H, m), 3.24-2.99 (3H, m).\",\n \"(1b) 4-Methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a suspension of 2-chloro-N-(2-hydroxyethyl)-N-methyl-5-nitropyridine-3-carboxamide (259.2 mg, 1.00 mmol) obtained in Example (1a) in tetrahydrofuran (50 mL), sodium hydride (63% content, 68.8 mg, 1.81 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 22 hours.\",\n \"The reaction mixture was cooled in an ice water bath.\",\n \"A 1 N aqueous sodium hydroxide solution (10 mL) was added thereto, and the mixture was stirred at room temperature for 20 minutes.\",\n \"The reaction mixture was diluted by addition of ethyl acetate, and the organic layer was separated and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure to obtain the title compound (173.3 mg, yield: 78%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.35 (1H, d, J=3.0 Hz), 9.23 (1H, d, J=3.0 Hz), 4.76-4.70 (2H, m), 3.83-3.73 (2H, m), 3.27 (3H, s).\",\n \"(1c) 7-Amino-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a mixture of 4-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (173.3 mg, 0.78 mmol) obtained in Example (1b) in tetrahydrofuran (5 L) and methanol (5 mL), nickel(II) chloride hexahydrate (386 mg, 1.62 mmol) was added.\",\n \"Subsequently, the mixture was cooled in an ice water bath.\",\n \"Sodium borohydride (122 mg, 3.22 mmol) was added thereto over 10 minutes, and then, the mixture was stirred at room temperature for 30 minutes.\",\n \"The reaction mixture was diluted by addition of acetone and a saturated aqueous solution of sodium bicarbonate, further Celite 545® (approximately 0.6 g) was added thereto, and the mixture was stirred at room temperature for 30 minutes.\",\n \"The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure.\",\n \"The residue was purified by reverse-phase silica gel column chromatography (Chromatorex ODS 100-200 mesh 50 mL, water/methanol=100/0-70/30) to obtain the title compound (96.4 mg, yield: 64%).\",\n \"1H NMR spectrum (CD3OD, 400 MHz) δ: 7.77 (1H, d, J=3.0 Hz), 7.47 (1H, d, J=3.0 Hz), 4.44 (2H, t, J=5.2 Hz), 3.61 (2H, t, J=5.2 Hz), 3.19 (3H, s).\",\n \"(1d) 5-Chloro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a mixture of 7-amino-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (40.0 mg, 0.21 mmol) obtained in Example (1c) and pyridine (1.0 mL, 12.4 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (56.5 mg, 0.23 mmol) was added, and the mixture was stirred at 80° C. for 2 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-80/20).\",\n \"The obtained solid was suspended by the addition of diisopropyl ether (1 mL), and then, the solid was collected by filtration and dried to obtain the title compound (31.9 mg, yield: 39%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.28 (1H, d, J=2.4 Hz), 8.08 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.02-6.98 (2H, m), 4.53 (2H, t, J=4.6 Hz), 4.08 (3H, s), 3.64 (2H, t, J=4.3 Hz), 3.19 (3H, s).\",\n \"MS spectrum (ES/APCI+): 398 (M+H), 400 (M+2+H).\",\n \"(Example 2) 5-Fluoro-2-methoxy-N-(4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a mixture of 7-amino-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (96.4 mg, 0.50 mmol) obtained in Example (1c) and pyridine (2.0 mL, 24.9 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (124.4 mg, 0.56 mmol) was added, and the mixture was stirred at 80° C. for 70 minutes in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15).\",\n \"The obtained solid was suspended by the addition of diisopropyl ether (1 mL), and then, the solid was collected by filtration and dried to obtain the title compound (145.4 mg, yield: 76%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.27 (1H, d, J=2.4 Hz), 8.08 (1H, d, J=3.0 Hz), 7.50 (1H, dd, J=7.3, 3.0 Hz), 7.25-7.20 (1H, m), 7.07 (1H, s), 7.02 (1H, dd, J=9.1, 4.3 Hz), 4.52 (2H, t, J=4.6 Hz), 4.06 (3H, s), 3.63 (2H, t, J=4.6 Hz), 3.19 (3H, s).\",\n \"MS spectrum (ES/APCI+): 382 (M+H).\",\n \"(Example 3) 5-Chloro-N-(4-ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide (3a) 4-Ethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (288 mg, yield for 2 steps: 49%) was obtained by production according to Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (502 mg, 2.47 mmol) and 2-(ethylamino)ethanol (223 mg, 2.50 mmol) as starting materials.\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.34 (1H, d, J=3.0 Hz), 9.22 (1H, d, J=3.0 Hz), 4.71-4.69 (2H, m), 3.76-3.74 (2H, m), 3.69 (2H, q, J=7.3 Hz), 1.26 (3H, t, J=7.3 Hz).\",\n \"(3b) 7-Amino-4-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of 4-ethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (288 mg, 1.22 mmol) obtained in Example (3a) and 10% palladium carbon (water content: 54.6%, 31 mg) in methanol (15 mL) was stirred at room temperature for 5 hours at normal pressure under the hydrogen atmosphere.\",\n \"Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.\",\n \"The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (247 mg, yield: 98%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.88 (1H, d, J=3.0 Hz), 7.60 (1H, d, J=3.0 Hz), 4.47 (2H, t, J=4.9 Hz), 3.68-3.63 (4H, m), 3.55 (2H, t, J=4.9 Hz), 1.25 (3H, t, J=7.3 Hz).\",\n \"(3c) 5-Chloro-N-(4-ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide The title compound (222 mg, yield: 90%) was obtained by production according to Example (1d) using 7-amino-4-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (124 mg, 0.60 mmol) obtained in Example (3b) and 5-chloro-2-methoxybenzenesulfonyl chloride (159 mg, 0.66 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.26 (1H, d, J=2.4 Hz), 8.07 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.05-6.98 (2H, m), 4.52 (2H, t, J=4.3 Hz), 4.08 (3H, s), 3.65-3.59 (4H, m), 1.22 (3H, t, J=7.0 Hz).\",\n \"MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).\",\n \"(Example 4) N-(4-Ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-5-fluoro-2-methoxybenzenesulfonamide The title compound (206 mg, yield: 88%) was obtained by production according to the method described in Example (1d) using 7-amino-4-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (123 mg, 0.59 mmol) obtained in Example (3b) and 5-fluoro-2-methoxybenzenesulfonyl chloride (150 mg, 0.67 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.26 (1H, d, J=3.0 Hz), 8.08 (1H, d, J=2.4 Hz), 7.50 (1H, dd, J=7.6, 3.3 Hz), 7.25-7.21 (1H, m), 7.10-7.07 (1H, m), 7.02 (1H, dd, J=9.1, 3.6 Hz), 4.51 (2H, t, J=4.6 Hz), 4.06 (3H, s), 3.65-3.58 (4H, m), 1.22 (3H, t, J=7.3 Hz).\",\n \"MS spectrum (ES/APCI+): 396 (M+H).\",\n \"(Example 5) 5-Chloro-2-methoxy-N-[5-oxo-4-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (5a) 5-Chloro-2-methoxybenzenesulfonamide To a solution of 5-chloro-2-methoxybenzenesulfonyl chloride (3 g, 12.4 mmol) in tetrahydrofuran (20 mL), a 28% aqueous ammonia solution (20 mL, 295 mmol) was added, and the mixture was stirred at room temperature for 19 hours.\",\n \"The reaction mixture was diluted by addition of 1 N hydrochloric acid, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure to obtain the title compound (2.74 g, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.91 (1H, d, J=3.0 Hz), 7.56-7.46 (1H, m), 7.00 (1H, d, J=8.5 Hz), 5.06 (2H, br s), 4.02 (3H, s).\",\n \"(5b) 5-Bromo-2-chloro-N-(2-hydroxyethyl)-N-(propan-2-yl)pyridine-3-carboxamide The title compound (1.20 g, yield: 88%) was obtained by production according to the method described in Example (1a) using 5-bromo-2-chloropyridine-3-carboxylic acid (1.00 g, 4.22 mmol) and 2-(propan-2-ylamino)ethanol (481 mg, 4.66 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.51-8.46 (1H, m), 7.82-7.73 (1H, m), 3.96-3.85 (2H, m), 3.72-3.54 (3H, m), 3.31-3.25 (1H, m), 1.38-1.09 (6H, m).\",\n \"(5c) 7-Bromo-4-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of 5-bromo-2-chloro-N-(2-hydroxyethyl)-N-(propan-2-yl)pyridine-3-carboxamide (600 mg, 1.87 mmol) obtained in Example (5b) in N,N-dimethylformamide (20 mL), sodium hydride (63% content, 141 mg, 3.70 mmol) was added under ice cooling, and the mixture was stirred at 80° C. for 3 hours and 20 minutes in an oil bath.\",\n \"The reaction mixture was cooled and diluted by addition of a saturated aqueous solution of sodium chloride, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a 5% aqueous sodium chloride solution three times and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (hexane/ethyl acetate=100/0-0/100) to obtain the title compound (142 mg, yield: 27%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.48-8.47 (1H, m), 8.43-8.42 (1H, m), 5.06-4.99 (1H, m), 4.52 (2H, t, J=4.6 Hz), 3.52 (2H, t, J=4.6 Hz), 1.21 (6H, d, J=6.7 Hz).\",\n \"(5d) 5-Chloro-2-methoxy-N-[5-oxo-4-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide A mixture of 7-bromo-4-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (142 mg, 0.50 mmol) obtained in Example (5c), 5-chloro-2-methoxybenzenesulfonamide (114 mg, 0.51 mmol) obtained in Example (5a), potassium carbonate (145 mg, 1.05 mmol), N,N′-dimethylethylene-1,2-diamine (0.27 mL, 2.5 mmol), and copper(I) iodide (48.8 mg, 0.26 mmol) in acetonitrile (5 mL) was heated to reflux for 6 hours and 30 minutes in an oil bath.\",\n \"The reaction mixture was cooled, diluted by addition of 1 N hydrochloric acid, and then stirred at room temperature for 30 minutes.\",\n \"The reaction mixture was filtered through pad of Celite 545®, and the filtrate was subjected to extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15).\",\n \"The obtained solid was suspended by the addition of diisopropyl ether, and then, the solid was collected by filtration and dried to obtain the title compound (44.4 mg, yield: 21%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.25 (1H, d, J=2.4 Hz), 8.03 (1H, d, J=2.4 Hz), 7.75 (1H, d, J=3.0 Hz), 7.48 (1H, dd, J=8.8, 2.7 Hz), 7.02-6.98 (2H, m), 5.02-4.95 (1H, m), 4.47 (2H, t, J=4.6 Hz), 4.08 (3H, s), 3.48 (2H, t, J=4.6 Hz), 1.19 (6H, d, J=6.7 Hz).\",\n \"MS spectrum (ES/APCI+): 426 (M+H), 428 (M+2+H).\",\n \"(Example 6) 5-Chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (6a) 4-(2-Hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (318 mg, yield for 2 steps: 51%) was obtained by production according to the method described in Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (501 mg, 2.47 mmol) and 2,2-iminodiethanol (257 mg, 2.44 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.24 (1H, d, J=2.4 Hz), 8.56 (1H, d, J=2.4 Hz), 4.23-4.14 (1H, m), 4.06-3.96 (1H, m), 3.90-3.82 (2H, m), 3.73-3.59 (2H, m), 3.44-3.32 (1H, m), 3.06-3.00 (1H, m), 2.53-2.47 (1H, m).\",\n \"(6b) 7-Amino-4-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (125 mg, yield: 90%) was obtained by production according to the method described in Example (3c) using 4-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (158 mg, 0.62 mmol) obtained in Example (6a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.90 (1H, d, J=3.0 Hz), 7.58 (1H, d, J=3.0 Hz), 4.52 (2H, t, J=4.9 Hz), 3.92-3.88 (2H, m), 3.81-3.78 (2H, m), 3.68-3.65 (3H, m).\",\n \"(6c) 5-Chloro-N-[4-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (199 mg, yield: 83%) was obtained by production according to Example (1d) using 7-amino-4-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (125 mg, 0.56 mmol) obtained in Example (6b) and 5-chloro-2-methoxybenzenesulfonyl chloride (150 mg, 0.62 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.34 (1H, s), 8.08 (1H, d, J=3.0 Hz), 7.94 (1H, d, J=3.0 Hz), 7.70-7.62 (2H, m), 7.26 (1H, dd, J=10.9, 2.4 Hz), 4.82-4.79 (1H, m), 4.44 (2H, t, J=4.6 Hz), 3.87 (3H, s), 3.63 (2H, t, J=4.6 Hz), 3.59-3.51 (4H, m).\",\n \"MS spectrum (ES/APCI+): 428 (M+H), 430 (M+2+H).\",\n \"(Example 7) 5-Chloro-2-methoxy-N-[4-(2-methoxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (7a) 4-(2-Methoxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of 4-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (158 mg, 0.62 mmol) obtained in Example (6a) in tetrahydrofuran (4 mL), methyl iodide (0.062 mL, 1.0 mmol) and sodium hydride (63%, 32 mg, 0.84 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 4 hours.\",\n \"To the mixture, methyl iodide (0.1 mL, 1.6 mmol) and sodium hydride (63%, 80 mg, 2.1 mmol) were further added, and the mixture was stirred at room temperature for 20 hours.\",\n \"Methyl iodide (0.1 mL, 1.6 mmol) and sodium hydride (63%, 60 mg, 1.6 mmol) were further added thereto, and the mixture was stirred at room temperature for 7 hours and 30 minutes.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium chloride, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (76.7 mg, yield: 46%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.30 (1H, d, J=3.0 Hz), 9.23 (1H, d, J=3.0 Hz), 4.72 (2H, t, J=3.9 Hz), 3.87-3.84 (2H, m), 3.81 (2H, t, J=4.9 Hz), 3.65 (2H, t, J=4.9 Hz), 3.37 (3H, s).\",\n \"(7b) 7-Amino-4-(2-methoxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (65.3 mg, yield: 96%) was obtained by production according to the method described in Example (3c) using 4-(2-methoxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (76.7 mg, 0.29 mmol) obtained in Example (7a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.88 (1H, d, J=3.0 Hz), 7.58 (1H, d, J=3.0 Hz), 4.49 (2H, t, J=5.2 Hz), 3.78 (2H, t, J=4.9 Hz), 3.67-3.61 (6H, m), 3.37 (3H, s).\",\n \"(7c) 5-Chloro-2-methoxy-N-[4-(2-methoxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (86.9 mg, yield: 72%) was obtained by production according to Example (1d) using 7-amino-4-(2-methoxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (65.3 mg, 0.28 mmol) obtained in Example (7b) and 5-chloro-2-methoxybenzenesulfonyl chloride (81.5 mg, 0.34 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.25 (1H, d, J=2.4 Hz), 8.07 (1H, d, J=2.4 Hz), 7.75 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.15-7.11 (1H, m), 7.00 (1H, d, J=8.5 Hz), 4.56-4.52 (2H, m), 4.06 (3H, s), 3.76-3.70 (4H, m), 3.61 (2H, t, J=4.9 Hz), 3.35 (3H, s).\",\n \"MS spectrum (ES/APCI+): 442 (M+H), 444 (M+2+H).\",\n \"(Example 8) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (8a) 2-[(2,4-Dimethoxybenzyl)amino]ethanol To a mixture of 2,4-dimethoxybenzaldehyde (16.20 g, 97.5 mmol) and 2-aminoethanol (5.98 g, 97.9 mmol) in methanol (120 mL), anhydrous sodium sulfate (6.23 g, 43.9 mmol) was added, and the mixture was stirred at room temperature for 20 hours.\",\n \"Subsequently, to the mixture, sodium borohydride (1.84 g, 48.6 mmol) was added over 15 minutes, and the mixture was stirred at 22° C. for 30 minutes.\",\n \"To the reaction mixture, acetic acid (2.8 mL, 49 mmol) was added, and the mixture was stirred for 10 minutes and concentrated into approximately ½ of the amount under reduced pressure.\",\n \"The concentrated mixture was diluted by addition of water and a saturated aqueous solution of sodium bicarbonate, followed by extraction with methylene chloride.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, n-hexane (100 mL) and ethyl acetate (4 mL) were added, and the precipitated solid was collected by filtration, washed with n-hexane, and then dried to obtain the title compound (18.44 g, yield: 90%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.12 (1H, d, J=8.2 Hz), 6.47-6.42 (2H, m), 3.82 (3H, s), 3.80 (3H, s), 3.74 (2H, S), 3.65-3.63 (2H, m), 2.76-2.74 (2H, m).\",\n \"(8b) 2-Chloro-N-(2,4-dimethoxybenzyl)-N-(2-hydroxyethyl)-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (4.91 g, 24.2 mmol) and oxalyl chloride (2.6 mL, 30 mmol) in methylene chloride (120 mL), N,N-dimethylformamide (0.10 mL, 1.3 mmol) was added at room temperature, and the mixture was stirred at the same temperature as above for 30 minutes.\",\n \"The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.\",\n \"To a solution of 2-[(2,4-dimethoxybenzyl)amino]ethanol (5.11 g, 24.2 mmol) obtained in Example (8a) and N,N-diisopropylethylamine (8.25 mL, 48.5 mmol) in tetrahydrofuran (50 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (70 mL) was added over 20 minutes under ice cooling, and the reaction mixture was stirred at the same temperature as above for 90 minutes.\",\n \"To the reaction mixture, water (0.05 mL) was added, and then, the mixture was concentrated under reduced pressure.\",\n \"The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and anhydrous magnesium sulfate and charcoal were added thereto.\",\n \"After filtration through pad of Celite 545 ®, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether (50 mL) and ethyl acetate (10 mL) were added to precipitate a solid.\",\n \"The suspension was stirred at room temperature for 30 minutes.\",\n \"The precipitated solid was collected by filtration, washed with a mixed solvent of diisopropyl ether/ethyl acetate=5/1, and then dried to obtain the title compound (8.30 g, yield: 87%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.24 (0.8H, d, J=2.7 Hz), 9.21 (0.2H, d, J=2.7 Hz), 8.57 (0.2H, d, J=2.7 Hz), 8.44 (0.8H, d, J=2.7 Hz), 7.38 (0.2H, d, J=8.2 Hz), 6.99 (0.8H, d, J=8.2 Hz), 6.54-6.48 (0.4H, m), 6.45-6.40 (1.6H, m), 5.13 (0.2H, d, J=14.9 Hz), 4.53 (0.2H, d, J=14.9 Hz), 4.38-3.54 (10.8H, m), 3.24-3.19 (0.4H, t, J=5.1 Hz), 2.42 (0.4H, t, J=5.1 Hz).\",\n \"(8c) 4-(2,4-Dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (ca.\",\n \"1.9 mol/L, 14.4 mL, 27.4 mmol) was diluted with tetrahydrofuran (450 mL).\",\n \"A solution of 2-chloro-N-(2,4-dimethoxybenzyl)-N-(2-hydroxyethyl)-5-nitropyridine-3-carboxamide (7.22 g, 18.2 mmol) obtained in Example (8b) in tetrahydrofuran (450 mL) was added thereto over 70 minutes under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes and further stirred at room temperature for 30 minutes.\",\n \"To the reaction mixture, a saturated aqueous solution of ammonium chloride (100 mL) was added, and then, the reaction mixture was concentrated into approximately ⅕ of the amount under reduced pressure.\",\n \"The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate twice.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane/methylene chloride=1/1/1-3/2/2).\",\n \"To the obtained solid, diisopropyl ether (20 mL) and ethyl acetate (10 mL) were added, and the suspension was stirred at room temperature for overnight.\",\n \"The precipitated solid was collected by filtration, washed with a mixed solvent of diisopropyl ether/ethyl acetate=2/1, and then dried to obtain the title compound (4.18 g, yield: 64%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.34 (1H, d, J=2.7 Hz), 9.20 (1H, d, J=2.7 Hz), 7.34-7.32 (1H, m), 6.50-6.48 (2H, m), 4.76 (2H, s), 4.53-4.51 (2H, m), 3.84 (3H, s), 3.81 (3H, s), 3.78-3.76 (2H, m).\",\n \"(8d) 7-Amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of 4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (4.18 g, 11.6 mmol) obtained in Example (8c) and 10% palladium carbon (water content: 54.6%, 1.36 g) in tetrahydrofuran (110 mL) and ethanol (55 mL) was stirred at room temperature for 3 hours at normal pressure under the hydrogen atmosphere.\",\n \"Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.\",\n \"The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (3.93 g, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.86 (1H, d, J=3.1 Hz), 7.62 (1H, d, J=3.1 Hz), 7.31-7.28 (1H, m), 6.49-6.47 (2H, m), 4.75 (2H, s), 4.25 (2H, t, J=4.9 Hz), 3.82 (3H, s), 3.81 (3H, s), 3.64 (2H, br s), 3.55 (2H, t, J=4.9 Hz).\",\n \"(8e) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (229 mg, 0.70 mmol) obtained in Example (8d) and pyridine (3.0 mL, 37.3 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (190 mg, 0.79 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (349 mg, yield: 94%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=3.0 Hz), 8.07 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.48 (1H, dd, J=8.8, 2.7 Hz), 7.30-7.22 (2H, m), 7.01 (1H, d, J=9.1 Hz), 6.49-6.46 (2H, m), 4.70 (2H, s), 4.32 (2H, t, J=4.6 Hz), 4.09 (3H, s), 3.81-3.80 (6H, m), 3.60 (2H, t, J=4.6 Hz).\",\n \"MS spectrum (ES/APCI+): 534 (M+H), 536 (M+2+H).\",\n \"(Example 9) 5-Chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of 5-chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (335 mg, 0.63 mmol) obtained in Example (8e) in chloroform (5 mL), anisole (0.136 mL, 1.25 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.165 mL, 1.88 mmol) were added at room temperature, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of chloroform and a saturated aqueous solution of sodium bicarbonate and stirred at room temperature for 10 minutes.\",\n \"The organic layer was separated, and the aqueous layer was subjected to extraction with a mixed solvent of ethyl acetate/tetrahydrofuran=2/1 three times.\",\n \"All the organic layers were combined and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration to obtain the title compound (154 mg, yield: 64%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, s), 8.53 (1H, br t, J=5.2 Hz), 8.11-8.08 (2H, m), 7.69-7.64 (2H, m), 7.26 (1H, d, J=8.5 Hz), 4.37-4.35 (2H, m), 3.88 (3H, s), 3.38-3.34 (2H, m).\",\n \"MS spectrum (ES/APCI+): 384 (M+H), 386 (M+2+H).\",\n \"(Example 10) 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (10a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (200 mg, 0.61 mmol) obtained in Example (8d) and pyridine (6 mL, 74.6 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (158 mg, 0.70 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the title compound (305 mg, yield: 97%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=2.4 Hz), 8.08 (1H, d, J=2.4 Hz), 7.52-7.49 (1H, m), 7.26-7.20 (2H, m), 7.04-7.00 (1H, m), 6.95 (1H, br s), 6.48-6.46 (2H, m), 4.70 (2H, s), 4.31 (2H, br t, J=4.3 Hz), 4.08 (3H, s), 3.81-3.80 (6H, m), 3.59 (2H, br t, J=4.3 Hz).\",\n \"(10b) 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (305 mg, 0.59 mmol) obtained in Example (10a) in chloroform (5 mL), anisole (0.128 mL, 1.17 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.155 mL, 1.77 mmol) were added at room temperature, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of ethyl acetate and a saturated aqueous solution of sodium bicarbonate and stirred at room temperature for 1.5 hours.\",\n \"The precipitated solid was collected by filtration to obtain the title compound (192 mg, yield: 89%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.28 (1H, s), 8.52 (1H, br t, J=4.9 Hz), 8.11-8.08 (2H, m), 7.51-7.46 (2H, m), 7.26-7.23 (1H, m), 4.36 (2H, t, J=4.3 Hz), 3.86 (3H, s), 3.40-3.35 (2H, m).\",\n \"MS spectrum (ES/APCI+): 368 (M+H).\",\n \"(Example 11) 2,5-Dimethoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (11a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (200 mg, 0.61 mmol) obtained in Example (8d) and pyridine (5 mL, 62 mmol), 2,5-dimethoxybenzenesulfonyl chloride (158 mg, 0.67 mmol) was added, and the mixture was stirred at 80° C. for 3 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (290 mg, yield: 90%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=3.0 Hz), 8.09-8.08 (1H, m), 7.30-7.25 (2H, m), 7.07-6.98 (3H, m), 6.48-6.45 (2H, m), 4.70 (2H, s), 4.30 (2H, t, J=4.6 Hz), 4.04 (3H, s), 3.81-3.79 (6H, m), 3.75 (3H, s), 3.58 (2H, t, J=4.6 Hz).\",\n \"(11b) 2,5-Dimethoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a solution of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide (290 mg, 0.55 mmol) obtained in Example (11a) in chloroform (4 mL), anisole (0.12 mL, 1.1 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.15 mL, 1.7 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was neutralized by the addition of a saturated aqueous solution of sodium bicarbonate, followed by extraction with chloroform.\",\n \"The organic layer was dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (144 mg, yield: 77%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.16 (1H, s), 8.51 (1H, t, J=5.2 Hz), 8.09 (2H, dd, J=10.3, 3.0 Hz), 7.21-7.12 (3H, m), 4.35 (2H, t, J=4.3 Hz), 3.81 (3H, s), 3.72 (3H, s), 3.39-3.34 (2H, m).\",\n \"MS spectrum (ES/APCI+): 380 (M+H).\",\n \"(Example 12) 2-Methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (12a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (150 mg, 0.46 mmol) obtained in Example (8d) and pyridine (4 mL, 50 mmol), 2-methoxybenzenesulfonyl chloride (104 mg, 0.50 mmol) was added, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (212 mg, yield: 93%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.23 (1H, d, J=2.4 Hz), 8.07-8.06 (1H, m), 7.79-7.77 (1H, m), 7.55-7.51 (1H, m), 7.30-7.24 (1H, m), 7.08-6.98 (2H, m), 6.92 (1H, s), 6.48-6.43 (2H, m), 4.69 (2H, s), 4.29 (2H, t, J=4.3 Hz), 4.09 (3H, s), 3.81-3.78 (6H, m), 3.56 (2H, t, J=4.6 Hz).\",\n \"(12b) 2-Methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl)benzenesulfonamide To a suspension of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (212 mg, 0.43 mmol) obtained in Example (12a) in chloroform (4 mL), anisole (0.1 mL, 0.9 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.11 mL, 1.3 mmol) were added, and the mixture was stirred at room temperature for 3 hours.\",\n \"The reaction mixture was neutralized by the addition of a saturated aqueous solution of sodium bicarbonate, followed by extraction with chloroform twice.\",\n \"The organic layer was dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (55.2 mg, yield: 37%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.12 (1H, s), 8.52-8.48 (1H, m), 8.10-8.06 (2H, m), 7.70 (1H, dd, J=7.9, 1.8 Hz), 7.61-7.56 (1H, m), 7.20 (1H, d, J=8.5 Hz), 7.03 (1H, t, J=7.6 Hz), 4.34 (2H, t, J=4.3 Hz), 3.88 (3H, s), 3.37-3.31 (2H, m).\",\n \"MS spectrum (ES/APCI+): 350 (M+H).\",\n \"(Example 13) 5-Chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide (13a) 5-Chloro-2-(trifluoromethoxy)benzenesulfonyl chloride To chlorosulfonic acid (30.0 mL, 451 mmol), 4-chlorophenyl trifluoromethyl ether (2.60 mL, 18.1 mmol) was added, and the mixture was stirred at room temperature for 46 hours.\",\n \"The reaction mixture was carefully poured into ice (approximately 300 mL), followed by extraction with methylene chloride twice.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/methylene chloride=1/1) to obtain the title compound (approximately 83% content, 4.67 g, yield: 73%) as a mixture containing positional isomers.\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (0.83H, d, J=2.7 Hz), 8.02 (0.17H, br d, J=2.7 Hz), 7.75 (0.83H, dd, J=8.8, 2.7 Hz), 7.71 (0.17H, d, J=8.6 Hz), 7.55-7.52 (0.17H, m), 7.50-7.47 (0.83H, m).\",\n \"(13b) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (260 mg, 0.79 mmol) obtained in Example (8d) and pyridine (8 mL, 99 mmol), 5-chloro-2-(trifluoromethoxy)benzenesulfonyl chloride (approximately 83% content, 325 mg, 0.92 mmol) obtained in Example (13a) was added at room temperature, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (305 mg, yield: 66%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.29 (1H, d, J=3.0 Hz), 8.17 (1H, d, J=3.0 Hz), 7.90 (1H, d, J=3.0 Hz), 7.58-7.54 (1H, m), 7.38-7.27 (3H, m), 6.49-6.44 (2H, m), 4.73 (2H, s), 4.33 (2H, t, J=4.6 Hz), 3.81 (6H, s), 3.63-3.60 (2H, m).\",\n \"(13c) 5-Chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide To a solution of 5-chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (305 mg, 0.52 mmol) obtained in Example (13b) and anisole (0.113 mL, 1.04 mmol) in chloroform (8 mL), trifluoroacetic acid (3 mL, 39 mmol) and trifluoromethanesulfonic acid (0.137 mL, 1.56 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2.5 hours.\",\n \"To the reaction mixture, water was added, and the mixture was stirred at room temperature for 1 hour, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (171 mg, yield: 75%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.78 (1H, s), 8.58-8.53 (1H, m), 8.13-8.06 (2H, m), 7.91-7.85 (2H, m), 7.65-7.60 (1H, m), 4.39 (2H, t, J=4.3 Hz), 3.41-3.36 (2H, m).\",\n \"MS spectrum (ES/APCI+): 438 (M+H), 440 (M+2+H).\",\n \"(Example 14) 5-Chloro-N-(2,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide (14a) 2,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (280 mg, yield for 2 steps: 44%) was obtained by production according to Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (550 mg, 2.71 mmol) and 1-(methylamino)propan-2-ol (240 mg, 2.69 mmol) as starting materials.\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.23 (2H, s), 4.92-4.85 (1H, m), 3.69-3.56 (2H, m), 3.27 (3H, s), 1.24 (3H, d, J=12.8 Hz).\",\n \"(14b) 7-Amino-2,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (200 mg, yield: 82%) was obtained by production according to the method described in Example (1c) using 2,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (280 mg, 1.18 mmol) obtained in Example (14a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.87 (1H, d, J=3.0 Hz), 7.50 (1H, d, J=3.0 Hz), 4.77-4.70 (1H, m), 4.00-3.91 (1H, m), 3.65 (2H, br s), 3.49-3.44 (1H, m), 3.35-3.27 (1H, m), 3.23 (3H, s), 1.43 (5H, d, J=6.7 Hz).\",\n \"(14c) 5-Chloro-N-(2,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide The title compound (90 mg, yield: 46%) was obtained by production according to Example (1d) using 7-amino-2,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (99 mg, 0.48 mmol) obtained in Example (14b) and 5-chloro-2-methoxybenzenesulfonyl chloride (132.5 mg, 0.55 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.39 (1H, s), 8.08 (1H, d, J=3.0 Hz), 7.82 (1H, d, J=3.0 Hz), 7.69-7.66 (2H, m), 7.28-7.23 (1H, m), 4.73-4.67 (1H, m), 3.86 (3H, s), 3.55-3.49 (1H, m), 3.40-3.29 (2H, m), 3.07 (3H, s), 1.26 (4H, d, J=6.1 Hz).\",\n \"MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).\",\n \"(Example 15) N-(2,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-5-fluoro-2-methoxybenzenesulfonamide The title compound (104 mg, yield: 55%) was obtained by production according to Example (1d) using 7-amino-2,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (99 mg, 0.48 mmol) obtained in Example (14b) and 5-fluoro-2-methoxybenzenesulfonyl chloride (114 mg, 0.51 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.38 (1H, s), 8.08 (1H, d, J=2.4 Hz), 7.82-7.81 (1H, m), 7.53-7.47 (2H, m), 7.24 (1H, dd, J=8.5, 4.3 Hz), 4.72-4.67 (1H, m), 3.85 (3H, s), 3.54-3.48 (1H, m), 3.39-3.30 (1H, m), 3.07 (3H, s), 1.25 (3H, d, J=6.1 Hz).\",\n \"MS spectrum (ES/APCI+): 396 (M+H).\",\n \"(Example 16) 5-Chloro-N-(3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide (16a) 3,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (234 mg, yield for 2 steps: 37%) was obtained by production according to the method described in Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (550 mg, 2.71 mmol) and 2-(methylamino)propan-1-ol (240 mg, 2.69 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.59 (1H, d, J=3.0 Hz), 9.23-9.20 (1H, m), 4.70 (1H, dd, J=13.1, 5.2 Hz), 4.47 (1H, d, J=12.8 Hz), 3.84-3.76 (1H, m), 3.25 (3H, s), 1.36 (4H, d, J=7.3 Hz).\",\n \"(16b) 7-Amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (168 mg, yield: 82%) was obtained by production according to the method described in Example (1c) using 3,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (234 mg, 0.99 mmol) obtained in Example (16a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.00 (1H, d, J=3.0 Hz), 7.88 (1H, d, J=3.0 Hz), 4.44 (1H, dd, J=12.5, 6.4 Hz), 4.28-4.23 (1H, m), 3.81-3.71 (1H, m), 3.60 (2H, br s), 3.18 (3H, s), 1.32 (3H, d, J=6.7 Hz).\",\n \"(16c) 5-Chloro-N-(3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-methoxybenzenesulfonamide The title compound (73 mg, yield: 44%) was obtained by production according to Example (1d) using 7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (84 mg, 0.41 mmol) obtained in Example (16b) and 5-chloro-2-methoxybenzenesulfonyl chloride (111 mg, 0.46 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.36-8.32 (2H, m), 7.74 (1H, d, J=3.1 Hz), 7.46 (1H, dd, J=8.9, 2.7 Hz), 7.06 (1H, br s), 7.00 (1H, d, J=8.5 Hz), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.26 (1H, d, J=12.8 Hz), 4.08 (3H, s), 3.73-3.67 (1H, m), 3.17 (3H, s), 1.30 (3H, d, J=6.7 Hz).\",\n \"MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).\",\n \"(Example 17) N-(3,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-5-fluoro-2-methoxybenzenesulfonamide The title compound (78 mg, yield: 50%) was obtained by production according to Example (1d) using 7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (83 mg, 0.40 mmol) obtained in Example (16b) and 5-fluoro-2-methoxybenzenesulfonyl chloride (104 mg, 0.46 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.36-8.31 (2H, m), 7.49 (1H, dd, J=7.6, 3.4 Hz), 7.24-7.20 (1H, m), 7.08 (1H, br s), 7.02 (1H, dd, J=9.2, 4.3 Hz), 4.51 (1H, dd, J=12.5, 5.2 Hz), 4.25 (1H, d, J=12.8 Hz), 4.08 (3H, s), 3.73-3.66 (1H, m), 3.16 (3H, s), 1.29 (3H, d, J=7.3 Hz).\",\n \"MS spectrum (ES/APCI+): 396 (M+H).\",\n \"(Example 18) 5-Chloro-N-[(3S)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (18a) (2S)-2-[(2,4-Dimethoxybenzyl)amino]propan-1-ol The title compound (2.98 g, yield: 99%) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (2.22 g, 13.4 mmol) and (2S)-2-aminopropan-1-ol (1 g, 13.3 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.13 (1H, d, J=7.9 Hz), 6.50-6.42 (2H, m), 3.85-3.79 (7H, m), 3.77-3.60 (3H, m), 3.26 (1H, dd, J=10.6, 6.4 Hz), 2.84-2.76 (1H, m), 1.06 (3H, d, J=6.7 Hz).\",\n \"(18b) (3S)-4-(2,4-Dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (781.8 mg, yield for 2 steps: 60%) was obtained by production according to the method described in Examples (1a) and (1b) using 2-chloro-5-nitropyridine-3-carboxylic acid (700 mg, 3.46 mmol) and (2S)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol (785 mg, 3.49 mmol) obtained in Example (18a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.62-9.61 (1H, m), 9.20 (1H, d, J=3.0 Hz), 7.33 (1H, d, J=8.5 Hz), 6.50-6.47 (2H, m), 4.95 (1H, d, J=14.6 Hz), 4.65-4.55 (2H, m), 4.31 (1H, d, J=12.8 Hz), 4.04-3.97 (1H, m), 3.84 (3H, s), 3.81 (3H, s), 1.23 (3H, d, J=6.7 Hz).\",\n \"(18c) (3S)-3-Methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of (3S)-4-(2,4-dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (450 mg, 1.21 mmol) obtained in Example (18b) and anisole (0.2 mL, 1.8 mmol) in chloroform (5 mL), trifluoroacetic acid (3 mL, 39 mmol) and trifluoromethanesulfonic acid (0.2 mL, 2.3 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of chloroform, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (228 mg, yield: 85%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.49-9.47 (1H, m), 9.26-9.24 (1H, m), 6.49 (1H, br s), 4.60 (1H, d, J=12.1 Hz), 4.47-4.40 (1H, m), 4.02-3.94 (1H, m), 1.42-1.39 (3H, m).\",\n \"(18d) (3S)-3,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a solution of (3S)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (228 mg, 1.02 mmol) obtained in Example (18c) in N,N-dimethylformamide (5 mL), sodium hydride (63% content, 53 mg, 1.39 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 20 minutes.\",\n \"Subsequently, the mixture was cooled in an ice water bath.\",\n \"Methyl iodide (0.127 mL, 2.04 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour and 45 minutes.\",\n \"The reaction mixture was diluted by addition of ethyl acetate, washed with a 5% aqueous sodium chloride solution three times, and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (160 mg, yield: 66%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.59 (1H, d, J=3.0 Hz), 9.22-9.21 (1H, m), 4.70 (1H, dd, J=12.8, 5.5 Hz), 4.47 (1H, d, J=12.8 Hz), 3.84-3.77 (1H, m), 3.25 (3H, s), 1.36 (3H, d, J=7.3 Hz).\",\n \"(18e) (3S)-7-Amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (175 mg, yield: quantitative) was obtained by production according to the method described in Example (3c) using (3S)-3,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (160 mg, 0.67 mmol) obtained in Example (18d).\",\n \"1H NMR spectrum (CD3OD, 400 MHz) δ: 7.87-7.85 (1H, m), 7.79-7.78 (1H, m), 5.47-5.44 (1H, m), 4.45-4.39 (1H, m), 4.22 (1H, d, J=12.8 Hz), 3.92-3.84 (2H, m), 3.15 (3H, s), 1.32-1.23 (3H, m).\",\n \"(18f) 5-Chloro-N-[(3S)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (87 mg, yield: 63%) was obtained by production according to Example (1d) using (3S)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1, 4]oxazepin-5(2H)-one (69 mg, 0.34 mmol) obtained in Example (18e) and 5-chloro-2-methoxybenzenesulfonyl chloride (91 mg, 0.38 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.34 (2H, dd, J=12.1, 2.4 Hz), 7.74 (1H, d, J=2.4 Hz), 7.46 (1H, dd, J=8.8, 2.7 Hz), 7.10 (1H, s), 7.00 (1H, d, J=9.1 Hz), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.26 (1H, d, J=12.8 Hz), 4.07 (3H, s), 3.74-3.66 (1H, m), 3.17 (3H, s), 1.30 (3H, d, J=7.3 Hz).\",\n \"MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).\",\n \"(Example 19) N-[(3S)-3,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide The title compound (81 mg, yield: 61%) was obtained by production according to Example (1d) using (3S)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (69 mg, 0.34 mmol) obtained in Example (18e) and 5-fluoro-2-methoxybenzenesulfonyl chloride (88 mg, 0.39 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.34 (2H, dd, J=14.9, 2.7 Hz), 7.49 (1H, dd, J=7.9, 3.0 Hz), 7.24-7.19 (1H, m), 7.08 (1H, s), 7.02 (1H, dd, J=9.1, 4.3 Hz), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.25 (1H, d, J=12.8 Hz), 4.07 (3H, s), 3.73-3.66 (1H, m), 3.16 (3H, s), 1.29 (3H, d, J=6.7 Hz).\",\n \"MS spectrum (ES/APCI+): 396 (M+H).\",\n \"(Example 20) 5-Chloro-N-[(3R)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (20a) (2R)-2-[(2,4-Dimethoxybenzyl)amino]propan-1-ol The title compound (3.10 g, yield: quantitative) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (2.25 g, 13.5 mmol) and (2R)-2-aminopropan-1-ol (1.02 g, 13.6 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.13 (1H, d, J=7.9 Hz), 6.50-6.42 (2H, m), 3.86-3.79 (7H, m), 3.77-3.61 (3H, m), 3.26 (1H, dd, J=10.6, 6.4 Hz), 2.84-2.76 (1H, m), 1.06 (3H, d, J=6.1 Hz).\",\n \"(20b) (3R)-4-(2,4-Dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (783 mg, yield for 2 steps: 61%) was obtained using 2-chloro-5-nitropyridine-3-carboxylic acid (700 mg, 3.46 mmol) and (2R)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol (778 mg, 3.45 mmol) obtained in Example (20a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.62 (1H, d, J=3.0 Hz), 9.20 (1H, d, J=3.0 Hz), 7.33 (1H, d, J=8.5 Hz), 6.50-6.47 (2H, m), 4.95 (1H, d, J=14.0 Hz), 4.65-4.54 (2H, m), 4.31 (1H, d, J=13.4 Hz), 4.04-3.97 (1H, m), 3.84 (3H, s), 3.81 (3H, s), 1.23 (3H, d, J=7.3 Hz).\",\n \"(20c) (3R)-3,4-Dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (120 mg, yield for 2 steps: 48%) was obtained by production according to the method described in Examples (18c) and (18d) using (3R)-4-(2,4-dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (390 mg, 1.04 mmol) obtained in Example (20b).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.59 (1H, d, J=2.4 Hz), 9.21 (1H, d, J=2.4 Hz), 4.70 (1H, dd, J=13.1, 5.2 Hz), 4.47 (1H, d, J=13.1 Hz), 3.84-3.77 (1H, m), 3.25 (3H, s), 1.36 (3H, d, J=6.7 Hz).\",\n \"(20d) (3R)-7-Amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (87.9 mg, yield: 84%) was obtained by production according to the method described in Example (1c) using (3R)-3,4-dimethyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (120 mg, 0.51 mmol) obtained in Example (20c).\",\n \"1H NMR spectrum (CD3OD, 400 MHz) δ: 7.86 (1H, d, J=3.0 Hz), 7.79 (1H, d, J=3.0 Hz), 4.42 (1H, dd, J=12.5, 7.0 Hz), 4.22 (1H, dd, J=12.5, 1.5 Hz), 3.93-3.86 (1H, m), 3.15 (3H, s), 1.27 (3H, d, J=6.7 Hz).\",\n \"(20e) 5-Chloro-N-[(3R)-3,4-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (82 mg, yield: 96%) was obtained by production according to Example (1d) using (3R)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (43 mg, 0.21 mmol) obtained in Example (20d) and 5-chloro-2-methoxybenzenesulfonyl chloride (58 mg, 0.24 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.33 (2H, dd, J=8.8, 2.7 Hz), 7.73 (1H, d, J=3.0 Hz), 7.46 (1H, dd, J=8.8, 2.7 Hz), 7.02-6.97 (2H, m), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.26 (1H, d, J=12.8 Hz), 4.09 (3H, s), 3.73-3.67 (1H, m), 3.16 (3H, s), 1.30 (3H, d, J=6.7 Hz).\",\n \"MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).\",\n \"(Example 21) N-[(3R)-3,4-Dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide The title compound (74 mg, yield: 90%) was obtained by production according to Example (1d) using (3R)-7-amino-3,4-dimethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (43 mg, 0.21 mmol) obtained in Example (20d) and 5-fluoro-2-methoxybenzenesulfonyl chloride (56 mg, 0.25 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.33 (2H, dd, J=12.5, 2.7 Hz), 7.49 (1H, dd, J=7.3, 3.0 Hz), 7.24-7.19 (1H, m), 7.04-7.00 (2H, m), 4.51 (1H, dd, J=12.8, 5.5 Hz), 4.25 (1H, d, J=12.8 Hz), 4.08 (3H, s), 3.72-3.66 (1H, m), 3.16 (3H, s), 1.29 (3H, d, J=6.7 Hz).\",\n \"MS spectrum (ES/APCI+): 396 (M+H).\",\n \"(Example 22) 5-Chloro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (22a) (3S)-7-Amino-4-(2,4-dimethoxybenzyl)-3-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a mixture of (3S)-4-(2,4-dimethoxybenzyl)-3-methyl-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (330 mg, 0.88 mmol) obtained in Example (18b) in tetrahydrofuran (4 mL) and methanol (4 mL), nickel(II) chloride hexahydrate (432 mg, 1.82 mmol) was added.\",\n \"Subsequently, the mixture was cooled in an ice water bath.\",\n \"Sodium borohydride (134 mg, 3.54 mmol) was added thereto over 10 minutes, and then, the mixture was stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of acetone, then Celite 545® (approximately 0.6 g) was added thereto, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was filtered, and the solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (303 mg, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.10 (1H, d, J=3.0 Hz), 7.89 (1H, d, J=3.0 Hz), 7.31-7.26 (1H, m), 6.49-6.44 (2H, m), 4.93 (1H, d, J=14.6 Hz), 4.57 (1H, d, J=14.6 Hz), 4.38 (1H, dd, J=12.8, 5.8 Hz), 4.12 (1H, d, J=12.8 Hz), 4.00-3.74 (7H, m), 3.57 (2H, br s), 1.21 (3H, d, J=7.3 Hz).\",\n \"(22b) 5-Chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-4-(2,4-dimethoxybenzyl)-3-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (150 mg, 0.44 mmol) obtained in Example (22a) and pyridine (3 mL, 37 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (121 mg, 0.50 mmol) was added, and the mixture was stirred at 80° C. for 1 hour in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (200 mg, yield: 83%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.38 (1H, d, J=2.4 Hz), 8.31 (1H, d, J=2.4 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=9.1, 2.4 Hz), 7.21 (1H, d, J=9.1 Hz), 7.01 (1H, d, J=9.1 Hz), 6.92 (1H, s), 6.47-6.43 (2H, m), 4.91 (1H, d, J=15.2 Hz), 4.51-4.41 (2H, m), 4.15-4.11 (1H, m), 4.09 (3H, s), 3.85-3.80 (1H, m), 3.80-3.79 (6H, m), 1.17 (3H, d, J=6.7 Hz).\",\n \"(22c) 5-Chloro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide To a solution of 5-chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (200 mg, 0.36 mmol) obtained in Example (22b) and anisole (0.1 mL, 0.9 mmol) in chloroform (3 mL), trifluoroacetic acid (1 mL, 13 mmol) and trifluoromethanesulfonic acid (0.1 mL, 1.1 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and then, the residue was diluted with chloroform, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (105 mg, yield: 72%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.31 (1H, d, J=3.0 Hz), 8.22 (1H, d, J=2.4 Hz), 7.74 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=9.1, 2.4 Hz), 7.02-6.95 (2H, m), 6.10 (1H, br s), 4.41 (1H, d, J=12.1 Hz), 4.23 (1H, dd, J=12.8, 7.3 Hz), 4.08 (3H, s), 1.31 (3H, d, J=6.7 Hz).\",\n \"MS spectrum (ES/APCI+): 398 (M+H), 400 (M+2+H).\",\n \"(Example 23) 5-Fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (23a) N-[(3S)-4-(2,4-Dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-4-(2,4-dimethoxybenzyl)-3-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (150 mg, 0.44 mmol) obtained in Example (22a) and pyridine (3 mL, 37 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (120 mg, 0.53 mmol) was added, and the mixture was stirred at 80° C. for 2 hours and 20 minutes in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (189 mg, yield: 81%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.39 (1H, d, J=3.0 Hz), 8.30-8.29 (1H, m), 7.50 (1H, dd, J=7.9, 3.0 Hz), 7.31-7.20 (2H, m), 7.03 (1H, dd, J=9.1, 3.6 Hz), 6.95 (1H, br s), 6.46-6.44 (2H, m), 4.91 (1H, d, J=14.6 Hz), 4.49 (1H, d, J=14.6 Hz), 4.43 (1H, dd, J=12.8, 5.5 Hz), 4.16-4.11 (1H, m), 4.09 (3H, s), 3.84-3.79 (7H, m), 1.16 (3H, d, J=6.7 Hz).\",\n \"(23b) 5-Fluoro-2-methoxy-N-[(3S)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide To a solution of N-[(3S)-4-(2,4-dimethoxybenzyl)-3-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (189 mg, 0.35 mmol) obtained in Example (23a) and anisole (0.1 mL, 0.9 mmol) in chloroform (3 mL), trifluoroacetic acid (1 mL, 13 mmol) and trifluoromethanesulfonic acid (0.1 mL, 1.1 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and then, the residue was diluted with chloroform, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether was added, and the precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (73.1 mg, yield: 54%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.31 (1H, d, J=2.4 Hz), 8.23 (1H, d, J=2.4 Hz), 7.49 (1H, dd, J=7.6, 3.3 Hz), 7.25-7.20 (1H, m), 7.07-7.00 (2H, m), 6.14 (1H, br s), 4.41 (1H, d, J=11.5 Hz), 4.22 (1H, dd, J=12.8, 7.3 Hz), 4.07 (3H, s), 3.88-3.82 (1H, m), 1.30 (3H, d, J=7.3 Hz).\",\n \"MS spectrum (ES/APCI+): 382 (M+H).\",\n \"(Example 24) 5-Chloro-N-[(3S)-3-ethyl-4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (24a) (2S)-2-[(2,4-Dimethoxybenzyl)amino]butan-1-ol The title compound (2.54 g, yield: 97%) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (1.81 g, 10.9 mmol) and (2S)-2-aminobutan-1-ol (0.98 g, 11.0 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.12 (1H, d, J=8.5 Hz), 6.48-6.41 (2H, m), 3.83 (3H, s), 3.80 (3H, s), 3.71 (2H, s), 3.66 (1H, dd, J=10.3, 4.3 Hz), 3.31 (1H, dd, J=10.3, 6.1 Hz), 2.60-2.52 (1H, m), 1.54-1.38 (2H, m), 0.90 (3H, t, J=7.3 Hz).\",\n \"(24b) (3S)-7-Bromo-4-(2,4-dimethoxybenzyl)-3-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (379 mg, yield for 2 steps: 78%) was obtained by production according to the method described in Examples (1a) and (1b) using 5-bromo-2-chloropyridine-3-carboxylic acid (500 mg, 2.11 mmol) and (2S)-2-[(2,4-dimethoxybenzyl)amino]butan-1-ol (506 mg, 2.11 mmol) obtained in Example (24a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.90 (1H, d, J=2.4 Hz), 8.38 (1H, d, J=2.4 Hz), 7.34-7.31 (1H, m), 6.49-6.46 (2H, m), 5.08 (1H, d, J=14.6 Hz), 4.62 (1H, dd, J=13.1, 5.2 Hz), 4.41 (1H, d, J=14.6 Hz), 4.11-4.09 (1H, m), 3.83 (3H, s), 3.81 (3H, s), 3.69-3.63 (1H, m), 1.62-1.52 (2H, m), 1.00 (3H, t, J=7.3 Hz).\",\n \"(24c) (3S)-7-Bromo-3-ethyl-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (85.1 mg, yield for 2 steps: 66%) was obtained by production according to the method described in Examples (18c) and (18d) using (3S)-7-bromo-4-(2,4-dimethoxybenzyl)-3-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (189 mg, 0.45 mmol) obtained in Example (24b).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.86 (1H, d, J=2.4 Hz), 8.39 (1H, d, J=2.4 Hz), 4.72 (1H, dd, J=13.1, 5.2 Hz), 4.30 (1H, d, J=12.8 Hz), 3.48-3.41 (1H, m), 3.22 (3H, s), 1.72-1.64 (2H, m), 1.05 (3H, t, J=7.6 Hz).\",\n \"(24d) 5-Chloro-N-[(3S)-3-ethyl-4-methyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (63.2 mg, yield: 50%) was obtained by production according to the method described in Example (5d) using (3S)-7-bromo-3-ethyl-4-methyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (85.1 mg, 0.30 mmol) obtained in Example (24c) and 5-chloro-2-methoxybenzenesulfonamide (75.8 mg, 0.34 mmol) obtained in Example (5a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.39-8.31 (2H, m), 7.74 (1H, d, J=3.0 Hz), 7.46 (1H, dd, J=8.8, 2.7 Hz), 7.13 (1H, br s), 6.99 (1H, d, J=9.1 Hz), 4.67 (1H, dd, J=13.4, 5.5 Hz), 4.22 (1H, d, J=12.8 Hz), 4.07 (3H, s), 3.43-3.37 (1H, m), 3.19 (3H, s), 1.70-1.60 (2H, m), 1.02 (3H, t, J=7.3 Hz).\",\n \"MS spectrum (ES/APCI+): 426 (M+H), 428 (M+2+H).\",\n \"(Example 25) 5-Chloro-N-[(3S)-3-ethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (133 mg, yield for 2 steps: 72%) was obtained by production according to the method described in Examples (5d) and (9) using (3S)-7-bromo-4-(2,4-dimethoxybenzyl)-3-ethyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (189 mg, 0.45 mmol) obtained in Example (24b) and 5-chloro-2-methoxybenzenesulfonamide (104 mg, 0.47 mmol) obtained in Example (5a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.31 (1H, d, J=2.4 Hz), 8.25 (1H, d, J=3.0 Hz), 7.75 (1H, d, J=3.0 Hz), 7.47 (1H, dd, J=9.1, 2.4 Hz), 7.29-7.25 (1H, m), 7.00 (1H, d, J=9.1 Hz), 6.27 (1H, br s), 4.42 (1H, d, J=12.8 Hz), 4.33 (1H, dd, J=12.8, 6.7 Hz), 4.07 (3H, s), 3.59-3.53 (1H, m), 1.73-1.60 (2H, m), 1.05 (3H, t, J=7.3 Hz).\",\n \"MS spectrum (ES/APCI+): 412 (M+H), 414 (M+2+H).\",\n \"(Example 26) 5-Chloro-2-methoxy-N-[(3S)-5-oxo-3-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (26a) (2S)-2-[(2,4-Dimethoxybenzyl)amino]-3-methylbutan-1-ol The title compound (2.53 g, yield: 99%) was obtained by production according to the method described in Examples (8a) using 2,4-dimethoxybenzaldehyde (1.68 g, 10.9 mmol) and (2S)-2-amino-3-methylbutan-1-ol (1.04 g, 10.1 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.11 (1H, d, J=7.9 Hz), 6.50-6.42 (2H, m), 3.88-3.81 (7H, m), 3.71 (2H, d, J=4.3 Hz), 3.65 (1H, dd, J=10.3, 4.3 Hz), 3.35 (1H, dd, J=10.3, 6.7 Hz), 2.40-2.35 (1H, m), 1.84-1.73 (1H, m), 0.95 (3H, d, J=6.7 Hz), 0.89 (3H, d, J=6.7 Hz).\",\n \"(26b) (3S)-7-Bromo-4-(2,4-dimethoxybenzyl)-3-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (1.43 g, yield for 2 steps: 77%) was obtained by production according to the method described in Examples (1a) and (1b) using 5-bromo-2-chloropyridine-3-carboxylic acid (1.00 g, 4.23 mmol) and (2S)-2-[(2,4-dimethoxybenzyl)amino]-3-methylbutan-1-ol (1.07 g, 4.22 mmol) obtained in Example (26a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.84 (1H, d, J=2.4 Hz), 8.37 (1H, d, J=2.4 Hz), 7.38-7.35 (1H, m), 6.50-6.43 (2H, m), 5.33 (1H, d, J=14.0 Hz), 4.66 (1H, dd, J=12.8, 5.5 Hz), 4.17-4.11 (1H, m), 4.00 (1H, d, J=12.8 Hz), 3.83 (3H, s), 3.81 (3H, s), 3.40 (1H, dd, J=10.9, 5.5 Hz), 1.85-1.78 (1H, m), 1.05 (3H, d, J=6.7 Hz), 1.02 (3H, d, J=6.7 Hz).\",\n \"(26c) 5-Chloro-2-methoxy-N-[(3S)-5-oxo-3-(propan-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (186 mg, yield for 2 steps: 53%) was obtained by production according to the method described in Examples (5d) and (9) using (3S)-7-bromo-4-(2,4-dimethoxybenzyl)-3-(propan-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (355 mg, 0.82 mmol) obtained in Example (26b) and 5-chloro-2-methoxybenzenesulfonamide (199 mg, 0.90 mmol) obtained in Example (5a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.29 (2H, dd, J=16.4, 3.0 Hz), 7.75 (1H, d, J=2.4 Hz), 7.47 (1H, dd, J=8.8, 2.7 Hz), 7.10 (1H, s), 7.00 (1H, d, J=8.5 Hz), 6.36-6.33 (1H, m), 4.47-4.39 (2H, m), 4.07 (3H, s), 3.35-3.29 (1H, m), 1.95-1.88 (1H, m), 1.08-1.00 (6H, m).\",\n \"MS spectrum (ES/APCI+): 426 (M+H), 428 (M+2+H).\",\n \"(Example 27) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (27a) (2R)-3-(Benzyloxy)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol The title compound (4.18 g, yield: quantitative) was obtained by production according to the method described in Example (8a) using 2,4-dimethoxybenzaldehyde (2.00 g, 12.0 mmol) and (2R)-2-amino-3-(benzyloxy)propan-1-ol (2.18 g, 12.0 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.36-2.26 (5H, m), 7.12 (1H, d, J=7.8 Hz), 6.45-6.42 (2H, m), 4.46 (2H, s), 3.81-3.68 (9H, m), 3.52 (2H, d, J=5.9 Hz), 3.44 (1H, dd, J=11.0, 4.3 Hz), 2.95-2.90 (1H, m).\",\n \"(27b) N-[(2R)-1-(Benzyloxy)-3-hydroxypropan-2-yl]-2-chloro-N-(2,4-dimethoxybenzyl)-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (1.21 g, 5.97 mmol) in methylene chloride (30 mL), oxalyl chloride (0.64 mL, 7.5 mmol) and N,N-dimethylformamide (0.024 mL, 0.31 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 30 minutes.\",\n \"The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.\",\n \"To a solution of (2R)-3-(benzyloxy)-2-[(2,4-dimethoxybenzyl)amino]propan-1-ol (1.98 g, 5.97 mmol) obtained in Example (27a) and N,N-diisopropylethylamine (2.05 mL, 12.1 mmol) in tetrahydrofuran (15 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (15 mL) was added over 10 minutes under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes.\",\n \"To the reaction mixture, water (0.05 mL) was added, and then, the mixture was concentrated under reduced pressure.\",\n \"The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/2-2/3) to obtain the title compound (2.74 g, yield: 89%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.21-9.18 (1H, m), 8.59-8.25 (1H, m), 7.58-6.98 (6H, m), 6.54-6.30 (2H, m), 4.97-2.83 (14H, m).\",\n \"(27c) (3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (ca.\",\n \"1.9 mol/L, 4.2 mL, 8.0 mmol) was diluted with tetrahydrofuran (130 mL).\",\n \"A solution of N-[(2R)-1-(benzyloxy)-3-hydroxypropan-2-yl]-2-chloro-N-(2,4-dimethoxybenzyl)-5-nitropyridine-3-carboxamide (2.73 g, 5.29 mmol) obtained in Example (27b) in tetrahydrofuran (130 mL) was added thereto over 40 minutes under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes and further stirred at room temperature for 40 minutes.\",\n \"To the reaction mixture, a saturated aqueous solution of ammonium chloride (50 mL) was added, and then, the mixture was concentrated into approximately ⅕ of the amount under reduced pressure.\",\n \"The concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate twice.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1) to obtain the title compound (1.93 g, yield: 76%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.53 (1H, d, J=3.1 Hz), 9.12 (1H, d, J=3.1 Hz), 7.35-7.19 (6H, m), 6.49-6.46 (2H, m), 5.06 (1H, d, J=14.1 Hz), 4.88 (1H, dd, J=12.9, 5.1 Hz), 4.52 (1H, d, J=14.1 Hz), 4.46 (1H, d, J=11.7 Hz), 4.40 (1H, d, J=11.7 Hz), 4.26 (1H, d, J=12.9 Hz), 4.16-4.10 (1H, m), 3.83 (6H, s) 3.56 (1H, dd, J=9.4, 7.4 Hz), 3.48 (1H, dd, J=9.4, 6.1 Hz).\",\n \"(27d) (3S)-7-Amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of (3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (1.93 g, 4.03 mmol) obtained in Example (27c) and 10% palladium carbon (water content: 54.6%, 0.48 g) in tetrahydrofuran (26 mL) and ethanol (13 mL) was stirred at room temperature for 5 hours at normal pressure under the hydrogen atmosphere.\",\n \"Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.\",\n \"The solvent in the filtrate was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=1/0-20/1) to obtain the title compound (1.57 g, yield: 87%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (1H, d, J=3.1 Hz), 7.87 (1H, d, J=3.1 Hz), 7.35-7.26 (6H, m), 6.46-6.44 (2H, m), 5.09 (1H, d, J=14.9 Hz), 4.67 (1H, dd, J=12.7, 5.3 Hz), 4.53-4.42 (3H, m), 4.08-3.97 (2H, m), 3.80 (6H, s), 3.63 (1H, dd, J=9.6, 7.2 Hz), 3.56-3.47 (3H, m).\",\n \"(27e) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (226 mg, 0.50 mmol) obtained in Example (27d) and pyridine (0.81 mL, 37.3 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (134 mg, 0.55 mmol) was added, and the mixture was stirred at 80° C. for 30 minutes in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) to obtain the title compound (323 mg, yield: 98%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.36 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.74 (1H, d, J=2.7 Hz), 7.46 (1H, dd, J=9.0, 2.7 Hz), 7.34-7.21 (6H, m), 7.00 (1H, d, J=9.0 Hz), 6.90 (1H, br s), 6.45-6.43 (2H, m), 5.04 (1H, d, J=14.5 Hz), 4.73 (1H, dd, J=12.9, 5.1 Hz), 4.49-4.39 (3H, m), 4.08-4.05 (4H, m), 4.01-3.97 (1H, m), 3.79 (3H, s), 3.77 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.43 (1H, dd, J=9.6, 6.5 Hz).\",\n \"(27f) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-methoxybenzenesulfonamide (324 mg, 0.50 mmol) obtained in Example (27e) and anisole (0.17 mL, 1.6 mmol) in chloroform (2.5 mL), trifluoroacetic acid (0.76 mL, 9.9 mmol) and trifluoromethanesulfonic acid (0.13 mL, 1.5 mmol) were added, and the mixture was stirred at room temperature for 3 hours.\",\n \"The reaction mixture was poured into a mixture of sodium bicarbonate (0.83 g, 9.9 mmol) and water (5 mL), and the mixture was stirred at room temperature for 30 minutes.\",\n \"To the reaction mixture, sodium bicarbonate (0.13 g, 1.5 mmol) was further added, and then, the mixture was concentrated under reduced pressure.\",\n \"The concentrated mixture was diluted by addition of tetrahydrofuran (5 mL).\",\n \"2 N sulfuric acid (0.50 mL, 1.0 mmol) was added thereto, and the mixture was stirred at room temperature for 10 minutes.\",\n \"To the reaction mixture, a 2 N aqueous sodium hydroxide solution (0.50 mL, 1.0 mmol) was added, and the mixture was concentrated under reduced pressure.\",\n \"To the concentrated mixture, a saturated aqueous solution of sodium chloride was added, and the mixture was washed with ethyl acetate.\",\n \"The aqueous layer was rendered acidic by the addition of 1 N hydrochloric acid, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1 twice.\",\n \"The organic layer was dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (162 mg, yield: 79%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.35 (1H, br d, J=4.3 Hz), 8.24 (1H, d, J=3.1 Hz), 8.07 (1H, d, J=3.1 Hz), 7.68-7.64 (2H, m), 7.25 (1H, d, J=9.0 Hz), 5.04 (1H, t, J=5.5 Hz), 4.40-4.32 (2H, m), 3.87 (3H, s), 3.48-3.36 (3H, m).\",\n \"MS spectrum (ES/APCI−): 412 (M−H), 414 (M+2−H).\",\n \"(Example 28) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (28a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (310 mg, 0.69 mmol) obtained in Example (27d) and pyridine (1.1 mL, 13.7 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (171 mg, 0.76 mmol) was added, and the mixture was stirred at 80° C. for 30 minutes in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the concentrated mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) to obtain the title compound (425 mg, yield: 97%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.37 (1H, d, J=2.7 Hz), 8.29 (1H, d, J=2.7 Hz), 7.49 (1H, dd, J=7.4, 3.1 Hz), 7.34-7.19 (7H, m), 7.02 (1H, dd, J=9.0, 3.9 Hz), 6.97 (1H, br s), 6.45-6.42 (2H, m), 5.03 (1H, d, J=14.5 Hz), 4.72 (1H, dd, J=12.7, 5.3 Hz), 4.48-4.39 (3H, m), 4.07-3.96 (5H, m), 3.79 (3H, s), 3.77 (3H, s), 3.54 (1H, dd, J=9.6, 7.4 Hz), 3.42 (1H, dd, J=9.6, 6.5 Hz).\",\n \"(28b) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (213 mg, 0.33 mmol) obtained in Example (28a) and anisole (0.11 mL, 1.0 mmol) in chloroform (1.7 mL), trifluoroacetic acid (0.51 mL, 6.6 mmol) and trifluoromethanesulfonic acid (0.09 mL, 1.0 mmol) were added, and the mixture was stirred at room temperature for 4 hours.\",\n \"The reaction mixture was poured into a mixture of sodium bicarbonate (0.65 g, 7.7 mmol) and water (3.4 mL), and the mixture was stirred at room temperature for 30 minutes.\",\n \"The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of tetrahydrofuran (3.4 mL).\",\n \"2 N sulfuric acid (0.34 mL, 0.68 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour.\",\n \"To the reaction mixture, a 2 N aqueous sodium hydroxide solution (0.34 mL, 0.68 mmol) was added, and the mixture was concentrated under reduced pressure.\",\n \"To the concentrated mixture, a saturated aqueous solution of sodium chloride was added, and the mixture was washed with ethyl acetate.\",\n \"The aqueous layer was rendered acidic by the addition of 1 N hydrochloric acid, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1 twice.\",\n \"The organic layer was dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (113 mg, yield: 85%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.27 (1H, br s), 8.34 (1H, br d, J=3.9 Hz), 8.24 (1H, d, J=2.7 Hz), 8.07 (1H, d, J=2.7 Hz), 7.51-7.47 (2H, m), 7.26-7.22 (1H, m), 5.04 (1H, t, J=5.5 Hz), 4.38-4.32 (2H, m), 3.86 (3H, s), 3.50-3.38 (3H, m).\",\n \"MS spectrum (ES/APCI+): 398 (M+H).\",\n \"(Example 29) 5-Bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (29a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-bromo-2-methoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (200 mg, 0.45 mmol) obtained in Example (27d) and pyridine (0.72 mL, 8.9 mmol), 5-bromo-2-methoxybenzenesulfonyl chloride (140 mg, 0.49 mmol) was added, and the mixture was stirred at 80° C. for 2 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (318 mg, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.37 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.87 (1H, d, J=2.0 Hz), 7.60 (1H, dd, J=8.6, 2.3 Hz), 7.33-7.21 (5H, m), 6.95 (2H, d, J=8.6 Hz), 6.44 (2H, d, J=6.7 Hz), 5.04 (1H, d, J=14.5 Hz), 4.73 (1H, dd, J=12.9, 5.1 Hz), 4.49-4.39 (3H, m), 4.08-4.05 (4H, m), 3.99 (1H, dd, J=12.3, 6.6 Hz), 3.79 (3H, s), 3.77 (3H, s), 3.55 (1H, t, J=8.6 Hz), 3.44 (1H, dd, J=9.4, 6.6 Hz).\",\n \"(29b) 5-Bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-bromo-2-methoxybenzenesulfonamide (318 mg, 0.46 mmol) obtained in Example (29a) and anisole (0.15 mL, 1.4 mmol) in chloroform (2.5 mL), trifluoroacetic acid (0.7 mL, 9.1 mmol) and trifluoromethanesulfonic acid (0.12 mL, 1.4 mmol) were added, and the mixture was stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of water (5 mL) and tetrahydrofuran (2.5 mL) and stirred at room temperature for 1 hour.\",\n \"To the reaction mixture, sodium bicarbonate (0.92 g, 10.9 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.\",\n \"To the mixture, a 2 N aqueous sodium hydroxide solution (0.5 mL, 1.0 mmol) was added, and the mixture was washed with ethyl acetate.\",\n \"To the aqueous layer, 2 N hydrochloric acid (0.75 mL, 1.5 mmol) was added, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1.The organic layer was dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (147 mg, yield: 71%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, s), 8.36 (1H, d, J=3.9 Hz), 8.23 (1H, d, J=2.7 Hz), 8.06 (1H, d, J=2.7 Hz), 7.80-7.76 (1H, m), 7.75 (1H, d, J=2.7 Hz), 7.19 (1H, d, J=9.4 Hz), 5.05 (1H, t, J=5.3 Hz), 4.37-4.35 (2H, m), 3.86 (3H, s), 3.50-3.38 (3H, m).\",\n \"MS spectrum (ES/APCI+): 458 (M+H), 460 (M+2+H).\",\n \"(Example 30) N-[(3S)-3-(Hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide (30a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (180 mg, 0.40 mmol) obtained in Example (27d) and pyridine (0.65 mL, 8.0 mmol), 2,5-dimethoxybenzenesulfonyl chloride (104 mg, 0.44 mmol) was added, and the mixture was stirred at 80° C. for 2 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (266 mg, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.42 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.33-7.21 (8H, m), 7.03 (1H, dd, J=9.0, 3.1 Hz), 6.98 (1H, d, J=9.0 Hz), 6.45-6.41 (2H, m), 5.03 (1H, d, J=14.5 Hz), 4.71 (1H, dd, J=12.7, 5.3 Hz), 4.47-4.38 (3H, m), 4.06-3.95 (5H, m), 3.79 (3H, s), 3.77 (3H, s), 3.73 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.42 (1H, dd, J=9.6, 6.5 Hz).\",\n \"(30b) N-[(3S)-3-(Hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl]-2,5-dimethoxybenzenesulfonamide (266 mg, 0.41 mmol) obtained in Example (30a) and anisole (0.13 mL, 1.2 mmol) in chloroform (2.5 mL), trifluoroacetic acid (0.63 mL, 8.2 mmol) and trifluoromethanesulfonic acid (0.11 mL, 1.2 mmol) were added, and the mixture was stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of water (5 mL) and tetrahydrofuran (2.5 mL) and stirred at room temperature for 1 hour.\",\n \"To the reaction mixture, sodium bicarbonate (0.83 g, 9.8 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.\",\n \"To the reaction mixture, a 2 N aqueous sodium hydroxide solution (0.5 mL, 1.0 mmol) was added, and the mixture was washed with ethyl acetate.\",\n \"To the aqueous layer, 2 N hydrochloric acid (0.75 mL, 1.5 mmol) was added, followed by extraction with a mixed solvent of chloroform/isopropanol=3/1.The organic layer was dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (74 mg, yield: 44%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.17 (1H, br s), 8.35 (1H, d, J=3.9 Hz), 8.25 (1H, d, J=2.7 Hz), 8.07 (1H, d, J=2.7 Hz), 7.21 (1H, d, J=2.7 Hz), 7.19-7.13 (2H, m), 4.36-4.32 (2H, m), 3.81 (3H, s), 3.72 (3H, s), 3.49-3.35 (3H, m).\",\n \"MS spectrum (ES/APCI+): 410 (M+H).\",\n \"(Example 31) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (31a) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-(trifluoromethoxy)benzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (220 mg, 0.49 mmol) obtained in Example (27d) and pyridine (0.79 mL, 9.8 mmol), 5-chloro-2-(trifluoromethoxy)benzenesulfonyl chloride (approximately 83% content, 159 mg, 0.54 mmol) obtained in Example (13a) was added, and the mixture was stirred at 80° C. for 1 hour in an oil bath.\",\n \"The reaction mixture was cooled and then diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-65/35) to obtain the title compound (239 mg, yield: 69%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.45 (1H, d, J=2.7 Hz), 8.28 (1H, d, J=2.7 Hz), 7.88 (1H, d, J=2.7 Hz), 7.56 (1H, dd, J=8.8, 2.5 Hz), 7.39-7.21 (7H, m), 6.99 (1H, br s), 6.46-6.42 (2H, m), 5.05 (1H, d, J=14.5 Hz), 4.75 (1H, dd, J=12.9, 5.1 Hz), 4.50-4.39 (3H, m), 4.10-4.00 (2H, m), 3.79 (3H, s), 3.78 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.44 (1H, dd, J=9.6, 6.5 Hz).\",\n \"(31b) 5-Chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-chloro-2-(trifluoromethoxy)benzenesulfonamide (234 mg, 0.33 mmol) obtained in Example (31a) and anisole (0.11 mL, 1.0 mmol) in chloroform (1.6 mL), trifluoroacetic acid (0.51 mL, 6.6 mmol) and trifluoromethanesulfonic acid (0.09 mL, 1.0 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was diluted by addition of water (3.2 mL) and tetrahydrofuran (1.6 mL) and stirred at room temperature for 1 hour.\",\n \"To the reaction mixture, sodium bicarbonate (0.67 g, 7.9 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.\",\n \"The reaction mixture was concentrated under reduced pressure.\",\n \"To the concentrated mixture, a 2 N aqueous sodium hydroxide solution (0.33 mL, 0.66 mmol) was added, and the mixture was washed with ethyl acetate.\",\n \"To the aqueous layer, 1 N hydrochloric acid (0.66 mL, 0.66 mmol) was added, followed by extraction with a mixed solvent of methylene chloride/isopropanol=4/1.The organic layer was dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (101 mg, yield: 65%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.77 (1H, br s), 8.41 (1H, br d, J=4.3 Hz), 8.21 (1H, d, J=2.7 Hz), 8.11 (1H, d, J=2.7 Hz), 7.91 (1H, d, J=2.7 Hz), 7.87 (1H, dd, J=8.8, 2.7 Hz), 7.64-7.60 (1H, m), 5.07 (1H, t, J=5.5 Hz), 4.43-4.34 (2H, m), 3.52-3.37 (3H, m).\",\n \"MS spectrum (ESI+): 468 (M+H), 470 (M+2+H).\",\n \"(Example 32) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (32a) 5-Fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride The title compound (approximately 50% content, 2.49 g, yield: 81%) was obtained as a mixture containing positional isomers by production according to the method described in Example (13a) using 4-fluorophenyl trifluoromethyl ether (2.00 g, 11.1 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.87-7.82 (1H, m), 7.65-7.60 (0 5H, m), 7.57-7.47 (1H, m), 7.42 (0 5H, t, J=9.0 Hz).\",\n \"(32b) N-[(3S)-3-[(Benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide To a mixture of (3S)-7-amino-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (410 mg, 0.91 mmol) obtained in Example (27d) and pyridine (1.48 mL, 18.2 mmol), 5-fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride (approximately 50% content, 280 mg, 1.00 mmol) obtained in Example (32a) was added, and the mixture was stirred at 80° C. for 1 hour in an oil bath.\",\n \"The reaction mixture was cooled and then diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-65/35) to obtain the title compound (265 mg, yield: 42%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.44 (1H, d, J=2.7 Hz), 8.27 (1H, d, J=2.7 Hz), 7.61 (1H, dd, J=7.4, 3.1 Hz), 7.45-7.40 (1H, m), 7.34-7.22 (7H, m), 7.01 (1H, br s), 6.46-6.42 (2H, m), 5.04 (1H, d, J=14.5 Hz), 4.74 (1H, dd, J=12.9, 5.1 Hz), 4.49-4.39 (3H, m), 4.10-3.99 (2H, m), 3.79 (3H, s), 3.78 (3H, s), 3.55 (1H, dd, J=9.6, 7.6 Hz), 3.43 (1H, dd, J=9.6, 6.3 Hz).\",\n \"(32c) 5-Fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide To a solution of N-[(3S)-3-[(benzyloxy)methyl]-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide (258 mg, 0.37 mmol) obtained in Example (32b) and anisole (0.12 mL, 1.1 mmol) in chloroform (1.8 mL), trifluoroacetic acid (0.57 mL, 7.5 mmol) and trifluoromethanesulfonic acid (0.10 mL, 1.1 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was diluted by addition of water (3.6 mL) and tetrahydrofuran (1.8 mL) and stirred at room temperature for 1 hour.\",\n \"To the reaction mixture, sodium bicarbonate (0.75 g, 9.0 mmol) was carefully added, and the mixture was stirred at room temperature for 10 minutes.\",\n \"The reaction mixture was concentrated under reduced pressure.\",\n \"To the concentrated mixture, a 2 N aqueous sodium hydroxide solution (0.37 mL, 0.74 mmol) was added, followed by extraction with ethyl acetate.\",\n \"To the aqueous layer, 1 N hydrochloric acid (0.75 mL, 0.75 mmol) was added, followed by extraction with a mixed solvent of methylene chloride/isopropanol=4/1.The organic layer was dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate was added, and the precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (135 mg, yield: 80%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.77 (1H, br s), 8.40 (1H, br d, J=4.3 Hz), 8.21 (1H, d, J=2.7 Hz), 8.11 (1H, d, J=2.7 Hz), 7.76-7.72 (1H, m), 7.69-7.63 (2H, m), 5.07 (1H, t, J=5.3 Hz), 4.44-4.34 (2H, m), 3.54-3.37 (3H, m).\",\n \"MS spectrum (ESI+): 452 (M+H).\",\n \"(Example 33) 5-Chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (33a) (6S)—N-(2,4-Dimethoxybenzyl)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine To a solution of tert-butyl [(2S)-1,4-dihydroxybutan-2-yl]carbamate (2.00 g, 9.74 mmol) in methylene chloride (50 mL), imidazole (1.99 g, 11.5 mmol) and tert-butyl(chloro)diphenylsilane (5.89 g, 21.4 mmol) were added, and the mixture was stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-90/10) to obtain tert-butyl [(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]carbamate.\",\n \"To tert-butyl [(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]carbamate thus obtained, trifluoroacetic acid (50 mL, 653 mmol) was added, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and the residue was neutralized by the addition of saturated sodium bicarbonate, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of (6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine.\",\n \"To a solution of the crude product of (6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine thus obtained in methanol (9.35 mL), 2,4-dimethoxybenzaldehyde (2.11 g, 12.7 mmol) and triethylamine (9.56 mL, 69.2 mmol) were added, and the mixture was stirred at room temperature for 1 hour.\",\n \"Subsequently, to the reaction mixture, anhydrous sodium sulfate (0.901 g, 6.34 mmol) was added, and the mixture was stirred at room temperature for 18 hours.\",\n \"Subsequently, to the reaction mixture, sodium borohydride (0.24 g, 6.34 mmol) was added under ice cooling, and the reaction mixture was stirred at the same temperature as above for 1 hour.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-40/60) to obtain the title compound (8.08 g, yield for 3 steps: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.70-7.59 (8H, m), 7.45-7.30 (12H, m), 7.04 (1H, d, J=8.2 Hz), 6.51-6.35 (2H, m), 3.82 (3H, s), 3.81 (3H, s), 3.74-3.51 (6H, m), 2.90-2.75 (1H, m), 1.77-1.56 (2H, m).\",\n \"(33b) (3S)-4-(2,4-Dimethoxybenzyl)-3-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (2.24 g, 11.04 mmol) in methylene chloride (110 mL), oxalyl chloride (1.42 mL, 16.6 mmol) and N,N-dimethylformamide (1.42 mL, 5.52 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 2 hours.\",\n \"The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.\",\n \"Subsequently, to a solution of (6S)—N-(2,4-dimethoxybenzyl)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-amine (8.08 g, 11.04 mmol) obtained in Example (33a) and N,N-diisopropylethylamine (3.85 mL, 22.1 mmol) in tetrahydrofuran (110 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (20 mL) was added under ice cooling, and the mixture was stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-80/20) to obtain 2-chloro-N-(2,4-dimethoxybenzyl)-5-nitro-N-[(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]pyridine-3-carboxamide (7.193 g, yield: 71%).\",\n \"To a solution of 2-chloro-N-(2,4-dimethoxybenzyl)-5-nitro-N-[(6S)-2,2,11,11-tetramethyl-3,3,10,10-tetraphenyl-4,9-dioxa-3,10-disiladodecan-6-yl]pyridine-3-carboxamide (1.09 g, 1.19 mmol) thus obtained in tetrahydrofuran (15 mL), a solution of tetrabutylammonium fluoride in tetrahydrofuran (1 mol/L, 3.57 mL, 3.57 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 24 hours.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (233 mg, yield: 49%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.58 (1H, d, J=2.5 Hz), 9.19 (1H, d, J=2.5 Hz), 7.37 (1H, d, J=8.2 Hz), 6.52-6.47 (2H, m), 5.12 (1H, d, J=14.3 Hz), 4.76 (1H, dd, J=12.9, 5.5 Hz), 4.48 (1H, d, J=14.3 Hz), 4.31-4.22 (2H, m), 3.84 (3H, s), 3.81 (3H, s), 3.79-3.67 (2H, m), 1.89-1.79 (1H, m), 1.75-1.65 (1H, m).\",\n \"(33c) (3S)-7-Amino-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (60.0 mg, yield: quantitative) was obtained by production according to the method described in Example (3c) using (3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (64.0 mg, 0.16 mmol) obtained in Example (33b).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (1H, d, J=2.7 Hz), 7.86 (1H, d, J=2.7 Hz), 7.33-7.31 (1H, m), 6.48-6.46 (2H, m), 5.10 (1H, d, J=14.5 Hz), 4.54 (1H, dd, J=12.9, 5.5 Hz), 4.45 (1H, d, J=14.5 Hz), 4.08 (1H, d, J=12.9 Hz), 4.05-3.97 (1H, m), 3.82 (3H, s), 3.80 (3H, s), 3.76-3.49 (5H, m), 1.90-1.70 (2H, m).\",\n \"(33d) 5-Chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (67 mg, yield: 72%) was obtained by production according to Example (1d) using (3S)-7-amino-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (60.0 mg, 0.16 mmol) obtained in Example (33c) and 5-chloro-2-methoxybenzenesulfonyl chloride (42.6 mg, 0.18 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.40 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.74 (1H, dd, J=3.7, 2.5 Hz), 7.49-7.43 (1H, m), 7.34-7.24 (1H, m), 7.00 (1H, dd, J=9.0, 3.9 Hz), 6.48-6.43 (2H, m), 5.08 (1H, dd, J=14.4, 3.6 Hz), 4.59 (1H, dt, J=12.7, 4.7 Hz), 4.41 (1H, dd, J=14.4, 3.6 Hz), 4.15-4.03 (8H, m), 3.80 (3H, s), 3.75-3.62 (2H, m), 1.85-1.58 (2H, m).\",\n \"(33e) 5-Chloro-N-[(3S)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide The title compound (42 mg, yield: 85%) was obtained by production according to the method described in Example (9) using 5-chloro-N-[(3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (67 mg, 0.12 mmol) obtained in Example (33d).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.48 (1H, d, J=5.9 Hz), 8.14 (1H, d, J=2.7 Hz), 8.08 (1H, d, J=2.7 Hz), 7.68 (1H, d, J=2.4 Hz), 7.65 (1H, dd, J=5.9, 2.4 Hz), 7.25 (1H, d, J=8.8 Hz), 4.32-4.29 (2H, m), 3.87 (3H, s), 3.63-3.40 (3H, m), 1.60-1.55 (2H, m).\",\n \"MS spectrum (ES/APCI+): 428 (M+H), 430 (M+2+H).\",\n \"(Example 34) 2-[(3S)-7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (34a) 2-[(3S)-4-(2,4-Dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide To a mixture of (3S)-4-(2,4-dimethoxybenzyl)-3-(2-hydroxyethyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (120 mg, 0.30 mmol) obtained in Example (33b) in acetonitrile (3 mL) and a phosphate buffer solution (pH 6.86) (2 mL), 2-azaadamantane-N-oxyl (45.3 mg, 0.030 mmol) and sodium chlorate (32.3 mg, 0.036 mmol) were added, subsequently an aqueous sodium hypochlorite solution (available chlorine concentration: >5%, 2.35 mL, 0.9 mmol) was added under ice cooling, and the mixture was stirred for 3 hours under ice cooling.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium thiosulfate and a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of [(3S)-4-(2,4-dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]acetic acid.\",\n \"To a solution of the crude product of [(3S)-4-(2,4-dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]acetic acid thus obtained in N,N-dimethylformamide (10 mL), dimethylamine hydrochloride (36.3 mg, 0.45 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (114 mg, 0.59 mmol), 1-hydroxybenzotriazole monohydrate (91.0 mg, 0.59 mmol), and triethylamine (0.206 mL, 1.49 mmol) were added, and the mixture was stirred at room temperature for 17 hours.\",\n \"The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (108 mg, yield for 2 steps: 82%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.62 (1H, d, J=2.7 Hz), 9.21 (1H, dd, J=4.9, 2.7 Hz), 7.44-7.36 (1H, m), 6.52-6.45 (2H, m), 5.00-4.90 (2H, m), 4.70-4.56 (2H, m), 4.28 (1H, d, J=12.5 Hz), 3.82 (3H, s), 3.80 (3H, s), 2.85 (3H, s), 2.82 (3H, s), 2.61 (1H, td, J=16.2, 9.4 Hz), 2.39 (1H, dq, J=16.2, 4.4 Hz).\",\n \"(34b) 2-[(3S)-7-Amino-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide The title compound (90.0 mg, yield: 89%) was obtained by production according to the method described in Example (3c) using 2-[(3S)-4-(2,4-dimethoxybenzyl)-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (108 mg, 0.24 mmol) obtained in Example (34a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.14 (1H, t, J=2.9 Hz), 7.90 (1H, t, J=3.5 Hz), 7.40-7.30 (1H, m), 6.50-6.43 (2H, m), 4.93 (1H, t, J=15.3 Hz), 4.70 (1H, dq, J=12.6, 2.5 Hz), 4.55 (1H, dd, J=14.5, 3.9 Hz), 4.52-4.45 (1H, m), 4.08 (1H, dd, J=12.6, 6.8 Hz), 3.91 (3H, s), 3.79 (3H, s), 2.92 (3H, s), 2.85 (3H, s), 2.76-2.64 (1H, m), 2.37 (1H, td, J=10.6, 5.5 Hz).\",\n \"(34c) 2-[(3S)-7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N, N-dimethylacetamide The title compound (40 mg, yield: 30%) was obtained by production according to Example (1d) using 2-[(3S)-7-amino-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (90.0 mg, 0.22 mmol) obtained in Example (34b) and 5-chloro-2-methoxybenzenesulfonyl chloride (57.6 mg, 0.24 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.43 (1H, d, J=2.7 Hz), 8.30 (1H, d, J=2.7 Hz), 7.73 (1H, d, J=2.4 Hz), 7.46 (1H, dd, J=8.9, 2.7 Hz), 7.32-7.24 (1H, m), 7.01 (1H, dd, J=8.9, 2.4 Hz), 6.49-6.42 (2H, m), 4.91 (1H, d, J=14.1 Hz), 4.75 (1H, dd, J=12.7, 5.3 Hz), 4.56-4.46 (2H, m), 4.06 (3H, s), 3.91-3.83 (1H, m), 3.78 (3H, s), 3.78 (3H, s), 2.91 (3H, s), 2.79 (3H, s), 2.58 (1H, dd, J=16.0, 9.4 Hz), 2.31 (1H, dd, J=16.0, 4.7 Hz).\",\n \"(34d) 2-[(3S)-7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide The title compound (12 mg, yield: 40%) was obtained by production according to the method described in Example (9) using 2-[(3S)-7-{[(5-chloro-2-methoxyphenyl)sulfonyl]amino}-4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-3-yl]-N,N-dimethylacetamide (40.0 mg, 0.065 mmol) obtained in Example (34c).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.32 (1H, br s), 8.19 (1H, d, J=2.7 Hz), 8.09 (1H, d, J=2.7 Hz), 7.68-7.65 (2H, m), 7.25 (1H, d, J=8.6 Hz), 4.40-4.28 (2H, m), 3.92-3.83 (4H, m), 3.80-3.74 (1H, m), 2.88 (3H, s), 2.82 (3H, s), 2.79-2.64 (2H, m).\",\n \"MS spectrum (ES/APCI+): 469 (M+H), 471 (M+2+H).\",\n \"(Example 35) 5-Chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (35a) {1-[(2,4-Dimethoxybenzyl)amino]cyclopropyl}methanol The title compound (1.90 g, yield: 91%) was obtained by production according to the method described in Example (8a) using (1-aminocyclopropyl)methanol (0.75 g, 0.24 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.14 (1H, d, J=8.2 Hz), 6.46-6.42 (2H, m), 3.83 (3H, s), 3.79 (3H, s), 3.74 (2H, s), 3.51 (2H, s), 3.48 (1H, s), 0.70-0.68 (2H, m), 0.52-0.49 (2H, m).\",\n \"(35b) 2-Chloro-N-(2,4-dimethoxybenzyl)-N-[1-(hydroxymethyl)cyclopropyl]-5-nitropyridine-3-carboxamide To a suspension of 2-chloro-5-nitropyridine-3-carboxylic acid (1.587 g, 7.83 mmol) in methylene chloride (80 mL), oxalyl chloride (0.84 mL, 9.8 mmol) and N,N-dimethylformamide (0.30 mL, 3.92 mmol) were added at room temperature, and the mixture was stirred at the same temperature as above for 2 hours.\",\n \"The reaction mixture was concentrated under reduced pressure to prepare a crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride.\",\n \"To a solution of {1-[(2,4-dimethoxybenzyl)amino]cyclopropyl}methanol (1.859 g, 7.83 mmol) obtained in Example (35a) and N,N-diisopropylethylamine (2.73 mL, 15.7 mmol) in tetrahydrofuran (60 mL), a solution of the crude product of 2-chloro-5-nitropyridine-3-carboxylic acid chloride in tetrahydrofuran (20 mL) was added under ice cooling, and the reaction mixture was stirred at room temperature for 30 minutes.\",\n \"The reaction mixture was diluted by addition of water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-40/60) to obtain the title compound (2.155 g, yield: 65%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.25 (0.14H, d, J=2.7 Hz), 9.19 (0.86H, d, J=2.7 Hz), 8.47 (0.14H, d, J=2.7 Hz), 7.06 (1H, br d, J=8.2 Hz), 6.43-6.36 (2H, m), 4.04-3.03 (11H, m), 1.28-1.23 (4H, m).\",\n \"(35c) 4′-(2,4-Dimethoxybenzyl)-7′-nitrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one To a solution of 2-chloro-N-(2,4-dimethoxybenzyl)-N-[1-(hydroxymethyl)cyclopropyl]-5-nitropyridine-3-carboxamide (400 mg, 0.95 mmol) obtained in Example (35b) in N,N-dimethylformamide (47 mL), potassium carbonate (393 mg, 2.84 mmol) was added, and the mixture was stirred at room temperature for 22 hours and subsequently stirred at 50° C. for 2 hours and at 70° C. for 2 hours.\",\n \"The reaction mixture was cooled, and insoluble matter was filtered off.\",\n \"The residue was washed with ethyl acetate.\",\n \"The filtrate and the washes were combined.\",\n \"The solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-50/50) to obtain the title compound (238 mg, yield: 65%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.23-9.19 (1H, m), 9.11-9.08 (1H, m), 7.22 (1H, d, J=7.8 Hz), 6.49-6.45 (2H, m), 4.27-4.08 (3H, m), 3.92-3.74 (7H, m), 1.32-1.20 (2H, m), 0.97-0.87 (2H, m).\",\n \"(35d) 7′-Amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one A mixture of 4′-(2,4-dimethoxybenzyl)-7′-nitrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (238 mg, 0.62 mmol) obtained in Example (35c) and 10% palladium carbon (water content: 54.6%, 100 mg) in tetrahydrofuran (30 mL), and methanol (30 mL) was stirred at room temperature for 3 hours at normal pressure under the hydrogen atmosphere.\",\n \"Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.\",\n \"The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (227 mg, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.84 (1H, d, J=2.2 Hz), 7.48 (1H, d, J=2.2 Hz), 7.20 (1H, d, J=8.2 Hz), 6.48-6.43 (2H, m), 4.70 (2H, br s), 3.82 (3H, s), 3.81 (3H, s), 3.69 (2H, s), 3.48 (2H, d, J=3.1 Hz), 0.93 (2H, br s), 0.63 (2H, br s).\",\n \"(35e) 5-Chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide The title compound (80 mg, yield: 56%) was obtained by production according to the method described in Examples (1d) and (9) using 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (124 mg, 0.35 mmol) obtained in Example (35d) and 5-chloro-2-methoxybenzenesulfonyl chloride (92.5 mg, 0.38 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.84 (1H, s), 8.08 (1H, d, J=2.7 Hz), 7.94 (1H, d, J=2.7 Hz), 7.68-7.62 (2H, m), 7.25 (1H, d, J=8.6 Hz), 4.26 (2H, s), 3.87 (3H, s), 0.74 (4H, br s).\",\n \"MS spectrum (ES/APCI+): 410 (M+H), 412 (M+2+H).\",\n \"(Example 36) 5-Fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide The title compound (81 mg, yield for 2 steps: 71%) was obtained by production according to the method described in Examples (1d) and (9) using 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (103 mg, 0.29 mmol) obtained in Example (35d) and 5-fluoro-2-methoxybenzenesulfonyl chloride (71.6 mg, 0.32 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.27 (1H, br s), 8.83 (1H, s), 8.08 (1H, d, J=3.1 Hz), 7.95 (1H, d, J=3.1 Hz), 7.51-7.46 (2H, m), 7.26-7.22 (1H, m), 4.25 (2H, s), 3.86 (3H, s), 0.74 (4H, br s).\",\n \"MS spectrum (ES/APCI+): 394 (M+H).\",\n \"(Example 37) 5-Chloro-2-methoxy-N-(5-oxo-4-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (37a) 7-Nitro-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (324 mg, yield for 2 steps: 39%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (591 mg, 2.92 mmol) and 2-anilinoethanol (400 mg, 2.92 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.32 (1H, d, J=3.1 Hz), 9.28 (1H, d, J=3.1 Hz), 7.50-7.46 (2H, m), 7.39-7.35 (1H, m), 7.33-7.30 (2H, m), 4.87-4.85 (2H, m), 4.15-4.13 (2H, m).\",\n \"(37b) 7-Amino-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (243 mg, yield: 84%) was obtained by production according to the method described in Example (3b) using 7-nitro-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (324 mg, 1.14 mmol) obtained in Example (37a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.93 (1H, d, J=3.1 Hz), 7.60 (1H, d, J=3.1 Hz), 7.46 (2H, t, J=7.6 Hz), 7.37-7.31 (3H, m), 4.58 (2H, t, J=5.1 Hz), 3.96 (2H, t, J=5.1 Hz), 3.69 (2H, br s).\",\n \"(37c) 5-Chloro-2-methoxy-N-(5-oxo-4-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide The title compound (77 mg, yield: 71%) was obtained by production according to Example (1d) using 7-amino-4-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (60 mg, 0.24 mmol) obtained in Example (37b) and 5-chloro-2-methoxybenzenesulfonyl chloride (62 mg, 0.26 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.39 (1H, br s), 8.16 (1H, d, J=2.4 Hz), 7.98 (1H, d, J=2.4 Hz), 7.69-7.67 (2H, m), 7.44 (2H, t, J=7.3 Hz), 7.36 (2H, d, J=7.3 Hz), 7.32-7.25 (2H, m), 4.56 (2H, t, J=4.6 Hz), 3.95 (2H, t, J=4.6 Hz), 3.88 (3H, s).\",\n \"MS spectrum (ES/APCI+): 460 (M+H), 462 (M+2+H).\",\n \"(Example 38) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (38a) 7-Nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (1.24 g, yield: quantitative) was obtained by production according to Example (18c) using 4-(2,4-dimethoxybenzyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (2.00 g, 5.57 mmol) obtained in Example (8c).\",\n \"1H NMR spectrum (CD3OD, 400 MHz) δ: 9.30 (1H, d, J=2.7 Hz), 9.19 (1H, d, J=2.7 Hz), 4.70-4.69 (2H, m), 3.67-3.65 (2H, m).\",\n \"(38b) 7-Nitro-4-(pyridin-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one A mixture of 7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (100 mg, 0.48 mmol) obtained in Example (38a), 2-bromopyridine (90.6 mg, 0.57 mmol), tris(dibenzylideneacetone)dipalladium(0) (87.6 mg, 0.010 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (11.1 mg, 0.019 mmol), and cesium carbonate (0.312 g, 0.96 mmol) in dioxane (10 mL) was heated to reflux for 18 hours in an oil bath.\",\n \"The reaction mixture was cooled.\",\n \"The solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate/methanol=100/0/0-0/100/0-0/85/15) to obtain the title compound (41 mg, yield: 30%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.30 (1H, d, J=2.7 Hz), 9.25 (1H, d, J=2.7 Hz), 8.46-8.44 (1H, m), 8.06 (1H, d, J=8.2 Hz), 7.83-7.79 (1H, m), 7.22-7.19 (1H, m), 4.90 (2H, t, J=4.3 Hz), 4.57 (2H, t, J=4.3 Hz.\",\n \"(38c) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (58 mg, yield for 2 steps: 88%) was obtained by production according to Examples (3b) and (1d) using 7-nitro-4-(pyridin-2-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (41.0 mg, 0.14 mmol) obtained in Example (38b) and 5-chloro-2-methoxybenzenesulfonyl chloride (35.2 mg, 0.15 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.45 (1H, br s), 8.47 (1H, d, J=3.9 Hz), 8.18 (1H, br s), 7.95-7.86 (3H, m), 7.70-7.67 (2H, m), 7.29-7.25 (2H, m), 4.53 (2H, br s), 4.30 (2H, br s), 3.88 (3H, s).\",\n \"MS spectrum (ES/APCI+): 461 (M+H), 463 (M+2+H).\",\n \"(Example 39) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (39a) 7-Nitro-4-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (104 mg, yield: 76%) was obtained by production according to the method described in Example (38b) using 7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (100 mg, 0.48 mmol) obtained in Example (38a) and 3-iodopyridine (118 mg, 0.57 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.34-9.30 (2H, m), 8.62-8.61 (2H, m), 7.74-7.71 (1H, m), 7.44 (1H, dd, J=8.0, 4.9 Hz), 4.89 (2H, t, J=4.1 Hz), 4.18 (2H, t, J=4.1 Hz).\",\n \"(39b) 5-Chloro-2-methoxy-N-[5-oxo-4-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (13 mg, yield for 2 steps: 8%) was obtained by production according to the method described in Examples (3b) and (1d) using 7-nitro-4-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (104 mg, 0.36 mmol) obtained in Example (39a) and 5-chloro-2-methoxybenzenesulfonyl chloride (21.7 mg, 0.09 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.40 (1H, br s), 8.62 (1H, d, J=2.4 Hz), 8.50-8.49 (1H, m), 8.18 (1H, d, J=2.9 Hz), 8.01 (1H, d, J=2.9 Hz), 7.84 (1H, br d, J=8.3 Hz), 7.69-7.67 (2H, m), 7.49 (1H, dd, J=8.1, 4.6 Hz), 7.27-7.25 (1H, m), 4.59 (2H, t, J=4.1 Hz), 4.01 (2H, t, J=4.1 Hz), 3.88 (3H, s).\",\n \"MS spectrum (ES/APCI+): 461 (M+H), 463 (M+2+H).\",\n \"(Example 40) 5-Chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide (40a) 5-Chloro-2-(trifluoromethoxy)benzenesulfonyl chloride To a suspension of 5-chloro-2-(trifluoromethoxy)aniline (5.00 g, 23.6 mmol) and dibenzyl disulfide (4.66 g, 18.9 mmol) in acetonitrile (75 mL), Isoamyl nitrite (3.46 mL, 26.0 mmol) was slowly added at 60° C. in an oil bath, and the mixture was stirred at the same temperature as above for 2 hours.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-95/5) to prepare 2-(benzylsulfanyl)-4-chlorophenyl trifluoromethyl ether (3.86 g, yield: 51%).\",\n \"To a mixture of the obtained 2-(benzylsulfanyl)-4-chlorophenyl trifluoromethyl ether (4.84 g, 15.2 mmol), acetic acid (4.5 mL) and water (3 mL) in acetonitrile (120 mL), 1,3-dichloro-5,5-dimethylhydantoin (5.98 g, 30.4 mmol) was added under ice cooling, and the mixture was stirred at the same temperature as above for 3 hours.\",\n \"The mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate, extracted with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (hexane/ethyl acetate=100/0-85/15) to obtain the title compound (3.64 g, yield: 81%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.09 (1H, d, J=2.3 Hz), 7.75 (1H, dd, J=9.0, 2.7 Hz), 7.50-7.47 (1H, m).\",\n \"(40b) 5-Chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-(trifluoromethoxy)benzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (95.0 mg, 0.267 mmol) obtained in Example (35d) and pyridine (0.432 mL, 5.35 mmol), 5-chloro-2-(trifluoromethoxy)benzenesulfonyl chloride (86.8 mg, 0.294 mmol) in Example (40a) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the title compound (142 mg, yield: 87%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.23 (1H, d, J=2.7 Hz), 7.91 (1H, d, J=2.7 Hz), 7.87 (1H, d, J=2.7 Hz), 7.57 (1H, dd, J=8.8, 2.5 Hz), 7.39-7.35 (1H, m), 7.17 (1H, d, J=8.2 Hz), 6.46-6.44 (2H, m), 4.68 (1H, br s), 3.96 (1H, br s), 3.81 (3H, s), 3.80 (3H, s), 0.93 (2H, br s), 0.69 (2H, br s).\",\n \"(40c) 5-Chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide To a solution of 5-chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-(trifluoromethoxy)benzenesulfonamide (142 mg, 0.231 mmol) obtained in Example (40b) in chloroform (8 mL), anisole (0.0504 mL, 0.463 mmol), trifluoroacetic acid (4 mL, 52 mmol) and trifluoromethanesulfonic acid (0.0609 mL, 0.694 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the title compound (84 mg, yield: 78%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.73 (1H, br s), 8.87 (1H, br s), 8.11 (1H, d, J=2.4 Hz), 7.93-7.86 (3H, m), 7.61 (1H, d, J=8.8 Hz), 4.30 (2H, br s), 0.80 (2H, br s), 0.77 (2H, br s).\",\n \"MS spectrum (ES/APCI+): 464 (M+H), 466 (M+2+H).\",\n \"(Example 41) 5-Fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide (41a) 5-Fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride The title compound (0.82 g, yield for 2 steps: 29%) was obtained by production according to the method described in Example (40a) using 5-fluoro-2-(trifluoromethoxy)aniline (2.00 g, 10.3 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ:7.84 (1H, dd, J=6.8, 2.9 Hz), 7.56-7.47 (2H, m).\",\n \"(41b) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (100 mg, 0.281 mmol) obtained in Example (35d) and pyridine (0.453 mL, 5.63 mmol), 5-fluoro-2-(trifluoromethoxy)benzenesulfonyl chloride (94.1 mg, 0.338 mmol) in Example (41a) was added at room temperature, and the mixture was stirred at 80° C. for 5 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (156 mg, yield: 93%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.27 (1H, d, J=2.7 Hz), 7.94 (1H, d, J=2.7 Hz), 7.63 (1H, dd, J=7.4, 3.1 Hz), 7.32-7.28 (2H, m), 7.16 (1H, d, J=8.2 Hz), 6.46-6.43 (2H, m), 4.69 (1H, br s), 3.95 (2H, br s), 3.81 (3H, s), 3.80 (3H, s), 0.92 (2H, br s), 0.69 (2H, br s).\",\n \"(41c) 5-Fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide To a suspension of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-5-fluoro-2-(trifluoromethoxy)benzenesulfonamide (156 mg, 0.261 mmol) obtained in Example (41b) in chloroform (5 mL), anisole (84.7 mg, 0.783 mmol), trifluoroacetic acid (0.40 mL, 5.2 mmol) and trifluoromethanesulfonic acid (0.0687 mL, 0.783 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hours.\",\n \"To the mixture, an additional trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for further 2 hours.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with chloroform.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-95/5) to obtain the title compound (97 mg, yield: 83%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.75 (1H, br s), 8.88 (1H, br s), 8.11 (1H, d, J=2.7 Hz), 7.92 (1H, d, J=2.7 Hz), 7.75-7.66 (3H, m), 4.30 (2H, br s), 0.82-0.75 (4H, m).\",\n \"MS spectrum (ES/APCI+): 448 (M+H).\",\n \"(Example 42) 2-Ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (42a) 5-Fluoro-2-ethoxybenzenesulfonyl chloride The title compound (3.16 g, yield: 36%) was obtained by production according to the method described in Example (13a) using 1-ethoxy-4-fluorobenzene (5.11 g, 36.5 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.70 (1H, dd, J=7.4, 3.1 Hz), 7.41-7.36 (1H, m), 7.07 (1H, dd, J=9.4, 3.9 Hz), 4.26 (2H, q, J=6.8 Hz), 1.55 (3H, t, J=6.8 Hz).\",\n \"(42b) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (100 mg, 0.281 mmol) obtained in Example (35d) and pyridine (0.453 mL, 5.63 mmol), 5-Fluoro-2-ethoxybenzenesulfonyl chloride (73.9 mg, 0.310 mmol) obtained in Example (42a) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (146 mg, yield: 93%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.20 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=7.4, 3.1 Hz), 7.23-7.14 (2H, m), 7.02-6.95 (2H, m), 6.46-6.43 (2H, m), 4.66 (1H, br s), 4.29 (2H, q, J=7.0 Hz), 3.92 (1H, br s), 3.80 (3H, s), 3.79 (3H, s), 1.58 (3H, t, J=7.0 Hz), 0.87 (2H, br s), 0.63 (2H, br s).\",\n \"(42c) 2-Ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a suspension of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide (146 mg, 0.262 mmol) obtained in Example (42b) in chloroform (4 mL), anisole (0.0571 mL, 0.524 mmol), trifluoroacetic acid (2 mL, 26.1 mmol) and trifluoromethanesulfonic acid (0.0689 mL, 0.786 mmol) were added at room temperature, and the mixture was stirred at room temperature for 3 hours.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with chloroform.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain a crude solid.\",\n \"To a suspension of the crude solid in ethanol (3 mL), a 1 N aqueous sodium hydroxide solution (0.40 mL) was added and the mixture was stirred at room temperature until dissolved.\",\n \"The mixture was concentrated under reduced pressure, diluted by addition of water, and then filtered.\",\n \"A 1 N hydrochloric acid (0.40 mL) was added to the filtrate, the precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (95 mg, yield: 89%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.15 (1H, s), 8.83 (1H, s), 8.09 (1H, d, J=2.7 Hz), 7.95 (1H, d, J=2.7 Hz), 7.52-7.44 (2H, m), 7.24 (1H, dd, J=9.0, 4.3 Hz), 4.26 (br 2H, s), 4.16 (2H, q, J=7.0 Hz), 1.26 (3H, t, J=7.0 Hz), 0.77-0.71 (4H, m).\",\n \"MS spectrum (ES/APCI+): 408 (M+H).\",\n \"(Example 43) 2,5-Dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (43a) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2,5-dimethoxybenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (90.0 mg, 0.253 mmol) obtained in Example (35d) and pyridine (0.408 mL, 5.06 mmol), 2,5-dimethoxybenzenesulfonyl chloride (65.9 mg, 0.279 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 3 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate=100/0-0/100) to obtain the title compound (143 mg, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.22 (1H, d, J=2.7 Hz), 7.88 (1H, br d, J=2.7 Hz), 7.37-7.28 (2H, m), 7.15 (1H, br d, J=8.6 Hz), 7.04 (1H, dd, J=9.0, 3.1 Hz), 6.97 (1H, d, J=9.0 Hz), 6.45-6.43 (2H, m), 4.66 (2H, br s), 3.99 (3H, s), 3.91 (2H, br s), 3.80 (3H, s), 3.79 (3H, s), 3.73 (3H, s), 0.86 (2H, br s), 0.61 (2H, br s).\",\n \"(43b) 2,5-Dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a suspension of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1, 4]oxazepin]-7′-yl]-2,5-dimethoxybenzenesulfonamide (0.143 mg, 0.257 mmol) obtained in Example (43a) in chloroform (4 mL), anisole (0.0561 mL, 0.515 mmol), trifluoroacetic acid (2 mL, 26 mmol) and trifluoromethanesulfonic acid (0.0678 mL, 0.772 mmol) were added under ice cooling, the mixture was stirred at the same temperature as above for 3 hours and subsequently stirred at room temperature for 2 hours.\",\n \"The reaction mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate under ice cooling, followed by extraction with chloroform.\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-90/10) to obtain the crude solid.\",\n \"To a suspension of the crude solid in ethanol (3 mL), a 1 N aqueous sodium hydroxide solution (1 mL) was added and the mixture was stirred at room temperature until dissolved.\",\n \"The mixture was concentrated under reduce pressure, diluted by addition of ethyl acetate and water.\",\n \"Most of the organic solvent was distillated off under reduce pressure, and then filtered.\",\n \"A 1 N hydrochloric acid (1 mL) was added the filtrate, the precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (55 mg, yield: 53%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.17 (1H, br s), 8.83 (1H, br s), 8.07 (1H, d, J=2.7 Hz), 7.95 (1H, d, J=2.7 Hz), 7.20-7.15 (3H, m), 4.24 (2H, br s), 3.81 (3H, s), 3.71 (3H, s), 0.74 (4H, br s).\",\n \"MS spectrum (ES/APCI+): 406 (M+H).\",\n \"(Example 44) 5-Chloro-2-methoxy-N-[5-oxo-3-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (44a) 2-[(2,4-Dimethoxybenzyl)amino]-2-(pyridin-3-yl)ethanol The title compound (approximately 77% content, 0.9217 g, yield: 69%) as a mixture containing 2.5-dimethoxybenzylalcohol was obtained by production according to the method of Example (8a) using 2,4-dimethoxybenzaldehyde (627.6 mg, 3.78 mmol) and 2-amino-2-(pyridin-3-yl)ethanol (495.3 mg, 3.59 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.54-8.51 (1.32H, m), 7.70-7.68 (0.66H, m), 7.29-7.26 (0.66H, m), 7.17 (0.34H, d, J=8.2 Hz), 7.03-7.01 (0.66H, d, J=7.8 Hz), 6.48-6.40 (2H, m), 4.61 (0.68H, s), 3.85-3.79 (6.66H, m), 3.76-3.70 (1.32H, m), 3.56-3.52 (1.32H, m).\",\n \"(44b) 4-(2,4-Dimethoxybenzyl)-7-nitro-3-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (283.2 mg, yield for 2 steps: 27%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (501.1 mg, 2.47 mmol) and 2-[(2,4-dimethoxybenzyl)amino]-2-(pyridin-3-yl)ethanol (approximately 77% content, 0.912 g, 2.44 mmol) obtained in Example (44a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.66 (1H, d, J=2.7 Hz), 9.10 (1H, d, J=2.7 Hz), 8.51 (1H, dd, J=4.7, 1.6 Hz), 8.42 (1H, br d, J=2.3 Hz), 7.42 (1H, d, J=8.2 Hz), 7.35-7.32 (1H, m), 7.21-7.17 (1H, m), 6.49 (1H, dd, J=8.2, 2.3 Hz), 6.40 (1H, d, J=2.3 Hz), 5.19 (1H, d, J=5.3 Hz), 5.10 (1H, d, J=14.5 Hz), 5.02 (1H, dd, J=13.1, 5.3 Hz), 4.56 (1H, d, J=13.3 Hz), 4.50 (1H, d, J=14.5 Hz), 3.80 (3H, s), 3.72 (3H, s).\",\n \"(44c) 7-Amino-4-(2,4-dimethoxybenzyl)-3-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (270.0 mg, yield: quantitative) was obtained by production according to the method of Example (8d) using 4-(2,4-dimethoxybenzyl)-7-nitro-3-(pyridin-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (287.5 mg, 0.659 mmol) obtained in example (44b).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.48 (1H, dd, J=4.9, 1.6 Hz), 8.40 (1H, d, J=2.3 Hz), 8.20 (1H, d, J=2.7 Hz), 7.81 (1H, d, J=2.7 Hz), 7.39-7.35 (2H, m), 7.17 (1H, dd, J=8.0, 4.9 Hz), 6.47 (1H, dd, J=8.2, 2.3 Hz), 6.39 (1H, d, J=2.3 Hz), 5.10 (1H, d, J=14.5 Hz), 4.97 (1H, d, J=5.3 Hz), 4.75 (1H, dd, J=13.1, 5.3 Hz), 4.38-4.34 (2H, m), 3.80 (3H, s), 3.72 (3H, s), 3.60 (2H, br s).\",\n \"(44d) 5-Chloro-2-methoxy-N-[5-oxo-3-(pyridin-3-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (191.0 mg, yield for 2 steps: 64%) was obtained by production according to the method described in Examples (1d) and (9) using 7-amino-4-(2,4-dimethoxybenzyl)-3-(pyridine-3-yl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (267.5 mg, 0.66 mmol) obtained in Example (44c) and 5-chloro-2-methoxybenzenesulfonyl chloride (166.7 mg, 0.69 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.33 (1H, br s), 8.93 (1H, br d, J=5.5 Hz), 8.48-8.46 (2H, m), 8.35 (1H, d, J=2.7 Hz), 8.04 (1H, d, J=2.7 Hz), 7.70-7.69 (2H, m), 7.60-7.57 (1H, m), 7.33 (1H, dd, J=7.8, 4.7 Hz), 7.26 (1H, d, J=9.0 Hz), 4.93 (1H, t, J=5.5 Hz), 4.78 (1H, dd, J=12.9, 5.5 Hz), 4.51 (1H, br d, J=12.9 Hz).\",\n \"MS spectrum (ES/APCI+): 461 (M+H), 463 (M+2+H).\",\n \"(Example 45) 7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepine-3-carboxamide (45a) O-Benzyl-N-[(benzyloxy)carbonyl]serine To a suspension of O-benzylserine (5.00 g, 25.6 mmol) in 1,4-dioxane (50 mL), a 2 N aqueous sodium hydroxide solution (26.8 mL, 53.8 mmol) was added, and the mixture was stirred at room temperature for 10 minutes.\",\n \"Subsequently, to the mixture, benzyl chloroformate (3.82 mL, 26.9 mmol) was added, and the mixture was stirred at room temperature for 3 hours.\",\n \"The reaction mixture was concentrated under reduce pressure, and diluted by addition of a 5 N hydrochloric acid (10.8 mL, 54.2 mmol), followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"To the residue, n-hexane (20 mL) and ethyl acetate (1 mL) were added, and the precipitated solid was collected by filtration, washed with n-hexane, and then dried to obtain the title compound (7.24 g, yield: 86%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.37-7.27 (10H, m), 5.64 (1H, br d, J=8.2 Hz), 5.15 (1H, br d, J=12.1 Hz), 5.11 (1H, br d, J=12.1 Hz), 4.57-4.53 (3H, m), 3.96 (1H, br dd, J=9.4, 3.1 Hz), 3.72 (1H, br dd, J=9.4, 3.3 Hz).\",\n \"(45b) Benzyl [3-(benzyloxy)-1-(dimethylamino)-1-oxopropan-2-yl]carbamate To a solution of O-benzyl-N-[(benzyloxy)carbonyl]serine (1.50 g, 4.55 mmol) obtained in example (45a), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.06 g, 5.53 mmol) and 1-hydroxybenzotriazole (0.68 g, 5.0 mmol) in methylene chloride (22 mL), dimethylamine in tetrahydrofuran (2.0 mol/L, 5.5 mL, 11 mmol) was added under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes and subsequently at room temperature for 1 hour.\",\n \"The mixture was diluted by addition of a 1 N hydrochloric acid (50 mL), followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=2/1-1/0) to obtain the title compound (1.47 g, yield: 91%) 1H NMR spectrum (CDCl3, 400 MHz) δ: 7.35-7.26 (10H, m), 5.75 (1H, d, J=8.2 Hz), 5.10 (2H, br s), 4.95-4.90 (1H, m), 4.54 (1H, d, J=12.1 Hz), 4.49 (1H, d, J=12.1 Hz), 3.66 (1H, dd, J=9.4, 5.5 Hz), 3.59 (1H, dd, J=9.4, 7.0 Hz), 3.05 (3H, s), 2.97 (3H, s).\",\n \"(45c) N,N-Dimethylserinamide A mixture of benzyl [3-(benzyloxy)-1-(dimethylamino)-1-oxopropan-2-yl]carbamate (1.46 g, 4.10 mmol) obtained in Example (45b) and 10% palladium carbon (water content: 54.6%, 0.28 g) in ethanol (41 mL) was stirred at room temperature for 1 hour at normal pressure under the hydrogen atmosphere.\",\n \"Subsequently the mixture was stirred at 50° C. for 24 hours in an oil bath at normal pressure under the hydrogen atmosphere.\",\n \"Hydrogen in the reaction container was replaced with nitrogen, and then, the reaction mixture was filtered through pad of Celite 545®.\",\n \"The solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (approximately 70% content, 0.60 g, yield: 78%) as a mixture containing O-benzyl-N,N-dimethylserinamide 1H NMR spectrum (CDCl3, 400 MHz) δ: 7.36-7.29 (1H, m), 4.53 (0.4H, br s), 3.98 (0.2H, dd, J=7.0, 5.9 Hz), 3.77 (0.8H, dd, J=7.0, 4.7 Hz), 3.66 (0.8H, dd, J=10.9, 4.7 Hz), 3.57 (0.2H, dd, J=9.2, 5.9 Hz), 3.50-3.44 (1H, m), 3.10 (2.4H, s), 3.04 (0.6H, s), 2.98 (2.4H, s), 2.97 (0.6H, s).\",\n \"(45d) N2-(2,4-Dimethoxybenzyl)-N,N-dimethylserinamide The title compound (0.76 g, yield: 85%) was obtained by production according to the method of Example (8a) using 2,4-dimethoxybenzaldehyde (0.68 g, 4.1 mmol) and N,N-dimethylserinamide (approximately 70% content, 0.60 g, 3.2 mmol) obtained in Example (45c).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.14 (1H, d, J=7.8 Hz), 6.44-6.41 (2H, m), 3.82 (3H, s), 3.80 (3H, s), 3.73-3.63 (3H, m) 3.59 (1H, dd, J=7.8, 4.7 Hz), 3.37 (1H, dd, J=10.2, 7.8 Hz), 2.99 (3H, s), 2.89 (3H, s).\",\n \"(45e) 4-(2,4-Dimethoxybenzyl)-N,N-dimethyl-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-3-carboxamide The title compound (0.55 g, yield for 2 steps: 46%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (0.55 g, 2.7 mmol) and N2-(2,4-dimethoxybenzyl)-N,N-dimethylserinamide (0.76 g, 2.7 mmol) obtained in example (45d).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.73 (1H, d, J=2.7 Hz), 9.12 (1H, d, J=2.7 Hz), 7.37 (1H, d, J=8.2 Hz), 6.51-6.47 (2H, m), 5.04 (1H, d, J=14.5 Hz), 4.95-4.89 (2H, m), 4.43 (1H, d, J=14.5 Hz), 4.34 (1H, d, J=12.1 Hz), 3.83 (3H, s), 3.81 (3H, s), 3.04 (3H, s), 2.88 (3H, s).\",\n \"(45f) 7-Amino-4-(2,4-dimethoxybenzyl)-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-3-carboxamide The title compound (342.7 mg, yield: 67%) was obtained by production according to the method of Example (8d) using 4-(2,4-dimethoxybenzyl)-N,N-dimethyl-7-nitro-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-3-carboxamide (552.0 mg, 1.24 mmol) obtained in Example (45e).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.19 (1H, d, J=2.7 Hz), 7.79 (1H, d, J=2.7 Hz), 7.35 (1H, d, J=8.2 Hz), 6.49-6.45 (2H, m), 5.09 (1H, d, J=14.5 Hz), 4.79-4.73 (2H, m), 4.31 (1H, d, J=14.5 Hz), 4.18-4.13 (1H, m), 3.81 (3H, s), 3.81 (3H, s), 3.55 (1H, br d, J=9.4 Hz), 3.00 (3H, s), 2.90 (3H, s).\",\n \"(45g) 7-{[(5-Chloro-2-methoxyphenyl)sulfonyl]amino}-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepine-3-carboxamide The title compound (261.1 mg, yield for 2 steps: 69%) was obtained by production according to the method described in Examples (1d) and (9) using 7-amino-4-(2,4-dimethoxybenzyl)-N,N-dimethyl-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepine-3-carboxamide (340.2 mg, 0.82 mmol) obtained in Example (45f) and 5-Chloro-2-methoxybenzenesulfonyl chloride (207.3 mg, 0.86 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.40 (1H, d, J=2.7 Hz), 8.14 (1H, d, J=2.7 Hz), 7.74 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=9.0, 2.7 Hz), 7.34 (1H, br s), 7.12 (1H, br s), 7.01 (1H, d, J=9.0 Hz), 4.72 (1H, br d, J=12.5 Hz), 4.56 (1H, br dd, J=6.6, 3.5 Hz), 4.27 (1H, dd, J=12.5, 6.6 Hz), 4.08 (3H, s), 3.11 (3H, s), 3.05 (3H, s).\",\n \"MS spectrum (ES/APCI+): 455 (M+H), 457 (M+2+H).\",\n \"Example 46 5-chloro-2-methoxy-N-[3-(morpholin-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide (46a) 2-[(2,4-Dimethoxybenzyl)amino]-3-hydroxy-1-(morpholin-4-yl)propan-1-one The title compound (1.39 g, yield for 3 steps: 88%) was obtained by production according to the method described in Examples (45b), (45c) and (8a) using O-benzyl-N-[(benzyloxy)carbonyl]serine (1.50 g, 4.55 mmol) obtained in example (45a), morpholine (0.96 mL, 11 mmol) and 2,4-dimethoxybenzaldehyde (0.71 g, 4.3 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 7.11 (1H, d, J=8.2 Hz), 6.44-6.41 (2H, m), 3.82 (3H, s), 3.80 (3H, s), 3.75 (1H, d, J=12.9 Hz), 3.68-3.51 (9H, m), 3.44-3.39 (3H, m).\",\n \"(46b) 4-(2,4-Dimethoxybenzyl)-3-(morpholin-4-ylcarbonyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one The title compound (0.87 g, yield for 2 steps: 45%) was obtained by production according to the method described in Examples (1a) and (35c) using 2-chloro-5-nitropyridine-3-carboxylic acid (0.85 g, 4.2 mmol) and 2-[(2,4-dimethoxybenzyl)amino]-3-hydroxy-1-(morpholin-4-yl)propan-1-one (1.40 g, 4.3 mmol) obtained in Example (46a).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 9.75 (1H, d, J=2.7 Hz), 9.13 (1H, d, J=2.7 Hz), 7.33 (1H, d, J=8.2 Hz), 6.51-6.47 (2H, m), 4.99 (1H, d, J=14.1 Hz), 4.86-4.79 (2H, m), 4.53 (1H, d, J=14.1 Hz), 4.36 (1H, d, J=12.9 Hz), 3.83 (3H, s), 3.81 (3H, s), 3.74-3.29 (8H, m).\",\n \"(46c) 5-Chloro-2-methoxy-N-[3-(morpholin-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]benzenesulfonamide The title compound (255.5 mg, yield for 3 steps: 28%) was obtained by production according to the method described in Examples (8d), (1d) and (9) using 4-(2,4-dimethoxybenzyl)-3-(morpholin-4-ylcarbonyl)-7-nitro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (0.87 g, 1.8 mmol) obtained in Example (46b) and 5-chloro-2-methoxybenzenesulfonyl chloride (0.32 g, 1.3 mmol).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 10.28 (1H, br s), 8.36 (1H, br d, J=5.5 Hz), 8.32 (1H, d, J=2.7 Hz), 8.03 (1H, d, J=2.7 Hz), 7.68-7.65 (2H, m), 7.26 (1H, d, J=8.6 Hz), 4.76 (1H, t, J=5.5 Hz), 4.62 (1H, dd, J=12.9, 5.5 Hz), 4.33 (1H, d, J=12.5 Hz), 3.88 (3H, s), 3.60-3.37 (8H, m).\",\n \"MS spectrum (ES/APCI+): 497 (M+H), 499 (M+2+H).\",\n \"(Example 47) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide (potassium salt of Example 9) (47a) 5-Chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (1.31 g, 3.98 mmol) obtained in Example (8d) and pyridine (20 mL, 249 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (1.035 g, 4.29 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 2.5 hours in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was purified in an automatic chromatography apparatus (ethyl acetate/methanol=100/0-85/15) to obtain the title compound (2.17 g, yield: quantitative).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.24 (1H, d, J=3.0 Hz), 8.07 (1H, d, J=3.0 Hz), 7.74 (1H, d, J=2.4 Hz), 7.48 (1H, dd, J=8.8, 2.7 Hz), 7.30-7.22 (2H, m), 7.01 (1H, d, J=9.1 Hz), 6.49-6.46 (2H, m), 4.70 (2H, s), 4.32 (2H, t, J=4.6 Hz), 4.09 (3H, s), 3.81-3.80 (6H, m), 3.60 (2H, t, J=4.6 Hz).\",\n \"(47b) 5-Chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of 5-chloro-N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (2.17 g, 4.06 mmol) obtained in Example (47a) in chloroform (30 mL), anisole (0.88 mL, 8.1 mmol), trifluoroacetic acid (15 mL, 195 mmol) and trifluoromethanesulfonic acid (0.73 mL, 8.3 mmol) were added at room temperature, and the mixture was stirred at room temperature for 1 hour.\",\n \"The reaction mixture was concentrated under reduced pressure, and the concentrated mixture was diluted by addition of chloroform and a saturated aqueous solution of sodium bicarbonate.\",\n \"The precipitated solid was collected by filtration.\",\n \"An organic layer of the filtrate was separated, and dried over anhydrous sodium sulfate.\",\n \"After filtration, the solvent was distilled off under reduced pressure.\",\n \"The residue was combined with the above precipitated solid, diisopropyl ether was added thereto, and the suspension was stirred at room temperature for 1 hour.\",\n \"The precipitated solid was collected by filtration, and then dried to obtain the title compound (1.2921 g, yield: 83%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.53 (1H, br t, J=5.2 Hz), 8.11-8.08 (2H, m), 7.69-7.64 (2H, m), 7.26 (1H, d, J=8.5 Hz), 4.37-4.35 (2H, m), 3.88 (3H, s), 3.38-3.34 (2H, m).\",\n \"(47c) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide To a suspension of 5-chloro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (1.0921 g, 2.845 mmol) obtained in Example (47b) in ethanol (12 mL), a solution of 0.5 N potassium hydroxide in ethanol (5.68 mL, 2.85 mmol) was added at room temperature, and the mixture was stirred at room temperature for 1 hour.\",\n \"The precipitated solid was collected by filtration, washed with ethanol and then dried to obtain the title compound (1.1065 g, yield: 92%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.19 (1H, br t, J=5.2 Hz), 7.70 (1H, br t, J=2.4 Hz), 7.65-7.61 (2H, m), 7.35-7.32 (1H, m), 6.99 (1H, d, J=9.1 Hz), 4.18 (2H, t, J=5.2 Hz), 3.70-3.62 (3H, m), 3.22 (2H, q, J=5.2 Hz).\",\n \"(Example 48) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide (potassium salt of Example 10) (48a) N-[4-(2,4-Dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide To a mixture of 7-amino-4-(2,4-dimethoxybenzyl)-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (3.83 g, 11.2 mmol) obtained in Example (8d) and pyridine (18.1 mL, 223 mmol), 5-fluoro-2-methoxybenzenesulfonyl chloride (2.76 g, 12.3 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 1 hour in an oil bath.\",\n \"The reaction mixture was cooled to room temperature, diluted with water (90 mL) to precipitate a solid, and the suspension was stirred at room temperature for 1 hour.\",\n \"The precipitated solid was collected by filtration, and washed with water to obtain the crude solid.\",\n \"A suspension of the crude solid in ethanol (60 mL) was stirred at 80° C. for 1 hour in an oil bath.\",\n \"After cooling, the suspension was stirred in an ice water bath for 30 minutes.\",\n \"The precipitated solid was collected by filtration, washed with cold ethanol, and then dried to obtain the title compound (4.87 g, yield: 84%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.34 (1H, br s), 8.09 (1H, d, J=2.7 Hz), 7.97 (1H, t, J=2.7 Hz), 7.52-7.47 (2H, m), 7.26-7.23 (1H, m), 7.09 (1H, d, J=8.2 Hz), 6.58 (1H, d, J=2.7 Hz), 6.49 (1H, dd, J=8.2, 2.7 Hz), 4.57 (2H, s), 4.28 (2H, br t, J=4.7 Hz), 3.86 (3H, s), 3.77 (3H, s), 3.75 (3H, s), 3.53 (2H, br t, J=4.7 Hz).\",\n \"(48b) 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide To a suspension of N-[4-(2,4-dimethoxybenzyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-5-fluoro-2-methoxybenzenesulfonamide (4.86 g, 9.39 mmol) obtained in Example (48a) and anisole (2.04 mL, 18.8 mmol) in chloroform (45 mL), trifluoroacetic acid (14.4 mL, 188 mmol) and trifluoromethanesulfonic acid (1.65 mL, 18.8 mmol) were added at room temperature, and the mixture was stirred at room temperature for 30 minutes.\",\n \"The reaction mixture was carefully poured into a suspension of sodium bicarbonate (17.4 g, 207 mmol) in water (90 mL) at room temperature, and the mixture was stirred at room temperature for 10 minutes.\",\n \"Most of the organic solvents were distilled off under reduced pressure, the concentrated mixture was diluted by addition of ethyl acetate (90 mL), a precipitated solid was collected by filtration, and washed with water and ethyl acetate to obtain the crude solid.\",\n \"To a suspension of the crude solid in ethanol (50 mL), a 1 N aqueous solution of potassium hydroxide (10.3 mL, 10.3 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 minutes.\",\n \"The reaction mixture was filtered, and the residue on the filter paper was washed with water and ethanol.\",\n \"The filtrate and washings were combined, a 1 N hydrochloric acid (10.3 mL, 10.3 mmol) was added thereto, and the suspension was stirred in an ice water bath for 20 minutes.\",\n \"The precipitated solid was collected by filtration, washed with cold ethanol, and then dried to obtain the slightly crude solid.\",\n \"To a suspension of the slightly crude solid in ethanol (50 mL), a 1 N aqueous solution of potassium hydroxide (8.8 mL, 8.8 mmol) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes.\",\n \"A 1 N hydrochloric acid (8.8 mL, 8.8 mmol) was added thereto, and the suspension was stirred at room temperature for 30 minutes.\",\n \"The precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (2.16 g, yield: 63%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.28 (1H, br s), 8.52 (1H, br t, J=4.9 Hz), 8.11-8.08 (2H, m), 7.51-7.46 (2H, m), 7.26-7.23 (1H, m), 4.36 (2H, t, J=4.3 Hz), 3.86 (3H, s), 3.40-3.35 (2H, m).\",\n \"(48c) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide To a suspension of 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (1.950 g, 5.308 mmol) obtained in example (48b) in a mixed solvent of ethanol (53.5 mL) and water (0.478 mL), a solution of 0.5 N potassium hydroxide in ethanol (11.15 mL, 5.574 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours.\",\n \"The precipitated solid was collected by filtration, washed with ethanol and then dried to obtain the title compound (2.200 g, yield: quantitative).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.19 (1H, br t, J=5.2 Hz), 7.72 (1H, d, J=2.7 Hz), 7.63 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.16-7.11 (1H, m), 6.98 (1H, dd, J=9.0, 4.3 Hz), 4.18 (2H, t, J=5.2 Hz), 3.65 (3H, s), 3.23 (2H, q, J=5.2 Hz).\",\n \"(Example 49) Sodium [(5-fluoro-2-methoxyphenyl)sulfonyl](5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1, 4]oxazepin-7-yl)azanide (sodium salt of Example 10) To a suspension of 5-Fluoro-2-methoxy-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)benzenesulfonamide (101.9 mg, 0.277 mmol) obtained in example (48b) in ethanol (2.7 mL), a 2 N aqueous solution of sodium hydroxide (0.138 mL, 0.277 mmol) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes.\",\n \"The precipitated solid was collected by filtration, washed with ethanol and then dried to obtain the title compound (98.4 mg, yield: 91%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.20 (1H, br t, J=5.1 Hz), 7.71 (1H, d, J=2.7 Hz), 7.62 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.16-7.11 (1H, m), 6.97 (1H, dd, J=9.0, 4.3 Hz), 4.17 (2H, t, J=5.1 Hz), 3.66 (3H, s), 3.22 (2H, q, J=5.1 Hz).\",\n \"(Example 50) Potassium {[5-chloro-2-(trifluoromethoxy)phenyl]sulfonyl}(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)azanide (potassium salt of Example 13) The title compound (85.2 mg, yield: 78%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-(5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl)-2-(trifluoromethoxy)benzenesulfonamide (100 mg, 0.228 mmol) obtained in example (13c) and a solution of 0.5 N potassium hydroxide in ethanol (0.478 mL, 0.240 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.22 (1H, br t, J=5.2 Hz), 7.78-7.73 (2H, m), 7.63-7.62 (1H, m), 7.53-7.51 (1H, m), 7.36-7.33 (1H, m), 4.19 (2H, t, J=5.2 Hz), 3.23 (2H, q, J=5.2 Hz).\",\n \"(Example 51) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl][(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 27) The title compound (124.1 mg, yield: 94%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (121.3 mg, 0.293 mmol) obtained in Example (27f) and a solution of 0.5 N potassium hydroxide in ethanol (0.962 mL, 0.482 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.93 (1H, br s), 7.77 (1H, d, J=2.7 Hz), 7.70 (1H, d, J=2.7 Hz), 7.64 (1H, d, J=2.7 Hz), 7.34 (1H, dd, J=8.6, 2.7 Hz), 6.99 (1H, d, J=8.6 Hz), 4.92 (1H, br t, J=5.7 Hz), 4.20-4.12 (2H, m), 3.66 (3H, s), 3.46-3.41 (3H, m).\",\n \"(Example 52) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl][(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 28) The title compound (78.7 mg, yield: 84%) was obtained by production according to the method described in Examples 47c using 5-fluoro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (75.5 mg, 0.190 mmol) obtained in Example (28b) and a solution of 0.5 N potassium hydroxide in ethanol (0.386 mL, 0.194 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.92 (1H, br s), 7.77 (1H, br s), 7.71 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.16-7.11 (1H, m), 6.97 (1H, dd, J=9.0, 4.3 Hz), 4.91 (1H, t, J=5.5 Hz), 4.20-4.12 (2H, m), 3.65 (3H, s), 3.46-3.40 (3H, m).\",\n \"(Example 53) Potassium [(5-bromo-2-methoxyphenyl)sulfonyl][(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 29) The title compound (92.7 mg, yield: 82%) was obtained by production according to the method described in Example (47c) using 5-bromo-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-methoxybenzenesulfonamide (104.4 mg, 0.228 mmol) obtained in Example (29b) and a solution of 0.5 N potassium hydroxide in ethanol (0.451 mL, 0.228 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.93 (1H, br d, J=3.5 Hz), 7.78-7.75 (2H, m), 7.68 (1H, d, J=2.7 Hz), 7.44 (1H, dd, J=9.0, 2.7 Hz), 6.93 (1H, d, J=9.0 Hz), 4.92 (1H, t, J=5.5 Hz), 4.20-4.14 (2H, m), 3.63 (3H, s), 3.46-3.41 (3H, m).\",\n \"(Example 54) Potassium {[5-chloro-2-(trifluoromethoxy)phenyl]sulfonyl}[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]azanide (potassium salt of Example 31) The title compound (44 mg, yield: 58%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-[(3S)-3-(hydroxymethyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl]-2-(trifluoromethoxy)benzenesulfonamide (70 mg, 0.15 mmol) obtained in Example (31b) and a solution of 0.5 N potassium hydroxide in ethanol (0.31 mL, 0.16 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 7.96 (1H, br d, J=3.5 Hz), 7.78 (1H, d, J=2.7 Hz), 7.77 (1H, d, J=2.7 Hz), 7.72 (1H, d, J=2.7 Hz), 7.51 (1H, dd, J=8.6, 2.7 Hz), 7.34-7.32 (1H, m), 4.95-4.92 (1H, m), 4.21-4.14 (2H, m), 3.43-3.39 (3H, m).\",\n \"(Example 55) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 35) (55a) 5-Chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1, 4]oxazepin]-7′-yl]-2-methoxybenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (0.9040 g, 2.54 mmol) obtained in Example (35d) and pyridine (4.1 mL, 51 mmol), 5-chloro-2-methoxybenzenesulfonyl chloride (0.6450 g, 2.68 mmol) was added at room temperature, and the mixture was stirred at 80° C. for 20 minutes in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was diluted with water, followed by extraction with ethyl acetate.\",\n \"The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and anhydrous magnesium sulfate and charcoal were added thereto.\",\n \"After filtration through pad of Celite 545®, the solvent was distilled off under reduced pressure.\",\n \"To the residue, diisopropyl ether (7 mL) and ethyl acetate (7 mL) were added to precipitate a solid.\",\n \"The suspension was stirred at room temperature for 30 minutes.\",\n \"The precipitated solid was collected by filtration, washed with diisopropyl ether, and then dried to obtain the title compound (1.3007 g, yield: 92%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.20 (1H, d, J=2.7 Hz), 7.84 (1H, d, J=2.7 Hz), 7.73 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=9.0, 2.7 Hz), 7.16-7.14 (1H, m), 7.02-6.99 (2H, m), 6.46-6.43 (2H, m), 4.66 (2H, br s), 4.06 (3H, s), 3.93 (2H, br s), 3.81 (3H, s), 3.79 (3H, s), 0.88 (2H, br s), 0.64 (2H, br s).\",\n \"(55b) 5-Chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a mixture of 5-chloro-N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-methoxybenzenesulfonamide (1.2938 g, 2.31 mmol) obtained in Example (55a) and anisole (0.51 mL, 4.7 mmol) in chloroform (11.5 mL), trifluoroacetic acid (3.60 mL, 47.0 mmol) and trifluoromethanesulfonic acid (0.41 mL, 4.7 mmol) were added under ice cooling, and the mixture was stirred at the same temperature as above for 3 hours and subsequently stirred at room temperature for 5 hours.\",\n \"The reaction mixture was carefully poured into a suspension of sodium bicarbonate (3.88 g, 46.2 mmol) in water (11.5 mL) at room temperature, and the mixture was stirred at room temperature for 1 hour.\",\n \"Most of the organic solvents were distilled off under reduced pressure, the concentrated mixture was diluted by addition of water (30 mL) and ethyl acetate (30 mL), a precipitated solid was collected by filtration, and washed with water and ethyl acetate to obtain the crude solid.\",\n \"To a suspension of the crude solid in a mixed solvent of ethanol (11.5 mL) and water (11.5 mL), a 1 N aqueous solution of potassium hydroxide (3.45 mL, 3.48 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 minutes.\",\n \"After filtration, a 2 N hydrochloric acid (1.74 mL, 3.49 mmol) was added to the filtrate, and the precipitated solid was collected by filtration, washed with water and ethanol, and then dried to obtain the title compound (0.6970 g, yield: 74%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.29 (1H, br s), 8.84 (1H, br s), 8.08 (1H, d, J=3.1 Hz), 7.95 (1H, d, J=3.1 Hz), 7.67 (1H, dd, J=9.0, 2.7 Hz), 7.63 (1H, d, J=2.7 Hz), 7.25 (1H, d, J=9.0 Hz), 4.26 (2H, s), 3.88 (3H, s), 0.75-0.73 (4H, m).\",\n \"(55c) Potassium [(5-chloro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide To a suspension of 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (40.0 mg, 0.098 mmol) obtained in Example (55b) in ethanol (2 mL), a solution of 0.5 N potassium hydroxide in ethanol (0.195 mL, 0.098 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours.\",\n \"The mixture was concentrated under reduced pressure, acetone (1 mL) was added thereto, the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (42 mg, yield: 96%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.48 (1H, br s), 7.68 (1H, d, J=2.7 Hz), 7.61 (1H, d, J=2.7 Hz), 7.54 (1H, d, J=2.7 Hz), 7.32 (1H, dd, J=8.6, 2.7 Hz), 6.98 (1H, d, J=8.6 Hz), 4.07 (2H, s), 3.65 (3H, s), 0.68-0.60 (4H, m).\",\n \"(Example 56) Sodium [(5-chloro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (sodium salt of Example 35) To a suspension of 5-chloro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (95.2 mg, 0.232 mmol) obtained in Example (55b) in ethanol (2.3 mL), a 2 N aqueous solution of sodium hydroxide 0.116 mL, 0.233 mmol) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes.\",\n \"The mixture was concentrated under reduced pressure, acetone (2.3 mL) was added thereto, the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (106.2 mg, yield: quantitative).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.49 (1H, br s), 7.69 (1H, d, J=2.7 Hz), 7.62 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.33 (1H, dd, J=8.6, 2.7 Hz), 6.99 (1H, d, J=8.6 Hz), 4.07 (2H, s), 3.67 (3H, s), 0.67-0.60 (4H, m).\",\n \"(Example 57) Potassium [(5-fluoro-2-methoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 36) The title compound (41 mg, yield: 94%) was obtained by production according to the method described in Example (47c) using 5-fluoro-2-methoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (40.0 mg, 0.102 mmol) obtained in Example 36 and a solution of 0.5 N potassium hydroxide in ethanol (0.203 mL, 0.102 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ:8.48 (1H, br s), 7.68 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.39 (1H, dd, J=9.0, 3.1 Hz), 7.15-7.10 (1H, m), 6.96 (1H, dd, J=9.0, 4.3 Hz), 4.06 (2H, br s), 3.64 (3H, br s), 0.66-0.61 (4H, m).\",\n \"(Example 58) Potassium {[5-chloro-2-(trifluoromethoxy)phenyl]sulfonyl}(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 40) The title compound (63 mg, yield: 94%) was obtained by production according to the method described in Example (47c) using 5-chloro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)-2-(trifluoromethoxy)benzenesulfonamide (62.0 mg, 0.134 mmol) obtained in Example (40c) and a solution of 0.5 N potassium hydroxide in ethanol (0.267 mL, 0.134 mmol).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.51 (1H, br s), 7.76-7.72 (2H, m), 7.56-7.51 (2H, m), 7.35 (1H, d, J=9.0 Hz), 4.08 (2H, br s), 0.65-0.63 (4H, m).\",\n \"(Example 59) Potassium (2-ethoxy-5-fluorophenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 42) (59a) N-[4′-(2,4-Dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide To a mixture of 7′-amino-4′-(2,4-dimethoxybenzyl)spiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-5′(4′H)-one (0.9073 g, 2.55 mmol) obtained in Example (35d) and pyridine (4.1 mL, 51 mmol), 5-fluoro-2-ethoxybenzenesulfonyl chloride (0.6401 g, 2.68 mmol) obtained in Example (42a) was added at room temperature, and the mixture was stirred at 80° C. for 20 minutes in an oil bath.\",\n \"The reaction mixture was cooled and then concentrated under reduced pressure, and the residue was diluted with water (50 mL) and ethyl acetate (50 mL), the aqueous layer was separated off, the organic layer was diluted with tetrahydrofuran (150 mL), and anhydrous magnesium sulfate and charcoal were added thereto.\",\n \"After filtration through pad of Celite 545®, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate (14 mL) was added to precipitate a solid, and the suspension was stirred at room temperature for 1 hour.\",\n \"The precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (1.2525 g, yield: 88%).\",\n \"1H NMR spectrum (CDCl3, 400 MHz) δ: 8.20 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=7.4, 3.1 Hz), 7.23-7.14 (2H, m), 7.02-6.95 (2H, m), 6.46-6.43 (2H, m), 4.66 (2H, br s), 4.29 (2H, q, J=7.0 Hz), 3.92 (2H, br s), 3.80 (3H, s), 3.79 (3H, s), 1.58 (3H, t, J=7.0 Hz), 0.87 (2H, br s), 0.63 (2H, br s).\",\n \"(59b) 2-Ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide To a mixture of N-[4′-(2,4-dimethoxybenzyl)-5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl]-2-ethoxy-5-fluorobenzenesulfonamide (1.2658 g, 2.27 mmol) obtained in Example (59a) and anisole (0.50 mL, 4.6 mmol) in chloroform (11.5 mL), trifluoroacetic acid (3.45 mL, 45.1 mmol) and trifluoromethanesulfonic acid (0.40 mL, 4.0 mmol) were added under ice cooling, and the mixture was stirred at the same temperature as above for 30 minutes and subsequently stirred at room temperature for 5 hours.\",\n \"The reaction mixture was carefully poured into a suspension of sodium bicarbonate (3.82 g, 45.5 mmol) in water (11.5 mL) at room temperature, isopropyl alcohol (5 mL) was added thereto, and the mixture was stirred at room temperature for 20 minutes.\",\n \"Most of the organic solvents were distilled off under reduced pressure, the concentrated mixture was diluted by addition of water (50 mL) followed by extraction with a mixed solvent of ethyl acetate (100 mL) and tetrahydrofuran (50 mL).\",\n \"The organic layer was washed with a saturated aqueous solution of sodium chloride, and anhydrous magnesium sulfate and charcoal were added thereto.\",\n \"After filtration through pad of Celite 545®, the solvent was distilled off under reduced pressure.\",\n \"To the residue, ethyl acetate (12 mL) was added to precipitate a solid, and the suspension was stirred at room temperature for 30 minutes.\",\n \"The precipitated solid was collected by filtration, washed with ethyl acetate, and then dried to obtain the title compound (0.7940 g, yield: 86%).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 10.15 (1H, s), 8.83 (1H, s), 8.09 (1H, d, J=2.7 Hz), 7.95 (1H, d, J=2.7 Hz), 7.52-7.44 (2H, m), 7.24 (1H, dd, J=9.0, 4.3 Hz), 4.26 (br 2H, s), 4.16 (2H, q, J=7.0 Hz), 1.26 (3H, t, J=7.0 Hz), 0.77-0.71 (4H, m).\",\n \"(59c) Potassium [(2-ethoxy-5-fluorophenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide To a suspension of 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (70.0 mg, 0.172 mmol) obtained in example (59b) in ethanol (5 mL), a solution of 0.5 N potassium hydroxide in ethanol (0.343 mL, 0.172 mmol) was added at room temperature, and the mixture was stirred at room temperature for 3 hours.\",\n \"The solvent was distillated off under reduce pressure to obtain the title compound (77 mg, yield: quantitative).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.45 (1H, br s), 7.70 (1H, d, J=2.7 Hz), 7.54 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.11-7.06 (1H, m), 6.95 (1H, dd, J=9.0, 4.3 Hz), 4.06 (2H, s), 3.93 (2H, q, J=6.9 Hz), 1.12 (3H, t, J=6.9 Hz), 0.67-0.59 (4H, m).\",\n \"(Example 60) Sodium [(2-ethoxy-5-fluorophenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (sodium salt of Example 42) To a suspension of 2-ethoxy-5-fluoro-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (97.3 mg, 0.239 mmol) obtained in example (59b) in ethanol (2.4 mL), a 2 N aqueous solution of sodium hydroxide (0.119 mL, 0.239 mmol) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes.\",\n \"The mixture was concentrated under reduced pressure, acetone (2.4 mL) was added thereto, the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (104.1 mg, yield: quantitative).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.47 (1H, br s), 7.71 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.41 (1H, dd, J=9.0, 3.1 Hz), 7.13-7.07 (1H, m), 6.96 (1H, dd, J=9.0, 4.3 Hz), 4.06 (2H, s), 3.94 (2H, q, J=7.0 Hz), 1.13 (3H, t, J=7.0 Hz), 0.66-0.59 (4H, m).\",\n \"(Example 61) Potassium [(2,5-dimethoxyphenyl)sulfonyl](5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)azanide (potassium salt of Example 43) To a suspension of 2,5-dimethoxy-N-(5′-oxo-4′,5′-dihydrospiro[cyclopropane-1,3′-pyrido[3,2-f][1,4]oxazepin]-7′-yl)benzenesulfonamide (43.0 mg, 0.106 mmol) obtained in Example (43b) in ethanol (5 mL), a solution of 0.5 N potassium hydroxide in ethanol (0.211 mL, 0.106 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours.\",\n \"The solvent was distilled off under reduce pressure to obtain the title compound (51 mg, yield: quantitative).\",\n \"1H NMR spectrum (DMSO-d6, 400 MHz) δ: 8.47 (1H, br s), 7.68 (1H, d, J=2.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.29 (1H, d, J=3.1 Hz), 6.89 (1H, d, J=8.6 Hz), 6.84 (1H, dd, J=8.6, 3.1 Hz), 4.05 (2H, br s), 3.66 (3H, s), 3.63 (3H, s), 0.67-0.57 (4H, m).\",\n \"Test Examples (Test Example 1) Inhibitory Test of TNAP Activity COS1 cells (DS Pharma Biomedical Co., Ltd.) were transfected with human TNAP (OriGene Technologies, Inc.) using Lipofectamine LTX & Plus reagent (Invitrogen Corp.).\",\n \"On the next day, the medium was replaced with a fresh medium, and the cells were cultured in an incubator for 3 days.\",\n \"After 3 days, the culture supernatant was collected and concentrated by centrifugation at 5000 G for 30 minutes using Amicon 14, 104 cut (Merck Millipore).\",\n \"The concentrated culture supernatant was dialyzed against 5 L of 50 mM Tris/200 mM NaCl/1 mM MgCl2/20 μM ZnCl2 twice and used as an enzyme source (enzyme solution).\",\n \"The substrate pNPP (ProteoChem Inc.) was adjusted to 3.1 mM with Milli-Q water, and a solution of each test compound dissolved in dimethyl sulfoxide (DMSO; Wako Pure Chemical Industries, Ltd.) by 6 serial dilutions at a 5-fold common ratio from 100 μM, or DMSO was added thereto at a final concentration of 1% by volume.\",\n \"The enzyme solution adjusted to 2 μg/mL with an assay buffer (200 mM Tris/2 mM MgCl2/0.04 mM ZnCl2/0.01% Tween 20) was added in the same amount of the substrate solution and incubated at room temperature for 60 minutes.\",\n \"Then, the absorbance (ABS: 405 nm) was measured using a microplate reader (model plus 384, Molecular Devices, LLC), and the concentration of produced p-nitrophenol was calculated.\",\n \"The inhibition of human TNAP activity by the test compound was evaluated on the basis of the concentration IC50 at which each test compound suppressed 50% of p-nitrophenol production.\",\n \"The results are shown in Table 1.TABLE 1 Example compound No.\",\n \"IC50 (nM) 1 6.3 2 12.7 3 12.8 4 22.9 5 71.3 6 6.1 7 10.7 8 9.1 9 1.4 10 4.0 11 4.8 12 13.4 13 3.4 14 36.2 15 95.7 16 6.2 17 12.6 18 3.9 19 6.4 20 27.1 21 46.0 22 1.7 23 3.5 24 7.2 25 1.7 26 8.7 27 1.5 28 3.6 29 1.2 30 3.8 31 1.6 32 4.1 33 1.9 34 6.7 35 1.1 36 2.2 37 43.4 38 24.4 39 13.2 40 1.9 41 2.7 42 0.6 43 1.0 44 1.4 45 14.6 46 25.2 The compound of the present invention exhibits the excellent inhibition of human TNAP activity and is useful as a pharmaceutical agent for the treatment or prophylaxis of ectopic calcification.\",\n \"(Test Example 2) Specific Inhibitory Test of TNAP Activity COS1 cells (DS Pharma Biomedical Co., Ltd.) were transfected with human IAP (small-intestinal alkaline phosphatase, purchased from OriGene Technologies, Inc.) or human PLAP (placental alkaline phosphatase, purchased from OriGene Technologies, Inc.) using Lipofectamine LTX & Plus reagent (Invitrogen Corp.).\",\n \"On the next day, the medium was replaced with a fresh medium, and the cells were cultured in an incubator for 3 days.\",\n \"After 3 days, the culture supernatant was collected and concentrated by centrifugation at 5000 G for 30 minutes using Amicon 14, 104 cut (Merck Millipore).\",\n \"The concentrated culture supernatant was dialyzed against 5 L of 50 mM Tris/200 mM NaCl/1 mM MgCl2/20 μM ZnCl2 twice and used as an enzyme source (enzyme solution).\",\n \"The substrate pNPP (ProteoChem Inc.) was adjusted to 3.1 mM with Milli-Q water, and a solution of each test compound dissolved in dimethyl sulfoxide (DMSO; Wako Pure Chemical Industries, Ltd.) by 6 serial dilutions at a 5-fold common ratio from 100 μM, or DMSO was added thereto at a final concentration of 1% by volume.\",\n \"The enzyme solution of human IAP or human PLAP adjusted to 2 μg/mL with an assay buffer (200 mM Tris/2 mM MgCl2/0.04 mM ZnCl2/0.01% Tween 20) was added in the same amount of the substrate solution and incubated at room temperature for 60 minutes.\",\n \"Then, the absorbance (ABS: 405 nm) was measured using a microplate reader (model plus 384, Molecular Devices, LLC), and the concentration of produced p-nitrophenol was calculated.\",\n \"The inhibition of human IAP or PLAP activity by the test compound was evaluated on the basis of the concentration IC50 at which each test compound suppressed 50% of p-nitrophenol production.\",\n \"The compound of the present invention exhibits the excellent specific inhibition of TNAP activity and is useful as a pharmaceutical drug for the treatment or prevention of ectopic calcification.\",\n \"(Test Example 3) Inhibitory Test of Plasma TNAP Activity in B6 Mouse (Charles River Laboratories Japan, Inc.) After blood sampling from the tail vein using a heparin-treated hematocrit capillary tube (EM Meister Hematocrit Capillary Tube, AS ONE Corp.) (as the sample before compound administration), each test compound suspended in a 0.5% methylcellulose solution (powder purchased from Wako Pure Chemical Industries, Ltd. was adjusted to 0.5% with Otsuka distilled water) was administered orally to the mouse.\",\n \"1, 2, 4, 6, and 24 hours after the administration, blood was collected from the tail vein using a heparin-treated hematocrit capillary tube to obtain a plasma sample.\",\n \"The plasma sample was added to an assay buffer (1 M Tris, 1 M MgCl2, 20 mM ZnCl2, and water, pH 7.5), and the mixture was left standing for 5 minutes.\",\n \"Then, the absorbance at 405 nm was measured and used as a blank.\",\n \"The substrate pNPP was added to the plasma sample and incubated at room temperature for 180 minutes.\",\n \"Then, the absorbance (ABS: 405 nm) was measured using a microplate reader (model plus 384, Molecular Devices, LLC), and the concentration of produced p-nitrophenol was calculated.\",\n \"The blank was subtracted from all measurement values to calculate TNAP activity at each time point with the TNAP activity of the sample before compound administration defined as 100%.\",\n \"The pharmaceutical effect of the test compound was evaluated by the average inhibition of plasma ALP (80-90% containing TNAP) activity for 6 hours from 0 hour to 6 hours after the administration of the test compound.\",\n \"It was calculated according to the following expression: 100−((plasma ALP activity at 0 hr+plasma ALP activity at 1 hr)*½+(plasma ALP activity at 1 hr+plasma ALP activity at 2 hr)*½+(plasma ALP activity at 2 hr+plasma ALP activity at 4 hr)*2/2+(plasma ALP activity at 4 hr+plasma ALP activity at 6 hr)*2/2)/6.The results are shown in Table 2.TABLE 2 Plasma ALP inhibition Example compound No.\",\n \"(6 h ave. inhibition %) 47 54.7 48 61.6 50 56.0 51 63.7 52 61.3 53 59.2 54 74.8 55 58.9 57 53.5 58 50.3 59 66.2 61 67.5 The compound of the present invention exhibits an excellent in vivo TNAP inhibitory effect and is useful as a pharmaceutical agent for the treatment or prophylaxis of ectopic calcification.\",\n \"(Test Example 4) In Vivo Anti-Calcification Test in Vitamin D-Induced Calcification Model A DBA/2 mouse (male, 6 weeks old when used, Charles River Laboratories Japan, Inc.) was given powder feed (FR-2 powder feed, Funabashi Farm Co., Ltd.) containing each test compound.\",\n \"3.75 mg/kg cholecalciferol (Sigma-Aldrich Corp.) was intraperitoneally administered for 3 days from the next day.\",\n \"Seven days after the final cholecalciferol administration, the animal was sacrificed, and the thoracic aorta and the kidney were sampled.\",\n \"The tissue samples were freeze-dried (FREEZE DRYER, FRD-50M, Iwaki Asahi Techno Glass Corp.).\",\n \"Then, 10% formic acid (undiluted solution purchased from Kishida Chemical Co., Ltd. was adjusted to 10% with Milli-Q water) was added to each tissue sample, which was then homogenized using QIAGEN Retsch MM300 TissueLyser (Qiagen N.V.).\",\n \"The homogenate was centrifuged, and the supernatant was used as a sample.\",\n \"The calcium concentration in the sample was measured as absorbance (ABS 612 nm, Microplate reader, model plus 384, Molecular Devices, LLC) using Calcium assay kit (Wako Pure Chemical Industries, Ltd.) to calculate the amount of calcium in the tissue.\",\n \"The compound of the present invention exhibits an excellent anti-calcification effect and is useful as a therapeutic agent for the treatment or prevention of ectopic calcification.\",\n \"(Test Example 5) In Vivo Anti-Calcification Test in Nephrectomized Mouse A 5/6 nephrectomized DBA/2 mouse (male, 8 weeks old) was purchased from CLEA Japan, Inc.\",\n \"This mouse was loaded with 1.2% high-phosphorus diet (Oriental Yeast Co., Ltd.).\",\n \"Each test compound suspended in a 0.5% methylcellulose solution (powder purchased from Wako Pure Chemical Industries, Ltd. was adjusted to 0.5% with Otsuka distilled water) was administered orally twice daily for three months.\",\n \"After three months, the animal was sacrificed, and the kidney was sampled.\",\n \"The tissue sample was freeze-dried (FREEZE DRYER, FRD-50M, Iwaki Asahi Techno Glass Corp.).\",\n \"Then, 10% formic acid (undiluted solution purchased from Kishida Chemical Co., Ltd. was adjusted to 10% with Milli-Q water) was added to the tissue sample, which was then homogenized using QIAGEN Retsch MM300 TissueLyser (Qiagen N.V.).\",\n \"The homogenate was centrifuged, and the supernatant was used as a sample.\",\n \"The calcium concentration in the sample was measured as absorbance (ABS 612 nm, Microplate reader, model plus 384, Molecular Devices, LLC) using Calcium assay kit (Wako Pure Chemical Industries, Ltd.) to calculate the amount of calcium in the tissue.\",\n \"The compound of the present invention exhibits an excellent anti-calcification effect and is useful as a pharmaceutical drug for the treatment or prophylaxis of ectopic calcification.\",\n \"(Test Example 6) Pharmacokinetic Test The pharmacokinetic test can be conducted according to a method well-known in the field of pharmacodynamics.\",\n \"Each test compound was suspended in a 0.5% aqueous methylcellulose solution.\",\n \"The obtained suspension was orally administered at a dose in an appropriate range (e.g., 0.01 mg/kg to 10 mg/kg) to an animal (e.g., a mouse, a rat, a dog, or a cynomolgus monkey) generally used in the pharmacokinetic test.\",\n \"Also, the test compound was dissolved in saline.\",\n \"The obtained solution was intravenously (e.g., through the tail vein, the cephalic vein, or the saphenous vein) administered at a dose in an appropriate range (e.g., 0.1 mg/kg to 10 mg/kg) to an animal (e.g., a mouse, a rat, a dog, or a cynomolgus monkey) generally used in the pharmacokinetic test.\",\n \"After given times (e.g., 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours) from the administration, blood was collected from an appropriate blood collection site (e.g., the jugular vein, the cephalic vein, or the saphenous vein).\",\n \"The obtained blood was centrifuged to prepare a plasma sample.\",\n \"The concentration of the test compound contained in the plasma sample was measured by quantitative analysis using a liquid chromatography-mass spectrometer (LC-MS/MS).\",\n \"The pharmacokinetics of the test compound were evaluated on the basis of maximum plasma concentration (Cmax), area under the plasma drug concentration-time curve (AUC), total clearance (CL), and bioavailability and analyzed using software (Phoenix, etc.).\",\n \"Cmax represents the maximum plasma concentration of the orally administered test compound.\",\n \"AUC was calculated according to the trapezium rule from the plasma concentrations of the test compound from the time when the test compound was administered up to the final time when the test compound was quantifiable.\",\n \"The bioavailability was calculated according to the following expression: [(AUC after oral administration/Dose of the oral administration)/(AUC after intravenous administration/Dose of the intravenous administration)].\",\n \"The compound of the present invention exhibits excellent pharmacokinetics (Cmax, AUC, CL, or bioavailability) and is useful as a pharmaceutical (particularly, a pharmaceutical for the treatment or prevention of ectopic calcification).\",\n \"Preparation Examples (Preparation Example 1) Capsule Compound of Example 1 50 mg Lactose 128 mg Corn starch 70 mg Magnesium stearate 2 mg 250 mg A powder having the formulation mentioned above is mixed and sifted through a 60-mesh sieve.\",\n \"Then, this powder is put in a gelatin capsule shell to prepare a capsule.\",\n \"(Preparation Example 2) Tablet Compound of Example 1 50 mg Lactose 126 mg Corn starch 23 mg Magnesium stearate 1 mg 200 mg A powder having the formulation mentioned above is mixed, granulated using corn starch paste, and dried, followed by compression in a tableting machine to prepare tablets (200 mg each).\",\n \"This tablet can be coated, if necessary.\",\n \"The novel pyridine compound represented by the general formula (I) of the present invention or the pharmacologically acceptable salt thereof has an excellent TNAP inhibitory effect and is useful as a pharmaceutical.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874768"}}},{"rowIdx":4494693,"cells":{"text":{"kind":"list like","value":[["ROOFING SYSTEMS AND METHODS","A method includes providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.","A first polymer or predominantly polymer material foam precursor is dispensed to the production line, and allowed to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density.","A second polymer or predominantly polymer material foam precursor is dispensed to the production line and allowed to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density.","The combined thickness of the foam core layer for the insulation board and the core layer for the cover board is set by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors."],["1.A method, comprising: providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor; dispensing to the production line a first polymer or predominantly polymer material foam precursor; allowing the first foam precursor to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density; dispensing to the production line a second polymer or predominantly polymer material foam precursor; allowing the second foam precursor to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density; and setting the combined thickness of the foam core layer for the insulation board and the core layer for the cover board by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors and positioned downstream of the dispensing of the second polymer or predominantly polymer foam precursor.","2.The method of claim 1, further comprising providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","3.The method of claim 1, further comprising setting the thickness of the foam core layer for the insulation board by constraining the expansion of the first polymer or predominantly polymer material foam precursor using an upstream forming conveyor disposed above the rising first polymer or predominantly polymer material foam precursor, the upstream forming conveyor positioned upstream of the dispensing of the second polymer or predominantly polymer foam precursor.","4.The method of claim 3, further comprising providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","5.The method of claim 1, wherein the expansion of the first polymer or predominantly polymer material foam precursor is not constrained by any forming conveyor other than the downstream forming conveyor.","6.The method of claim 5, further comprising providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","7.The method of claim 1, further comprising providing an upper facer material on top of the second polymer or predominantly polymer material foam precursor, to form a top facer of a composite panel comprising the insulation board and the cover board.","8.The method of claim 1, wherein dispensing the first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.","9.The method of claim 1, wherein dispensing the second polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.","10.The method of claim 1, wherein dispensing a first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polystyrene.","11.The method of claim 1, further comprising cutting the cover board and the insulation board to length.","12.The method of claim 1, further comprising installing the insulation board and the cover board on a roof.","13.The method of claim 1, further comprising applying and bonding a bottom facer to the foam core layer of the insulation board with a reinforcing means interposed between the bottom facer and a bottom major surface of the core layer of the insulation board, the reinforcing means positioned to coincide with a fastener pattern for securing the roofing system panels being formed to a roof deck and increase a per-fastener wind-uplift pull through rating for the roofing system panels being formed.","14.The method of claim 13, wherein the reinforcing means comprises reinforcing patches.","15.The method of claim 13, wherein the reinforcing means comprises reinforcing strips.","16.The method of claim 1, wherein the density of the core layer of the cover board after setting is between 6 lb/ft3 and 25 lb/ft3.17.The method of claim 1, wherein the density of the core layer of the cover board after setting is between 4 lb/ft3 and 25 lb/ft3.18.The method of claim 1, wherein the density of the core layer of the insulation board after setting is less than 4 lb/ft3.19.The method of claim 1, wherein the density of the core layer of the insulation board after setting is less than 2.5 lb/ft3."],["<SOH> BACKGROUND OF THE INVENTION <EOH>The subject invention relates to low-slope roofs that are typically found on commercial and industrial buildings and in particular to prefabricated high-density polymer or predominantly polymer material cover boards and cover board composites and prefabricated roofing panel composites which include high-density polymer or predominantly polymer material cover boards and low-density polymer or predominantly polymer material foam insulation boards, for use on such low-slope roofs and to a method of making the cover boards, the cover board composites, and the roofing panel composites.","Commercial and industrial buildings typically have roofs with low-slope roof decks.","The roofing systems for these roofs with low-slope roof decks typically include one or more layers of a low-density roofing insulation, a layer of roofing cover boards that overlie the low-density roofing insulation layer(s), and a waterproofing membrane that overlies the layer of cover boards.","The layer(s) of low-density insulation, such as a low-density polymer-based foam insulation, if not protected, can be partially crushed or otherwise damaged from worker traffic over the insulation, the placement of heaving objects on the insulation, the weather, and other causes commonly encountered in roofing construction.","The layer of roofing cover boards that overlies the one or more layers of low-density insulation, protects the more fragile low density insulation from damage, acts as a fire barrier, provides a suitable substrate for the attachment of the overlying waterproofing membrane, and augments the insulating function of the low-density insulation.","The uppermost waterproofing membrane layer overlying the cover board layer protects the underlying cover board and insulation layers from moisture and other adverse climatic conditions.","Normally, these three components (the low-density insulation boards, the roofing cover boards, and the waterproofing membrane) of the roofing system are separately manufactured and separately and successively applied to the low-slope roof deck.","While these roofing systems function very well, there has remained a need to provide improved roofing cover boards and prefabricated cover board composites and to provide prefabricated roofing panel composites that include at least an insulation board and the improved roofing cover board, and that, preferably, include an insulation board and prefabricated the roofing cover board composite having a waterproofing membrane.","With the use of such improved roofing cover boards and cover board composites and prefabricated roofing panel composites, roofing systems for low-slope roof decks can be improved and/or the time, labor, and other costs associated with the installation of roofing systems on low-slope roof decks can be reduced.","The subject invention provides improved roofing cover boards, improved prefabricated roofing cover board and waterproofing membrane composites, improved prefabricated roofing panel cover board and insulation board composites, improved prefabricated roofing panel cover board, insulation board, and waterproofing membrane composites, and improved prefabricated roofing panel cover board, insulation board, baseboard, and waterproofing membrane composites.","The subject invention also provides these roofing cover boards, roofing cover board composites, and roofing panel composites with reinforcing patches or strips that increase the per fastener wind uplift pull through rating for the cover boards, cover board composites, and roofing panel composites to thereby further reduce the labor and ultimately the overall installed cost of roofing systems utilizing these cover boards, cover board composites, and roofing panel composites.","The subject invention also provides a method for making the improved roofing cover board and the prefabricated roofing panel composites including the improved roofing cover board that is highly productive, relatively economical, and efficient."],["<SOH> SUMMARY OF THE INVENTION <EOH>According to one aspect, a method comprises providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.","The method further comprises dispensing to the production line a first polymer or predominantly polymer material foam precursor, and allowing the first foam precursor to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density.","The method further comprises dispensing to the production line a second polymer or predominantly polymer material foam precursor and allowing the second foam precursor to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density.","The method further comprises setting the combined thickness of the foam core layer for the insulation board and the core layer for the cover board by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors and positioned downstream of the dispensing of the second polymer or predominantly polymer foam precursor.","In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","In some embodiments, the method further comprises setting the thickness of the foam core layer for the insulation board by constraining the expansion of the first polymer or predominantly polymer material foam precursor using an upstream forming conveyor disposed above the rising first polymer or predominantly polymer material foam precursor, the upstream forming conveyor positioned upstream of the dispensing of the second polymer or predominantly polymer foam precursor.","In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","In some embodiments, the expansion of the first polymer or predominantly polymer material foam precursor is not constrained by any forming conveyor other than the downstream forming conveyor.","In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","In some embodiments, the method further comprises providing an upper facer material on top of the second polymer or predominantly polymer material foam precursor, to form a top facer of a composite panel comprising the insulation board and the cover board.","In some embodiments, dispensing the first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.","In some embodiments, dispensing the second polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.","In some embodiments, dispensing a first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polystyrene.","In some embodiments, the method further comprises cutting the cover board and the insulation board to length.","In some embodiments, the method further comprises installing the insulation board and the cover board on a roof.","In some embodiments, the method further comprises applying and bonding a bottom facer to the foam core layer of the insulation board with a reinforcing means interposed between the bottom facer and a bottom major surface of the core layer of the insulation board, the reinforcing means positioned to coincide with a fastener pattern for securing the roofing system panels being formed to a roof deck and increase a per-fastener wind-uplift pull through rating for the roofing system panels being formed.","The reinforcing means may comprise reinforcing patches.","The reinforcing means may comprise reinforcing strips.","The density of the core layer of the cover board after setting may be between 6 lb/ft 3 and 25 lb/ft 3 .","The density of the core layer of the cover board after setting may be between 4 lb/ft 3 and 25 lb/ft 3 .","The density of the core layer of the insulation board after setting may be less than 4 lb/ft 3 .","The density of the core layer of the insulation board after setting may be less than 2.5 lb/ft 3 ."],["This patent application is a continuation of pending U.S. patent application Ser.","No.","15/193,729, filed Jun.","27, 2016 and titled “Roofing Systems and Methods”, which is a division of U.S. patent application Ser.","No.","14/293,004, filed Jun.","2, 2014 and titled “Roofing Systems and Methods”, (now U.S. Pat.","No.","9,404,261), which is a continuation of U.S. patent application Ser.","No.","13/908,505, filed Jun.","3, 2013 and titled “Prefabricated Roofing Panel Composite”, (now abandoned), which is a division of U.S. patent application Ser.","No.","13/209,710, filed Aug. 15, 2011, (now U.S. Pat.","No.","8,479,467), which is a continuation-in-part of U.S. patent application Ser.","No.","12/703,308, filed Feb. 10, 2010 and titled “Roofing Cover Board, Roofing Panel Composites and Method”, (now U.S. Pat.","No.","8,105,685), which is a continuation of U.S. patent application Ser.","No.","11/519,042, filed Sep. 11, 2006 and titled “Roofing Cover Board, Roofing Panel Composites, and Method” (now U.S. Pat.","No.","7,811,663), which is a continuation-in-part of U.S. patent application Ser.","No.","10/984,122, filed Nov. 9, 2004 and titled “Roofing Cover Board, Roofing Panel Composite, and Method” (now abandoned), the entire disclosures of which are hereby incorporated by reference herein for all purposes.","BACKGROUND OF THE INVENTION The subject invention relates to low-slope roofs that are typically found on commercial and industrial buildings and in particular to prefabricated high-density polymer or predominantly polymer material cover boards and cover board composites and prefabricated roofing panel composites which include high-density polymer or predominantly polymer material cover boards and low-density polymer or predominantly polymer material foam insulation boards, for use on such low-slope roofs and to a method of making the cover boards, the cover board composites, and the roofing panel composites.","Commercial and industrial buildings typically have roofs with low-slope roof decks.","The roofing systems for these roofs with low-slope roof decks typically include one or more layers of a low-density roofing insulation, a layer of roofing cover boards that overlie the low-density roofing insulation layer(s), and a waterproofing membrane that overlies the layer of cover boards.","The layer(s) of low-density insulation, such as a low-density polymer-based foam insulation, if not protected, can be partially crushed or otherwise damaged from worker traffic over the insulation, the placement of heaving objects on the insulation, the weather, and other causes commonly encountered in roofing construction.","The layer of roofing cover boards that overlies the one or more layers of low-density insulation, protects the more fragile low density insulation from damage, acts as a fire barrier, provides a suitable substrate for the attachment of the overlying waterproofing membrane, and augments the insulating function of the low-density insulation.","The uppermost waterproofing membrane layer overlying the cover board layer protects the underlying cover board and insulation layers from moisture and other adverse climatic conditions.","Normally, these three components (the low-density insulation boards, the roofing cover boards, and the waterproofing membrane) of the roofing system are separately manufactured and separately and successively applied to the low-slope roof deck.","While these roofing systems function very well, there has remained a need to provide improved roofing cover boards and prefabricated cover board composites and to provide prefabricated roofing panel composites that include at least an insulation board and the improved roofing cover board, and that, preferably, include an insulation board and prefabricated the roofing cover board composite having a waterproofing membrane.","With the use of such improved roofing cover boards and cover board composites and prefabricated roofing panel composites, roofing systems for low-slope roof decks can be improved and/or the time, labor, and other costs associated with the installation of roofing systems on low-slope roof decks can be reduced.","The subject invention provides improved roofing cover boards, improved prefabricated roofing cover board and waterproofing membrane composites, improved prefabricated roofing panel cover board and insulation board composites, improved prefabricated roofing panel cover board, insulation board, and waterproofing membrane composites, and improved prefabricated roofing panel cover board, insulation board, baseboard, and waterproofing membrane composites.","The subject invention also provides these roofing cover boards, roofing cover board composites, and roofing panel composites with reinforcing patches or strips that increase the per fastener wind uplift pull through rating for the cover boards, cover board composites, and roofing panel composites to thereby further reduce the labor and ultimately the overall installed cost of roofing systems utilizing these cover boards, cover board composites, and roofing panel composites.","The subject invention also provides a method for making the improved roofing cover board and the prefabricated roofing panel composites including the improved roofing cover board that is highly productive, relatively economical, and efficient.","SUMMARY OF THE INVENTION According to one aspect, a method comprises providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.","The method further comprises dispensing to the production line a first polymer or predominantly polymer material foam precursor, and allowing the first foam precursor to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density.","The method further comprises dispensing to the production line a second polymer or predominantly polymer material foam precursor and allowing the second foam precursor to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density.","The method further comprises setting the combined thickness of the foam core layer for the insulation board and the core layer for the cover board by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors and positioned downstream of the dispensing of the second polymer or predominantly polymer foam precursor.","In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","In some embodiments, the method further comprises setting the thickness of the foam core layer for the insulation board by constraining the expansion of the first polymer or predominantly polymer material foam precursor using an upstream forming conveyor disposed above the rising first polymer or predominantly polymer material foam precursor, the upstream forming conveyor positioned upstream of the dispensing of the second polymer or predominantly polymer foam precursor.","In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","In some embodiments, the expansion of the first polymer or predominantly polymer material foam precursor is not constrained by any forming conveyor other than the downstream forming conveyor.","In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.","In some embodiments, the method further comprises providing an upper facer material on top of the second polymer or predominantly polymer material foam precursor, to form a top facer of a composite panel comprising the insulation board and the cover board.","In some embodiments, dispensing the first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.","In some embodiments, dispensing the second polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.","In some embodiments, dispensing a first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polystyrene.","In some embodiments, the method further comprises cutting the cover board and the insulation board to length.","In some embodiments, the method further comprises installing the insulation board and the cover board on a roof.","In some embodiments, the method further comprises applying and bonding a bottom facer to the foam core layer of the insulation board with a reinforcing means interposed between the bottom facer and a bottom major surface of the core layer of the insulation board, the reinforcing means positioned to coincide with a fastener pattern for securing the roofing system panels being formed to a roof deck and increase a per-fastener wind-uplift pull through rating for the roofing system panels being formed.","The reinforcing means may comprise reinforcing patches.","The reinforcing means may comprise reinforcing strips.","The density of the core layer of the cover board after setting may be between 6 lb/ft3 and 25 lb/ft3.The density of the core layer of the cover board after setting may be between 4 lb/ft3 and 25 lb/ft3.The density of the core layer of the insulation board after setting may be less than 4 lb/ft3.The density of the core layer of the insulation board after setting may be less than 2.5 lb/ft3.BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a schematic perspective view of a prefabricated high-density polymer or predominantly polymer material cover board of the subject invention.","FIG.","2 is a schematic perspective view of a cover board composite of the subject invention that includes a prefabricated high-density polymer or predominantly polymer material cover board and a top facer.","FIG.","3 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.","FIG.","4 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board composite with a top facer and a low-density polymer or predominantly polymer material foam insulation board.","FIG.","5 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board, a low-density polymer or predominantly polymer material foam insulation board, and a high-density polymer or predominantly polymer material baseboard.","FIG.","6 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board composite with a top facer, a low-density polymer or predominantly polymer material foam insulation board, a high-density polymer or predominantly polymer material baseboard.","FIG.","7 is a schematic side view of a first production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.","FIG.","8 is a schematic side view of a second production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.","FIG.","9 is a schematic side view of a production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board, a low-density polymer or predominantly polymer material foam insulation board, and a high-density polymer or predominantly polymer material baseboard.","FIG.","10 is a schematic side view of a third production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.","FIG.","11 is a fragmentary, transverse schematic, perspective view of a cover board composite of the subject invention, at a fastener location, wherein the composite includes a reinforcement for increasing the fastener wind-uplift pull through rating of the cover board composite.","The Figure also shows a portion of a fastener plate that can be used with the composite.","FIG.","12 is a fragmentary, partially exploded, transverse schematic, perspective view of the cover board composite of FIG.","11 at a fastener location.","FIG.","13 is a fragmentary, transverse schematic, perspective view of a prefabricated cover board/insulation board panel composite of the subject invention, at a fastener location, wherein the panel composite includes a reinforcement for increasing the fastener wind-uplift pull through rating of the panel composite.","The Figure also shows a portion of a fastener plate that can be used with the panel composite.","FIG.","14 is a fragmentary, schematic, perspective view of a prefabricated cover board/insulation board/baseboard panel composite of the subject invention, at a fastener location, wherein the panel composite includes a reinforcement for increasing the fastener wind-uplift pull through rating of the panel composite.","The Figure also shows a portion of a fastener plate that can be used with the composite.","FIG.","15 is a schematic bottom view of the prefabricated cover board, cover board/insulation board panel, or cover board/insulation board/baseboard panel composites of FIGS.","11 to 14, with the bottom facer removed, to show a reinforcement patch pattern for increasing the fastener wind-uplift pull through rating of the composites.","FIG.","16 is a schematic bottom view of the prefabricated cover board, cover board/insulation board panel, or cover board/insulation board/baseboard panel composites of FIGS.","11 to 14, with the bottom facer removed, to show a double-layer reinforcement patch pattern for increasing the fastener wind-uplift pull through rating of the composites.","FIG.","17 is a schematic bottom view of the prefabricated cover board, cover board/insulation board panel, or cover board/insulation board/baseboard panel composites of FIGS.","11 to 14, with the bottom facer removed, to show a reinforcement strip pattern for increasing the fastener wind-uplift pull through rating of the composites.","DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG.","1 is a schematic perspective view of the cover board 10 of the subject invention, which has a high-density polymer or predominantly polymer material core layer 12.The high-density polymer or predominantly polymer material core layer 12 of the cover board 10 has a density of at least 4 lbs/ft3 and preferably between 6 lbs/ft3 and 25 lbs/ft3.The high-density polymer or predominantly polymer material core layer 12 of the cover board 10 has a thickness of about 0.08 inches or greater and, preferably, a thickness between about 0.25 inches and about 0.75 inches.","The density and thickness of the high-density polymer or predominantly polymer material core layer 12 of the cover board 10 are selected to provide the cover board with the compressive strength to resist deformation and protect low-density insulation layers overlaid by the cover board from damage, and to provide surface characteristics that promote the bonding of a top facer, e.g.","a waterproofing membrane, to the high-density core layer of the cover board.","The high-density polymer or predominantly polymer material core layer 12 has a top major surface 14 and a bottom major surface 16 that are each defined by the length and the width of the high-density polymer or predominantly polymer material core layer.","The high-density polymer or predominantly polymer material core layer 12 typically has a width of about four feet or greater and a length of about four feet or greater, preferably, about eight feet or greater and could have lengths that are limited only by the ability to store, transport, and handle the high-density polymer or predominantly polymer material cover board 10 prior to installation.","The cover board 10 may have top and/or bottom facers that are not shown in FIG.","1.When used, the top and/or bottom facers typically overlie the entire or substantially the entire major surface 14 and/or 16 of the high-density polymer or predominantly polymer material core layer 12 to which the facers are bonded.","The top and bottom facers of the high-density polymer or predominantly polymer material cover board 10 may be any sheet material that provides suitable top and bottom major surfaces for the cover board, such as but not limited to paper, foil, woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","The high-density polymer or predominantly polymer material core layer 12 of the cover board 10 may be made of various high-density polymer or predominantly polymer materials [e.g.","a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic material or a high-density material made of a blend of these materials; a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a high-density foam material made of a blend of these materials; a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s); a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a high-density material made of other thermoset matrix polymers; etc.].","However, a preferred material for the high-density core layer 12 is a high-density polyisocyanurate or predominantly polyisocyanurate material or foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic.","Examples of various fillers that may be used in the predominantly polymer materials of the high-density core layer 12 include but are not limited to powdered, liquid, and fiber fillers.","The high-density polymer and predominantly polymer materials of the core layer 12 may also include fiber reinforcements, fungi growth-inhibiting agents, and fire-retardants to reduce the cost of and/or modify the properties of the high-density core layer 12, such as but not limited to the compressive strength, the toughness, the flexibility, the friability, and the fire resistance of the core layer.","Examples of fillers that may be used in the high-density predominantly polymer material core layer 12 are fillers such as but not limited to limestone (CaCO3), fiberglass, recycled polyisocyanurate dust, extenders/plasticizers, ground up foam insulation, ground up rubber, wood dust, etc.","The prefabricated high-density polymer or predominantly polymer material cover board of the subject invention is relatively lightweight and easily cut.","This makes the cover board easier to install and increases the productivity of workers installing the cover boards.","The high-density polymer or predominantly polymer material cover board of the subject invention does not support mold growth and the cover board is not negatively impacted by the application of solvents, hot asphalt, or adhesives.","FIG.","2 is a schematic perspective view of a prefabricated cover board and facer composite 20 of the subject invention.","The composite 20 includes the cover board 10 and a facer 22, e.g.","a waterproofing membrane.","Other than the inclusion of a top facer 22, the prefabricated cover board and facer composite 20 is the same as the cover board 10 of FIG.","1.The top facer 22 of the composite 20 may be any sheet material that provides a suitable top major surface for the cover board and facer composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","A preferred sheet material for the top facer 22 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.","Where the composite 20 is fully adhered to an underlying roofing layer (e.g.","an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 22 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.","a EPDM, PVC, or TPO membrane).","Where the top facer 22 is a waterproofing membrane, the facer may extend beyond the high-density polymer or predominantly polymer material core layer of the cover board 10 on one or more of the four sides of the core layer (e.g.","beyond a side edge and an end edge of the top major surface of the core layer) to form membrane overlaps for sealing to the membranes of other composites 20.While not shown, the composite may also include a bottom facer that is bonded to the bottom major surface of the high-density polymer or predominantly polymer material core layer of the cover board.","When used, the bottom facer of the composite 20 may be any sheet material that provides a suitable bottom major surface for the cover board and facer composite for bonding to an underlying layer of the roofing system, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","FIG.","3 is a schematic perspective view of a first prefabricated roofing panel composite 30 of the subject invention.","The prefabricated roofing panel composite 30 includes a high-density polymer or predominantly polymer material cover board 32 and an insulation board 34 that, as shown, are bonded directly together.","The prefabricated roofing panel composite 30 has a top major surface 36 and a bottom major surface 38 that are each defined by the length and the width of the roofing panel composite.","The prefabricated roofing panel composite 30 typically has a width of about four feet or greater and a length of about four feet or greater, preferably, about eight feet or greater and could have lengths that are limited only by the ability to store, transport and handle the roofing panel composites prior to installation.","In the prefabricated roofing panel composite 30, the cover board 32 has a high-density polymer or predominantly polymer material core layer 40.The high-density polymer or predominantly polymer material core layer 40 of the cover board 32 in the prefabricated roofing panel composite 30 has a density of at least 4 lbs/ft3 and preferably, between 6 lbs/ft3 and 25 lbs/ft3.The high-density polymer or predominantly polymer material core layer 40 of the cover board 32 in the prefabricated roofing panel composite has a thickness of about 0.08 inches or greater and, preferably, a thickness between about 0.25 inches and about 0.75 inches.","The density and thickness of the high-density polymer or predominantly polymer material core layer 40 of the cover board 32 are selected to provide the cover board with the compressive strength to resist deformation and protect the low-density insulation board 34 that is overlaid by the cover board from damage, and to provide surface characteristics that promote the bonding of a top facer, e.g.","a waterproofing membrane, to the high-density core layer 40 of the cover board.","The insulation board 34 in the prefabricated roofing panel composite 30 includes a low-density polymer or predominantly polymer material foam core layer 42.The low-density polymer or predominantly polymer material foam core layer 42 of the insulation board 34 has a density less than 6 lbs/ft3, preferably less than 4 lbs/ft3, and typically a density of less than 2.5 lbs/ft3.The low-density polymer or predominantly polymer material foam core layer 42 has a thickness of about 0.50 inches or greater and, preferably, a thickness between about 0.50 inches and about 6 inches.","The density and thickness of the low-density polymer or predominantly polymer material foam core layer 42 of the insulation board 34 are selected to provide the prefabricated roofing panel composite 30 with the desired insulating properties for the roofing system application.","The high-density polymer or predominantly polymer material core layer 40 of the cover board 32 may be made of various high-density polymer or predominantly polymer materials [e.g.","a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic material or a high-density material made of a blend of these materials; a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a high-density foam material made of a blend of these materials; a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic fillers); a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a high-density material made of other thermoset matrix polymers; etc.].","However, a preferred material for the high-density core layer 40 is a high-density polyisocyanurate or predominantly polyisocyanurate material or foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or filler(s) such as but not limited to those listed above in connection with the cover board 10.The low-density polymer or predominantly polymer material foam core layer 42 of the insulation board 34 may be made of various low-density polymer or predominantly polymer foam materials [e.g.","a low-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a low-density foam material made of a blend of these materials; a low-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a low-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or filler(s), a low-density foam material made of other thermoset matrix polymers; etc.].","However, a preferred material for the low-density core layer 42 is a low-density polyisocyanurate or predominantly polyisocyanurate foam material up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s).","When the high-density core layer 40 is made of a predominantly polymer material, the high-density predominantly polymer material of the core layer 40 may contain various powdered, liquid, and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.","to reduce the cost and/or modify the properties of the high-density core layer 40 (such as but not limited to the compressive strength, the flexibility, the friability, the fire resistance of the core layer).","When the low-density core layer 42 is made of a predominantly polymer material foam, the low-density predominantly polymer material foam core layer 42 may contain various powdered, liquid, and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.","to reduce the cost and/or modify the properties of the low-density predominantly polymer material foam core layer.","Examples of fillers that may be used in the high-density core layer 40 of the cover board 32 and the low-density core layer 42 of the insulation board 34 are fillers such as but not limited to limestone (CaCO3), fiberglass, recycled polyisocyanurate dust, extenders/plasticizers, ground up foam insulation, ground up rubber, wood dust, etc.","While, as shown in FIG.","3, the prefabricated roofing panel composite 30 has no facers, the prefabricated roofing panel composite 30 could have a common facer intermediate and bonded to both the bottom major surface of the cover board core layer 40 and the top major surface of the insulation board core layer 42, a top facer bonded to the top major surface of the cover board core layer 40, and/or a bottom facer bonded to the bottom major surface of the insulation board core layer 42.When used, the common facer of the prefabricated roofing panel composite 30 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board 32 and insulation board 34, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.","When used, the top facer of the prefabricated roofing panel composite 30 overlies the entire or substantially the entire top major surface of the high-density core layer 40 of the cover board 32.The top facer of the prefabricated roofing panel composite 30 may be any sheet material that provides a suitable top major surface for the prefabricated roofing panel composite 30, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","When used, the bottom facer of the prefabricated roofing panel composite 30 overlies the entire or substantially the entire bottom surface of the low-density foam core layer 42 of the insulation board 34.The bottom facer of the prefabricated roofing panel composite 30 may be any sheet material that provides a suitable bottom major surface for the roofing panel composite 30, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","FIG.","4 is a schematic perspective view of a prefabricated roofing panel composite 50 of the subject invention.","The prefabricated roofing panel composite 50 includes the high-density polymer or predominantly polymer material cover board 32 and the low-density polymer or predominantly polymer material foam insulation board 34 that, as shown in FIG.","4, are bonded directly together, and a top facer 52.Other than the inclusion of the top facer 52, the prefabricated roofing panel composite 50 is the same as the prefabricated roofing panel composite 30 of FIG.","3.The top facer 52 of the prefabricated roofing panel composite 50 is bonded to and overlies the entire or substantially the entire top surface of the high-density polymer or predominantly polymer material core layer of the cover board 32.The top facer 52 of the prefabricated roofing panel composite 50 may be any sheet material that provides a suitable top major surface for the cover board of the prefabricated roofing panel composite 50, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","A preferred sheet material for the top facer 52 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.","Where the prefabricated roofing panel composite 50 is fully adhered to an underlying roofing layer (e.g.","an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 52 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.","a EPDM, PVC, or TPO membrane).","Where the top facer 52 is a waterproofing membrane, the facer may extend beyond the high-density core layer of the cover board 32 on one or more of the four sides of the core layer, e.g.","beyond a side edge and an end edge of the top major surface of the core layer to provide overlaps for sealing with the membranes of adjacent panels.","While, as shown in FIG.","4, the prefabricated roofing panel composite 50 only has a top facer 52, the prefabricated roofing panel composite 50 could have a common facer intermediate and bonded to both the bottom major surface of the cover board 32 core layer 40 and the top major surface of the insulation board 34 core layer 42, and/or a bottom facer bonded to the bottom major surface of the insulation board 34 core layer 42.When used, the common facer of the prefabricated roofing panel composite 50 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board 32 and insulation board 34, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.","When used, the bottom facer of the prefabricated roofing panel composite 50 overlies the entire or substantially the entire bottom surface of the low-density foam core layer of the insulation board 34.The bottom facer of the prefabricated roofing panel composite 50 may be any sheet material that provides a suitable bottom major surface for the roofing panel composite 50, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","FIG.","5 is a schematic perspective view of a prefabricated roofing panel composite 60 of the subject invention that includes: a high-density polymer or predominantly polymer material cover board 62, a low-density polymer or predominantly polymer material foam insulation board 64, and a high-density polymer or predominantly polymer material baseboard 66.The high-density polymer or predominantly polymer material cover board 62 and baseboard 66 may have the same density or different densities.","As shown in FIG.","5, the cover board 62, the insulation board 64, and the baseboard 66 are bonded directly together.","The prefabricated roofing panel composite 60 has a top major surface 68 and a bottom major surface 70 that are each defined by the length and the width of the prefabricated roofing panel composite.","The prefabricated roofing panel composite 60 typically has a width of about four feet or greater and a length of about four feet or greater, preferably, about eight feet or greater and could have lengths that are limited only by the ability to store, transport and handle the roofing panel composites prior to installation.","In the prefabricated roofing panel composite 60, the cover board 62 has a high-density polymer or predominantly polymer material core layer 72 and the baseboard 66 has a high-density polymer or predominantly polymer material core layer 74.The high-density polymer or predominantly polymer material core layers 72 and 74 each have a density of at least 4 lbs/ft3 and preferably, between 6 lbs/ft3 and 25 lbs/ft3.The high-density polymer or predominantly polymer material core layer 72 of the cover board 62 and the high-density polymer or predominantly polymer material core layer 74 of the baseboard 66 each have a thickness of about 0.08 inches or greater and, preferably, a thickness between about 0.25 inches and about 0.75 inches.","The density and thickness of the high-density polymer or predominantly polymer material core layer 72 of the cover board 62 are selected to provide the cover board with the compressive strength to resist deformation and protect the low-density insulation board 64 that is overlaid by the cover board from damage, and to provide surface characteristics that promote the bonding of a top facer, e.g.","a waterproofing membrane, to the core layer 72 of the cover board.","The insulation board 64 in the prefabricated roofing panel composite 60 includes a low-density polymer or predominantly polymer foam core layer 76.The low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 has a density less than 6 lbs/ft3, preferably less than 4 lbs/ft3, and typically a density of less than about 2.5 lbs/ft3.The low-density polymer or predominantly polymer material foam core layer 76 has a thickness of about 0.50 inches or greater and, preferably, a thickness between about 0.50 inches and about 6 inches.","The density and thickness of the low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 are selected to provide the prefabricated roofing panel composite 60 with the desired insulating properties for the roofing system application.","The high-density polymer or predominantly polymer material core layers 72 and 74 of the cover board 62 and the baseboard 66 may be made of various high-density polymer or predominantly polymer materials [e.g.","a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic material or a high-density material made of a blend of these materials; a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a high-density foam material made of a blend of these materials; a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s); a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a high-density material made of other thermoset matrix polymers; etc.].","However, a preferred material for the high-density core layers 72 and 74 is a high-density polyisocyanurate or predominantly polyisocyanurate material or foam material up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s).","The low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 may be made of various low-density polymer or predominantly polymer foam materials [e.g.","a low-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a low-density foam material made of a blend of these materials; a low-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a low-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a low-density material made of other thermoset matrix polymers; etc.].","However, a preferred material for the low-density core layer 76 is a low-density polyisocyanurate or predominantly polyisocyanurate foam material up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s).","When the high-density core layers 72 and 74 are made of a predominantly polymer material, the high-density predominantly polymer material of the core layers 72 and 74 may contain various powdered, liquid, and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.","to reduce the cost and/or modify the properties of the high-density core layers 72 and 74 (such as but not limited to the compressive strength, the flexibility, the friability, the fire resistance of the core layer).","When the low-density core layer 76 is made of a predominantly polymer material foam, the low-density predominantly polymer material foam core layer 76 may contain various powdered, liquid and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.","to reduce the cost and/or modify the properties of the low-density foam core layer.","Examples of fillers that may be used in the high-density core layers 72 of the cover board 62 and the baseboard 66 and the low-density core layer 76 of the insulation board 64 are fillers such as but not limited to limestone (CaCO3), fiberglass, recycled polyisocyanurate dust, extenders/plasticizers, ground up foam insulation, ground up rubber, wood dust, etc.","While, as shown in FIG.","5, the prefabricated roofing panel composite 60 has no facers, the prefabricated roofing panel composite 60 could have a common facer intermediate and bonded to both the bottom major surface of the cover board core layer 72 and the top major surface of the insulation board core layer 76, a common facer intermediate and bonded to both the bottom major surface of the insulation board core layer 76 and the top major surface of the baseboard core layer 74, a top facer bonded to the top major surface of the cover board core layer 72, and/or a bottom facer bonded to the bottom major surface of the baseboard core layer 74.When used, the common facers of the prefabricated roofing panel composite 60 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board 62, the insulation board 64, and the baseboard 66, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.","When used, the top facer of the prefabricated roofing panel composite 60 overlies the entire or substantially the entire top major surface of the high-density core layer 72 of the cover board 62.The top facer of the prefabricated roofing panel composite 60 may be any sheet material that provides a suitable top major surface for the prefabricated roofing panel composite 60, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","When used, the bottom facer of the prefabricated roofing panel composite 60 overlies the entire or substantially the entire bottom surface of the high-density core layer 74 of the baseboard 66.The bottom facer of the prefabricated roofing panel composite 60 may be any sheet material that provides a suitable bottom major surface for the roofing panel composite 60, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","FIG.","6 is a schematic perspective view of a prefabricated roofing panel composite 80 of the subject invention.","The prefabricated roofing panel composite 80 includes the high-density polymer or predominantly polymer material cover board 62, the low-density polymer or predominantly polymer material foam insulation board 64, and the high-density polymer or predominantly polymer material baseboard 66, that, as shown in FIG.","6, are bonded directly together, and a top facer 82.Other than the inclusion of a top facer 82, the prefabricated roofing panel composite 80 of FIG.","6 is the same as the prefabricated roofing panel composite 60 of FIG.","5.The top facer 82 of the prefabricated roofing panel composite 80 is bonded to and overlies the entire or substantially the entire top surface of the high-density polymer or predominantly polymer material core layer of the cover board 62.The top facer 82 of the prefabricated roofing panel composite 80 may be any sheet material that provides a suitable top major surface for the cover board and facer composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","A preferred sheet material for the top facer 82 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.","Where the prefabricated roofing panel composite 80 is fully adhered to an underlying roofing layer (e.g.","an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 82 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.","a EPDM, PVC, or TPO membrane).","Where the top facer 82 is a waterproofing membrane, the facer may extend beyond the high-density polymer or predominantly polymer material core layer of the cover board 62 on one or more of the four sides of the core layer, e.g.","beyond a side edge and an end edge of the top major surface of the core layer to provide membrane overlaps for sealing with the membranes of adjacent panels.","While, as shown in FIG.","6, the prefabricated roofing panel composite 80 only has a top facer 82, the prefabricated roofing panel composite 80 could have a common facer intermediate and bonded to both the bottom major surface of the cover board core layer and the top major surface of the insulation board core layer, a common facer intermediate and bonded to both the bottom major surface of the insulation board core layer and the top major surface of the baseboard core layer, and/or a bottom facer bonded to the bottom major surface of the baseboard core layer.","When used, the common facers of the prefabricated roofing panel composite 80 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board and insulation board and the insulation board and the baseboard, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.","When used, the bottom facer of the prefabricated roofing panel composite 80 overlies the entire or substantially the entire bottom surface of the high-density core layer of the baseboard 66.The bottom facer of the prefabricated roofing panel composite 80 may be any sheet material that provides a suitable bottom major surface for the prefabricated roofing panel composite 80, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","FIG.","7 is a schematic side view of a first production line 100 that can be used with the method of the subject invention to continuously make prefabricated roofing panel composites of the subject invention in line, such as the prefabricated roofing panel composites 30 of FIG.","3 and 50 of FIG.","4.The prefabricated roofing panel composites 30 and 50 each include a high-density polymer or predominantly polymer material cover board 32 and a low-density polymer or predominantly polymer material foam insulation board 34.The production line 100 includes: a first forming station 102 for forming the low-density polymer or predominantly polymer material foam insulation board 34 of the prefabricated roofing panel composites 30 and 50; a second forming station 104 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50; and a cutting station 106 for cutting the prefabricated roofing panel composites 30 and 50 to length.","The first forming station 102 for forming the low-density foam insulation board 34 includes a conventional dispenser 108 for dispensing a low-density polymer or predominantly polymer material foam precursor 110 (e.g.","a low-density polyisocyanurate or predominantly polyisocyanurate foam precursor) onto a facer, when used, overlying a conveyor 112 of two spaced-apart opposed forming conveyers 112 and 114 or directly onto the conveyor 112.As the foam precursor 110 passes between the forming conveyors 112 and 114, foams and at least partially sets, the forming conveyors 112 and 114 cooperate to set the thickness of the low-density polymer or predominantly polymer material foam core layer 42 of the low-density polymer or predominantly polymer foam insulation board 34 formed from the precursor 110.The first forming station 102 also includes supplies (e.g.","rolls) of facer materials 116 and 118 that can be fed over and/or beneath the low-density polymer or predominantly polymer material foam precursor 110 to form a common facer of the prefabricated roofing panel composites 30 and 50 and a bottom facer of the prefabricated roofing panel composites 30 and 50.The second forming station 104 of the production line 100 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50 includes a conventional dispenser 120 for dispensing a high-density polymer or predominantly polymer material or foam precursor 122 (e.g.","a high-density polyisocyanurate or predominantly polyisocyanurate foam precursor) onto the low-density polymer or predominantly polymer material foam core layer 42 or, when used, a common facer overlying the low-density polymer or predominantly polymer material foam core layer 42.With the high-density polymer or predominantly polymer material precursor 122 overlying the low-density foam core layer 42 or, when used, the common facer, the high-density polymer or predominantly polymer material precursor 122 and the low-density foam core layer 42 pass between two spaced-apart opposed forming conveyers 112 and 124 where the high-density polymer or predominantly polymer material core layer 38 is formed and bonded directly to the low-density foam core layer 42 or to the common facer overlying the low-density foam core layer 42.The spaced-apart opposed forming conveyors 112 and 124 cooperate to set the thickness of both the high-density polymer or predominantly polymer material core layer 40 and the prefabricated roofing panel composite 30 or 50.The second forming station 104 also includes supplies (e.g.","rolls) of a facer material 126 that is fed over the high-density polymer or predominantly polymer material precursor 122 to form the top facer 52 of both the high-density cover board 32 and the prefabricated roofing panel composite 50.With the high-density core layer 40 and the low-density foam core layer 42 of the prefabricated roofing panel composite 30 or 50 bonded together in the second forming station 104 to form a continuous length of the prefabricated roofing panel composite 30 or 50, the prefabricated roofing panel composite 30 or 50 is then cut to length to complete the formation of the prefabricated roofing panel composite 30 or 50.In the cutting station 106 a cutter, such as but not limited to a reciprocating cutter 128, cuts the prefabricated roofing panel composite 30 or 50 coming from the second forming station 104 to length.","While the production line 100, as shown, is capable of applying three facer materials 116, 118, and 126 to the insulation board 34 and the cover board 32 to form the prefabricated roofing panel composites 30 and 50.The application of any one, any two, or all of the facing materials 116, 118 and 126 to the insulation board and cover board can be omitted to form the prefabricated roofing panel composite 30 and all but the top facing material can be omitted to form the prefabricated roofing panel composite 50 with the desired number of facers.","The facers 116, 118 and 126 normally prevent the polymer or predominantly polymer layers from sticking to the conveyors.","However, with a shift in the chemistry of the precursors 110 and 122 to affect the tackiness of the layers produced so that they do not stick to the surfaces of the conveyors or by applying release films or coatings to the surfaces of the conveyers that will not allow the layers produced to stick to the surfaces of the conveyors, when desired, any one or all of the facing materials are not needed for and could be eliminated from the manufacturing process.","FIG.","8 is a schematic side view of a second production line 200 that can be used with the method of the subject invention to continuously make prefabricated roofing panel composites of the subject invention, such as the prefabricated roofing panel composites 30 of FIG.","3 and 50 of FIG.","4.The prefabricated roofing panel composites 30 and 50 each include a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.","The production line 200 includes: an in-feed conveyor 202 for continuously feeding a series of low-density polymer or predominantly polymer material foam insulation boards 34 of the prefabricated roofing panel composite into a forming station 204; the forming station 204 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50; and a cutting station 206 for cutting the prefabricated roofing panel composites 30 and 50 to length.","The low-density polymer or predominantly polymer material foam insulation boards 34 may include a top facer that, when used, forms a common facer of the prefabricated roofing panel composites 30 and 50 and may include a bottom facer that, when used, forms a bottom facer of the prefabricated roofing panel composites.","Preferably, the low-density polymer or predominantly polymer material foam insulation boards 34 are fed into the forming station 204 lengthwise with the ends of successive insulation boards 34 in the continuous series of insulation boards abutting each other.","The forming station 204 of the production line 200 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composite 30 includes a conventional dispenser 208 for dispensing the high-density polymer or predominantly polymer material precursor 210 (e.g.","a high-density polyisocyanurate or predominantly polyisocyanurate precursor) directly onto the low-density foam core layers 42 of the insulation boards 34 or, when used the common facers overlying the low-density foam core layers of the low-density foam insulation boards.","With the high-density polymer or predominantly polymer material precursor 210 directly overlying the low-density foam core layers 42 of the insulation boards or the common facers 36 carried by the low-density foam insulation boards 34, the high-density polymer or predominantly polymer material precursor 210 and the low-density foam insulation boards 34 pass between two spaced-apart opposed forming conveyers 212 and 214 where the high-density polymer or predominantly polymer material core layers 38 of the cover boards 32 are formed and bonded directly to the low-density foam core layers 42 of the insulation boards 34 or to the common facers overlying the low-density foam insulation board 34.The spaced-apart opposed forming conveyors 212 and 214 cooperate to set the thickness of both the high-density polymer or predominantly polymer material core layer 40 and the prefabricated roofing panel composite 30 or 50.The forming station 204 also includes supplies (e.g.","rolls) of a facer material 216 that is fed over the high-density polymer or predominantly polymer material precursor 210 to form the top facer 52 of both the high-density polymer or predominantly polymer material cover board 32 and the prefabricated roofing panel composite 50.With the high-density core layer 40 and the low-density foam core layer 42 of the prefabricated roofing panel composite 30 or 50 bonded together in the forming station 204 to form a continuous length of the prefabricated roofing panel composite 30 or 50, the prefabricated roofing panel composite 30 or 50 is then cut to length to complete the formation of the prefabricated roofing panel composite 30 or 50.In the cutting station 206 a cutter, such as but not limited to a reciprocating cutter 218, cuts the prefabricated roofing panel composite 30 coming from the forming station 204 to length.","The production line 200, as shown, is capable of making the prefabricated roofing panel composite 30 by feeding preformed low-density polymer or predominantly polymer material foam insulation boards 34 into the forming station 204 and omitting the application of the facer material 216 to the cover board 32 and is capable of making the prefabricated roofing panel composite 50 by feeding preformed low-density polymer or predominantly polymer material foam insulation boards 34 into the forming station 204 and applying of the facer material 216 to the cover board 32.The facer 216 normally prevents the high-density polymer or predominantly polymer material layer from sticking to the conveyor 212.However, with a shift in the chemistry of the precursor 210 to affect the tackiness of the layer produced so that the layer does not stick to the surface of the conveyor 212 or by applying a release film or coating to the surface of the conveyer 212 that will not allow the layer produced to stick to the surface of the conveyor, when desired, the facing materials 216 is not needed for and could be eliminated from the manufacturing process.","FIG.","9 is a schematic side view of a production line 300 that can be used with the method of the subject invention to continuously make a prefabricated roofing panel composite of the subject invention, such as the prefabricated roofing panel composites 60 of FIG.","5 and 80 of FIG.","6.These prefabricated roofing panel composites each include: a high-density polymer or predominantly polymer material cover board 62, a low-density polymer or predominantly polymer material foam insulation board 64, and a high-density polymer or predominantly polymer material baseboard 66.The production line 300 includes: a first forming station 302 for forming the high-density polymer or predominantly polymer material baseboard 66 of the prefabricated roofing panel composites 60 and 80; a second forming station 304 for forming the low-density polymer or predominantly polymer material foam insulation board 64 of the prefabricated roofing panel composites 60 and 80; a third forming station 306 for forming the high-density polymer or predominantly polymer material cover board 62 of the prefabricated roofing panel composites 60 and 80; and a cutting station 308 for cutting the prefabricated roofing panel composites 60 and 80 to length.","The first forming station 302 for forming the high-density polymer or predominantly polymer material baseboard 56 includes a conventional dispenser 310 for dispensing a high-density polymer or predominantly polymer material precursor 312 (e.g.","a high-density polyisocyanurate or predominantly polyisocyanurate precursor) onto a facer, when used, overlying a conveyor 314 of two spaced-apart opposed forming conveyers 314 and 316 or directly onto the conveyor 314.As the precursor 310 passes between the forming conveyors 314 and 316, forms and at least partially sets, the forming conveyors 314 and 316 cooperate to set the thickness of the high-density polymer or predominantly polymer material core layer 74 of the high-density baseboard 66 formed from the precursor 310.The first forming station 302 also includes supplies (e.g.","rolls) of facer materials 318 and 320 that may be fed over and/or beneath the high-density polymer or predominantly polymer material precursor 310 to form, when used, a common facer of the prefabricated roofing panel composites 60 and 80 and a bottom facer of the prefabricated roofing panel composites 60 and 80.The second forming station 304 of the production line 300 for forming the low-density polymer or predominantly polymer material foam insulation board 64 of the prefabricated roofing panel composites 60 and 80 includes a conventional dispenser 322 for dispensing a low-density polymer or predominantly polymer material foam precursor 324 (e.g.","a low-density polyisocyanurate or predominantly polyisocyanurate foam precursor) directly onto the high-density core layer 74 or, when used, onto a common facer overlying the high-density core layer 74 of the baseboard 66.With the low-density polymer or predominantly polymer material foam precursor 324 directly overlying high-density core layer 74 or the common facer overlying the high-density core layer 74 of the baseboard 66, the low-density polymer or predominantly polymer material foam precursor 324 and the high-density core layer 74 pass between two spaced-apart opposed forming conveyers 314 and 326 where the low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 is formed and bonded to the high-density core layer 74 or the common facer overlying the high-density core layer 74 of the baseboard 66.The spaced-apart opposed forming conveyors 314 and 326 cooperate to set the thickness of the low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64.The second forming station 304 also includes supplies (e.g.","rolls) of a facer material 328 that can be fed over the low-density polymer or predominantly polymer material foam precursor 324 to form a common facer of the prefabricated roofing panel composites 60 and 80.The third forming station 306 of the production line 300 for forming the high-density polymer or predominantly polymer material cover board 62 of the prefabricated roofing panel composites 60 and 80 includes a conventional dispenser 330 for dispensing a high-density polymer or predominantly polymer material precursor 332 (e.g.","a high-density polyisocyanurate or predominantly polyisocyanurate precursor) directly onto the low-density foam core layer 76 or the common facer overlying the low-density foam core layer 76 of the insulation board 64.With the high-density polymer or predominantly polymer material precursor 332 overlying the low-density foam core layer 76 or the common facer overlying the low-density foam core layer 76, the high-density polymer or predominantly polymer material precursor 332, the low-density foam insulation board 64, and the high-density baseboard 66 pass between two spaced-apart opposed forming conveyers 314 and 334 where the high-density polymer or predominantly polymer material core layer 72 of the cover board 62 is formed and bonded to the low-density foam core layer 76 or the common facer overlying the low-density foam core layer 76 of the insulation board 64.The spaced-apart opposed forming conveyors 314 and 334 cooperate to set the thickness of both the high-density polymer or predominantly polymer material core layer 72 and the prefabricated roofing panel composite 60 or 80.The third forming station 306 also includes supplies (e.g.","rolls) of a facer material 336 that is fed over the high-density polymer or predominantly polymer material precursor 332 to form the top facer 82 of both the high-density cover board 62 and the prefabricated roofing panel composite 80.With the high-density polymer or predominantly polymer material cover board 62, the low-density polymer or predominantly polymer material foam insulation board 64, and the high-density polymer or predominantly polymer material baseboard 66 of the prefabricated roofing panel composites 60 or 80 bonded together in the third forming station 306 to form a continuous length of the prefabricated roofing panel composite 60 or 80, the prefabricated roofing panel composite 60 or 80 is then cut to length to complete the formation of the prefabricated roofing panel composite 60 or 80.In the cutting station 308 a cutter, such as but not limited to a reciprocating cutter 338, cuts the continuous prefabricated roofing panel composite 60 or 80 coming from the third forming station 306 to length.","While the production line 300, as shown, is capable of applying four facer materials 318, 320, 328, and 336 to the baseboard 66, the insulation board 64 and the cover board 62 to form the prefabricated roofing panel composites 60 and 80.The application of any one, any two, any three or all of the facing materials 318, 320, 328, and 336 to the baseboard, the insulation board and the cover board can be omitted to form the prefabricated roofing panel composite 60 and all but the top facing material can be omitted to form the prefabricated roofing panel composite 80 with the desired number of facers.","The facers 318, 320, 328, and 336 normally prevent the composite layers from sticking to the conveyors.","However, with a shift in the chemistry of the precursors 312, 324, and 332 to affect the tackiness of the layers produced so that they do not stick to the surfaces of the conveyors or by applying release films or coatings to the surfaces of the conveyers that will not allow the layers produced to stick to the surfaces of the conveyors, when desired, any one or all of the facing materials are not needed for and could be eliminated from the manufacturing process.","FIG.","10 is a schematic side view of another production line 400 that can be used with the method of the subject invention to continuously make prefabricated roofing panel composites of the subject invention in line, such as the prefabricated roofing panel composites 30 of FIG.","3 and 50 of FIG.","4.The prefabricated roofing panel composites 30 and 50 each include a high-density polymer or predominantly polymer material cover board 32 and a low-density polymer or predominantly polymer material foam insulation board 34.The production line 400 includes: a forming station 402 for forming the low-density polymer or predominantly polymer material foam insulation board 34 and the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50; and a cutting station 404 for cutting the prefabricated roofing panel composites 30 and 50 to length.","The forming station 402 for forming the low-density foam insulation board 34 and the high-density cover board includes a conventional dispenser 406 for dispensing a low-density polymer or predominantly polymer material foam precursor 408 (e.g.","a low-density polyisocyanurate or predominantly polyisocyanurate foam precursor) onto a facer, when used, overlying a conveyor 410 of two spaced-apart opposed forming conveyers 410 and 412 or directly onto the conveyor 410.The forming station 402 also includes a conventional dispenser 414 for dispensing a high-density polymer or predominantly polymer material precursor 416 (e.g.","a high-density polyisocyanurate or predominantly polyisocyanurate material precursor) onto the low-density polymer or predominantly polymer material foam precursor of the core layer 42 or, when used, a common facer overlying the low-density polymer or predominantly polymer material foam precursor of the core layer 42.As the layers of precursor 408 and 416 pass between the forming conveyors 410 and 412, the precursors form and at least partially set, the forming conveyors 410 and 412 cooperate to set the thickness of the low-density polymer or predominantly polymer material foam core layer 42 of insulation board 34 formed from the precursor 408, the thickness of the high-density polymer or predominantly polymer material core layer 40 of cover board 32 formed from the precursor 416, and the thickness of the prefabricated roofing panel composite 30 or 50.The forming station 402 also includes supplies (e.g.","rolls) of facer materials 418, 420, and 422 that can be fed over and/or beneath the low-density polymer or predominantly polymer material foam precursor 408 to form a common facer of the prefabricated roofing panel composites 30 and 50 and a bottom facer of the prefabricated roofing panel composites 30 and 50 and that can be fed over the high-density polymer or predominantly polymer material precursor 416 to form a top facer of the prefabricated roofing panel composites 30 and 50.With the high-density core layer 40 and the low-density foam core layer 42 of the prefabricated roofing panel composite 30 or 50 bonded together to form a continuous length of the prefabricated roofing panel composite 30 or 50, the prefabricated roofing panel composite 30 or 50 is then cut to length to complete the formation of the prefabricated roofing panel composite 30 or 50.In the cutting station 404 a cutter, such as but not limited to a reciprocating cutter 424, cuts the prefabricated roofing panel composite 30 or 50 coming from the forming station 402 to length.","While the production line 400, as shown, is capable of applying three facer materials 418, 420 and 422 to the insulation board 34 and the cover board 32 to form the prefabricated roofing panel composites 30 and 50.The application of any one, any two, or all of the facing materials 418, 420, and 422 to the insulation board and cover board can be omitted to form the prefabricated roofing panel composite 30 and all but the top facing material can be omitted to form the prefabricated roofing panel composite 50 with the desired number of facers.","The facers 418, 420, and 422 normally prevent the layers of the composite from sticking to the conveyors.","However, with a shift in the chemistry of the precursors 408 and 416 to affect the tackiness of the layers produced so that they do not stick to the surfaces of the conveyors or by applying release films or coatings to the surfaces of the conveyers that will not allow the layers produced to stick to the surfaces of the conveyors, when desired, any one or all of the facing materials are not needed for and could be eliminated from the manufacturing process.","Preferably, the low-density polymer or predominantly polymer material foam precursors 110, 324, and 408 are low-density polyisocyanurate or predominantly polymer foam precursors.","Preferably, the high-density polymer or predominantly polymer material precursors 122, 210, 312, 332, and 416 are high-density polyisocyanurate or predominantly polyisocyanurate material precursors.","The high-density polymer or predominantly polymer material precursors 122, 210, 312, 332, and 416 can be formulated to produce high-density materials or foams by significantly reducing or eliminating the blowing agent(s) from the precursors 122, 210, 312, 332, and 416.Pentane (HFC), micro-spheres, CO2 and water (as well as other materials) will act as blowing agents for the precursors.","The relatively high-density layers produced using these types of precursors have improved strength characteristics over the low-density foams normally produced for insulation products.","As the amount of blowing agent is reduced in the precursors 122, 210, 312, 332, and 416, the density and the compressive strength of the high-density layers produced increase.","These types of high-density core layers are much more resistant to deformation than the typical low-density foam core layers.","FIGS.","11 and 12 are fragmentary, transverse schematic, perspective views of a prefabricated cover board composite 520 of the subject invention.","The composite 520 includes the cover board 10 of FIG.","1, a top facer 522 (e.g.","a waterproofing membrane), a bottom facer 524, and a plurality of wind-uplift reinforcement patches 526 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or strips 528 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17).","Conventional fastener plates, such as but not limited to the disc shaped metallic fastener plate 530, are typically used at each fastener penetration of the prefabricated cover board composite 520 to spread the forces exerted on the top major surface of the composite by the nails or other mechanical fasteners securing the composite to a roof deck over a greater surface area and thereby reduce the pressures exerted by the fasteners (not shown) on the top major surface of the composite.","Other than the inclusion of a top facer 522, a bottom facer 524, and a plurality of wind-uplift reinforcements, such as the wind-uplift reinforcement patches 526 or strips 528 the prefabricated cover board composite 520 is the same as the cover board 10 of FIG.","1.The top facer 522 that is bonded to the top major surface of the high-density polymer or predominantly polymer material core layer of the cover board composite 520 may be any sheet material that provides a suitable top major surface for the cover board composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","A preferred sheet material for the top facer 522 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.","Where the cover board composite 520 is fully adhered to an underlying roofing layer (e.g.","an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 522 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.","a EPDM, PVC, or TPO membrane).","Where the top facer 522 is a waterproofing membrane, the facer may extend beyond the high-density polymer or predominantly polymer material core layer of the cover board 10 on one or more of the four sides of the core layer (e.g.","beyond a side edge and an end edge of the top major surface of the core layer) to form membrane overlaps for sealing to the membranes of other composites 520.The bottom facer 524 is bonded to and typically coextensive with the bottom major surface of the high-density polymer or predominantly polymer material core layer of the cover board composite 520.The bottom facer 524 of the composite 520 may be any sheet material that provides a suitable bottom major surface for the cover board composite 520, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","However, a preferred bottom facer 524, is a coated or uncoated woven or nonwoven fiberglass mat such as but not limited to the preferred top facer 522.The wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches 526 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or the wind-uplift reinforcement strips 528 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17), may be made of various reinforcement sheet or mat materials, such as but not limited to sheets or mats of glass, polyester, polypropylene, metal, wool, and other synthetic and natural fibers and combinations of such fibers.","However, a preferred reinforcement material for the wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches and strips is a scrim such as fiberglass scrim with a minimum tensile strength of 30 lbs per linear inch and preferably, a minimum tensile strength of at least 100 lbs per linear inch, e.g.","a fiberglass scrim that is 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands is 0.019 inches.","When a cover board composite is subjected to wind-uplift forces from high winds during service, the wind-uplift forces exerted on a cover board composite, if not controlled, will tend to place the top portion of the composite in compression and the bottom portion of the composite in tension at the fastener locations to thereby place the composite under stress at these locations.","Repeated cycles of stress exerted on a cover board composite at the fastener locations during service can result in a failure of the composite at one or more of the fastener locations.","The wind-uplift reinforcements of the subject invention, e.g.","the wind-uplift reinforcement patches 526 or reinforcement strips 528, greatly increase the pressures that the cover board composite can withstand before failure at a fastener location.","While the cover board composite still flexes, the wind-uplift reinforcements of the subject invention extend or increase the load the bottom facer can withstand before the bottom facer 524 fails at a fastener location.","The wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches 526 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or the wind-uplift reinforcement strips 528 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17) are interposed between the bottom facer 524 and the bottom major surface of the core layer to coincide with a selected fastener pattern or selected fastener patterns for securing the cover board composite 520 to a roof deck and increase a per-fastener wind-uplift pull through rating for the cover board composite.","FIG.","13 is a fragmentary, transverse schematic, perspective view of a prefabricated cover board/insulation board panel composite 540 of the subject invention.","The panel composite 540 includes the cover board/insulation board panel composite 30 of FIG.","3, which includes a cover board 32 with a high-density polymer or predominantly polymer material core layer and an insulation board 34 with a low-density polymer or predominantly polymer material core layer; a top facer 542 (e.g.","a waterproofing membrane); a bottom facer 544; and a plurality of wind-uplift reinforcement patches 546 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or strips 548 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17).","Fastener plates, such as but not limited to the fastener plate 550, are typically used at each fastener penetration of the prefabricated cover board/insulation board panel composite 540 to spread the forces exerted on the top major surface of the panel composite by the fasteners securing the composite to a roof deck over a greater surface area and thereby reduce the pressures exerted by the fasteners (not shown) on the top major surface of the panel composite.","Other than the inclusion of a top facer 542, a bottom facer 544, and a plurality of wind-uplift reinforcements, such as the wind-uplift reinforcement patches 546 or strips 548 the prefabricated cover board/insulation board panel composite 540 is the same as the cover board/insulation board panel composite 30 of FIG.","3.The top facer 542 that is bonded to the top major surface of the high-density polymer or predominantly polymer material core layer of the cover board 32 may be any sheet material that provides a suitable top major surface for the cover board/insulation board panel composite 540, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","A preferred sheet material for the top facer 542 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.","The bottom facer 544 is bonded to and typically coextensive with the bottom major surface of the low-density polymer or predominantly polymer material core layer of the insulation board 34.The bottom facer 544 of the composite 540 may be any sheet material that provides a suitable bottom major surface for the cover board/insulation board composite 540, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","However, a preferred bottom facer 544, is a coated or uncoated woven or nonwoven fiberglass mat such as but not limited to the preferred the top facer 542.The wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches 546 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or the wind-uplift reinforcement strips 548 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17), may be made of various reinforcement sheet or mat materials, such as but not limited to sheets or mats of glass, polyester, polypropylene, metal, wool, and other synthetic and natural fibers and combinations of such fibers.","However, a preferred reinforcement material for the wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches and strips is a scrim such as fiberglass scrim with a minimum tensile strength of 30 lbs per linear inch and preferably, a minimum tensile strength of at least 100 lbs per linear inch, e.g.","a fiberglass scrim that is 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands is 0.019 inches.","The wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches 546 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or the wind-uplift reinforcement strips 548 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17) are interposed between the bottom facer 544 and the bottom major surface of the insulation board core layer to coincide with a selected fastener pattern or selected fastener patterns for securing the cover board, insulation board panel composite 540 to a roof deck and increase a per-fastener wind-uplift pull through rating for the cover board/insulation board panel composite.","The wind-uplift reinforcements of the cover board/insulation board panel composite 540 perform the same or substantially the same function as the wind-uplift reinforcements of the cover board composite 520.FIG.","14 is a fragmentary, transverse schematic, perspective view of a prefabricated cover board/insulation board/baseboard panel composite 560 of the subject invention.","The panel composite 560 includes the roofing panel composite 60 of FIG.","5, which includes a cover board 62 with a high-density polymer or predominantly polymer material core layer, an insulation board 64 with a low-density polymer or predominantly polymer material foam core layer; a baseboard 66 with a high-density polymer or predominantly polymer material core layer; a top facer 562 (e.g.","a waterproofing membrane), a bottom facer 564, and a plurality of wind-uplift reinforcement patches 566 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or strips 568 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17).","Fastener plates, such as but not limited to the fastener plate 570, are typically used at each fastener penetration of the prefabricated cover board/insulation board/baseboard panel composite 560 to spread the forces exerted on the top major surface of the composite by the fasteners securing the composite to a roof deck over a greater surface area and thereby reduce the pressures exerted by the fasteners (not shown) on the top major surface of the panel composite.","Other than the inclusion of a top facer 562, a bottom facer 564, and a plurality of wind-uplift reinforcements, such as the wind-uplift reinforcement patches 566 or strips 568 the prefabricated cover board/insulation board/baseboard panel composite 560 is the same as the cover board/insulation board/baseboard panel composite 60 of FIG.","5.The top facer 562 that is bonded to the top major surface of the high-density polymer or predominantly polymer material core layer of the cover board 62 may be any sheet material that provides a suitable top major surface for the cover board/insulation board/baseboard panel composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","A preferred sheet material for the top facer 522 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.","The bottom facer 564 is bonded to and typically coextensive with the bottom major surface of the high-density polymer or predominantly polymer material core layer of the baseboard 66.The bottom facer 564 of the composite 560 may be any sheet material that provides a suitable bottom major surface for the cover board/insulation board/baseboard composite 560, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.","However, a preferred bottom facer 564, is a coated or uncoated woven or nonwoven fiberglass mat such as but not limited to the preferred top facer 562.The wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches 566 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or the wind-uplift reinforcement strips 568 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17), may be made of various reinforcement sheet or mat materials, such as but not limited to sheets or mats of glass, polyester, polypropylene, metal, wool, and other synthetic and natural fibers and combinations of such fibers.","However, a preferred reinforcement material for the wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches and strips is a scrim such as fiberglass scrim with a minimum tensile strength of 30 lbs per linear inch and preferably, a minimum tensile strength of at least 100 lbs per linear inch, e.g.","a fiberglass scrim that is 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands is 0.019 inches.","The wind-uplift reinforcements, e.g.","the wind-uplift reinforcement patches 566 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.","15 and 16) or the wind-uplift reinforcement strips 568 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.","17) are interposed between the bottom facer 564 and the bottom major surface of the baseboard core layer to coincide with a selected fastener pattern or selected fastener patterns for securing the cover board/insulation board/baseboard panel composite 560 to a roof deck and increase a per-fastener wind-uplift pull through rating for the cover board/insulation board/baseboard panel composite.","The wind-uplift reinforcements of the cover board/insulation board/baseboard panel composite 560 perform the same or substantially the same function as the wind-uplift reinforcements of the cover board composite 520.FIGS.","15 and 16 show an eight-fastener wind-uplift reinforcement patch placement pattern, utilizing a single patch and a double patch arrangement, for securing the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 to a roofing deck.","The eight-fastener wind-uplift reinforcement patch placement pattern shown is exemplary and it is to be understood that the wind-uplift reinforcement patch placement patterns for the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 can be selected to accommodate any desired fastener placement pattern including any one or more of the fastener placement patterns commonly utilized in the roofing industry.","In the embodiment shown in FIG.","15, single wind-uplift reinforcement patches 526, 546, and 566 are utilized.","In the embodiment of FIG.","16, double wind-uplift patches 528, 548, and 568 are utilized with the overlying wind-uplift reinforcement patches having a 45° offset relative to the wind-uplift reinforcement patches overlaid.","Preferably, the wind-uplift reinforcement patches 528, 548, and 568 are at least three inches by three inches and centered over each of the fastener placement locations.","Examples of preferred wind-uplift reinforcement patches are: generally square patches that have dimensions between about three inches by about three inches and about six inches by about six inches; generally round patches that have diameters between about three inches and about six inches; and generally rectangular, oval and other shaped patches having a minor dimension between about three inches and about six inches and a major dimension between about three inches and about six inches.","Preferably, the top surface of a cover board composite 520, a cover board/insulation board panel composite 540, or a cover board/insulation board/baseboard panel composite 560 utilizing the single or double wind-uplift reinforcement patches will be visibly marked to indicate the locations of the wind-uplift reinforcement patches on the underside of the composite so that a roofing installer will know exactly where to pass fasteners for securing the composite to a roof deck through the composite and the wind-uplift reinforcement patches located on the underside of the composite in the fastener placement pattern being utilized to secure the composite to a roof deck.","For example, visible X and/or 0 markings could be placed on the top surface of a composite that are centered over the centers of each of the single or double wind-uplift reinforcement patches on the underside of the composite.","FIG.","17 shows a wind-uplift reinforcement strip placement pattern, which can be used for an eight-fastener placement or other fastener placement pattern, for securing the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 to a roofing deck.","The wind-uplift reinforcement strip placement pattern shown for the wind-uplift reinforcement strips 528, 548 and 568 is exemplary and it is to be understood that the reinforcement strip placement patterns for the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 can be selected to accommodate any desired fastener placement pattern including any one or more of the fastener placement patterns commonly utilized in the roofing industry.","Preferably, the wind-uplift reinforcement strips 528, 548 and 568 are between about three and about six inches wide, run the length and/or width of the composite, and have their longitudinal centerlines centered over fastener placement locations.","Preferably, the top surface of a cover board composite 520, a cover board/insulation board panel composite 540, or a cover board/insulation board/baseboard panel composite 560 utilizing the wind-uplift reinforcement strips will be visibly marked to indicate the locations of the wind-uplift reinforcement strips on the underside of the composite so that a roofing installer will know exactly where to pass fasteners for securing the composite to a roof deck through the composite and the wind-uplift reinforcement strips located on the underside of the composite in the fastener placement pattern being utilized to secure the composite to a roof deck.","For example, visible solid or dashed line markings or visible solid or dashed line markings with X and 0 markings in various fastener placement patterns could be placed on the top surface of a composite with the line markings centered over and extending along the longitudinal centerlines of the wind-uplift reinforcement strips on the underside of the composite.","Tests were conducted to determine fastener pull through strength for a 0.25 inch thick polyisocyanurate cover board: a) with only a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board; b) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and a scrim reinforcement interposed between the bottom facer and the bottom major surface of the cover board and also substantially coextensive with the bottom major surface of the cover board; c) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and six inch wide scrim reinforcement strips interposed between the bottom facer and the bottom major surface of the cover board, running the length of the cover board, and having longitudinal centerlines centered over the fastener penetration locations; d) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and three inch wide scrim reinforcement strips interposed between the bottom facer and the bottom major surface of the cover board, running the length of the cover board, and having longitudinal centerlines centered over the fastener penetration locations; e) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and six inch square scrim reinforcement patches interposed between the bottom facer and the bottom major surface of the cover board and centered over the fastener penetration locations; and f) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and two layers of six inch square scrim reinforcement patches interposed between the bottom facer and the bottom major surface of the cover board and centered over the fastener penetration locations.","The scrim material used in the tests was a fiberglass scrim having a tensile strength of 105 lbs per linear inch.","The scrim material was 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands was 0.019 inches.","The measured per fastener wind-uplift pull through strengths for these composites was: a) coated nonwoven glass fiber facer alone—160 lbf (pounds of force); b) coated nonwoven glass fiber facer and scrim reinforcement that is substantially coextensive with the bottom major surface of the cover board—300 lbf; c) coated nonwoven glass fiber facer and six-inch wide scrim reinforcement strips 275 lbf; d) coated nonwoven glass fiber facer and three-inch wide scrim reinforcement strips—250 lbf; e) coated nonwoven glass fiber facer and six inch square scrim reinforcement patches—240 lbf; and f) coated nonwoven glass fiber facer and two layers of six-inch square scrim reinforcement patches—350 lbf.","The coverage rate of the scrim reinforcement (area of the bottom major surface of a cover board or other roofing panel composite covered by scrim reinforcement) for the scrim reinforcement embodiments set forth immediately above will vary with the fastener location pattern utilized.","However, for the scrim reinforcement embodiments set forth immediately above, an eight fastener location pattern on a four by eight foot cover board or other roofing panel composite (i.e.","a cover board or other roofing panel composite with a 32 ft2 bottom major surface) results in the following coverage rates: a) coated nonwoven glass fiber facer alone—0 ft2 coverage; b) coated nonwoven glass fiber facer and scrim reinforcement that is substantially coextensive with the bottom major surface of the cover board—32 ft2 coverage; c) coated nonwoven glass fiber facer and six inch wide scrim reinforcement strips 8 ft2 coverage; d) coated nonwoven glass fiber facer and three inch wide scrim reinforcement strips—4 ft2 coverage; e) coated nonwoven glass fiber facer and six inch square scrim reinforcement patches—2 ft2 coverage; and f) coated nonwoven glass fiber facer and two layers of six inch square scrim reinforcement patches—2 ft2 coverage with 4 ft2 of scrim utilized.","With embodiment “f” (coated nonwoven glass fiber facer and two layers of six inch square scrim reinforcement patches—2 ft2 coverage with 4 ft2 of scrim utilized) a 90 pounds/ft2 wind-uplift rating may be achieved for a cover board using only eight fasteners to secure the cover board whereas for embodiment “a” (coated nonwoven glass fiber facer alone) sixteen fasteners must be utilized to achieve a 90 pound/ft2 wind-uplift rating for the cover board.","Fasteners and their installation commonly represent approximately 40% of cover board installation costs.","The scrim reinforcements of the subject invention enable a reduction in the number of fasteners required to achieve a specific wind-uplift rating for an installed cover board.","Thus, for a roofing system with a specific wind-uplift rating, the scrim reinforcements of the subject invention can significantly reduce the labor and ultimately, the overall installed cost of the roofing system.","Of course, an installer can retain the normal number of fasteners utilized per cover board and significantly increase the wind-uplift rating for the installed cover board.","In addition, while the use of a scrim reinforcement that is substantially coextensive with the bottom major surface of a cover board or other roofing panel composite can significantly increase the per fastener wind-uplift pull through rating, the scrim reinforcement of the subject invention can substantially reduce the square footage of scrim reinforcement required to significantly increase the per fastener wind-uplift pull through rating (e.g.","32 ft2 for full scrim reinforcement coverage vs. 8 ft2, 4 ft2, or 2 ft2 coverage for reinforcements of the subject invention for an eight fastener location pattern on a four by eight foot cover board or other roofing panel composite).","In describing the invention, certain embodiments have been used to illustrate the invention and the practices thereof.","However, the invention is not limited to these specific embodiments as other embodiments and modifications within the spirit of the invention will readily occur to those skilled in the art on reading this specification.","For example, the prefabricated roofing panel composites could be in an upside down orientation to that shown and described in connection with FIGS.","7 to 9.Thus, the invention is not intended to be limited to the specific embodiments disclosed, but is to be limited only by the claims appended hereto."]],"string":"[\n [\n \"ROOFING SYSTEMS AND METHODS\",\n \"A method includes providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.\",\n \"A first polymer or predominantly polymer material foam precursor is dispensed to the production line, and allowed to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density.\",\n \"A second polymer or predominantly polymer material foam precursor is dispensed to the production line and allowed to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density.\",\n \"The combined thickness of the foam core layer for the insulation board and the core layer for the cover board is set by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors.\"\n ],\n [\n \"1.A method, comprising: providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor; dispensing to the production line a first polymer or predominantly polymer material foam precursor; allowing the first foam precursor to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density; dispensing to the production line a second polymer or predominantly polymer material foam precursor; allowing the second foam precursor to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density; and setting the combined thickness of the foam core layer for the insulation board and the core layer for the cover board by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors and positioned downstream of the dispensing of the second polymer or predominantly polymer foam precursor.\",\n \"2.The method of claim 1, further comprising providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"3.The method of claim 1, further comprising setting the thickness of the foam core layer for the insulation board by constraining the expansion of the first polymer or predominantly polymer material foam precursor using an upstream forming conveyor disposed above the rising first polymer or predominantly polymer material foam precursor, the upstream forming conveyor positioned upstream of the dispensing of the second polymer or predominantly polymer foam precursor.\",\n \"4.The method of claim 3, further comprising providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"5.The method of claim 1, wherein the expansion of the first polymer or predominantly polymer material foam precursor is not constrained by any forming conveyor other than the downstream forming conveyor.\",\n \"6.The method of claim 5, further comprising providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"7.The method of claim 1, further comprising providing an upper facer material on top of the second polymer or predominantly polymer material foam precursor, to form a top facer of a composite panel comprising the insulation board and the cover board.\",\n \"8.The method of claim 1, wherein dispensing the first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.\",\n \"9.The method of claim 1, wherein dispensing the second polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.\",\n \"10.The method of claim 1, wherein dispensing a first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polystyrene.\",\n \"11.The method of claim 1, further comprising cutting the cover board and the insulation board to length.\",\n \"12.The method of claim 1, further comprising installing the insulation board and the cover board on a roof.\",\n \"13.The method of claim 1, further comprising applying and bonding a bottom facer to the foam core layer of the insulation board with a reinforcing means interposed between the bottom facer and a bottom major surface of the core layer of the insulation board, the reinforcing means positioned to coincide with a fastener pattern for securing the roofing system panels being formed to a roof deck and increase a per-fastener wind-uplift pull through rating for the roofing system panels being formed.\",\n \"14.The method of claim 13, wherein the reinforcing means comprises reinforcing patches.\",\n \"15.The method of claim 13, wherein the reinforcing means comprises reinforcing strips.\",\n \"16.The method of claim 1, wherein the density of the core layer of the cover board after setting is between 6 lb/ft3 and 25 lb/ft3.17.The method of claim 1, wherein the density of the core layer of the cover board after setting is between 4 lb/ft3 and 25 lb/ft3.18.The method of claim 1, wherein the density of the core layer of the insulation board after setting is less than 4 lb/ft3.19.The method of claim 1, wherein the density of the core layer of the insulation board after setting is less than 2.5 lb/ft3.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>The subject invention relates to low-slope roofs that are typically found on commercial and industrial buildings and in particular to prefabricated high-density polymer or predominantly polymer material cover boards and cover board composites and prefabricated roofing panel composites which include high-density polymer or predominantly polymer material cover boards and low-density polymer or predominantly polymer material foam insulation boards, for use on such low-slope roofs and to a method of making the cover boards, the cover board composites, and the roofing panel composites.\",\n \"Commercial and industrial buildings typically have roofs with low-slope roof decks.\",\n \"The roofing systems for these roofs with low-slope roof decks typically include one or more layers of a low-density roofing insulation, a layer of roofing cover boards that overlie the low-density roofing insulation layer(s), and a waterproofing membrane that overlies the layer of cover boards.\",\n \"The layer(s) of low-density insulation, such as a low-density polymer-based foam insulation, if not protected, can be partially crushed or otherwise damaged from worker traffic over the insulation, the placement of heaving objects on the insulation, the weather, and other causes commonly encountered in roofing construction.\",\n \"The layer of roofing cover boards that overlies the one or more layers of low-density insulation, protects the more fragile low density insulation from damage, acts as a fire barrier, provides a suitable substrate for the attachment of the overlying waterproofing membrane, and augments the insulating function of the low-density insulation.\",\n \"The uppermost waterproofing membrane layer overlying the cover board layer protects the underlying cover board and insulation layers from moisture and other adverse climatic conditions.\",\n \"Normally, these three components (the low-density insulation boards, the roofing cover boards, and the waterproofing membrane) of the roofing system are separately manufactured and separately and successively applied to the low-slope roof deck.\",\n \"While these roofing systems function very well, there has remained a need to provide improved roofing cover boards and prefabricated cover board composites and to provide prefabricated roofing panel composites that include at least an insulation board and the improved roofing cover board, and that, preferably, include an insulation board and prefabricated the roofing cover board composite having a waterproofing membrane.\",\n \"With the use of such improved roofing cover boards and cover board composites and prefabricated roofing panel composites, roofing systems for low-slope roof decks can be improved and/or the time, labor, and other costs associated with the installation of roofing systems on low-slope roof decks can be reduced.\",\n \"The subject invention provides improved roofing cover boards, improved prefabricated roofing cover board and waterproofing membrane composites, improved prefabricated roofing panel cover board and insulation board composites, improved prefabricated roofing panel cover board, insulation board, and waterproofing membrane composites, and improved prefabricated roofing panel cover board, insulation board, baseboard, and waterproofing membrane composites.\",\n \"The subject invention also provides these roofing cover boards, roofing cover board composites, and roofing panel composites with reinforcing patches or strips that increase the per fastener wind uplift pull through rating for the cover boards, cover board composites, and roofing panel composites to thereby further reduce the labor and ultimately the overall installed cost of roofing systems utilizing these cover boards, cover board composites, and roofing panel composites.\",\n \"The subject invention also provides a method for making the improved roofing cover board and the prefabricated roofing panel composites including the improved roofing cover board that is highly productive, relatively economical, and efficient.\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>According to one aspect, a method comprises providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.\",\n \"The method further comprises dispensing to the production line a first polymer or predominantly polymer material foam precursor, and allowing the first foam precursor to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density.\",\n \"The method further comprises dispensing to the production line a second polymer or predominantly polymer material foam precursor and allowing the second foam precursor to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density.\",\n \"The method further comprises setting the combined thickness of the foam core layer for the insulation board and the core layer for the cover board by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors and positioned downstream of the dispensing of the second polymer or predominantly polymer foam precursor.\",\n \"In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"In some embodiments, the method further comprises setting the thickness of the foam core layer for the insulation board by constraining the expansion of the first polymer or predominantly polymer material foam precursor using an upstream forming conveyor disposed above the rising first polymer or predominantly polymer material foam precursor, the upstream forming conveyor positioned upstream of the dispensing of the second polymer or predominantly polymer foam precursor.\",\n \"In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"In some embodiments, the expansion of the first polymer or predominantly polymer material foam precursor is not constrained by any forming conveyor other than the downstream forming conveyor.\",\n \"In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"In some embodiments, the method further comprises providing an upper facer material on top of the second polymer or predominantly polymer material foam precursor, to form a top facer of a composite panel comprising the insulation board and the cover board.\",\n \"In some embodiments, dispensing the first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.\",\n \"In some embodiments, dispensing the second polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.\",\n \"In some embodiments, dispensing a first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polystyrene.\",\n \"In some embodiments, the method further comprises cutting the cover board and the insulation board to length.\",\n \"In some embodiments, the method further comprises installing the insulation board and the cover board on a roof.\",\n \"In some embodiments, the method further comprises applying and bonding a bottom facer to the foam core layer of the insulation board with a reinforcing means interposed between the bottom facer and a bottom major surface of the core layer of the insulation board, the reinforcing means positioned to coincide with a fastener pattern for securing the roofing system panels being formed to a roof deck and increase a per-fastener wind-uplift pull through rating for the roofing system panels being formed.\",\n \"The reinforcing means may comprise reinforcing patches.\",\n \"The reinforcing means may comprise reinforcing strips.\",\n \"The density of the core layer of the cover board after setting may be between 6 lb/ft 3 and 25 lb/ft 3 .\",\n \"The density of the core layer of the cover board after setting may be between 4 lb/ft 3 and 25 lb/ft 3 .\",\n \"The density of the core layer of the insulation board after setting may be less than 4 lb/ft 3 .\",\n \"The density of the core layer of the insulation board after setting may be less than 2.5 lb/ft 3 .\"\n ],\n [\n \"This patent application is a continuation of pending U.S. patent application Ser.\",\n \"No.\",\n \"15/193,729, filed Jun.\",\n \"27, 2016 and titled “Roofing Systems and Methods”, which is a division of U.S. patent application Ser.\",\n \"No.\",\n \"14/293,004, filed Jun.\",\n \"2, 2014 and titled “Roofing Systems and Methods”, (now U.S. Pat.\",\n \"No.\",\n \"9,404,261), which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"13/908,505, filed Jun.\",\n \"3, 2013 and titled “Prefabricated Roofing Panel Composite”, (now abandoned), which is a division of U.S. patent application Ser.\",\n \"No.\",\n \"13/209,710, filed Aug. 15, 2011, (now U.S. Pat.\",\n \"No.\",\n \"8,479,467), which is a continuation-in-part of U.S. patent application Ser.\",\n \"No.\",\n \"12/703,308, filed Feb. 10, 2010 and titled “Roofing Cover Board, Roofing Panel Composites and Method”, (now U.S. Pat.\",\n \"No.\",\n \"8,105,685), which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"11/519,042, filed Sep. 11, 2006 and titled “Roofing Cover Board, Roofing Panel Composites, and Method” (now U.S. Pat.\",\n \"No.\",\n \"7,811,663), which is a continuation-in-part of U.S. patent application Ser.\",\n \"No.\",\n \"10/984,122, filed Nov. 9, 2004 and titled “Roofing Cover Board, Roofing Panel Composite, and Method” (now abandoned), the entire disclosures of which are hereby incorporated by reference herein for all purposes.\",\n \"BACKGROUND OF THE INVENTION The subject invention relates to low-slope roofs that are typically found on commercial and industrial buildings and in particular to prefabricated high-density polymer or predominantly polymer material cover boards and cover board composites and prefabricated roofing panel composites which include high-density polymer or predominantly polymer material cover boards and low-density polymer or predominantly polymer material foam insulation boards, for use on such low-slope roofs and to a method of making the cover boards, the cover board composites, and the roofing panel composites.\",\n \"Commercial and industrial buildings typically have roofs with low-slope roof decks.\",\n \"The roofing systems for these roofs with low-slope roof decks typically include one or more layers of a low-density roofing insulation, a layer of roofing cover boards that overlie the low-density roofing insulation layer(s), and a waterproofing membrane that overlies the layer of cover boards.\",\n \"The layer(s) of low-density insulation, such as a low-density polymer-based foam insulation, if not protected, can be partially crushed or otherwise damaged from worker traffic over the insulation, the placement of heaving objects on the insulation, the weather, and other causes commonly encountered in roofing construction.\",\n \"The layer of roofing cover boards that overlies the one or more layers of low-density insulation, protects the more fragile low density insulation from damage, acts as a fire barrier, provides a suitable substrate for the attachment of the overlying waterproofing membrane, and augments the insulating function of the low-density insulation.\",\n \"The uppermost waterproofing membrane layer overlying the cover board layer protects the underlying cover board and insulation layers from moisture and other adverse climatic conditions.\",\n \"Normally, these three components (the low-density insulation boards, the roofing cover boards, and the waterproofing membrane) of the roofing system are separately manufactured and separately and successively applied to the low-slope roof deck.\",\n \"While these roofing systems function very well, there has remained a need to provide improved roofing cover boards and prefabricated cover board composites and to provide prefabricated roofing panel composites that include at least an insulation board and the improved roofing cover board, and that, preferably, include an insulation board and prefabricated the roofing cover board composite having a waterproofing membrane.\",\n \"With the use of such improved roofing cover boards and cover board composites and prefabricated roofing panel composites, roofing systems for low-slope roof decks can be improved and/or the time, labor, and other costs associated with the installation of roofing systems on low-slope roof decks can be reduced.\",\n \"The subject invention provides improved roofing cover boards, improved prefabricated roofing cover board and waterproofing membrane composites, improved prefabricated roofing panel cover board and insulation board composites, improved prefabricated roofing panel cover board, insulation board, and waterproofing membrane composites, and improved prefabricated roofing panel cover board, insulation board, baseboard, and waterproofing membrane composites.\",\n \"The subject invention also provides these roofing cover boards, roofing cover board composites, and roofing panel composites with reinforcing patches or strips that increase the per fastener wind uplift pull through rating for the cover boards, cover board composites, and roofing panel composites to thereby further reduce the labor and ultimately the overall installed cost of roofing systems utilizing these cover boards, cover board composites, and roofing panel composites.\",\n \"The subject invention also provides a method for making the improved roofing cover board and the prefabricated roofing panel composites including the improved roofing cover board that is highly productive, relatively economical, and efficient.\",\n \"SUMMARY OF THE INVENTION According to one aspect, a method comprises providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.\",\n \"The method further comprises dispensing to the production line a first polymer or predominantly polymer material foam precursor, and allowing the first foam precursor to rise and at least partially set to form a foam core layer for an insulation board, the foam core layer for the insulation board having a first density.\",\n \"The method further comprises dispensing to the production line a second polymer or predominantly polymer material foam precursor and allowing the second foam precursor to rise and set to form a core layer for a cover board, the foam core layer for the cover board having a second density greater than the first density.\",\n \"The method further comprises setting the combined thickness of the foam core layer for the insulation board and the core layer for the cover board by constraining the expansion of the combined foam precursors using a downstream forming conveyor disposed above the rising foam precursors and positioned downstream of the dispensing of the second polymer or predominantly polymer foam precursor.\",\n \"In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"In some embodiments, the method further comprises setting the thickness of the foam core layer for the insulation board by constraining the expansion of the first polymer or predominantly polymer material foam precursor using an upstream forming conveyor disposed above the rising first polymer or predominantly polymer material foam precursor, the upstream forming conveyor positioned upstream of the dispensing of the second polymer or predominantly polymer foam precursor.\",\n \"In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"In some embodiments, the expansion of the first polymer or predominantly polymer material foam precursor is not constrained by any forming conveyor other than the downstream forming conveyor.\",\n \"In some embodiments, the method further comprises providing a common facer material on top of the first polymer or predominantly polymer material foam precursor, to form a common facer between the core layer for the insulation board and the core layer for the cover board.\",\n \"In some embodiments, the method further comprises providing an upper facer material on top of the second polymer or predominantly polymer material foam precursor, to form a top facer of a composite panel comprising the insulation board and the cover board.\",\n \"In some embodiments, dispensing the first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.\",\n \"In some embodiments, dispensing the second polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polyisocyanurate.\",\n \"In some embodiments, dispensing a first polymer or predominantly polymer material foam precursor comprises dispensing a foam precursor comprising polystyrene.\",\n \"In some embodiments, the method further comprises cutting the cover board and the insulation board to length.\",\n \"In some embodiments, the method further comprises installing the insulation board and the cover board on a roof.\",\n \"In some embodiments, the method further comprises applying and bonding a bottom facer to the foam core layer of the insulation board with a reinforcing means interposed between the bottom facer and a bottom major surface of the core layer of the insulation board, the reinforcing means positioned to coincide with a fastener pattern for securing the roofing system panels being formed to a roof deck and increase a per-fastener wind-uplift pull through rating for the roofing system panels being formed.\",\n \"The reinforcing means may comprise reinforcing patches.\",\n \"The reinforcing means may comprise reinforcing strips.\",\n \"The density of the core layer of the cover board after setting may be between 6 lb/ft3 and 25 lb/ft3.The density of the core layer of the cover board after setting may be between 4 lb/ft3 and 25 lb/ft3.The density of the core layer of the insulation board after setting may be less than 4 lb/ft3.The density of the core layer of the insulation board after setting may be less than 2.5 lb/ft3.BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a schematic perspective view of a prefabricated high-density polymer or predominantly polymer material cover board of the subject invention.\",\n \"FIG.\",\n \"2 is a schematic perspective view of a cover board composite of the subject invention that includes a prefabricated high-density polymer or predominantly polymer material cover board and a top facer.\",\n \"FIG.\",\n \"3 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.\",\n \"FIG.\",\n \"4 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board composite with a top facer and a low-density polymer or predominantly polymer material foam insulation board.\",\n \"FIG.\",\n \"5 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board, a low-density polymer or predominantly polymer material foam insulation board, and a high-density polymer or predominantly polymer material baseboard.\",\n \"FIG.\",\n \"6 is a schematic perspective view of a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board composite with a top facer, a low-density polymer or predominantly polymer material foam insulation board, a high-density polymer or predominantly polymer material baseboard.\",\n \"FIG.\",\n \"7 is a schematic side view of a first production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.\",\n \"FIG.\",\n \"8 is a schematic side view of a second production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.\",\n \"FIG.\",\n \"9 is a schematic side view of a production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board, a low-density polymer or predominantly polymer material foam insulation board, and a high-density polymer or predominantly polymer material baseboard.\",\n \"FIG.\",\n \"10 is a schematic side view of a third production line that can be used with the method of the subject invention to make a prefabricated roofing panel composite of the subject invention that includes a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.\",\n \"FIG.\",\n \"11 is a fragmentary, transverse schematic, perspective view of a cover board composite of the subject invention, at a fastener location, wherein the composite includes a reinforcement for increasing the fastener wind-uplift pull through rating of the cover board composite.\",\n \"The Figure also shows a portion of a fastener plate that can be used with the composite.\",\n \"FIG.\",\n \"12 is a fragmentary, partially exploded, transverse schematic, perspective view of the cover board composite of FIG.\",\n \"11 at a fastener location.\",\n \"FIG.\",\n \"13 is a fragmentary, transverse schematic, perspective view of a prefabricated cover board/insulation board panel composite of the subject invention, at a fastener location, wherein the panel composite includes a reinforcement for increasing the fastener wind-uplift pull through rating of the panel composite.\",\n \"The Figure also shows a portion of a fastener plate that can be used with the panel composite.\",\n \"FIG.\",\n \"14 is a fragmentary, schematic, perspective view of a prefabricated cover board/insulation board/baseboard panel composite of the subject invention, at a fastener location, wherein the panel composite includes a reinforcement for increasing the fastener wind-uplift pull through rating of the panel composite.\",\n \"The Figure also shows a portion of a fastener plate that can be used with the composite.\",\n \"FIG.\",\n \"15 is a schematic bottom view of the prefabricated cover board, cover board/insulation board panel, or cover board/insulation board/baseboard panel composites of FIGS.\",\n \"11 to 14, with the bottom facer removed, to show a reinforcement patch pattern for increasing the fastener wind-uplift pull through rating of the composites.\",\n \"FIG.\",\n \"16 is a schematic bottom view of the prefabricated cover board, cover board/insulation board panel, or cover board/insulation board/baseboard panel composites of FIGS.\",\n \"11 to 14, with the bottom facer removed, to show a double-layer reinforcement patch pattern for increasing the fastener wind-uplift pull through rating of the composites.\",\n \"FIG.\",\n \"17 is a schematic bottom view of the prefabricated cover board, cover board/insulation board panel, or cover board/insulation board/baseboard panel composites of FIGS.\",\n \"11 to 14, with the bottom facer removed, to show a reinforcement strip pattern for increasing the fastener wind-uplift pull through rating of the composites.\",\n \"DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG.\",\n \"1 is a schematic perspective view of the cover board 10 of the subject invention, which has a high-density polymer or predominantly polymer material core layer 12.The high-density polymer or predominantly polymer material core layer 12 of the cover board 10 has a density of at least 4 lbs/ft3 and preferably between 6 lbs/ft3 and 25 lbs/ft3.The high-density polymer or predominantly polymer material core layer 12 of the cover board 10 has a thickness of about 0.08 inches or greater and, preferably, a thickness between about 0.25 inches and about 0.75 inches.\",\n \"The density and thickness of the high-density polymer or predominantly polymer material core layer 12 of the cover board 10 are selected to provide the cover board with the compressive strength to resist deformation and protect low-density insulation layers overlaid by the cover board from damage, and to provide surface characteristics that promote the bonding of a top facer, e.g.\",\n \"a waterproofing membrane, to the high-density core layer of the cover board.\",\n \"The high-density polymer or predominantly polymer material core layer 12 has a top major surface 14 and a bottom major surface 16 that are each defined by the length and the width of the high-density polymer or predominantly polymer material core layer.\",\n \"The high-density polymer or predominantly polymer material core layer 12 typically has a width of about four feet or greater and a length of about four feet or greater, preferably, about eight feet or greater and could have lengths that are limited only by the ability to store, transport, and handle the high-density polymer or predominantly polymer material cover board 10 prior to installation.\",\n \"The cover board 10 may have top and/or bottom facers that are not shown in FIG.\",\n \"1.When used, the top and/or bottom facers typically overlie the entire or substantially the entire major surface 14 and/or 16 of the high-density polymer or predominantly polymer material core layer 12 to which the facers are bonded.\",\n \"The top and bottom facers of the high-density polymer or predominantly polymer material cover board 10 may be any sheet material that provides suitable top and bottom major surfaces for the cover board, such as but not limited to paper, foil, woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"The high-density polymer or predominantly polymer material core layer 12 of the cover board 10 may be made of various high-density polymer or predominantly polymer materials [e.g.\",\n \"a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic material or a high-density material made of a blend of these materials; a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a high-density foam material made of a blend of these materials; a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s); a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a high-density material made of other thermoset matrix polymers; etc.].\",\n \"However, a preferred material for the high-density core layer 12 is a high-density polyisocyanurate or predominantly polyisocyanurate material or foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic.\",\n \"Examples of various fillers that may be used in the predominantly polymer materials of the high-density core layer 12 include but are not limited to powdered, liquid, and fiber fillers.\",\n \"The high-density polymer and predominantly polymer materials of the core layer 12 may also include fiber reinforcements, fungi growth-inhibiting agents, and fire-retardants to reduce the cost of and/or modify the properties of the high-density core layer 12, such as but not limited to the compressive strength, the toughness, the flexibility, the friability, and the fire resistance of the core layer.\",\n \"Examples of fillers that may be used in the high-density predominantly polymer material core layer 12 are fillers such as but not limited to limestone (CaCO3), fiberglass, recycled polyisocyanurate dust, extenders/plasticizers, ground up foam insulation, ground up rubber, wood dust, etc.\",\n \"The prefabricated high-density polymer or predominantly polymer material cover board of the subject invention is relatively lightweight and easily cut.\",\n \"This makes the cover board easier to install and increases the productivity of workers installing the cover boards.\",\n \"The high-density polymer or predominantly polymer material cover board of the subject invention does not support mold growth and the cover board is not negatively impacted by the application of solvents, hot asphalt, or adhesives.\",\n \"FIG.\",\n \"2 is a schematic perspective view of a prefabricated cover board and facer composite 20 of the subject invention.\",\n \"The composite 20 includes the cover board 10 and a facer 22, e.g.\",\n \"a waterproofing membrane.\",\n \"Other than the inclusion of a top facer 22, the prefabricated cover board and facer composite 20 is the same as the cover board 10 of FIG.\",\n \"1.The top facer 22 of the composite 20 may be any sheet material that provides a suitable top major surface for the cover board and facer composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"A preferred sheet material for the top facer 22 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.\",\n \"Where the composite 20 is fully adhered to an underlying roofing layer (e.g.\",\n \"an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 22 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.\",\n \"a EPDM, PVC, or TPO membrane).\",\n \"Where the top facer 22 is a waterproofing membrane, the facer may extend beyond the high-density polymer or predominantly polymer material core layer of the cover board 10 on one or more of the four sides of the core layer (e.g.\",\n \"beyond a side edge and an end edge of the top major surface of the core layer) to form membrane overlaps for sealing to the membranes of other composites 20.While not shown, the composite may also include a bottom facer that is bonded to the bottom major surface of the high-density polymer or predominantly polymer material core layer of the cover board.\",\n \"When used, the bottom facer of the composite 20 may be any sheet material that provides a suitable bottom major surface for the cover board and facer composite for bonding to an underlying layer of the roofing system, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"FIG.\",\n \"3 is a schematic perspective view of a first prefabricated roofing panel composite 30 of the subject invention.\",\n \"The prefabricated roofing panel composite 30 includes a high-density polymer or predominantly polymer material cover board 32 and an insulation board 34 that, as shown, are bonded directly together.\",\n \"The prefabricated roofing panel composite 30 has a top major surface 36 and a bottom major surface 38 that are each defined by the length and the width of the roofing panel composite.\",\n \"The prefabricated roofing panel composite 30 typically has a width of about four feet or greater and a length of about four feet or greater, preferably, about eight feet or greater and could have lengths that are limited only by the ability to store, transport and handle the roofing panel composites prior to installation.\",\n \"In the prefabricated roofing panel composite 30, the cover board 32 has a high-density polymer or predominantly polymer material core layer 40.The high-density polymer or predominantly polymer material core layer 40 of the cover board 32 in the prefabricated roofing panel composite 30 has a density of at least 4 lbs/ft3 and preferably, between 6 lbs/ft3 and 25 lbs/ft3.The high-density polymer or predominantly polymer material core layer 40 of the cover board 32 in the prefabricated roofing panel composite has a thickness of about 0.08 inches or greater and, preferably, a thickness between about 0.25 inches and about 0.75 inches.\",\n \"The density and thickness of the high-density polymer or predominantly polymer material core layer 40 of the cover board 32 are selected to provide the cover board with the compressive strength to resist deformation and protect the low-density insulation board 34 that is overlaid by the cover board from damage, and to provide surface characteristics that promote the bonding of a top facer, e.g.\",\n \"a waterproofing membrane, to the high-density core layer 40 of the cover board.\",\n \"The insulation board 34 in the prefabricated roofing panel composite 30 includes a low-density polymer or predominantly polymer material foam core layer 42.The low-density polymer or predominantly polymer material foam core layer 42 of the insulation board 34 has a density less than 6 lbs/ft3, preferably less than 4 lbs/ft3, and typically a density of less than 2.5 lbs/ft3.The low-density polymer or predominantly polymer material foam core layer 42 has a thickness of about 0.50 inches or greater and, preferably, a thickness between about 0.50 inches and about 6 inches.\",\n \"The density and thickness of the low-density polymer or predominantly polymer material foam core layer 42 of the insulation board 34 are selected to provide the prefabricated roofing panel composite 30 with the desired insulating properties for the roofing system application.\",\n \"The high-density polymer or predominantly polymer material core layer 40 of the cover board 32 may be made of various high-density polymer or predominantly polymer materials [e.g.\",\n \"a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic material or a high-density material made of a blend of these materials; a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a high-density foam material made of a blend of these materials; a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic fillers); a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a high-density material made of other thermoset matrix polymers; etc.].\",\n \"However, a preferred material for the high-density core layer 40 is a high-density polyisocyanurate or predominantly polyisocyanurate material or foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or filler(s) such as but not limited to those listed above in connection with the cover board 10.The low-density polymer or predominantly polymer material foam core layer 42 of the insulation board 34 may be made of various low-density polymer or predominantly polymer foam materials [e.g.\",\n \"a low-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a low-density foam material made of a blend of these materials; a low-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a low-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or filler(s), a low-density foam material made of other thermoset matrix polymers; etc.].\",\n \"However, a preferred material for the low-density core layer 42 is a low-density polyisocyanurate or predominantly polyisocyanurate foam material up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s).\",\n \"When the high-density core layer 40 is made of a predominantly polymer material, the high-density predominantly polymer material of the core layer 40 may contain various powdered, liquid, and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.\",\n \"to reduce the cost and/or modify the properties of the high-density core layer 40 (such as but not limited to the compressive strength, the flexibility, the friability, the fire resistance of the core layer).\",\n \"When the low-density core layer 42 is made of a predominantly polymer material foam, the low-density predominantly polymer material foam core layer 42 may contain various powdered, liquid, and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.\",\n \"to reduce the cost and/or modify the properties of the low-density predominantly polymer material foam core layer.\",\n \"Examples of fillers that may be used in the high-density core layer 40 of the cover board 32 and the low-density core layer 42 of the insulation board 34 are fillers such as but not limited to limestone (CaCO3), fiberglass, recycled polyisocyanurate dust, extenders/plasticizers, ground up foam insulation, ground up rubber, wood dust, etc.\",\n \"While, as shown in FIG.\",\n \"3, the prefabricated roofing panel composite 30 has no facers, the prefabricated roofing panel composite 30 could have a common facer intermediate and bonded to both the bottom major surface of the cover board core layer 40 and the top major surface of the insulation board core layer 42, a top facer bonded to the top major surface of the cover board core layer 40, and/or a bottom facer bonded to the bottom major surface of the insulation board core layer 42.When used, the common facer of the prefabricated roofing panel composite 30 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board 32 and insulation board 34, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.\",\n \"When used, the top facer of the prefabricated roofing panel composite 30 overlies the entire or substantially the entire top major surface of the high-density core layer 40 of the cover board 32.The top facer of the prefabricated roofing panel composite 30 may be any sheet material that provides a suitable top major surface for the prefabricated roofing panel composite 30, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"When used, the bottom facer of the prefabricated roofing panel composite 30 overlies the entire or substantially the entire bottom surface of the low-density foam core layer 42 of the insulation board 34.The bottom facer of the prefabricated roofing panel composite 30 may be any sheet material that provides a suitable bottom major surface for the roofing panel composite 30, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"FIG.\",\n \"4 is a schematic perspective view of a prefabricated roofing panel composite 50 of the subject invention.\",\n \"The prefabricated roofing panel composite 50 includes the high-density polymer or predominantly polymer material cover board 32 and the low-density polymer or predominantly polymer material foam insulation board 34 that, as shown in FIG.\",\n \"4, are bonded directly together, and a top facer 52.Other than the inclusion of the top facer 52, the prefabricated roofing panel composite 50 is the same as the prefabricated roofing panel composite 30 of FIG.\",\n \"3.The top facer 52 of the prefabricated roofing panel composite 50 is bonded to and overlies the entire or substantially the entire top surface of the high-density polymer or predominantly polymer material core layer of the cover board 32.The top facer 52 of the prefabricated roofing panel composite 50 may be any sheet material that provides a suitable top major surface for the cover board of the prefabricated roofing panel composite 50, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"A preferred sheet material for the top facer 52 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.\",\n \"Where the prefabricated roofing panel composite 50 is fully adhered to an underlying roofing layer (e.g.\",\n \"an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 52 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.\",\n \"a EPDM, PVC, or TPO membrane).\",\n \"Where the top facer 52 is a waterproofing membrane, the facer may extend beyond the high-density core layer of the cover board 32 on one or more of the four sides of the core layer, e.g.\",\n \"beyond a side edge and an end edge of the top major surface of the core layer to provide overlaps for sealing with the membranes of adjacent panels.\",\n \"While, as shown in FIG.\",\n \"4, the prefabricated roofing panel composite 50 only has a top facer 52, the prefabricated roofing panel composite 50 could have a common facer intermediate and bonded to both the bottom major surface of the cover board 32 core layer 40 and the top major surface of the insulation board 34 core layer 42, and/or a bottom facer bonded to the bottom major surface of the insulation board 34 core layer 42.When used, the common facer of the prefabricated roofing panel composite 50 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board 32 and insulation board 34, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.\",\n \"When used, the bottom facer of the prefabricated roofing panel composite 50 overlies the entire or substantially the entire bottom surface of the low-density foam core layer of the insulation board 34.The bottom facer of the prefabricated roofing panel composite 50 may be any sheet material that provides a suitable bottom major surface for the roofing panel composite 50, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"FIG.\",\n \"5 is a schematic perspective view of a prefabricated roofing panel composite 60 of the subject invention that includes: a high-density polymer or predominantly polymer material cover board 62, a low-density polymer or predominantly polymer material foam insulation board 64, and a high-density polymer or predominantly polymer material baseboard 66.The high-density polymer or predominantly polymer material cover board 62 and baseboard 66 may have the same density or different densities.\",\n \"As shown in FIG.\",\n \"5, the cover board 62, the insulation board 64, and the baseboard 66 are bonded directly together.\",\n \"The prefabricated roofing panel composite 60 has a top major surface 68 and a bottom major surface 70 that are each defined by the length and the width of the prefabricated roofing panel composite.\",\n \"The prefabricated roofing panel composite 60 typically has a width of about four feet or greater and a length of about four feet or greater, preferably, about eight feet or greater and could have lengths that are limited only by the ability to store, transport and handle the roofing panel composites prior to installation.\",\n \"In the prefabricated roofing panel composite 60, the cover board 62 has a high-density polymer or predominantly polymer material core layer 72 and the baseboard 66 has a high-density polymer or predominantly polymer material core layer 74.The high-density polymer or predominantly polymer material core layers 72 and 74 each have a density of at least 4 lbs/ft3 and preferably, between 6 lbs/ft3 and 25 lbs/ft3.The high-density polymer or predominantly polymer material core layer 72 of the cover board 62 and the high-density polymer or predominantly polymer material core layer 74 of the baseboard 66 each have a thickness of about 0.08 inches or greater and, preferably, a thickness between about 0.25 inches and about 0.75 inches.\",\n \"The density and thickness of the high-density polymer or predominantly polymer material core layer 72 of the cover board 62 are selected to provide the cover board with the compressive strength to resist deformation and protect the low-density insulation board 64 that is overlaid by the cover board from damage, and to provide surface characteristics that promote the bonding of a top facer, e.g.\",\n \"a waterproofing membrane, to the core layer 72 of the cover board.\",\n \"The insulation board 64 in the prefabricated roofing panel composite 60 includes a low-density polymer or predominantly polymer foam core layer 76.The low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 has a density less than 6 lbs/ft3, preferably less than 4 lbs/ft3, and typically a density of less than about 2.5 lbs/ft3.The low-density polymer or predominantly polymer material foam core layer 76 has a thickness of about 0.50 inches or greater and, preferably, a thickness between about 0.50 inches and about 6 inches.\",\n \"The density and thickness of the low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 are selected to provide the prefabricated roofing panel composite 60 with the desired insulating properties for the roofing system application.\",\n \"The high-density polymer or predominantly polymer material core layers 72 and 74 of the cover board 62 and the baseboard 66 may be made of various high-density polymer or predominantly polymer materials [e.g.\",\n \"a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic material or a high-density material made of a blend of these materials; a high-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a high-density foam material made of a blend of these materials; a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s); a high-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a high-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a high-density material made of other thermoset matrix polymers; etc.].\",\n \"However, a preferred material for the high-density core layers 72 and 74 is a high-density polyisocyanurate or predominantly polyisocyanurate material or foam material up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s).\",\n \"The low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 may be made of various low-density polymer or predominantly polymer foam materials [e.g.\",\n \"a low-density polyisocyanurate, polyurethane, polystyrene, or phenolic foam material or a low-density foam material made of a blend of these materials; a low-density predominantly polyisocyanurate, polyurethane, polystyrene, or phenolic foam material with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s) or a low-density foam material made of a blend of these materials with up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s), a low-density material made of other thermoset matrix polymers; etc.].\",\n \"However, a preferred material for the low-density core layer 76 is a low-density polyisocyanurate or predominantly polyisocyanurate foam material up to 40% by weight, but typically between about 1% and about 25% by weight organic and/or inorganic filler(s).\",\n \"When the high-density core layers 72 and 74 are made of a predominantly polymer material, the high-density predominantly polymer material of the core layers 72 and 74 may contain various powdered, liquid, and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.\",\n \"to reduce the cost and/or modify the properties of the high-density core layers 72 and 74 (such as but not limited to the compressive strength, the flexibility, the friability, the fire resistance of the core layer).\",\n \"When the low-density core layer 76 is made of a predominantly polymer material foam, the low-density predominantly polymer material foam core layer 76 may contain various powdered, liquid and fiber fillers, fiber reinforcements, fire-retardants, fungi growth-inhibiting agents, etc.\",\n \"to reduce the cost and/or modify the properties of the low-density foam core layer.\",\n \"Examples of fillers that may be used in the high-density core layers 72 of the cover board 62 and the baseboard 66 and the low-density core layer 76 of the insulation board 64 are fillers such as but not limited to limestone (CaCO3), fiberglass, recycled polyisocyanurate dust, extenders/plasticizers, ground up foam insulation, ground up rubber, wood dust, etc.\",\n \"While, as shown in FIG.\",\n \"5, the prefabricated roofing panel composite 60 has no facers, the prefabricated roofing panel composite 60 could have a common facer intermediate and bonded to both the bottom major surface of the cover board core layer 72 and the top major surface of the insulation board core layer 76, a common facer intermediate and bonded to both the bottom major surface of the insulation board core layer 76 and the top major surface of the baseboard core layer 74, a top facer bonded to the top major surface of the cover board core layer 72, and/or a bottom facer bonded to the bottom major surface of the baseboard core layer 74.When used, the common facers of the prefabricated roofing panel composite 60 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board 62, the insulation board 64, and the baseboard 66, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.\",\n \"When used, the top facer of the prefabricated roofing panel composite 60 overlies the entire or substantially the entire top major surface of the high-density core layer 72 of the cover board 62.The top facer of the prefabricated roofing panel composite 60 may be any sheet material that provides a suitable top major surface for the prefabricated roofing panel composite 60, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"When used, the bottom facer of the prefabricated roofing panel composite 60 overlies the entire or substantially the entire bottom surface of the high-density core layer 74 of the baseboard 66.The bottom facer of the prefabricated roofing panel composite 60 may be any sheet material that provides a suitable bottom major surface for the roofing panel composite 60, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"FIG.\",\n \"6 is a schematic perspective view of a prefabricated roofing panel composite 80 of the subject invention.\",\n \"The prefabricated roofing panel composite 80 includes the high-density polymer or predominantly polymer material cover board 62, the low-density polymer or predominantly polymer material foam insulation board 64, and the high-density polymer or predominantly polymer material baseboard 66, that, as shown in FIG.\",\n \"6, are bonded directly together, and a top facer 82.Other than the inclusion of a top facer 82, the prefabricated roofing panel composite 80 of FIG.\",\n \"6 is the same as the prefabricated roofing panel composite 60 of FIG.\",\n \"5.The top facer 82 of the prefabricated roofing panel composite 80 is bonded to and overlies the entire or substantially the entire top surface of the high-density polymer or predominantly polymer material core layer of the cover board 62.The top facer 82 of the prefabricated roofing panel composite 80 may be any sheet material that provides a suitable top major surface for the cover board and facer composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"A preferred sheet material for the top facer 82 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.\",\n \"Where the prefabricated roofing panel composite 80 is fully adhered to an underlying roofing layer (e.g.\",\n \"an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 82 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.\",\n \"a EPDM, PVC, or TPO membrane).\",\n \"Where the top facer 82 is a waterproofing membrane, the facer may extend beyond the high-density polymer or predominantly polymer material core layer of the cover board 62 on one or more of the four sides of the core layer, e.g.\",\n \"beyond a side edge and an end edge of the top major surface of the core layer to provide membrane overlaps for sealing with the membranes of adjacent panels.\",\n \"While, as shown in FIG.\",\n \"6, the prefabricated roofing panel composite 80 only has a top facer 82, the prefabricated roofing panel composite 80 could have a common facer intermediate and bonded to both the bottom major surface of the cover board core layer and the top major surface of the insulation board core layer, a common facer intermediate and bonded to both the bottom major surface of the insulation board core layer and the top major surface of the baseboard core layer, and/or a bottom facer bonded to the bottom major surface of the baseboard core layer.\",\n \"When used, the common facers of the prefabricated roofing panel composite 80 may be any sheet material with good bonding surfaces that facilitates a good bond between the cover board and insulation board and the insulation board and the baseboard, such as but not limited to woven or nonwoven mats made of glass fibers, other fibers or filaments, scrims, etc.\",\n \"When used, the bottom facer of the prefabricated roofing panel composite 80 overlies the entire or substantially the entire bottom surface of the high-density core layer of the baseboard 66.The bottom facer of the prefabricated roofing panel composite 80 may be any sheet material that provides a suitable bottom major surface for the prefabricated roofing panel composite 80, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"FIG.\",\n \"7 is a schematic side view of a first production line 100 that can be used with the method of the subject invention to continuously make prefabricated roofing panel composites of the subject invention in line, such as the prefabricated roofing panel composites 30 of FIG.\",\n \"3 and 50 of FIG.\",\n \"4.The prefabricated roofing panel composites 30 and 50 each include a high-density polymer or predominantly polymer material cover board 32 and a low-density polymer or predominantly polymer material foam insulation board 34.The production line 100 includes: a first forming station 102 for forming the low-density polymer or predominantly polymer material foam insulation board 34 of the prefabricated roofing panel composites 30 and 50; a second forming station 104 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50; and a cutting station 106 for cutting the prefabricated roofing panel composites 30 and 50 to length.\",\n \"The first forming station 102 for forming the low-density foam insulation board 34 includes a conventional dispenser 108 for dispensing a low-density polymer or predominantly polymer material foam precursor 110 (e.g.\",\n \"a low-density polyisocyanurate or predominantly polyisocyanurate foam precursor) onto a facer, when used, overlying a conveyor 112 of two spaced-apart opposed forming conveyers 112 and 114 or directly onto the conveyor 112.As the foam precursor 110 passes between the forming conveyors 112 and 114, foams and at least partially sets, the forming conveyors 112 and 114 cooperate to set the thickness of the low-density polymer or predominantly polymer material foam core layer 42 of the low-density polymer or predominantly polymer foam insulation board 34 formed from the precursor 110.The first forming station 102 also includes supplies (e.g.\",\n \"rolls) of facer materials 116 and 118 that can be fed over and/or beneath the low-density polymer or predominantly polymer material foam precursor 110 to form a common facer of the prefabricated roofing panel composites 30 and 50 and a bottom facer of the prefabricated roofing panel composites 30 and 50.The second forming station 104 of the production line 100 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50 includes a conventional dispenser 120 for dispensing a high-density polymer or predominantly polymer material or foam precursor 122 (e.g.\",\n \"a high-density polyisocyanurate or predominantly polyisocyanurate foam precursor) onto the low-density polymer or predominantly polymer material foam core layer 42 or, when used, a common facer overlying the low-density polymer or predominantly polymer material foam core layer 42.With the high-density polymer or predominantly polymer material precursor 122 overlying the low-density foam core layer 42 or, when used, the common facer, the high-density polymer or predominantly polymer material precursor 122 and the low-density foam core layer 42 pass between two spaced-apart opposed forming conveyers 112 and 124 where the high-density polymer or predominantly polymer material core layer 38 is formed and bonded directly to the low-density foam core layer 42 or to the common facer overlying the low-density foam core layer 42.The spaced-apart opposed forming conveyors 112 and 124 cooperate to set the thickness of both the high-density polymer or predominantly polymer material core layer 40 and the prefabricated roofing panel composite 30 or 50.The second forming station 104 also includes supplies (e.g.\",\n \"rolls) of a facer material 126 that is fed over the high-density polymer or predominantly polymer material precursor 122 to form the top facer 52 of both the high-density cover board 32 and the prefabricated roofing panel composite 50.With the high-density core layer 40 and the low-density foam core layer 42 of the prefabricated roofing panel composite 30 or 50 bonded together in the second forming station 104 to form a continuous length of the prefabricated roofing panel composite 30 or 50, the prefabricated roofing panel composite 30 or 50 is then cut to length to complete the formation of the prefabricated roofing panel composite 30 or 50.In the cutting station 106 a cutter, such as but not limited to a reciprocating cutter 128, cuts the prefabricated roofing panel composite 30 or 50 coming from the second forming station 104 to length.\",\n \"While the production line 100, as shown, is capable of applying three facer materials 116, 118, and 126 to the insulation board 34 and the cover board 32 to form the prefabricated roofing panel composites 30 and 50.The application of any one, any two, or all of the facing materials 116, 118 and 126 to the insulation board and cover board can be omitted to form the prefabricated roofing panel composite 30 and all but the top facing material can be omitted to form the prefabricated roofing panel composite 50 with the desired number of facers.\",\n \"The facers 116, 118 and 126 normally prevent the polymer or predominantly polymer layers from sticking to the conveyors.\",\n \"However, with a shift in the chemistry of the precursors 110 and 122 to affect the tackiness of the layers produced so that they do not stick to the surfaces of the conveyors or by applying release films or coatings to the surfaces of the conveyers that will not allow the layers produced to stick to the surfaces of the conveyors, when desired, any one or all of the facing materials are not needed for and could be eliminated from the manufacturing process.\",\n \"FIG.\",\n \"8 is a schematic side view of a second production line 200 that can be used with the method of the subject invention to continuously make prefabricated roofing panel composites of the subject invention, such as the prefabricated roofing panel composites 30 of FIG.\",\n \"3 and 50 of FIG.\",\n \"4.The prefabricated roofing panel composites 30 and 50 each include a high-density polymer or predominantly polymer material cover board and a low-density polymer or predominantly polymer material foam insulation board.\",\n \"The production line 200 includes: an in-feed conveyor 202 for continuously feeding a series of low-density polymer or predominantly polymer material foam insulation boards 34 of the prefabricated roofing panel composite into a forming station 204; the forming station 204 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50; and a cutting station 206 for cutting the prefabricated roofing panel composites 30 and 50 to length.\",\n \"The low-density polymer or predominantly polymer material foam insulation boards 34 may include a top facer that, when used, forms a common facer of the prefabricated roofing panel composites 30 and 50 and may include a bottom facer that, when used, forms a bottom facer of the prefabricated roofing panel composites.\",\n \"Preferably, the low-density polymer or predominantly polymer material foam insulation boards 34 are fed into the forming station 204 lengthwise with the ends of successive insulation boards 34 in the continuous series of insulation boards abutting each other.\",\n \"The forming station 204 of the production line 200 for forming the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composite 30 includes a conventional dispenser 208 for dispensing the high-density polymer or predominantly polymer material precursor 210 (e.g.\",\n \"a high-density polyisocyanurate or predominantly polyisocyanurate precursor) directly onto the low-density foam core layers 42 of the insulation boards 34 or, when used the common facers overlying the low-density foam core layers of the low-density foam insulation boards.\",\n \"With the high-density polymer or predominantly polymer material precursor 210 directly overlying the low-density foam core layers 42 of the insulation boards or the common facers 36 carried by the low-density foam insulation boards 34, the high-density polymer or predominantly polymer material precursor 210 and the low-density foam insulation boards 34 pass between two spaced-apart opposed forming conveyers 212 and 214 where the high-density polymer or predominantly polymer material core layers 38 of the cover boards 32 are formed and bonded directly to the low-density foam core layers 42 of the insulation boards 34 or to the common facers overlying the low-density foam insulation board 34.The spaced-apart opposed forming conveyors 212 and 214 cooperate to set the thickness of both the high-density polymer or predominantly polymer material core layer 40 and the prefabricated roofing panel composite 30 or 50.The forming station 204 also includes supplies (e.g.\",\n \"rolls) of a facer material 216 that is fed over the high-density polymer or predominantly polymer material precursor 210 to form the top facer 52 of both the high-density polymer or predominantly polymer material cover board 32 and the prefabricated roofing panel composite 50.With the high-density core layer 40 and the low-density foam core layer 42 of the prefabricated roofing panel composite 30 or 50 bonded together in the forming station 204 to form a continuous length of the prefabricated roofing panel composite 30 or 50, the prefabricated roofing panel composite 30 or 50 is then cut to length to complete the formation of the prefabricated roofing panel composite 30 or 50.In the cutting station 206 a cutter, such as but not limited to a reciprocating cutter 218, cuts the prefabricated roofing panel composite 30 coming from the forming station 204 to length.\",\n \"The production line 200, as shown, is capable of making the prefabricated roofing panel composite 30 by feeding preformed low-density polymer or predominantly polymer material foam insulation boards 34 into the forming station 204 and omitting the application of the facer material 216 to the cover board 32 and is capable of making the prefabricated roofing panel composite 50 by feeding preformed low-density polymer or predominantly polymer material foam insulation boards 34 into the forming station 204 and applying of the facer material 216 to the cover board 32.The facer 216 normally prevents the high-density polymer or predominantly polymer material layer from sticking to the conveyor 212.However, with a shift in the chemistry of the precursor 210 to affect the tackiness of the layer produced so that the layer does not stick to the surface of the conveyor 212 or by applying a release film or coating to the surface of the conveyer 212 that will not allow the layer produced to stick to the surface of the conveyor, when desired, the facing materials 216 is not needed for and could be eliminated from the manufacturing process.\",\n \"FIG.\",\n \"9 is a schematic side view of a production line 300 that can be used with the method of the subject invention to continuously make a prefabricated roofing panel composite of the subject invention, such as the prefabricated roofing panel composites 60 of FIG.\",\n \"5 and 80 of FIG.\",\n \"6.These prefabricated roofing panel composites each include: a high-density polymer or predominantly polymer material cover board 62, a low-density polymer or predominantly polymer material foam insulation board 64, and a high-density polymer or predominantly polymer material baseboard 66.The production line 300 includes: a first forming station 302 for forming the high-density polymer or predominantly polymer material baseboard 66 of the prefabricated roofing panel composites 60 and 80; a second forming station 304 for forming the low-density polymer or predominantly polymer material foam insulation board 64 of the prefabricated roofing panel composites 60 and 80; a third forming station 306 for forming the high-density polymer or predominantly polymer material cover board 62 of the prefabricated roofing panel composites 60 and 80; and a cutting station 308 for cutting the prefabricated roofing panel composites 60 and 80 to length.\",\n \"The first forming station 302 for forming the high-density polymer or predominantly polymer material baseboard 56 includes a conventional dispenser 310 for dispensing a high-density polymer or predominantly polymer material precursor 312 (e.g.\",\n \"a high-density polyisocyanurate or predominantly polyisocyanurate precursor) onto a facer, when used, overlying a conveyor 314 of two spaced-apart opposed forming conveyers 314 and 316 or directly onto the conveyor 314.As the precursor 310 passes between the forming conveyors 314 and 316, forms and at least partially sets, the forming conveyors 314 and 316 cooperate to set the thickness of the high-density polymer or predominantly polymer material core layer 74 of the high-density baseboard 66 formed from the precursor 310.The first forming station 302 also includes supplies (e.g.\",\n \"rolls) of facer materials 318 and 320 that may be fed over and/or beneath the high-density polymer or predominantly polymer material precursor 310 to form, when used, a common facer of the prefabricated roofing panel composites 60 and 80 and a bottom facer of the prefabricated roofing panel composites 60 and 80.The second forming station 304 of the production line 300 for forming the low-density polymer or predominantly polymer material foam insulation board 64 of the prefabricated roofing panel composites 60 and 80 includes a conventional dispenser 322 for dispensing a low-density polymer or predominantly polymer material foam precursor 324 (e.g.\",\n \"a low-density polyisocyanurate or predominantly polyisocyanurate foam precursor) directly onto the high-density core layer 74 or, when used, onto a common facer overlying the high-density core layer 74 of the baseboard 66.With the low-density polymer or predominantly polymer material foam precursor 324 directly overlying high-density core layer 74 or the common facer overlying the high-density core layer 74 of the baseboard 66, the low-density polymer or predominantly polymer material foam precursor 324 and the high-density core layer 74 pass between two spaced-apart opposed forming conveyers 314 and 326 where the low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64 is formed and bonded to the high-density core layer 74 or the common facer overlying the high-density core layer 74 of the baseboard 66.The spaced-apart opposed forming conveyors 314 and 326 cooperate to set the thickness of the low-density polymer or predominantly polymer material foam core layer 76 of the insulation board 64.The second forming station 304 also includes supplies (e.g.\",\n \"rolls) of a facer material 328 that can be fed over the low-density polymer or predominantly polymer material foam precursor 324 to form a common facer of the prefabricated roofing panel composites 60 and 80.The third forming station 306 of the production line 300 for forming the high-density polymer or predominantly polymer material cover board 62 of the prefabricated roofing panel composites 60 and 80 includes a conventional dispenser 330 for dispensing a high-density polymer or predominantly polymer material precursor 332 (e.g.\",\n \"a high-density polyisocyanurate or predominantly polyisocyanurate precursor) directly onto the low-density foam core layer 76 or the common facer overlying the low-density foam core layer 76 of the insulation board 64.With the high-density polymer or predominantly polymer material precursor 332 overlying the low-density foam core layer 76 or the common facer overlying the low-density foam core layer 76, the high-density polymer or predominantly polymer material precursor 332, the low-density foam insulation board 64, and the high-density baseboard 66 pass between two spaced-apart opposed forming conveyers 314 and 334 where the high-density polymer or predominantly polymer material core layer 72 of the cover board 62 is formed and bonded to the low-density foam core layer 76 or the common facer overlying the low-density foam core layer 76 of the insulation board 64.The spaced-apart opposed forming conveyors 314 and 334 cooperate to set the thickness of both the high-density polymer or predominantly polymer material core layer 72 and the prefabricated roofing panel composite 60 or 80.The third forming station 306 also includes supplies (e.g.\",\n \"rolls) of a facer material 336 that is fed over the high-density polymer or predominantly polymer material precursor 332 to form the top facer 82 of both the high-density cover board 62 and the prefabricated roofing panel composite 80.With the high-density polymer or predominantly polymer material cover board 62, the low-density polymer or predominantly polymer material foam insulation board 64, and the high-density polymer or predominantly polymer material baseboard 66 of the prefabricated roofing panel composites 60 or 80 bonded together in the third forming station 306 to form a continuous length of the prefabricated roofing panel composite 60 or 80, the prefabricated roofing panel composite 60 or 80 is then cut to length to complete the formation of the prefabricated roofing panel composite 60 or 80.In the cutting station 308 a cutter, such as but not limited to a reciprocating cutter 338, cuts the continuous prefabricated roofing panel composite 60 or 80 coming from the third forming station 306 to length.\",\n \"While the production line 300, as shown, is capable of applying four facer materials 318, 320, 328, and 336 to the baseboard 66, the insulation board 64 and the cover board 62 to form the prefabricated roofing panel composites 60 and 80.The application of any one, any two, any three or all of the facing materials 318, 320, 328, and 336 to the baseboard, the insulation board and the cover board can be omitted to form the prefabricated roofing panel composite 60 and all but the top facing material can be omitted to form the prefabricated roofing panel composite 80 with the desired number of facers.\",\n \"The facers 318, 320, 328, and 336 normally prevent the composite layers from sticking to the conveyors.\",\n \"However, with a shift in the chemistry of the precursors 312, 324, and 332 to affect the tackiness of the layers produced so that they do not stick to the surfaces of the conveyors or by applying release films or coatings to the surfaces of the conveyers that will not allow the layers produced to stick to the surfaces of the conveyors, when desired, any one or all of the facing materials are not needed for and could be eliminated from the manufacturing process.\",\n \"FIG.\",\n \"10 is a schematic side view of another production line 400 that can be used with the method of the subject invention to continuously make prefabricated roofing panel composites of the subject invention in line, such as the prefabricated roofing panel composites 30 of FIG.\",\n \"3 and 50 of FIG.\",\n \"4.The prefabricated roofing panel composites 30 and 50 each include a high-density polymer or predominantly polymer material cover board 32 and a low-density polymer or predominantly polymer material foam insulation board 34.The production line 400 includes: a forming station 402 for forming the low-density polymer or predominantly polymer material foam insulation board 34 and the high-density polymer or predominantly polymer material cover board 32 of the prefabricated roofing panel composites 30 and 50; and a cutting station 404 for cutting the prefabricated roofing panel composites 30 and 50 to length.\",\n \"The forming station 402 for forming the low-density foam insulation board 34 and the high-density cover board includes a conventional dispenser 406 for dispensing a low-density polymer or predominantly polymer material foam precursor 408 (e.g.\",\n \"a low-density polyisocyanurate or predominantly polyisocyanurate foam precursor) onto a facer, when used, overlying a conveyor 410 of two spaced-apart opposed forming conveyers 410 and 412 or directly onto the conveyor 410.The forming station 402 also includes a conventional dispenser 414 for dispensing a high-density polymer or predominantly polymer material precursor 416 (e.g.\",\n \"a high-density polyisocyanurate or predominantly polyisocyanurate material precursor) onto the low-density polymer or predominantly polymer material foam precursor of the core layer 42 or, when used, a common facer overlying the low-density polymer or predominantly polymer material foam precursor of the core layer 42.As the layers of precursor 408 and 416 pass between the forming conveyors 410 and 412, the precursors form and at least partially set, the forming conveyors 410 and 412 cooperate to set the thickness of the low-density polymer or predominantly polymer material foam core layer 42 of insulation board 34 formed from the precursor 408, the thickness of the high-density polymer or predominantly polymer material core layer 40 of cover board 32 formed from the precursor 416, and the thickness of the prefabricated roofing panel composite 30 or 50.The forming station 402 also includes supplies (e.g.\",\n \"rolls) of facer materials 418, 420, and 422 that can be fed over and/or beneath the low-density polymer or predominantly polymer material foam precursor 408 to form a common facer of the prefabricated roofing panel composites 30 and 50 and a bottom facer of the prefabricated roofing panel composites 30 and 50 and that can be fed over the high-density polymer or predominantly polymer material precursor 416 to form a top facer of the prefabricated roofing panel composites 30 and 50.With the high-density core layer 40 and the low-density foam core layer 42 of the prefabricated roofing panel composite 30 or 50 bonded together to form a continuous length of the prefabricated roofing panel composite 30 or 50, the prefabricated roofing panel composite 30 or 50 is then cut to length to complete the formation of the prefabricated roofing panel composite 30 or 50.In the cutting station 404 a cutter, such as but not limited to a reciprocating cutter 424, cuts the prefabricated roofing panel composite 30 or 50 coming from the forming station 402 to length.\",\n \"While the production line 400, as shown, is capable of applying three facer materials 418, 420 and 422 to the insulation board 34 and the cover board 32 to form the prefabricated roofing panel composites 30 and 50.The application of any one, any two, or all of the facing materials 418, 420, and 422 to the insulation board and cover board can be omitted to form the prefabricated roofing panel composite 30 and all but the top facing material can be omitted to form the prefabricated roofing panel composite 50 with the desired number of facers.\",\n \"The facers 418, 420, and 422 normally prevent the layers of the composite from sticking to the conveyors.\",\n \"However, with a shift in the chemistry of the precursors 408 and 416 to affect the tackiness of the layers produced so that they do not stick to the surfaces of the conveyors or by applying release films or coatings to the surfaces of the conveyers that will not allow the layers produced to stick to the surfaces of the conveyors, when desired, any one or all of the facing materials are not needed for and could be eliminated from the manufacturing process.\",\n \"Preferably, the low-density polymer or predominantly polymer material foam precursors 110, 324, and 408 are low-density polyisocyanurate or predominantly polymer foam precursors.\",\n \"Preferably, the high-density polymer or predominantly polymer material precursors 122, 210, 312, 332, and 416 are high-density polyisocyanurate or predominantly polyisocyanurate material precursors.\",\n \"The high-density polymer or predominantly polymer material precursors 122, 210, 312, 332, and 416 can be formulated to produce high-density materials or foams by significantly reducing or eliminating the blowing agent(s) from the precursors 122, 210, 312, 332, and 416.Pentane (HFC), micro-spheres, CO2 and water (as well as other materials) will act as blowing agents for the precursors.\",\n \"The relatively high-density layers produced using these types of precursors have improved strength characteristics over the low-density foams normally produced for insulation products.\",\n \"As the amount of blowing agent is reduced in the precursors 122, 210, 312, 332, and 416, the density and the compressive strength of the high-density layers produced increase.\",\n \"These types of high-density core layers are much more resistant to deformation than the typical low-density foam core layers.\",\n \"FIGS.\",\n \"11 and 12 are fragmentary, transverse schematic, perspective views of a prefabricated cover board composite 520 of the subject invention.\",\n \"The composite 520 includes the cover board 10 of FIG.\",\n \"1, a top facer 522 (e.g.\",\n \"a waterproofing membrane), a bottom facer 524, and a plurality of wind-uplift reinforcement patches 526 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or strips 528 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17).\",\n \"Conventional fastener plates, such as but not limited to the disc shaped metallic fastener plate 530, are typically used at each fastener penetration of the prefabricated cover board composite 520 to spread the forces exerted on the top major surface of the composite by the nails or other mechanical fasteners securing the composite to a roof deck over a greater surface area and thereby reduce the pressures exerted by the fasteners (not shown) on the top major surface of the composite.\",\n \"Other than the inclusion of a top facer 522, a bottom facer 524, and a plurality of wind-uplift reinforcements, such as the wind-uplift reinforcement patches 526 or strips 528 the prefabricated cover board composite 520 is the same as the cover board 10 of FIG.\",\n \"1.The top facer 522 that is bonded to the top major surface of the high-density polymer or predominantly polymer material core layer of the cover board composite 520 may be any sheet material that provides a suitable top major surface for the cover board composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"A preferred sheet material for the top facer 522 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.\",\n \"Where the cover board composite 520 is fully adhered to an underlying roofing layer (e.g.\",\n \"an insulation layer) rather than being secured by mechanical fasteners, a sheet material may be used for the top facer 522 that serves the dual function of providing a facing during the manufacturing process and a waterproofing membrane on the finished product such as but not limited to a bituminous or modified bituminous membrane, or a single ply membrane (e.g.\",\n \"a EPDM, PVC, or TPO membrane).\",\n \"Where the top facer 522 is a waterproofing membrane, the facer may extend beyond the high-density polymer or predominantly polymer material core layer of the cover board 10 on one or more of the four sides of the core layer (e.g.\",\n \"beyond a side edge and an end edge of the top major surface of the core layer) to form membrane overlaps for sealing to the membranes of other composites 520.The bottom facer 524 is bonded to and typically coextensive with the bottom major surface of the high-density polymer or predominantly polymer material core layer of the cover board composite 520.The bottom facer 524 of the composite 520 may be any sheet material that provides a suitable bottom major surface for the cover board composite 520, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"However, a preferred bottom facer 524, is a coated or uncoated woven or nonwoven fiberglass mat such as but not limited to the preferred top facer 522.The wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches 526 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or the wind-uplift reinforcement strips 528 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17), may be made of various reinforcement sheet or mat materials, such as but not limited to sheets or mats of glass, polyester, polypropylene, metal, wool, and other synthetic and natural fibers and combinations of such fibers.\",\n \"However, a preferred reinforcement material for the wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches and strips is a scrim such as fiberglass scrim with a minimum tensile strength of 30 lbs per linear inch and preferably, a minimum tensile strength of at least 100 lbs per linear inch, e.g.\",\n \"a fiberglass scrim that is 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands is 0.019 inches.\",\n \"When a cover board composite is subjected to wind-uplift forces from high winds during service, the wind-uplift forces exerted on a cover board composite, if not controlled, will tend to place the top portion of the composite in compression and the bottom portion of the composite in tension at the fastener locations to thereby place the composite under stress at these locations.\",\n \"Repeated cycles of stress exerted on a cover board composite at the fastener locations during service can result in a failure of the composite at one or more of the fastener locations.\",\n \"The wind-uplift reinforcements of the subject invention, e.g.\",\n \"the wind-uplift reinforcement patches 526 or reinforcement strips 528, greatly increase the pressures that the cover board composite can withstand before failure at a fastener location.\",\n \"While the cover board composite still flexes, the wind-uplift reinforcements of the subject invention extend or increase the load the bottom facer can withstand before the bottom facer 524 fails at a fastener location.\",\n \"The wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches 526 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or the wind-uplift reinforcement strips 528 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17) are interposed between the bottom facer 524 and the bottom major surface of the core layer to coincide with a selected fastener pattern or selected fastener patterns for securing the cover board composite 520 to a roof deck and increase a per-fastener wind-uplift pull through rating for the cover board composite.\",\n \"FIG.\",\n \"13 is a fragmentary, transverse schematic, perspective view of a prefabricated cover board/insulation board panel composite 540 of the subject invention.\",\n \"The panel composite 540 includes the cover board/insulation board panel composite 30 of FIG.\",\n \"3, which includes a cover board 32 with a high-density polymer or predominantly polymer material core layer and an insulation board 34 with a low-density polymer or predominantly polymer material core layer; a top facer 542 (e.g.\",\n \"a waterproofing membrane); a bottom facer 544; and a plurality of wind-uplift reinforcement patches 546 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or strips 548 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17).\",\n \"Fastener plates, such as but not limited to the fastener plate 550, are typically used at each fastener penetration of the prefabricated cover board/insulation board panel composite 540 to spread the forces exerted on the top major surface of the panel composite by the fasteners securing the composite to a roof deck over a greater surface area and thereby reduce the pressures exerted by the fasteners (not shown) on the top major surface of the panel composite.\",\n \"Other than the inclusion of a top facer 542, a bottom facer 544, and a plurality of wind-uplift reinforcements, such as the wind-uplift reinforcement patches 546 or strips 548 the prefabricated cover board/insulation board panel composite 540 is the same as the cover board/insulation board panel composite 30 of FIG.\",\n \"3.The top facer 542 that is bonded to the top major surface of the high-density polymer or predominantly polymer material core layer of the cover board 32 may be any sheet material that provides a suitable top major surface for the cover board/insulation board panel composite 540, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"A preferred sheet material for the top facer 542 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.\",\n \"The bottom facer 544 is bonded to and typically coextensive with the bottom major surface of the low-density polymer or predominantly polymer material core layer of the insulation board 34.The bottom facer 544 of the composite 540 may be any sheet material that provides a suitable bottom major surface for the cover board/insulation board composite 540, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"However, a preferred bottom facer 544, is a coated or uncoated woven or nonwoven fiberglass mat such as but not limited to the preferred the top facer 542.The wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches 546 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or the wind-uplift reinforcement strips 548 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17), may be made of various reinforcement sheet or mat materials, such as but not limited to sheets or mats of glass, polyester, polypropylene, metal, wool, and other synthetic and natural fibers and combinations of such fibers.\",\n \"However, a preferred reinforcement material for the wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches and strips is a scrim such as fiberglass scrim with a minimum tensile strength of 30 lbs per linear inch and preferably, a minimum tensile strength of at least 100 lbs per linear inch, e.g.\",\n \"a fiberglass scrim that is 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands is 0.019 inches.\",\n \"The wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches 546 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or the wind-uplift reinforcement strips 548 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17) are interposed between the bottom facer 544 and the bottom major surface of the insulation board core layer to coincide with a selected fastener pattern or selected fastener patterns for securing the cover board, insulation board panel composite 540 to a roof deck and increase a per-fastener wind-uplift pull through rating for the cover board/insulation board panel composite.\",\n \"The wind-uplift reinforcements of the cover board/insulation board panel composite 540 perform the same or substantially the same function as the wind-uplift reinforcements of the cover board composite 520.FIG.\",\n \"14 is a fragmentary, transverse schematic, perspective view of a prefabricated cover board/insulation board/baseboard panel composite 560 of the subject invention.\",\n \"The panel composite 560 includes the roofing panel composite 60 of FIG.\",\n \"5, which includes a cover board 62 with a high-density polymer or predominantly polymer material core layer, an insulation board 64 with a low-density polymer or predominantly polymer material foam core layer; a baseboard 66 with a high-density polymer or predominantly polymer material core layer; a top facer 562 (e.g.\",\n \"a waterproofing membrane), a bottom facer 564, and a plurality of wind-uplift reinforcement patches 566 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or strips 568 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17).\",\n \"Fastener plates, such as but not limited to the fastener plate 570, are typically used at each fastener penetration of the prefabricated cover board/insulation board/baseboard panel composite 560 to spread the forces exerted on the top major surface of the composite by the fasteners securing the composite to a roof deck over a greater surface area and thereby reduce the pressures exerted by the fasteners (not shown) on the top major surface of the panel composite.\",\n \"Other than the inclusion of a top facer 562, a bottom facer 564, and a plurality of wind-uplift reinforcements, such as the wind-uplift reinforcement patches 566 or strips 568 the prefabricated cover board/insulation board/baseboard panel composite 560 is the same as the cover board/insulation board/baseboard panel composite 60 of FIG.\",\n \"5.The top facer 562 that is bonded to the top major surface of the high-density polymer or predominantly polymer material core layer of the cover board 62 may be any sheet material that provides a suitable top major surface for the cover board/insulation board/baseboard panel composite, such as but not limited to coated or uncoated paper, foil, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"A preferred sheet material for the top facer 522 is a nonwoven fiberglass mat that is heavily coated with a mineral coating such as but not limited to a calcium carbonate/clay/SBR latex coating.\",\n \"The bottom facer 564 is bonded to and typically coextensive with the bottom major surface of the high-density polymer or predominantly polymer material core layer of the baseboard 66.The bottom facer 564 of the composite 560 may be any sheet material that provides a suitable bottom major surface for the cover board/insulation board/baseboard composite 560, such as but not limited to coated or uncoated paper, coated or uncoated woven or nonwoven mats made of fiberglass or other fibers or filaments, scrims, etc.\",\n \"However, a preferred bottom facer 564, is a coated or uncoated woven or nonwoven fiberglass mat such as but not limited to the preferred top facer 562.The wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches 566 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or the wind-uplift reinforcement strips 568 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17), may be made of various reinforcement sheet or mat materials, such as but not limited to sheets or mats of glass, polyester, polypropylene, metal, wool, and other synthetic and natural fibers and combinations of such fibers.\",\n \"However, a preferred reinforcement material for the wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches and strips is a scrim such as fiberglass scrim with a minimum tensile strength of 30 lbs per linear inch and preferably, a minimum tensile strength of at least 100 lbs per linear inch, e.g.\",\n \"a fiberglass scrim that is 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands is 0.019 inches.\",\n \"The wind-uplift reinforcements, e.g.\",\n \"the wind-uplift reinforcement patches 566 (such as but not limited to the wind-uplift reinforcement patches shown in FIGS.\",\n \"15 and 16) or the wind-uplift reinforcement strips 568 (such as but not limited to the wind-uplift reinforcement strips shown in FIG.\",\n \"17) are interposed between the bottom facer 564 and the bottom major surface of the baseboard core layer to coincide with a selected fastener pattern or selected fastener patterns for securing the cover board/insulation board/baseboard panel composite 560 to a roof deck and increase a per-fastener wind-uplift pull through rating for the cover board/insulation board/baseboard panel composite.\",\n \"The wind-uplift reinforcements of the cover board/insulation board/baseboard panel composite 560 perform the same or substantially the same function as the wind-uplift reinforcements of the cover board composite 520.FIGS.\",\n \"15 and 16 show an eight-fastener wind-uplift reinforcement patch placement pattern, utilizing a single patch and a double patch arrangement, for securing the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 to a roofing deck.\",\n \"The eight-fastener wind-uplift reinforcement patch placement pattern shown is exemplary and it is to be understood that the wind-uplift reinforcement patch placement patterns for the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 can be selected to accommodate any desired fastener placement pattern including any one or more of the fastener placement patterns commonly utilized in the roofing industry.\",\n \"In the embodiment shown in FIG.\",\n \"15, single wind-uplift reinforcement patches 526, 546, and 566 are utilized.\",\n \"In the embodiment of FIG.\",\n \"16, double wind-uplift patches 528, 548, and 568 are utilized with the overlying wind-uplift reinforcement patches having a 45° offset relative to the wind-uplift reinforcement patches overlaid.\",\n \"Preferably, the wind-uplift reinforcement patches 528, 548, and 568 are at least three inches by three inches and centered over each of the fastener placement locations.\",\n \"Examples of preferred wind-uplift reinforcement patches are: generally square patches that have dimensions between about three inches by about three inches and about six inches by about six inches; generally round patches that have diameters between about three inches and about six inches; and generally rectangular, oval and other shaped patches having a minor dimension between about three inches and about six inches and a major dimension between about three inches and about six inches.\",\n \"Preferably, the top surface of a cover board composite 520, a cover board/insulation board panel composite 540, or a cover board/insulation board/baseboard panel composite 560 utilizing the single or double wind-uplift reinforcement patches will be visibly marked to indicate the locations of the wind-uplift reinforcement patches on the underside of the composite so that a roofing installer will know exactly where to pass fasteners for securing the composite to a roof deck through the composite and the wind-uplift reinforcement patches located on the underside of the composite in the fastener placement pattern being utilized to secure the composite to a roof deck.\",\n \"For example, visible X and/or 0 markings could be placed on the top surface of a composite that are centered over the centers of each of the single or double wind-uplift reinforcement patches on the underside of the composite.\",\n \"FIG.\",\n \"17 shows a wind-uplift reinforcement strip placement pattern, which can be used for an eight-fastener placement or other fastener placement pattern, for securing the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 to a roofing deck.\",\n \"The wind-uplift reinforcement strip placement pattern shown for the wind-uplift reinforcement strips 528, 548 and 568 is exemplary and it is to be understood that the reinforcement strip placement patterns for the cover board composite 520, the cover board/insulation board panel composite 540, and the cover board/insulation board/baseboard panel composite 560 can be selected to accommodate any desired fastener placement pattern including any one or more of the fastener placement patterns commonly utilized in the roofing industry.\",\n \"Preferably, the wind-uplift reinforcement strips 528, 548 and 568 are between about three and about six inches wide, run the length and/or width of the composite, and have their longitudinal centerlines centered over fastener placement locations.\",\n \"Preferably, the top surface of a cover board composite 520, a cover board/insulation board panel composite 540, or a cover board/insulation board/baseboard panel composite 560 utilizing the wind-uplift reinforcement strips will be visibly marked to indicate the locations of the wind-uplift reinforcement strips on the underside of the composite so that a roofing installer will know exactly where to pass fasteners for securing the composite to a roof deck through the composite and the wind-uplift reinforcement strips located on the underside of the composite in the fastener placement pattern being utilized to secure the composite to a roof deck.\",\n \"For example, visible solid or dashed line markings or visible solid or dashed line markings with X and 0 markings in various fastener placement patterns could be placed on the top surface of a composite with the line markings centered over and extending along the longitudinal centerlines of the wind-uplift reinforcement strips on the underside of the composite.\",\n \"Tests were conducted to determine fastener pull through strength for a 0.25 inch thick polyisocyanurate cover board: a) with only a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board; b) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and a scrim reinforcement interposed between the bottom facer and the bottom major surface of the cover board and also substantially coextensive with the bottom major surface of the cover board; c) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and six inch wide scrim reinforcement strips interposed between the bottom facer and the bottom major surface of the cover board, running the length of the cover board, and having longitudinal centerlines centered over the fastener penetration locations; d) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and three inch wide scrim reinforcement strips interposed between the bottom facer and the bottom major surface of the cover board, running the length of the cover board, and having longitudinal centerlines centered over the fastener penetration locations; e) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and six inch square scrim reinforcement patches interposed between the bottom facer and the bottom major surface of the cover board and centered over the fastener penetration locations; and f) with a coated nonwoven glass fiber bottom facer bonded to and substantially coextensive with the bottom major surface of the cover board and two layers of six inch square scrim reinforcement patches interposed between the bottom facer and the bottom major surface of the cover board and centered over the fastener penetration locations.\",\n \"The scrim material used in the tests was a fiberglass scrim having a tensile strength of 105 lbs per linear inch.\",\n \"The scrim material was 10 grams/ft2 with 8×8 strands per inch wherein the mean diameter of the strands was 0.019 inches.\",\n \"The measured per fastener wind-uplift pull through strengths for these composites was: a) coated nonwoven glass fiber facer alone—160 lbf (pounds of force); b) coated nonwoven glass fiber facer and scrim reinforcement that is substantially coextensive with the bottom major surface of the cover board—300 lbf; c) coated nonwoven glass fiber facer and six-inch wide scrim reinforcement strips 275 lbf; d) coated nonwoven glass fiber facer and three-inch wide scrim reinforcement strips—250 lbf; e) coated nonwoven glass fiber facer and six inch square scrim reinforcement patches—240 lbf; and f) coated nonwoven glass fiber facer and two layers of six-inch square scrim reinforcement patches—350 lbf.\",\n \"The coverage rate of the scrim reinforcement (area of the bottom major surface of a cover board or other roofing panel composite covered by scrim reinforcement) for the scrim reinforcement embodiments set forth immediately above will vary with the fastener location pattern utilized.\",\n \"However, for the scrim reinforcement embodiments set forth immediately above, an eight fastener location pattern on a four by eight foot cover board or other roofing panel composite (i.e.\",\n \"a cover board or other roofing panel composite with a 32 ft2 bottom major surface) results in the following coverage rates: a) coated nonwoven glass fiber facer alone—0 ft2 coverage; b) coated nonwoven glass fiber facer and scrim reinforcement that is substantially coextensive with the bottom major surface of the cover board—32 ft2 coverage; c) coated nonwoven glass fiber facer and six inch wide scrim reinforcement strips 8 ft2 coverage; d) coated nonwoven glass fiber facer and three inch wide scrim reinforcement strips—4 ft2 coverage; e) coated nonwoven glass fiber facer and six inch square scrim reinforcement patches—2 ft2 coverage; and f) coated nonwoven glass fiber facer and two layers of six inch square scrim reinforcement patches—2 ft2 coverage with 4 ft2 of scrim utilized.\",\n \"With embodiment “f” (coated nonwoven glass fiber facer and two layers of six inch square scrim reinforcement patches—2 ft2 coverage with 4 ft2 of scrim utilized) a 90 pounds/ft2 wind-uplift rating may be achieved for a cover board using only eight fasteners to secure the cover board whereas for embodiment “a” (coated nonwoven glass fiber facer alone) sixteen fasteners must be utilized to achieve a 90 pound/ft2 wind-uplift rating for the cover board.\",\n \"Fasteners and their installation commonly represent approximately 40% of cover board installation costs.\",\n \"The scrim reinforcements of the subject invention enable a reduction in the number of fasteners required to achieve a specific wind-uplift rating for an installed cover board.\",\n \"Thus, for a roofing system with a specific wind-uplift rating, the scrim reinforcements of the subject invention can significantly reduce the labor and ultimately, the overall installed cost of the roofing system.\",\n \"Of course, an installer can retain the normal number of fasteners utilized per cover board and significantly increase the wind-uplift rating for the installed cover board.\",\n \"In addition, while the use of a scrim reinforcement that is substantially coextensive with the bottom major surface of a cover board or other roofing panel composite can significantly increase the per fastener wind-uplift pull through rating, the scrim reinforcement of the subject invention can substantially reduce the square footage of scrim reinforcement required to significantly increase the per fastener wind-uplift pull through rating (e.g.\",\n \"32 ft2 for full scrim reinforcement coverage vs. 8 ft2, 4 ft2, or 2 ft2 coverage for reinforcements of the subject invention for an eight fastener location pattern on a four by eight foot cover board or other roofing panel composite).\",\n \"In describing the invention, certain embodiments have been used to illustrate the invention and the practices thereof.\",\n \"However, the invention is not limited to these specific embodiments as other embodiments and modifications within the spirit of the invention will readily occur to those skilled in the art on reading this specification.\",\n \"For example, the prefabricated roofing panel composites could be in an upside down orientation to that shown and described in connection with FIGS.\",\n \"7 to 9.Thus, the invention is not intended to be limited to the specific embodiments disclosed, but is to be limited only by the claims appended hereto.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874770"}}},{"rowIdx":4494694,"cells":{"text":{"kind":"list like","value":[["THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION","A graph of a plurality of resources in a computing environment is generated, with the graph associating a first resource of the plurality with a second resource of the plurality.","Based at least in part on measurements obtained at a point in a test computing environment that corresponds to a point in the computing environment, a graph representing the relationship between the first resource and the second resource is generated.","A threat model identifying potential risks to the computing environment is created from the graph."],["1.A computer-implemented method, comprising: obtaining a measurement at a determined location of a point in a distributed computing environment; determining, based at least in part on the measurement, a relationship between a first element in the distributed computing environment and a second element in the distributed computing environment; generating, based at least in part on the relationship, a graph comprising a plurality of nodes, with a first node of the plurality of nodes associated with the first element and a second node of the plurality of nodes associated with the second element; and generating, based at least in part on the graph, a threat model that identifies potential risks to the distributed computing environment.","2.The computer-implemented method of claim 1, wherein generating a threat model comprises: visiting at least a subset of the plurality of nodes; and determining, at a node visited, whether potential security risks exist at the node visited.","3.The computer-implemented method of claim 2, wherein potential security risks comprise one or more of an open firewall port, an unencrypted communication, an unauthorized process, or an out-of-date software library.","4.The computer-implemented method of claim 1, further comprising: analyzing the threat model; and implementing, based on a result of analyzing the threat model, one or more security rules to mitigate risks indicated by the threat model.","5.The computer-implemented method of claim 4, further comprising: detecting a violation of the one or more security rules; and performing a security action, wherein the security action is an action performed by the distributed computing environment to mitigate an effect of the violation.","6.The computer-implemented method of claim 5, wherein the security action includes rotating a cryptographic key.","7.A system, comprising: one or more processors; and memory including instructions that, as a result of execution by the one or more processors, cause the one or more processors to: obtain a representation of a plurality of resources in a computing environment, wherein the representation indicates a plurality of relationships among the plurality of resources; and generate, based at least in part on the representation, a threat model that identifies potential security risks to the computing environment as a result of a relationship of the plurality of relationships.","8.The system of claim 7, wherein potential security risks comprise one or more of an open firewall port, an unencrypted communication, an unauthorized process, or an out-of-date software library.","9.The system of claim 7, wherein generating a threat model comprises: analyzing at least a subset of the plurality of relationships; and determining, based on the analysis, whether potential security risks exist.","10.The system of claim 7, wherein the instructions further cause the one or more processors to: analyze the threat model; and implement, based on the analysis of the threat model, one or more security rules to mitigate risks revealed by the threat model.","11.The system of claim 7, wherein the instructions further cause the one or more processors to: determine, using the threat model, whether security risks exist; and implement one or more security rules to mitigate the security risks revealed by the threat model.","12.The system of claim 11, wherein the instructions further cause the one or more processors to mitigate an effect of a violation of the one or more security rules.","13.The system of claim 11, wherein the instructions further cause the one or more processors to update one or more security policies applicable to an entity of the system to mitigate a risk revealed by the threat model.","14.A non-transitory computer-readable storage medium having stored thereon executable instructions that, upon execution by one or more processors of a computer system, cause the computer system to at least: obtain a threat model that identifies potential risks to the computer system, wherein the threat model is based at least in part on a representation of at least a subset of elements in a distributed computing environment and indicates a plurality of potential security risks that exist for individual elements of the distributed computing environment; analyze the threat model to identify a risk; and implement, based on the analysis of the threat model, one or more security rules to mitigate the risk.","15.The non-transitory computer-readable storage medium of claim 14, wherein the executable instructions include executable instructions that, upon execution by the one or more processors of the computer system, cause the computer system to perform, upon a violation of the one or more security rules, a security action, wherein the security action is an action performed by the computer system to mitigate an effect of the violation.","16.The non-transitory computer-readable storage medium of claim 15, wherein the security action includes revoking access of an entity to a resource.","17.The non-transitory computer-readable storage medium of claim 14, wherein the executable instructions include executable instructions that, upon execution by the one or more processors of the computer system, cause the computer system to update, based on the threat model, one or more security policies corresponding to one or more entities of the computer system.","18.The non-transitory computer-readable storage medium of claim 14, wherein the threat model is obtained by a software agent executing within an operating system of a virtual machine being monitored on the computing system.","19.The non-transitory computer-readable storage medium of claim 14, wherein the executable instructions include executable instructions that, upon execution by the one or more processors of the computer system, cause the computer system to generate the threat model based at least in part on data received from elements of a distributed computing environment.","20.The non-transitory computer-readable storage medium of claim 19, wherein the data received from elements of the distributed computing environment is a graph comprising a plurality of nodes representing the elements of the distributed computing environment, and edges indicating a plurality of relationships among the plurality of nodes."],["<SOH> BACKGROUND <EOH>A distributed computing system includes a variety of resource types, such as software applications, data storage resources, and network resources.","The interactions and relationships of these various resources with each other, and with resources external to the distributed computing system, can be difficult to track, which makes security vulnerabilities of the distributed computing system difficult to identify.","Moreover, maintaining the security of the distributed computing system becomes increasingly challenging as applications are updated over time and as the complexity and usage of the system increases.","Furthermore, it can also be difficult to isolate and troubleshoot issues with the system, and even when issues are identified, reliably securing the system may be challenging.","Additionally, such distributed computing systems may not be configured to allow automated mitigation of such vulnerabilities."],["<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>Various embodiments in accordance with the present disclosure will be described with reference to the drawings, in which: FIG.","1 illustrates an example of a computing resource service provider environment with introspection points in accordance with an embodiment; FIG.","2 illustrates an example of introspection of virtual computing network environments in accordance with an embodiment; FIG.","3 illustrates an example of graph of resources in accordance with an embodiment; FIG.","4 illustrates an example of an introspection agent in accordance with an embodiment; FIG.","5 illustrates an example of an introspection agent in a virtualization layer in accordance with an embodiment; FIG.","6 illustrates an example of computing resource service provider in accordance with an embodiment; FIG.","7 is a flow chart that illustrates an example of generating a threat model from data collected at introspection points in accordance with an embodiment; FIG.","8 is a flow chart that illustrates an example of determining potential vulnerabilities in a computing environment in accordance with an embodiment; and FIG.","9 illustrates an environment in which various embodiments can be implemented.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","15/256,381, filed Sep. 2, 2016, entitled “THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION,” which is a continuation of U.S. patent application Ser.","No.","14/673,642, filed Mar.","30, 2015, now U.S. Pat.","No.","9,438,618, issued Sep. 6, 2016, entitled “THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION,” the disclosures of which are incorporated herein by reference for all purposes.","BACKGROUND A distributed computing system includes a variety of resource types, such as software applications, data storage resources, and network resources.","The interactions and relationships of these various resources with each other, and with resources external to the distributed computing system, can be difficult to track, which makes security vulnerabilities of the distributed computing system difficult to identify.","Moreover, maintaining the security of the distributed computing system becomes increasingly challenging as applications are updated over time and as the complexity and usage of the system increases.","Furthermore, it can also be difficult to isolate and troubleshoot issues with the system, and even when issues are identified, reliably securing the system may be challenging.","Additionally, such distributed computing systems may not be configured to allow automated mitigation of such vulnerabilities.","BRIEF DESCRIPTION OF THE DRAWINGS Various embodiments in accordance with the present disclosure will be described with reference to the drawings, in which: FIG.","1 illustrates an example of a computing resource service provider environment with introspection points in accordance with an embodiment; FIG.","2 illustrates an example of introspection of virtual computing network environments in accordance with an embodiment; FIG.","3 illustrates an example of graph of resources in accordance with an embodiment; FIG.","4 illustrates an example of an introspection agent in accordance with an embodiment; FIG.","5 illustrates an example of an introspection agent in a virtualization layer in accordance with an embodiment; FIG.","6 illustrates an example of computing resource service provider in accordance with an embodiment; FIG.","7 is a flow chart that illustrates an example of generating a threat model from data collected at introspection points in accordance with an embodiment; FIG.","8 is a flow chart that illustrates an example of determining potential vulnerabilities in a computing environment in accordance with an embodiment; and FIG.","9 illustrates an environment in which various embodiments can be implemented.","DETAILED DESCRIPTION In the following description, various embodiments will be described.","For purposes of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the embodiments.","However, it will also be apparent to one skilled in the art that the embodiments may be practiced without the specific details.","Furthermore, well-known features may be omitted or simplified in order not to obscure the embodiment being described.","Techniques described and suggested include determining, by a computing resource service provider, a set of introspection points in a distributed computing system.","The distributed computing system may include either or both physical and virtual computing systems.","The distributed computing system may further include one or more computing network environments.","The set of introspection points may be determined based on identifying characteristics that are accessible at the individual introspection points of the set of introspection points (e.g., network internet protocol addresses, encryption or decryption keys, software library versions, process names and identifiers, virtual machine identities, etc.).","At the individual introspection points, the identifying characteristics may be measured, and a graph may be generated based on the measurements and/or configuration information of the distributed computing system.","The generated graph may include a set of nodes representing elements (also referred to as resources or components) of the distributed computing system, with edges between the nodes indicating the relationships between the nodes.","One or more rules may be evaluated against the graph; for example, a rule may specify that credentials should have no greater privileges than necessary for accessing requested resources, and, from the graph data, it may be determined that credentials used to access a certain resource have greater privileges than actually used.","In such a case, the system may perform a security action, such as notifying an appropriate entity (e.g., network security personnel, an appropriate customer of the computing resource service provider, etc.)","of the rule violation or automatically modifying a security policy to constrain the privileges of the respective credentials to the minimum necessary.","In some embodiments, a threat model may be generated from the graph to illustrate the potential vulnerabilities and/or rule violations in the distributed computing system.","The described and suggested techniques improve the field of computing in distributed systems, and specifically the field of threat detection and mitigation in distributed systems, by providing a new and useful system for detecting threats to a wide variety of resource types in large scale distributed computing systems.","Additionally, the described and suggested techniques improve the functioning of computer systems by allowing automated updates in response to detected vulnerabilities and rule violations, thereby reducing the impact of a security breach of the system.","Moreover, the described and suggested techniques offer meaningful advantages over general monitoring systems by providing the ability to customers of a computing resource service provider to monitor a wide variety of resource types in a computing network environment from locations in the computing network environment normally only accessible to the computing resource service provider itself.","FIG.","1 illustrates an aspect of an environment 100 in which an embodiment may be practiced.","As illustrated in FIG.","1, the environment 100 may include a computing resource service provider 102 having providing services supported by a distributed computing system.","Such services may include, among others, a virtual computer system service 104 hosting a set of virtual machines 106, a data storage service 108 hosting a set of data storage resources 110, a policy management service 112 for managing a set of policies 114, and one or more other services 116.Resources within the environment 100, such as virtual machines of the set of virtual machines 106, may be accessible by users and customers via the Internet 118 through an application programming interface provided by the computing resource service provider 102.FIG.","1 also illustrates a set of introspection points 120A-120E for collecting information about resource usage within the system.","In embodiments of the present disclosure, a distributed computing environment, where a variety of resource types, hardware and software, are provided by the computing resource service provider 102, allows collection of information at a variety of introspection points within the overall system.","In some examples, an “application system” may refer to a set of machines that execute a software application.","In some cases, the set of machines may be multiple computing systems, such as servers, in communication with each other and/or in communication with other resources.","In a virtual computer system environment, the configuration of all of the virtual machine instances in the environment, including which virtual machines are in use, firewall rules for each of the virtual machines, and type, amount, and location of storage for each of the virtual machines may be stored as configuration information.","This configuration information may be stored in a form accessible to the computing resource service provider 102 of the virtual computer system service 104, such as in tables/records from a data store.","Configuration information could include such information as a list of virtual machine instances (e.g., the set of virtual machine 106) ascribed to a customer owner, a number and identity of processors of a virtual machine instance, open and closed firewall ports of a virtual machine instance, internet protocol addresses for the virtual machine, and software applications running on the virtual machine and which credentials are in use by which software application.","The computing resource service provider 102 may likewise detect and track each of the processes running in each virtual machine.","In this manner, the computing resource service provider 102 may detect and flag when a previously undetected process launches within a virtual machine.","Furthermore, the computing resource service provider 102 may also detect the software dependencies of processes installed in the virtual machine instance.","Based on the data collected, the computing resource service provider 102 may create a threat model enumerating potential security threats within the monitored system.","Analysis of the data may include walking each node/edge in the graph and determining, at each node, whether and what potential security risks exist (e.g., Ya, etc.","), and determining whether the resource represented by each node is in compliance with rules specified by a customer and/or computing resource service provider.","From this threat model a customer, the computing resource service provider 102, or other authorized entity (e.g., network security personnel), may implement a security rule to mitigate risks revealed by the threat model.","For example, based on list of software dependencies of processes running within the environment, a rule could be implemented to perform a security action if a process is detected to run using a version of a software library that is not the most recent version available.","The rule may be driven by the risk that older software libraries may contain security vulnerabilities that were fixed in a newer library.","In some examples, a “security action” may refer to an action performed by a computing system of the computing resource service provider to notify or mitigate a detected violation or threat to one or more elements in a computing environment under the control of the computing resource service provider.","Such security actions could include any of a variety of actions, such as preventing the process from running, logging the event (e.g., date, time, location of the process, virtual machine instance hosting the process, version of the software library, etc.","), automatically updating the library to the most recent version, or sending an alert to the customer or to network security personnel.","Other examples of security actions include updating one or more security policies (i.e., information defining permissions and constraints on users, applications, and other entities to access resources) corresponding to one or more entities (e.g., users, resources, applications, etc.)","of the computing environment, sending notifications to a notification service of a computing resource service provider, and queuing a message in a message queue of a queue service.","Still, other examples of security actions include causing a change to a network (e.g., change to a secure protocol) to which at least one network interface is attached, or triggering a forensics action (e.g., capturing network traffic, memory, or other state of a virtual machine).","Security actions could also include terminating a virtual machine instance, isolating a process or virtual machine from a network for later analysis, rotating or blocking one or more security credentials, rotating one or more cryptographic keys, revoking a user's or other entity's access to a resource, or installing a software update.","Still, other security actions could include capturing information (e.g., saving a snapshot) about the resource that potentially violates a rule, terminating and re-instantiating a virtual machine instance that appears to be behaving irregularly, storing a memory dump of a virtual machine instance, and/or reverting to a previous version of a data store.","A security action may also include updating the configuration of a computer resource to comply with one or more specified rules (e.g., close specific network ports, refuse communications from certain internet protocol address ranges, etc.).","Such rules may be implemented in a variety of ways, for example, by modifying firewall rules (e.g., allowing/blocking certain ports, internet protocol addresses, or network protocols), by updating a configuration corresponding to a virtual computing network environment and/or the set of virtual machines 106 running under a virtual computer system service.","Various types of security actions are described in the present disclosure, and any reference to security actions in the present disclosure is contemplated to include other types of security actions not expressly mentioned.","Likewise, the computing resource service provider 102 may track communications between processes and other entities internal or external to the local network of a virtual machine.","Such tracked communications may allow a customer, the computing resource service provider 102, or other authorized entity to identify firewall vulnerabilities.","For example, the computing resource service provider 102 may determine, based at least in part on the firewall configuration of a virtual machine, that a another computing system (virtual or physical) is allowed to communicate with the virtual machine.","However, in this example, after a period of monitoring, no actual communication occurs between the first and second virtual machines.","In this example, the computing resource service provider 102 may determine that, based at least in part on the lack of communication between the two virtual machine instances, that, even though permitted by the firewall, the communications channel between the first and second virtual machine instances should be closed.","Based on this determination, the computing resource service provider 102 may perform a security action, such as automatically updating one or more firewall rules to block communication between the first and second virtual machine, or communicating the security concern to one or more customer owners of the virtual machine instances.","Similarly, the computing resource service provider 102 may track requests (e.g., for access, for data, etc.)","by users, virtual machines, and other entities, and may track the corresponding credentials used with those requests.","By performing an analysis on the tracked requests after a period, the computing resource service provider 102 may determine that the credentials allow greater privileges than the privileges actually used.","For example, the credentials may be associated with read and write permissions to a database, but the credentials are actually only used for reading from the database; in such a case, the write permission may be, at best, unnecessary, and, at worst, a security risk.","In response, the computing resource service provider 102 may perform a security action, such as alerting the customer owner of a tracked virtual machine account for which the credentials are being used of the potential excess privileges associated with the credentials, or may, if directed to take such automatic actions, automatically reduce the privileges associated with the credentials only to those actually used/required by the requesting entity.","Tracked information may further include which network connections are using an encrypted protocol versus an unencrypted protocol.","Such information may be used to generate a threat model.","For example, if the computing resource service provider 102 detects the virtual machine instance communicating with the other computing system under an unencrypted protocol, the computing resource service provider 102 may notify a customer owner of one of the virtual machine instance of the potential risk associated with the unsecured communication channel.","Furthermore, data tracked at different times may be compared, such as to identify changes in behavior, performance, and security risks.","As an example, a software application may be updated to a new version and implemented within one or more virtual machine instances within the virtual computer system environment.","Information as described in the present disclosure may be tracked for a period of time and subsequently compared against information previously tracked when the software application was at a previous version.","Such comparisons may allow the computing resource service provider 102 and/or customer owner of the virtual machine instances to identify anomalies and security risks.","For example, using the case described above of a virtual machine and another computing system that had initially been allowed to communicate with each other but had never done so, upon a software update, the computing resource service provider 102 may detect that the virtual machine is now communicating with the other computing system (or vice versa).","In some situations, this communication may be desired behavior (e.g., they may have been intended to communicate with each other, but due to some configuration or software error, were unable to do so), and the tracked information may serve as confirmation that the software update had a desired effect.","In other situations, this communication may be unexpected; such as in a case where a software update contains a security vulnerability that some entity may be trying to exploit to gain access to the second virtual machine.","In either case, the computing resource service provider 102 may perform a security action which may include alerting the customer owner of the virtual machine instances and/or blocking communication between the first and second virtual machine instances until receiving express confirmation from the customer owner that such communication is permitted.","As illustrated in FIG.","1, the computing resource service provider 102 may designate a set of introspection points 120A-120E for tracking the described information.","The set of introspection points 120A-120E may be data collection points specified by a customer, computing resource service provider, or other authorized entity.","Information may be collected at the introspection points by one or more introspection agents.","Types of introspection points may include points between a web service request and the target of the request, locations in a network between an application and the endpoint of the communication, error logs and other various logs, infrastructure configuration information for the computing environment, security controls (e.g., users, credentials, permissions, etc.)","and policies for the computing environment, database permissions, and/or billing records.","Examples of types of information that may be collected at the set of introspection points 120A-120E include, requestor identifiers (ID), a service ID, date/time, application programming interface methods called, source and destination interne protocol addresses, cryptographic keys, hostnames, system process IDs, and/or user IDs.","Information collected at the introspection points may serve to identify what application programming interfaces are being used in the environment 100 and to what extent, which credentials or cryptographic keys are being used, information about network traffic flow, hostnames, domain names, running system processes, or user IDs.","For example, introspection point 120A illustrates an introspection point for collecting metadata about communications between one or more of the set of virtual machines 106.Similarly, introspection point 120B illustrates an introspection point for collecting metadata when a virtual machine of the set of virtual machines 106 attempts to access or receives data from one or more data storage resources of the set of data storage resources 110.For example, network communication monitored between a virtual machine and a data storage resource at the introspection point 120B may reveal whether the data passed between the virtual machine and the data storage resource is encrypted or not.","Similarly, network communication monitored between the virtual machine and the data storage resource at the introspection point 120B may yield information about the identity of a logical storage container being accessed at the data storage resource, what credentials were used to access the data storage resource, etc.","Likewise, introspection point 120C illustrates an introspection point for collecting metadata about credential usage and associated permissions, as defined within the set of policies 114.Additionally, introspection point 120C illustrates an introspection point for collecting metadata about communication between one or more computing devices communicating with a virtual machine of the set of virtual machines 106 through the Internet 118.Lastly, introspection point 120E illustrates an introspection point for collecting metadata about utilization of one or more of the other services 116 as may be provided by the computing resource service provider 102 to a virtual machine of the set of virtual machines 106 of the virtual computer system service 104.Note that although the set of introspection points 120A-120E are illustrated as individual points, it is understood that each of the set of introspection points 120A-120E may themselves be a subset of introspection points.","In some examples, “introspection” may refer to an examination of states, system behavior, data, and information flows with and between processes in a distributed computing environment.","In some examples, the term “introspection point” may refer to a data collection point, such as within a hypervisor, injection of executable code in application memory, or a software application with elevated access permissions (which may also be referred to as an “introspection agent”) executing on a computing system within the environment 100.The introspection point (or “sensor”) may be an endpoint of a network connection or may also include reading from logs generated through use of application programming interfaces of the computing resource service provider.","An introspection point for a customer of a computing resource service provider could also include billing records, or a system or service with access to billing records; for example, a customer may request to be notified if charges for certain types of usage exceed a particular rate or amount, if charges accrue in any region of the computing environment that has not generated charges before, or if any cumulative charges are measured to surge above a norm or expected range.","Introspection points may allow gathering of metadata from which may be determined the activity that is occurring at that point.","For example, if an application utilizes a public-key cryptography system (PKCS) interface, such as an interface that complies with PKCS#11, and/or other suitable standards, or some other interface for digitally signing data, the interface may be designated as an introspection point.","In this example, whenever the interface is called to sign data, metadata about the signing could be collected.","Likewise, an introspection point may be designated at any similar interface within the environment 100 of the computing resource service provider 102.In some embodiments, a customer owner of one or more virtual machine instances can specify to the computing resource service provider 102, such as through a web interface, the set of introspection points 120A-120E (i.e., sensors) where an introspection agent is to take measurements (i.e., gather information).","The customer owner may further specify a set of expected values or ranges for the measurements.","Additionally, the customer owner may specify security actions for the introspection agent to take (or caused to be taken) if certain measurements fall outside expected values or ranges, and may specify for allowed/disallowed behavior by components of the customer owner's systems.","For example, the customer owner may send a request to the computing resource service provider 102, such as through an application programming interface provided by the computing resource service provider 102, to implement a set of application agents responsible for monitoring software applications executing on the set of virtual machines 106 of the customer owner.","In this example, the customer owner may provide, through the interface, the computing resource service provider 102 with a list of software applications the customer owner expects to be executing on the one or more virtual machines and may request to be notified if the computing resource service provider 102 detects any variance.","In response to the request, in this example, the computing resource service provider 102 may configure the set of introspection agents to perform the security action of notifying the customer owner of any execution of a process not on the approved list in the set of virtual machines 106.In this manner, a customer owner may place (i.e., deploy), through the application programming interface, one or more sensors at specified locations in the customer owner's environment within the distributed computing system, if such sensors were not already deployed, without installing separate software applications and in locations within the distributed computing system that might otherwise be inaccessible to the customer owner.","In some cases, a sensor may be able to determine whether a communication to/from a software application is encrypted or decrypted, but, if encrypted, may be otherwise unable to determine any information about the data within the encrypted communication.","In some embodiments, however, upon instruction and consent from a customer, sensors may be inserted within an virtualization layer that is managing the execution of one or more of the customer's virtual machine instances, and instructed to detect an encryption protocol (e.g., transport Layer Security, Secure Sockets Layer (SSL), etc.)","handshake and obtain a key for decrypting the data in the transmitted communications (e.g., PreMasterSecret, etc.).","In this manner, such a sensor may be enabled to monitor data within encrypted communications.","The set of virtual machines 106 may be one or more virtual machines configured to emulate computer system hardware.","The set of virtual machines 106 may be implemented to run as a system virtual machine or as a process virtual machine (e.g., implemented to run under an operating system).","In some implementations, the set of virtual machines 106 run under a virtualization layer.","In some examples, a “virtualization layer” may refer to hardware or software that enables the physical hardware of the computing system to be used to provide computational resources upon which the set of virtual machines 106 may operate.","The virtualization layer may be any device, software, or firmware used for providing a virtual computing platform for the set of virtual machines 106.The virtual computing platform may include various virtual computer components, such as one or more virtual processors, virtual memory and the like.","The set of virtual machines 106 may be provided to customers of the computing service resource provider 102 and the customers may run an operating system or an application on virtual machines of the set of virtual machines 106.Further, the computing service resource provider 102 may use one or more of its own virtual machines for executing its applications.","Examples of a virtualization layer include a hypervisor.","In other embodiments, data collected at the introspection points 120A-120E is used to determine a set of reference/baseline values or ranges.","In some of these embodiments, the set of reference values or ranges may be determined by measuring (i.e., collecting) data at designated introspection points for a period of time in a test environment.","Thereafter, variance from the determined set of reference values or ranges in a live (i.e., production) environment may cause the computing resource service provider 102 to respond with a security action, such as requiring confirmation from a customer owner that the variance is acceptable before allowing the actions causing the variance to continue.","For example, if the computing resource service provider 102 identified a set of software applications executing within the test environment, the set of software applications may be recorded as expected to execute in a live environment.","However, if the computing resource service provider 102 subsequently identifies a software application, not on the list, executing in the live environment (e.g., different application or different version of an application observed to execute in the test environment), the computing resource service provider 102 may respond with a security action, such as notifying the customer owner (e.g., through a user interface alert, text message, e-mail message, etc.)","of the unexpectedly executing software application.","In some implementations, evaluation of the measurements taken at the introspection points 120A-120E and performance of security actions may occur in real-time.","That is, as measurements are taken and threats to the computing environment are determined, security actions (e.g., notifying a customer, adding constraints to a configuration of the computing environment to ensure compliance with a set of rules, etc.)","may be performed immediately.","In other implementations, measurements may be logged for evaluation and threat determination later or upon request.","In an example, a set of virtual machine instances of a customer may be configured and expected to execute the same set of software, execute the same set of resources, and perform in a similar manner.","Introspection points may be specified for the set of virtual machine instances; e.g., within virtual memory, monitoring network communications, calls to application programming interfaces, etc.).","After tracking information at these introspection points for a period, the computing resource service provider 102 may determine that a subset of the set of virtual machine instances exhibit a variance from expected values (e.g., executing a different version of a software application, attempting to access an unexpected resource, application errors, slower than expected performance, etc.).","Based on this determination, the computing resource service provider 102 may perform any of a variety of security actions, such as notifying the customer about the unexpected behavior from the subset of the set of virtual machine instances, performing diagnostics on the physical host of the subset, terminating and reinstantiating the virtual machine instances of the subset, etc.).","As noted, in some embodiments, an introspection point may be embodied by an introspection agent.","The introspection agent may be implemented as a software application executing on the virtual or physical computing system with elevated access privileges (e.g., superuser/root access).","The introspection agent may be implemented to execute within a virtualization layer (e.g., a hypervisor) or within a controlling domain of the virtualization layer.","Additionally or alternatively, the introspection agent may be implemented in hardware, such as within a universal serial bus dongle device communicatively coupled to a physical system within the distributed computing system of the computing resource service provider 102.Alternatively or additionally, an introspection agent may be implemented within a kernel of an operating system of the physical or virtual computing system.","The introspection agent may be configured to audit whenever a software process is launched, whenever a software process is stopped, and information about such software processes (e.g., file names, file locations, software dependencies, etc.).","For example, the introspection agent may be configured to detect whenever a “process launched” event occurs, and, when such event occurs, gather a set of information about the software process (e.g., all libraries loaded by the process, checksum of the process, information on how the software process was compiled, parameters passed to the software process call, etc.).","In some embodiments, the introspection agent may be loaded into virtual memory of a virtual machine running under a virtualization layer (e.g., a hypervisor) and caused to execute.","In other embodiments, the introspection agent may execute within the virtualization layer, and, based on a query of a virtual method table, determine and monitor a process space of the software processes in a specified virtual machine instance designated to be monitored.","Additionally or alternatively, in embodiments the introspection agent may hook into a syscall handler of the virtualization layer for the virtual machine instance being monitored.","Within the computing resource service provider 102 environment, there may also be a data store containing a set of reference values representing expected values or expected ranges of values for the measurements being taken at designated introspection points.","In response to variance from the expected value or range, the introspection agent may execute a security action, such as notifying a customer owner of a virtual machine instance that may be affected by the variance that the variance was observed.","The introspection agent may access the data store containing the set of reference values and compare the set of reference values with information measured at the introspection points to determine whether variance from expected values or ranges has occurred.","The computing resource service provider 102 may be a computing resource service provider, similar to the computing resource service provider 602 described in conjunction with FIG.","6, and may provide one or more computing resource services to its customers individually or as a combination of services of a distributed computer system.","The one or more computing resource services of the computing resource service provider 102 may be accessible over a network and may include services such as virtual computer system services, block-level data storage services, cryptography services, on-demand data storage services, notification services, authentication services, policy management services, task services, and/or other such services.","Not all embodiments described include all of the services described and additional services may be provided in addition to, or as an alternative to, services explicitly described.","Customers of the computing resource service provider 102 may communicate with one or more of the services via an interface, which may be a web services interface or any other type of customer interface.","Each service provided by the computing resource service provider 102 may have its own interface and subsets of the services may have corresponding individual interfaces in addition to, or as an alternative to, a common interface.","A customer may communicate with the computing resource service provider 102 through a network, whereby the network may be a communication network, such as the Internet 118, an intranet, an interne service provider (ISP) network and/or some other such network as described below.","The virtual computer system service 104 may be used by the computing resource service provider 102 for providing computer system resources for customers.","The virtual computer system service 104 may provide such computer system resources by instantiating virtual machine instances, such as the set of virtual machines 106, on physical hardware.","The physical hardware may include physical hosts which may include any device or equipment configured to execute instructions for performing data computation, manipulation, or storage tasks, such as a computer or server similar to the electronic client device 902 and the application server 908 described in conjunction with FIG.","9.The customer may interact with the virtual computer system service 104 to provision, place, and operate virtual machine instances.","The virtual machine instances may be used for various purposes, such as to operate as servers supporting a website, to operate business applications or, generally, to serve as compute power for the customer.","The data storage service 108 may provide a non-transitory persistent (non-volatile) storage for program and data files for use by computing systems, such as the set of virtual machines 106.Software applications executing within the set of virtual machines 106 may be stored within one or more data stores (also referred to as repositories) of the set of data storage resources 110.The data storage service 108 may additionally provide repositories for storing data used in accordance with the present disclosure.","The set of data storage resources 110 may be one or more storage resources, such as databases or storage resources as might be provided by services, such as the block level data storage service 610 or the on-demand data storage service 614 of FIG.","6.The policy management service 112 may be a service configured to authenticate users of the customer and manage policies on behalf of customers of the computing resource service provider 102, such as the policy management service 620 of FIG.","6.The set of policies 114 may be security policies associated with roles and credentials of an entity (e.g., user, customer, application, resource, etc.)","that specify the access privileges the entity may have to one or more resources.","The one or more other services 116 may be any other service provided by the computing resource service provider, the resource usage of which may be tracked at an introspection point, such as the introspection point 120E.","In an example, for a physical host of one or more virtual machines under the control of the computing resource service provider 102, the virtual memory of a virtual machine may be designated as an introspection point.","To collect data within the virtual memory, the computing resource service provider 102 may grant direct memory access (DMA) to an introspection agent executing on the physical host for inspecting contents of at least portions of the virtual memory.","Subsequently, the inspected contents of the virtual memory may be compared against reference values or ranges in order to detect any deviance from expected memory contents.","As another example, network communication channels may be designated as introspection points, and an introspection agent for analyzing data packets and performing net flow analysis may be integrated into networking hardware.","FIG.","2 illustrates an aspect of an environment 200 in which an embodiment may be practiced.","As illustrated in FIG.","2, the environment 200 may include one or more virtual computing network environments 203A-203B in communication with one or more clients 210A-210C through a network connection, such as through the Internet 218, where each of the virtual computing network environments 203A-203B may be comprised of a set of computing systems 204A-204N, physical or virtual.","Each of the set of computing systems 204A-204N, in turn, may include sets of various hardware and/or software components, such as a one or more processors 206A-206N and storage 208A-208N.","In the environment 200, an introspection point 220 may be specified for collection of information associated with incoming and outgoing communications between the virtual computing network environments 203A-203B each other and between the virtual computing network environment and one or more clients 210A-210C via the Internet 218.The one or more virtual computing network environments 203A-203B may be configurable pools of shared computing resources of a customer of a computing resource service provider, isolated from other virtual computing network environments.","Isolation of the virtual computing network environments may be achieved through allocation of a private interne protocol subnet, a virtual local area network, and/or encrypted communication channels between the shared resources within the virtual computing network environments.","A virtual computing network environment may include a set of virtual machine instances, such as set of computing systems 204A-204N of the virtual computing network environment 203A.","The set of computing systems 204A-204N may be a set of virtual machine instances.","Each of the set of computing systems 204A-204N may comprise resources from multiple services of the computing resource service provider 202.For example, the computing resource service provider 202 may, for the computing system 204A, utilize a virtual computer system service to instantiate a virtual machine, similar to the set of virtual machines 106 of the virtual computer system service 104 in FIG.","1, having one or more virtual processors 206A for the computing system 204A.","The sets of one or more virtual processors 206A-206N may be emulations of physical processors for a set of computing systems 204A-204N.","Likewise, the storage 208A-208N may be configured to emulate persistent storage (e.g., hard drives, network drives, databases, etc.).","The storage 208A may be, for example, on-demand storage, block-level storage, or a database provided by a data storage service, similar to the set of data storage resources 110 of the data storage service 108 in FIG.","1.Configuration information for each set of computing systems 204A-204N may be stored in a data store and accessible to the computing resource service provider 202.Each computing system of the set of computing systems 204A-204N may also have network ports for receiving requests from and establishing connections with computing systems internal and external to the respective virtual computing network environment 203A-203B.","On the storage 208A-208N of the set of computing systems 204A-204N may be stored software library files, various configuration files, and/or digital certificates.","As noted, the computing resource service provider 202 may be a computing resource service provider, similar to the computing resource service provider 602 described in conjunction with FIG.","6, and may provide one or more computing resource services to its customers individually or as a combination of services of a distributed computer system.","The one or more clients 210A-210C may be users or other entities attempting to access resources within one or more of the virtual computing network environments 203A-203B or may be customers of the computing resource service provider 202 attempting to access their own resources within their own virtual computing network environment.","The introspection point 220 may be configured to monitor network communications between computing systems of virtual computing network environment 203A and virtual computing network environment 203B.","Similarly, the introspection point may be configured to monitor network communications between the Internet 218 and virtual computing network environment 203A and/or virtual computing network environment 203B.","Monitoring network traffic at the introspection point may include analyzing at least a portion of data packets passing through the network connection.","As noted, the introspection point 220 depicted in FIG.","2 may actually be a set of introspection points, implemented as hardware or software, assigned/deployed at various points of the network of the computing resource service provider 202.Note also that, besides the introspection point 220, there may be other active introspection points, such as introspection points within the virtual computing network environment and between the services providing the resources for the set of computing systems 204A-204N (as described in more detail in the description of FIG.","1).","FIG.","3 illustrates an example visualization 300 of a graph of an embodiment of the present disclosure.","Specifically, FIG.","3 depicts a set of resources whose usage may be tracked at introspection points in the manner disclosed in the present disclosure.","The set of resources may include any suitable resources that may be provided by a computing resource service provider, and, as an illustrative example, FIG.","3 shows a set of processes 302A-302E executing within a distributed computing system environment, a set of network connections 304A-304D, a set of software libraries 306A-306B, and a service 308 of a set of services.","Thus, the tracked data, collected in the manner detailed in the descriptions of FIGS.","1 and 2, may be organized into a graph data structure.","The graph may be generated as having nodes representing resources (e.g., software libraries, services of a computing resource service provider, network addresses and ports, processors of a virtual machine, software processes, etc.)","and edges representing relationship (e.g., software library dependency, network connection, etc.)","between those nodes.","For example, information collected at introspection points may yield information linking processes to networks, processes to software libraries, networks to services, and other resources to other resources.","A visual map (also referred to as a visualization) may further be generated from the graph.","As an example, the visualization may be displayed using any suitable manner of displaying such a graph, such as through auto-generated JavaScript code provided to a web browser of a customer of the computing resource service provider.","Each of the set of processes 302A-302E represent a running process in a distributed computing system.","Examples of such processes include database applications, web servers, e-mail hosts, and video streaming software.","The set of network connections 304A-304D represent network connections linking processes of the set of processes 302A-302E to other resources, such as to another process or to a service provided by the computing resource service provider.","The network connections may be any suitable network and protocol for communication between computing devices and/or processes executing on computing devices.","Examples of a network includes the Internet, a local area network, a wide area network and Wi-Fi.","Information collected at an introspection point regarding a network may include a network address, network port, and a type of protocol being used.","The set of software libraries 306A-306B may be files containing configuration data and/or pre-written executable code for use by one or more of the set of processes 302A-302E.","As noted, the service 308 may be a service provided by the computing resource service provider, such as a policy management service, a data storage service, or any of the services 608-624 described in conjunction with FIG.","6.Information about a service collected at an introspection point may include what operations are being performed by the service, whether communications are encrypted or unencrypted, and credentials being used for communication with the service.","The service 308 may provide database services to a customer of the computing resource service provider.","Thus, the database resource 312 may represent a particular database provided to the customer.","The database may contain, tables, such as tables 316A-316B, for storing data records for the customer.","The permissions 314A-314B (also referred to as rights) may represent access permissions a user or other identity has to the particular table.","For example, permission 314A may be read/write access to the table 316A, whereas permission 314B may represent read-only access to the table 316B.","By identifying common characteristics from information collected at introspection points, relationships between nodes may be determined.","For example, information collected at an introspection point on a computing system executing the process 302A may reveal that the process 302A receives data from an internet protocol address/port identified as network 304B.","Additional information associated with the network 304B may include a process identifier of a process associated with the network 304B (e.g., the process 302A), an identity of a user agent communicating through the network (e.g., Internet Explorer, Chrome, etc.","), and/or an identity of a software application being communicated with (e.g., Apache HTTP Server, etc.).","Such information may be stored in a database usable for introspection and other analysis.","In embodiments of the present disclosure, the system may make conclusions about the relationships between the nodes.","For example, information collected at an introspection point at service 308 would reveal that the service 308 communicates data through the network 304B.","That is, by identifying that both the process 302A and the service 308 have the network 304B in common, the computing resource service provider can conclude that the process 302A is linked to the service 308 through the network 304B.","Likewise, it is shown in FIG.","3 that the process 302A communicates with process 302B through the network 304B.","Additionally, it is shown that process 302C has attempted to communicate with the process 302B through network 304C, and also that the process 302B has not responded to the process 302C.","It is also shown that process 302D also communicates with the service 308, but through network 304D.","In an example, it may be that configurations for processes 302B and 302D indicate that they are meant to communicate with each other, but from the graph of FIG.","3, it may be observed that said processes do not communicate directly with each other.","By drawing attention to such a mismatch between a configuration and the graph, the computing resource service provider may identify potential errors with configurations that prevent the intended operations of processes running within the distributed computing system.","As another example, it may be that there is nothing in a security policy or firewall configuration preventing communication between the processes 302B and 302D, but only that during the observational period, they have not done so.","Based on information, the computing resource service provider may determine that the processes 302B and 302D are not intended to communicate with each other and implement a firewall rule preventing communication between the two processes to ensure that, should the security of the virtual machine upon which either the process 302B or the process 302D is running be compromised, that the firewall rule would prevent one of the processes from accessing the other without authorization.","Alternatively, if two processes, such as the process 302B and the process 302D, are established as a baseline never to communicate with each other, and, subsequently they are observed to communicate with each other, the computing resource service provider may respond with a security action, such as alerting a customer owner or network security personnel.","Once relationships between nodes are identified, rules may be implemented, such as by a customer owner through a user interface provided by the computing resource service provider, to specify acceptable behavior of the resources represented by the nodes.","For example, a customer owner of a virtual machine upon which the process 302A is running may implement a rule specifying that communications between the process 302A and the service 308 must use an encrypted protocol.","Based on this rule, the computing resource service provider may confirm that the network 304B does not use an unencrypted protocol.","If the computing resource service provider detects that the protocol is unencrypted, the computing resource service provider may perform a security action, such as disallowing use of the network connection 304A to communicate with the service 308.Similarly, the customer owner may specify that all communications to/from the process 302A must be through an encrypted protocol, and the computing resource service provider may enforce this requirement on network 304A as well.","Another example of a rule that may be implemented in the system of the present disclosure is a rule that specifies that, unless expressly allowed by the customer owner, no software applications within a set of virtual machine instances of the customer owner should execute with root/superuser privileges.","Still another example of a rule is to specify that network port 22 of the set of virtual machine instances should be closed/blocked.","Another example of a rule is to specify that credentials cannot be used to access more than one type of service (e.g., file storage service versus database service, etc.).","Similarly, a rule could specify that certain credentials have write access to one service but only read access with a different service.","Likewise, information collected at an introspection point at the process 302A may reveal that the process 302A has software dependencies of library 306A and 306B.","Furthermore, information collected at introspection points at process 302C and process 302D reveal that they too depend on the library 306B.","Based at least in part on this information, the computing resource service provider can quickly determine that, if a new version of the library 306B is made available, then the processes 302A, 302C, and 302D may be impacted or may need to be updated.","Similarly, if the graph of the embodiment of the visualization represents a baseline (i.e., set of reference values or ranges), and/or if a subsequent generation of the graph reveals that the process 302A is using a different library than the library 306B, the computing resource service provider may respond by performing a security action.","Such security action could include automatically updating the process 302C and the process 302D to use the different library (if it is determined to be a new, stable version of the library 306B), reverting the process 302A to use the library 306B instead of the different library, or sending an alert to the customer of the computing resource service provider responsible for virtual machine the process 302A is running on that the process 302A is using an unexpected library.","The set of reference values or ranges as well as the appropriate security action to take could be specified by a customer owner of a virtual machine upon which the process is running.","For example, the customer owner could specify that a specified library must be a specific version and for the computing resource service provider to halt/prevent any process with dependencies of a different library version from running.","Configuration information associated with the resources, and the generated graph, a threat model describing potential security issues, such as threats to confidentiality, availability, and integrity of data and the applications, may be generated for customers of the computing resource service provider regarding their virtual computer system environment.","In some implementations, a customer of the computing resource service provider may specify rules to apply to the customer's virtual computing system environment, and the computing resource service provider may compare the specified rules to a current graph of the virtual computing system environment.","The computing resource service provider may provide, such as through a user interface, the results of the comparison to the customer, such as “The present configuration complies with the specified rule,” “The present configuration does not comply with the specified rule,” “Unable to evaluate the present configuration against the specified rule,” etc.","The users 310A-310N may be an individual, virtual or physical computing device, software process, or other entity authorized to access resources of a customer account.","Each of the users 310A-310N may have a unique name/identity within the account, and may present or otherwise prove the possession of security credentials, such as with a password, access key, and/or digital signature, to gain access to computing resources.","The users 310A-310N may represent one or more users that authenticate with the service 308 through the network 304B.","The other resources 318 include any of a variety of other resource types, including, but not limited to, files, credentials, or security policies.","In some embodiments, resources of similar types may be combined into a single node.","For example, in a distributed computing system there may be multiple identically configured web servers.","Rather than generating a graph with a node for each such web server, in these embodiments, the web servers may be represented by a single web server node.","Consequently, data collected at introspection points at or between any of the web servers may be used to generate links from the web server node to other resources accessed by any of the web servers.","Likewise, in another example, a distributed computing system may have clusters of web servers, application servers, and database servers.","For the graph in this example, the web servers may be “merged” (i.e., grouped together) to be represented by a single web server node, the database servers may merged to be represented by a single database server node, and the application servers may be merged to be represented by a single application server node.","Alternatively, all three types of servers may be merged/grouped into a single server node.","Thus, by analyzing data collected at the introspection points information may be gathered to determine if and which resources may be grouped/associated together.","For example, the gathered information may detect that a child process was forked from a parent process at a first time and that a similar child process was forked from another instance of the parent process at a second time.","Based on this information the two instances of the parent process may be merged into a node representing the unique parent process and the two child processes may be merged into a unique child process depending from the parent process, such as is illustrated by the process 302D (parent) and the process 302E (child).","For example, a web server parent process may spawn a PHP Hypertext Preprocessor (PHP) child process, and rather than have a dozen web server processes linked to a dozen PHP child processes in the graph, the parent processes and child processes may be separately merged to have a single web server parent process linked to a single PHP child process.","Merges may be additive; for example, if one of the aforementioned web server parent processes also spawns a second child process, that the other web servers do not, that second child process may still be linked to the merged web server parent node.","Such determinations may be made based on common information obtained at the introspection points for each of those processes.","These techniques may be applied to link and merge a variety of resource types.","The logical grouping of resource types (i.e., the types of resources that may be merged) may be defined by the customer owner, such as through an application programming interface provided by the computing resource service provider.","For example, customer owner may define five virtual machine instances belonging to the customer owner as “web servers” and may define seven other virtual machine instances and “application servers,” and so on.","In some implementations, default logical groupings of resources are specified by the computing resource service provider, and the customer can modify the default groupings as needed.","In some implementations, such logical groupings are automatically be determined by the computing resource service provider based on data collected at introspection points.","For example, by collecting data at each machine and examining what processes run on each machine, certain machines may be probabilistically classified in a first group and other machines may be probabilistically classified into a second group (e.g., at least a 50% chance of being in the first group or at least a 50% chance of being in the second group, inferred by similarities between machines/processes, etc.).","Note that the type and quantities of the sets of resources depicted in FIG.","3 is only illustrative, and the visualization of an actual implementation may include many thousands of nodes and many more resource types than shown in FIG.","3.FIG.","4 illustrates an aspect of an environment 400 in which an embodiment may be practiced.","Specifically, FIG.","4 depicts an introspection agent 408 collecting data at an introspection point 420 between a first computing resource 406A and a second computing resource 406B, comparing the collected data against reference values 404 stored in a data store 410, and sending an alert 422 to a customer of a computing resource service provider if a variance between the collected data and the reference values 404 is found.","Note that the embodiment depicted in FIG.","4 is one of many possible examples, and that the introspection agent 408 could be executing at various locations in the system, including on either of resources 406A-406B, a virtualization layer (e.g., hypervisor), a controlling domain of a virtualization layer, or a third resource not depicted.","The customer 402 may be a customer of the computing resource service provider that provides either or both of the resources 406A-406B for use by the customer 402.The reference values 404 may be one or more expected values or ranges for measurements at the introspection point 420.An example of reference values 404 may be a list of software applications running on resource 406A that have been approved to communicate with the resource 406B.","The data store 410 may be any type of data storage configured to store the reference values 404 for the computing resource service provider.","The resources 406A-406B are intended to represent any of a variety of computing resources, such as virtual machine instances, physical computing systems, on-demand data storage resources, archival data storage resources, or security policies.","Either or both 406A-406B may be provided by the computing resource service provider, or one of the resources 406A-406B may be a computing resource external to the computing resource service provider environment.","For example, resource 406A may be a computing resource within the environment of the computing resource service provider, while resource 406B may be computing system external to the computing resource service provider but accessible to the resource 406A through the Internet or other network.","The communication channel 418 may be any type of communication channel by which two or more devices may communicate, including physical network cables, wireless communications, universal serial bus (USB), serial, parallel, and other conduits.","The communication channel 418 may further be configured to communicate through, among others, the Internet, an intranet, wide area network (WAN), local area network (LAN), and direct connection.","The communication channel 418 may further be configured to facilitate communications of any type of communication protocol, including a cellular wireless communications protocol, such as fourth generation (4G) communications or long term evolution (LTE™), a wireless local area network (WLAN) communications protocol, such as an Institute for Electrical and Electronics Engineers (IEEE) 802.11, 802.16 or 802.21 communication protocol, or short range communications protocol, among others.","The introspection point 420 may be an introspection point similar to any of the introspection points 120A-120E described in conjunction with FIG.","1.In FIG.","4, the introspection point 420 is shown to be a data collection point for data flowing along the communication channel 418 between the resource 406A and the resource 406B.","The introspection agent 408 may be executable code injected and executing in application memory of one of resources 406A-406B, a software application with elevated access permissions executing a computing system with access to read the data at the introspection point 420, or may be implemented in hardware of the communication channel 418.Upon detection of a variance between measured values at the introspection point 420 and the reference values 404, the introspection agent 408 may cause the alert 422 to be sent to the customer 402.For example, the introspection agent 408 may determine from the data at the introspection point 420 that the communications channel 418 is not encrypted, and therefore may be vulnerable to infiltration by unauthorized entities.","The alert 422 may be an e-mail message, text message, message appearing in a popup window on a device of the customer, confirmation dialog, graphical indicator on a user interface provided by the computing resource service provider to the customer 402, or any other manner of notification to the customer 402 that a variance from expected values has been detected.","The alert 422 provides notice that a potential violation has been detected, thereby allowing the customer 402 to determine whether the potential violation is an actual violation of a security rule and/or take action to mitigate the potential violation.","For example, a customer of the computing resource service provider may specify a rule to take a security action to notify the customer if any month-to-date charges of the customer's virtual machine usage exceed an amount of two-hundred dollars.","As another example, where a computing resource service provider provides virtual computer system services in different geographic regions and a customer employs services of the computing resource service provider in a first region but none in a second region, the customer may specify a security action to be notified if charges begin accruing to the customer from the second region.","As still another example, if the system of an embodiment of the present disclosure determines, based on credential information collected at an introspection point of a customer computing environment, that a particular credential is being used insecurely, the alert 422 may provide notice to the customer that the particular credential may be in violation of a rule or may present a security vulnerability.","In some implementations, the alert 422 may notify the customer 402 of actions to be taken by the computing resource service provider to mitigate the potential violation, such as changes to access permissions or firewall rules, and the customer 402 may be given the opportunity to confirm, deny, or undo the respective actions.","FIG.","5 illustrates an aspect of an environment 500 in which an embodiment may be practiced.","Specifically, FIG.","5 illustrates how an introspection agent 508 may be configured to run within a virtualization layer 530 managing the execution of one or more virtual machines 506A-506N or may be configured to run in a controlling domain 504 of the virtualization layer 530.The introspection agent 508 may be executable code executing in the controlling domain 504 of a virtualization layer 530 or within the virtualization layer 530 itself.","The introspection agent 508 may be configured to monitor one or more introspection points 520A-520N of the virtual machines 506A-506N.","Upon detection of a variance between measured values at the one or more introspection points 520A-520N and reference values, the introspection agent 508 may cause a security action to be performed, such as sending an alert to a customer owner of the one or more virtual machines 506A-506N, isolating the virtual machine exhibiting a variance from the reference values from the network, or terminating the virtual machine exhibiting the variance.","The introspection points 520A-520N, as noted, may be a set of data collection points specified by a customer, computing resource service provider, or other authorized entity.","Types of introspection points may include points at an incoming network port, log information regarding the virtual machines 506A-506N, and configuration files for the virtual machines 506A-506N.","Collectable information at the introspection points 520A-520N may include credentials, whether communications are encrypted, security policies used, database permissions, and/or billing charges generated from usage of the virtual machines 506A-506N.","The controlling domain 504 may be a privileged virtual machine instance from which the one or more virtual machines 506A-506N of the virtualization layer 530 may be managed.","Unlike the one or more virtual machines 506A-506N, the controlling domain 504 may have direct access to the system hardware 528 (e.g., network interface controllers, hard drives, memory, etc.).","The virtualization layer 530 may enable the system hardware 528 to be used to provide computational resources upon which the one or more virtual machines 506A-506N may operate.","The virtualization layer 530 may be any device, software or firmware used for providing a virtual computer platform for the one or more virtual machines 506A-506N.","An example of virtualization layer is a hypervisor.","The virtual computer platform may include various virtual computer components, such as one or more virtual processors, virtual memory, virtual devices and the like.","The one or more virtual machines 506A-506N may be provided to customers of the computing resource service provider, and the customers may run operating systems, applications and/or other such computer system entities on the one or more virtual machines 506A-506N.","Thus, the introspection agent 508 running in either the controlling domain 504 or virtualization layer 530 may allow the introspection agent 508 to collect information at the introspection points 520A-520N of the virtual machines 506A-506N.","Note too, that, although not illustrated as such in FIG.","5, in some embodiments, the introspection agent 508 may additionally or alternatively execute in the system hardware 528, for example via an unified extensible firmware interface application or similar custom code on a peripheral hardware controller firmware of the system hardware 528.The system hardware 528 may include the hardware of a physical (i.e., non-virtual) computing device configured to execute instructions for performing data computation, manipulation, or storage tasks.","The system hardware 528 may include one or more processors, such as a central processing unit (CPU), a graphics processing unit (GPU) or a digital signal processor (DSP), memory, including static and dynamic memory, buses, and input and output ports that are compliant with any handshaking, communications or data transfer protocol.","The system hardware 528 may also include storage devices, such as storage disks and tapes, and/or networking equipment.","The virtualization layer 530 may enable the system hardware 528 to be used to provide computational resources upon which the one or more virtual machines 506A-506N may operate.","FIG.","6 shows an example of a customer connected to a computing resource service provider in accordance with at least one embodiment.","The computing resource service provider 602 may provide a variety of services to the customer 604 and the customer 604 may communicate with the computing resource service provider 602 via an interface 626, which may be a web services interface or any other type of customer interface.","While FIG.","6 shows one interface 626 for the services of the computing resource service provider 602, each service may have its own interface and, generally, subsets of the services may have corresponding interfaces in addition to or as an alternative to the interface 626.The customer 604 may be an organization that may utilize one or more of the services provided by the computing resource service provider 602 to maintain and deliver information to its employees, which may be located in various geographical locations.","Additionally, the customer 604 may be an individual that utilizes the services of the computing resource service provider 602 to deliver content to a working group located remotely.","As shown in FIG.","6, the customer 604 may communicate with the computing resource service provider 602 through a network 606, whereby the network 606 may be a communication network, such as the Internet, an intranet or an Internet service provider (ISP) network.","Some communications from the customer 604 to the computing resource service provider 602 may cause the computing resource service provider 602 to operate in accordance with one or more embodiments described or a variation thereof.","The computing resource service provider 602 may provide various computing resource services to its customers.","The services provided by the computing resource service provider 602, in this example, include a virtual computer system service 608, a block-level data storage service 610, a cryptography service 612, an on-demand data storage service 614, a notification service 616, an authentication system 618, a policy management service 620, a task service 622, and one or more other services 624.It is noted that not all embodiments described include the services 608-624 described with reference to FIG.","6 and additional services may be provided in addition to or as an alternative to services explicitly described.","As described, each of the services 608-624 may include one or more web service interfaces that enable the customer 604 to submit appropriately-configured API calls to the various services through web service requests.","In addition, each of the services may include one or more service interfaces that enable the services to access each other (e.g., to enable a virtual computer system of the virtual computer system service 608 to store data in or retrieve data from the on-demand data storage service 614 and/or to access one or more block-level data storage devices provided by the block level data storage service 610).","The virtual computer system service 608 may be a collection of computing resources configured to instantiate virtual machine instances on behalf of the customer 604.The customer 604 may interact with the virtual computer system service 608 (via appropriately configured and authenticated API calls) to provision and operate virtual computer systems that are instantiated on physical computing devices hosted and operated by the computing resource service provider 602.The virtual computer systems may be used for various purposes, such as to operate as servers supporting a website, to operate business applications or, generally, to serve as computing power for the customer.","Other applications for the virtual computer systems may be to support database applications, electronic commerce applications, business applications, and/or other applications.","Although the virtual computer system service 608 is shown in FIG.","8, any other computer system or computer system service may be utilized by the computing resource service provider 602, such as a computer system or computer system service that does not employ virtualization or instantiation and instead provisions computing resources on dedicated or shared computers/servers and/or other physical devices.","The block-level data storage service 610 may comprise one or more computing resources that collectively operate to store data for a customer 604 using block-level storage devices (and/or virtualizations thereof).","The block-level storage devices of the block-level data storage service 610 may, for instance, be operationally attached to virtual computer systems provided by the virtual computer system service 608 to serve as logical units (e.g., virtual drives) for the computer systems.","A block-level storage device may enable the persistent storage of data used/generated by a corresponding virtual computer system where the virtual computer system service 608 may only provide ephemeral data storage.","The computing resource service provider 602 also includes a cryptography service 612.The cryptography service 612 may utilize one or more storage services of the computing resource service provider 602 to store keys of the customers in encrypted form, whereby the keys may be usable to decrypt customer 604 keys accessible only to particular devices of the cryptography service 612.The computing resource service provider 602 further includes an on-demand data storage service 614.The on-demand data storage service 614 may be a collection of computing resources configured to synchronously process requests to store and/or access data.","The on-demand data storage service 614 may operate using computing resources (e.g., databases) that enable the on-demand data storage service 614 to locate and retrieve data quickly, to allow data to be provided in responses to requests for the data.","For example, the on-demand data storage service 614 may maintain stored data in a manner such that, when a request for a data object is retrieved, the data object can be provided (or streaming of the data object can be initiated) in a response to the request.","As noted, data stored in the on-demand data storage service 614 may be organized into data objects.","The data objects may have arbitrary sizes except, perhaps, for certain constraints on size.","Thus, the on-demand data storage service 614 may store numerous data objects of varying sizes.","The on-demand data storage service 614 may operate as a key value store that associates data objects with identifiers of the data objects which may be used by the customer 604 to retrieve or perform other operations in connection with the data objects stored by the on-demand data storage service 614.In the environment illustrated in FIG.","6, a notification service 616 is included.","The notification service 616 may comprise a collection of computing resources collectively configured to provide a web service or other interface and browser-based management console.","The management console can be used to configure topics for which customers seek to receive notifications, configure applications (or people), subscribe clients to the topics, publish messages, or configure delivery of the messages over clients' protocol of choice (i.e., hypertext transfer protocol (HTTP), e-mail and short message service (SMS), among others).","The notification service 616 may provide notifications to clients using a “push” mechanism without the need to periodically check or “poll” for new information and updates.","The notification service 616 may further be used for various purposes such as monitoring applications executing in the virtual computer system service 608, workflow systems, time-sensitive information updates, mobile applications, and many others.","As illustrated in FIG.","6, the computing resource service provider 602, in various embodiments, includes an authentication system 618 and a policy management service 620.The authentication system 618, in an embodiment, is a computer system (i.e., collection of computing resources) configured to perform operations involved in authentication of users of the customer.","For instance, one of the services 608-616 and 620-624 may provide information from a user to the authentication system 618 to receive information in return that indicates whether the user requests are authentic.","The policy management service 620, in an embodiment, is a computer system configured to manage policies on behalf of customers (such as customer 604) of the computing resource service provider 602.The policy management service 620 may include an interface that enables customers to submit requests related to the management of policy.","Such requests, for instance, may be requests to add, delete, change, or otherwise modify policy for a customer or for other administrative actions, such as providing an inventory of existing policies and the like.","The computing resource service provider 602, in various embodiments, is also equipped with a task service 622.The task service 622 is configured to receive a task package from the customer 604 and enable executing tasks as dictated by the task package.","The task service 622 may be configured to use any resource of the computing resource service provider 602, such as one or more instantiated virtual machines or virtual hosts, for executing the task.","The task service 623 may configure the one or more instantiated virtual machines or virtual hosts to operate using a selected operating system and/or a selected execution application in accordance with a requirement of the customer 604.The computing resource service provider 602 additionally maintains one or more other services 624 based at least in part on the needs of its customers 604.For instance, the computing resource service provider 602 may maintain a database service for its customers 604.A database service may be a collection of computing resources that collectively operate to run one or more databases for one or more customers 604.The customer 604 may operate and manage a database from the database service by utilizing appropriately configured API calls.","This, in turn, may allow a customer 604 to maintain and potentially scale the operations in the database.","Other services include, but are not limited to, object-level archival data storage services, services that manage and/or monitor other services.","FIG.","7 is a flow chart illustrating an example of a process 700 for generating a graph based at least in part on data collected at introspection points in accordance with various embodiments.","The process 700 may be performed by any suitable system such as a server in a data center, multiple computing devices in a distributed system of a computing resource service provider, or any electronic client device, such as the electronic client device 902 described in conjunction with FIG.","9.The process 700 includes a series of operations wherein introspection points are determined, data is collected at the introspection points, and a graph is generated from the collected data.","In 702, an introspection point for obtaining measurements/collecting data about resources of a computing environment may be determined.","For a given computing environment, there may be multiple resources with potentially several introspection points.","Consequently, there may be multiple instances of the process 700 being performed in parallel by the system.","The system performing the process 700 may initiate the operations of 702 in response to a request from a customer of a computing resource service provider.","For example, the computing resource service provider may provide introspection of a set of the customer's virtual machine instances as a service.","In other cases, the computing resource service provider may utilize introspection itself to analyze select sets of resources, select services, or the overall system.","The identifying data collected may be used to identify threats to the computing environment and determine whether systems and resources within the computing environment are in compliance with rules and security policies.","The introspection points may be determined based on identifying characteristics found in data that may be obtained at the introspection point.","For example, an introspection point at a network connection may provide information regarding source and destination internet protocol addresses, process IDs, and whether or not communications are encrypted.","In 704, measurements are taken at (i.e., information collected from) the introspection point.","The measurements/information may be obtained at the introspection points by an introspection agent implemented in software or hardware.","In some embodiments, the introspection agent may be running as part of a virtualization layer.","In other embodiments, the introspection agent may be implemented as a system-level software process running in the operating system of a customer virtual machine being measured.","In still other embodiments, the introspection agent may be implemented in hardware, such as networking hardware that analyzes data packets passing between devices in the computing environment.","In 706, the measurements may be parsed to isolate and retrieve identifying information; that is, information from which the system may determine relationships between resources and characteristics of the computing environment usable for assessing security threats.","As noted, such information may include identities of software processes, whether communications are encrypted, internet protocol addresses and ports, software dependencies, credentials, and access permissions.","In 708, a graph representing a set of objects (e.g., resources) in the computing environment may be generated.","The objects may be linked by common characteristics determined from the identifying information determined in 706 and configuration information.","As an example, a computing resource service provider may host three different virtual computing network environments, each virtual computing network environment including a set of virtual machine instances.","Each virtual computing network environment and/or set of virtual machine instances may have configuration information stored in a data store defining various aspects of the virtual computing network environments and their virtual machine instances, such as information specifying the operating systems running under each virtual machine, the data storage resources usable by each virtual machine, firewall settings, and/or internet protocol addresses of the virtual machines within each virtual computing network environment.","With reference to the configuration information and the measurements of 704, a graph of the relationships between the resources of each virtual network computing environment to each other and to the resources of the other virtual network computing environments may be generated.","In 710, the system performing the process 700 may determine whether additional data should be collected/measurements taken at the introspection points determined in 702.In some embodiments, measurements may be taken at intervals and compared with previous measurements.","In cases where measurements taken at a first time and measurements taken at a second time do not differ from expected values (e.g., from a set of reference values), the system performing the process 700 may return to 704 to take additional measurements.","On the other hand, if the measurements taken at the first time and the measurements taken at the second time unexpectedly differ (e.g., a software library has changed, a software process a previously unused port is being used, etc.","), the system performing the process 700 may proceed to 712 to generate a threat model.","In some embodiments, expected values and/or expected ranges of measurements may be specified by the computing resource service provider or by a customer of the computing resource service provider.","In other embodiments, the expected values and/or expected ranges of measurements may be determined, at least initially, from a baseline measurement of an exemplary virtual computing network environment.","Such expected values and ranges may be modified by the customer and/or computing resource service provider as needed.","In 712, each node and edge in the graph may be walked to generate a threat model of the measured computing system.","In some implementations, the threat model may be an interactive map/visualization of the computing system with various graphical indicators for drawing a user's attention to different potential threats and risk levels (e.g., “warning,” “error,” “secure,” “unsecure,” “unable to evaluate,” etc.).","The threat model may provide information identifying possible ways the computing environment could be attacked, number, and type of actual attacks detected, probability of harm, levels of risk, and suggestions on mitigating threats.","Note too that after 712, the operations of 702-712 may be repeated as often as required by the customer or computing resource service provider.","Note too that one or more of the operations performed in 702-712 may be performed in various orders and combinations, including in parallel.","FIG.","8 is a flow chart illustrating an example of a process 800 for generating a graph and performing a security action in accordance with various embodiments.","The process 800 may be performed by any suitable system such as a server in a data center, multiple computing devices in a distributed system of a computing resource service provider, or any electronic client device, such as the electronic client device 902 described in conjunction with FIG.","9.The process 800 includes a series of operations wherein configuration information for a set of resources is obtained, usage of the set of resources is tracked, a graph is generated, and based on an analysis of the graph, potential vulnerabilities (also referred to as risks) are identified and addressed.","In 802, configuration information for a set of resources (e.g., set of virtual machine instances, set of data storage resources in a distributed computing system, etc.)","is obtained.","Such configuration information may include firewall rules, identities of virtual machines running within the computing environment, access permissions for credentials used by users or virtual machines in the computing environment, and/or what databases are accessed by users and/or virtual machines in the computing environment.","In some implementation, the configuration information may be stored in a data store or in various data files accessible to the computing resource service provider.","In 804, information relating to usage of the set of resources (i.e., information is collected at introspection points, such as the introspection points set at 702 of FIG.","7) is tracked/logged.","As described in the present disclosure, such information may be tracked and logged by an introspection agent executing within the computing environment.","In 806, a graph, as described in the present disclosure, may be generated based on tracked resource usage information and the obtained configuration information.","In 808 and 810, the graph may be analyzed to assess the security state of the computing environment; i.e., to determine whether there are potential vulnerabilities within the computing environment.","For example, if the system performing the process 800 determines that a first virtual machine has an open network communication channel to a second virtual machine, but in practice does not communicate with the second virtual machine, the system performing the process 800 may flag this as a potential violation.","That is, should security of first virtual machine become compromised, the open communications channel may present a potential risk to the second virtual machine as well.","Similarly, if a software application is detected as using an old version of a software library, this too may be flagged as a potential violation.","In some implementations, analysis of the graph may include comparing the current generated graph to a previously generated graph to identify any differences, which may indicate potential vulnerabilities.","Likewise, if measurements tracked by an introspection agent deviate from a set of reference values representing expected values or ranges of the measurements, such an anomaly may be flagged as a potential threat or violation.","If no potential vulnerabilities are detected, the system performing the process 800 may return to 804 to continue to track resource usage.","However, if potential vulnerabilities are identified in 812, the system performing the process 800 may perform a security action.","Security actions may include notifying a customer owner of a virtual machine instance being monitored, or may additionally or alternatively include making changes to configuration information to mitigate the potential vulnerabilities (e.g., implementing firewall rules to close vulnerable ports, etc.).","In the event configuration information changes, either by the system performing the process 800 or by a customer, the system performing the process 812 may return to 802 to repeat the process 800 to determine whether the configuration change affects the potential violation or introduces new potential vulnerabilities.","Note that one or more of the operations performed in 802-812 may be performed in various orders and combinations, including in parallel.","Note that, unless otherwise specified, use of expressions regarding executable instructions (also referred to as code, applications, agents, etc.)","performing operations that instructions do not ordinarily perform unaided (e.g., transmission of data, calculations, etc.)","in the context of describing disclosed embodiments denote that the instructions are being executed by a machine, thereby causing the machine to perform the specified operations.","FIG.","9 illustrates aspects of an example environment 900 for implementing aspects in accordance with various embodiments.","As will be appreciated, although a web-based environment is used for purposes of explanation, different environments may be used, as appropriate, to implement various embodiments.","The environment includes an electronic client device 902, which can include any appropriate device operable to send and/or receive requests, messages or information over an appropriate network 904 and, in some embodiments, convey information back to a user of the device.","Examples of such client devices include personal computers, cell phones, handheld messaging devices, laptop computers, tablet computers, set-top boxes, personal data assistants, embedded computer systems, electronic book readers, and the like.","The network 904 can include any appropriate network, including an intranet, the Internet, a cellular network, a local area network, a satellite network, or any other network and/or combination thereof.","Components used for such a system can depend at least in part upon the type of network and/or environment selected.","Protocols and components for communicating via such a network are well known and will not be discussed in detail.","Communication over the network 904 can be enabled by wired or wireless connections and combinations thereof.","In this example, the network 904 includes the Internet, as the environment includes a web server 906 for receiving requests and serving content in response thereto, although for other networks an alternative device serving a similar purpose could be used as would be apparent to one of ordinary skill in the art.","The illustrative environment includes an application server 908 and a data store 910.It should be understood that there could be several application servers, layers, or other elements, processes, or components, which may be chained or otherwise configured, which can interact to perform tasks such as obtaining data from an appropriate data store.","Servers, as used, may be implemented in various ways, such as hardware devices or virtual computer systems.","In some contexts, servers may refer to a programming module being executed on a computer system.","As used, unless otherwise stated or clear from context, the term “data store” refers to any device or combination of devices capable of storing, accessing, and retrieving data, which may include any combination and number of data servers, databases, data storage devices, and data storage media, in any standard, distributed, virtual, or clustered environment.","The application server 908 can include any appropriate hardware, software, and firmware for integrating with the data store 910 as needed to execute aspects of one or more applications for the electronic client device 902, handling some or all of the data access and business logic for an application.","The application server 908 may provide access control services in cooperation with the data store 910 and is able to generate content including, text, graphics, audio, video and/or other content usable to be provided to the user, which may be served to the user by the web server 906 in the form of HyperText Markup Language (“HTML”), Extensible Markup Language (“XML”), JavaScript, Cascading Style Sheets (“CSS”), or another appropriate client-side structured language.","Content transferred to a client device may be processed by the electronic client device 902 to provide the content in one or more forms including, forms that are perceptible to the user audibly, visually, and/or through other senses including touch, taste, and/or smell.","The handling of all requests and responses, as well as the delivery of content between the electronic client device 902 and the application server 908, can be handled by the web server 906 using PHP: Hypertext Preprocessor (“PHP”), Python, Ruby, Perl, Java, HTML, XML, or another appropriate server-side structured language in this example.","It should be understood that the web server 906 and the application server 908 are not required and are merely example components, as structured code discussed can be executed on any appropriate device or host machine as discussed elsewhere.","Further, operations described as being performed by a single device may, unless otherwise clear from context, be performed collectively by multiple devices, which may form a distributed and/or virtual system.","The data store 910 can include several separate data tables, databases, data documents, dynamic data storage schemes, and/or other data storage mechanisms and media for storing data relating to a particular aspect of the present disclosure.","For example, the data store 910 may include mechanisms for storing production data 912 and user information 916, which can be used to serve content for the production side.","The data store 910 also is shown to include a mechanism for storing log data 914, which can be used for reporting, analysis, or other purposes.","It should be understood that there can be many other aspects that may need to be stored in the data store 910, such as page image information and access rights information, which can be stored in any of the above listed mechanisms as appropriate or in additional mechanisms in the data store 910.The data store 910 is operable, through logic associated therewith, to receive instructions from the application server 908 and obtain, update, or otherwise process data in response thereto.","The application server 908 may provide static, dynamic, or a combination of static and dynamic data in response to the received instructions.","Dynamic data, such as data used in web logs (blogs), shopping applications, news services, and other applications may be generated by server-side structured languages as described or may be provided by a content management system (“CMS”) operating on, or under the control of, the application server 908.In one example, a user, through a device operated by the user, might submit a search request for a certain type of item.","In this case, the data store 910 might access the user information 916 to verify the identity of the user and can access the catalog detail information to obtain information about items of that type.","The information then can be returned to the user, such as in a results listing on a web page that the user is able to view via a browser on the electronic client device 902.Information for a particular item of interest can be viewed in a dedicated page or window of the browser.","It should be noted, however, that embodiments of the present disclosure are not necessarily limited to the context of web pages, but may be more generally applicable to processing requests in general, where the requests are not necessarily requests for content.","Each server typically will include an operating system that provides executable program instructions for the general administration and operation of that server and typically will include a computer-readable storage medium (e.g., a hard disk, random access memory, read only memory, etc.)","storing instructions that, when executed by a processor of the server, allow the server to perform its intended functions.","Suitable implementations for the operating system and general functionality of the servers are known or commercially available and are readily implemented by persons having ordinary skill in the art, particularly in light of the disclosure.","The environment, in one embodiment, is a distributed and/or virtual computing environment utilizing several computer systems and components that are interconnected via communication links, using one or more computer networks or direct connections.","However, it will be appreciated by those of ordinary skill in the art that such a system could operate equally well in a system having fewer or a greater number of components than are illustrated in FIG.","9.Thus, the depiction of the example environment 900 in FIG.","9 should be taken as being illustrative in nature and not limiting to the scope of the disclosure.","The various embodiments further can be implemented in a wide variety of operating environments, which in some cases can include one or more user computers, computing devices, or processing devices that can be used to operate any of a number of applications.","User or client devices can include any of a number of general purpose personal computers, such as desktop, laptop, or tablet computers running a standard operating system, as well as cellular, wireless, and handheld devices running mobile software and capable of supporting a number of networking and messaging protocols.","Such a system also can include a number of workstations running any of a variety of commercially available operating systems and other known applications for purposes such as development and database management.","These devices also can include other electronic devices, such as dummy terminals, thin-clients, gaming systems, and other devices capable of communicating via a network.","These devices also can include virtual devices such as virtual machines, hypervisors, and other virtual devices capable of communicating via a network.","Various embodiments of the present disclosure utilize a network that would be familiar to those skilled in the art for supporting communications using any of a variety of commercially available protocols, such as Transmission Control Protocol/Internet Protocol (“TCP/IP”), User Datagram Protocol (“UDP”), protocols operating in various layers of the Open System Interconnection (“OSI”) model, File Transfer Protocol (“FTP”), Universal Plug and Play (“UpnP”), Network File System (“NFS”), Common Internet File System (“CIFS”), and AppleTalk.","The network 904 can be, for example, a local area network, a wide-area network, a virtual private network, the Internet, an intranet, an extranet, a public switched telephone network, an infrared network, a wireless network, a satellite network, and any combination thereof.","In embodiments utilizing a web server, the web server can run any of a variety of server or mid-tier applications, including Hypertext Transfer Protocol (“HTTP”) servers, FTP servers, Common Gateway Interface (“CGP”) servers, data servers, Java servers, Apache servers, and business application servers.","The server(s) also may be capable of executing programs or scripts in response to requests from user devices, such as by executing one or more web applications that may be implemented as one or more scripts or programs written in any programming language, such as Java®, C, C#, or C++, or any scripting language, such as Ruby, PHP, Perl, Python, or TCL, as well as combinations thereof.","The server(s) may also include database servers, including those commercially available from Oracle®, Microsoft®, Sybase®, and IBM® as well as open-source servers such as MySQL, Postgres, SQLite, MongoDB, and any other server capable of storing, retrieving, and accessing structured or unstructured data.","Database servers may include table-based servers, document-based servers, unstructured servers, relational servers, non-relational servers, or combinations of these and/or other database servers.","The environment can include a variety of data stores and other memory and storage media as discussed above.","These can reside in a variety of locations, such as on a storage medium local to (and/or resident in) one or more of the computers or remote from any or all of the computers across the network.","In a particular set of embodiments, the information may reside in a storage-area network (“SAN”) familiar to those skilled in the art.","Similarly, any necessary files for performing the functions attributed to the computers, servers or other network devices may be stored locally and/or remotely, as appropriate.","Where a system includes computerized devices, each such device can include hardware elements that may be electrically coupled via a bus, the elements including, for example, a central processing unit (“CPU” or “processor”), an input device (e.g., a mouse, keyboard, controller, touch screen, or keypad), and an output device (e.g., a display device, printer, or speaker).","Such a system may also include one or more storage devices, such as disk drives, optical storage devices, and solid-state storage devices, such as random access memory (“RAM”) or read-only memory (“ROM”), as well as removable media devices, memory cards, flash cards, etc.","Such devices also can include a computer-readable storage media reader, a communications device (e.g., a modem, a wireless or wired network card, an infrared communication device, etc.","), and working memory as described above.","The computer-readable storage media reader can be connected with, or configured to receive, a computer-readable storage medium, representing remote, local, fixed, and/or removable storage devices as well as storage media for temporarily and/or more permanently containing, storing, transmitting, and retrieving computer-readable information.","The system and various devices also typically will include a number of software applications, modules, services, or other elements located within a working memory device, including an operating system and application programs, such as a client application or web browser.","It should be appreciated that alternate embodiments may have numerous variations from that described above.","For example, customized hardware might also be used and/or particular elements might be implemented in hardware, software (including portable software, such as applets), or both.","Further, connection to other computing devices such as network input/output devices may be employed.","Storage media and computer readable media for containing code, or portions of code, can include any appropriate media known or used in the art, including storage media and communication media, such as volatile and non-volatile, removable and non-removable media implemented in any method or technology for storage and/or transmission of information such as computer readable instructions, data structures, program modules, or other data, including RAM, ROM, Electrically Erasable Programmable Read-Only Memory (“EEPROM”), flash memory, or other memory technology, Compact Disc Read-Only Memory (“CD-ROM”), digital versatile disk (DVD), or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices or any other medium which can be used to store the desired information and which can be accessed by the system device.","Based on the disclosure and teachings provided, a person of ordinary skill in the art will appreciate other ways and/or methods to implement the various embodiments.","The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.","However, it will be evident that various modifications and changes may be made thereunto without departing from the broader spirit and scope of the invention as set forth in the claims.","Other variations are within the spirit of the present disclosure.","Thus, while the techniques are susceptible to various modifications and alternative constructions, certain illustrated embodiments thereof are shown in the drawings and have been described above in detail.","It should be understood, however, that there is no intention to limit the invention to the specific form or forms disclosed, but on the contrary, the intention is to cover all modifications, alternative constructions and equivalents falling within the spirit and scope of the invention, as defined in the appended claims.","The use of the terms “a,” “an,” and “the” and similar referents in the context of describing the embodiments (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated or clearly contradicted by context.","The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted.","The term “connected,” when unmodified and referring to physical connections, is to be construed as partly or wholly contained within, attached to or joined together, even if there is something intervening.","Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated and each separate value is incorporated into the specification as if it were individually recited.","The use of the term “set” (e.g., “a set of items”) or “subset” unless otherwise noted or contradicted by context, is to be construed as a nonempty collection comprising one or more members.","Further, unless otherwise noted or contradicted by context, the term “subset” of a corresponding set does not necessarily denote a proper subset of the corresponding set, but the subset and the corresponding set may be equal.","Conjunctive language, such as phrases of the form “at least one of A, B, and C,” or “at least one of A, B and C,” is understood with the context as used in general to present that an item, term, etc., may be either A or B or C, or any nonempty subset of the set of A and B and C, unless specifically stated otherwise or otherwise clearly contradicted by context.","For instance, in the illustrative example of a set having three members, the conjunctive phrases “at least one of A, B, and C” and “at least one of A, B and C” refer to any of the following sets: {A}, {B}, {C}, {A, B}, {A, C}, {B, C}, {A, B, C}.","Thus, such conjunctive language is not generally intended to imply that certain embodiments require at least one of A, at least one of B and at least one of C each to be present.","Operations of processes described can be performed in any suitable order unless otherwise indicated or otherwise clearly contradicted by context.","Processes described (or variations and/or combinations thereof) may be performed under the control of one or more computer systems configured with executable instructions and may be implemented as code (e.g., executable instructions, one or more computer programs or one or more applications) executing collectively on one or more processors, by hardware or combinations thereof.","The code may be stored on a computer-readable storage medium, for example, in the form of a computer program comprising instructions executable by one or more processors.","The computer-readable storage medium may be non-transitory.","The use of any examples, or exemplary language (e.g., “such as”) provided, is intended merely to better illuminate embodiments of the invention and does not pose a limitation on the scope of the invention unless otherwise claimed.","No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.","Embodiments of this disclosure are described, including the best mode known to the inventors for carrying out the invention.","Variations of those embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description.","The inventors expect skilled artisans to employ such variations as appropriate and the inventors intend for embodiments of the present disclosure to be practiced otherwise than as specifically described.","Accordingly, the scope of the present disclosure includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law.","Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the scope of the present disclosure unless otherwise indicated or otherwise clearly contradicted by context.","All references, including publications, patent applications, and patents, cited are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety."]],"string":"[\n [\n \"THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION\",\n \"A graph of a plurality of resources in a computing environment is generated, with the graph associating a first resource of the plurality with a second resource of the plurality.\",\n \"Based at least in part on measurements obtained at a point in a test computing environment that corresponds to a point in the computing environment, a graph representing the relationship between the first resource and the second resource is generated.\",\n \"A threat model identifying potential risks to the computing environment is created from the graph.\"\n ],\n [\n \"1.A computer-implemented method, comprising: obtaining a measurement at a determined location of a point in a distributed computing environment; determining, based at least in part on the measurement, a relationship between a first element in the distributed computing environment and a second element in the distributed computing environment; generating, based at least in part on the relationship, a graph comprising a plurality of nodes, with a first node of the plurality of nodes associated with the first element and a second node of the plurality of nodes associated with the second element; and generating, based at least in part on the graph, a threat model that identifies potential risks to the distributed computing environment.\",\n \"2.The computer-implemented method of claim 1, wherein generating a threat model comprises: visiting at least a subset of the plurality of nodes; and determining, at a node visited, whether potential security risks exist at the node visited.\",\n \"3.The computer-implemented method of claim 2, wherein potential security risks comprise one or more of an open firewall port, an unencrypted communication, an unauthorized process, or an out-of-date software library.\",\n \"4.The computer-implemented method of claim 1, further comprising: analyzing the threat model; and implementing, based on a result of analyzing the threat model, one or more security rules to mitigate risks indicated by the threat model.\",\n \"5.The computer-implemented method of claim 4, further comprising: detecting a violation of the one or more security rules; and performing a security action, wherein the security action is an action performed by the distributed computing environment to mitigate an effect of the violation.\",\n \"6.The computer-implemented method of claim 5, wherein the security action includes rotating a cryptographic key.\",\n \"7.A system, comprising: one or more processors; and memory including instructions that, as a result of execution by the one or more processors, cause the one or more processors to: obtain a representation of a plurality of resources in a computing environment, wherein the representation indicates a plurality of relationships among the plurality of resources; and generate, based at least in part on the representation, a threat model that identifies potential security risks to the computing environment as a result of a relationship of the plurality of relationships.\",\n \"8.The system of claim 7, wherein potential security risks comprise one or more of an open firewall port, an unencrypted communication, an unauthorized process, or an out-of-date software library.\",\n \"9.The system of claim 7, wherein generating a threat model comprises: analyzing at least a subset of the plurality of relationships; and determining, based on the analysis, whether potential security risks exist.\",\n \"10.The system of claim 7, wherein the instructions further cause the one or more processors to: analyze the threat model; and implement, based on the analysis of the threat model, one or more security rules to mitigate risks revealed by the threat model.\",\n \"11.The system of claim 7, wherein the instructions further cause the one or more processors to: determine, using the threat model, whether security risks exist; and implement one or more security rules to mitigate the security risks revealed by the threat model.\",\n \"12.The system of claim 11, wherein the instructions further cause the one or more processors to mitigate an effect of a violation of the one or more security rules.\",\n \"13.The system of claim 11, wherein the instructions further cause the one or more processors to update one or more security policies applicable to an entity of the system to mitigate a risk revealed by the threat model.\",\n \"14.A non-transitory computer-readable storage medium having stored thereon executable instructions that, upon execution by one or more processors of a computer system, cause the computer system to at least: obtain a threat model that identifies potential risks to the computer system, wherein the threat model is based at least in part on a representation of at least a subset of elements in a distributed computing environment and indicates a plurality of potential security risks that exist for individual elements of the distributed computing environment; analyze the threat model to identify a risk; and implement, based on the analysis of the threat model, one or more security rules to mitigate the risk.\",\n \"15.The non-transitory computer-readable storage medium of claim 14, wherein the executable instructions include executable instructions that, upon execution by the one or more processors of the computer system, cause the computer system to perform, upon a violation of the one or more security rules, a security action, wherein the security action is an action performed by the computer system to mitigate an effect of the violation.\",\n \"16.The non-transitory computer-readable storage medium of claim 15, wherein the security action includes revoking access of an entity to a resource.\",\n \"17.The non-transitory computer-readable storage medium of claim 14, wherein the executable instructions include executable instructions that, upon execution by the one or more processors of the computer system, cause the computer system to update, based on the threat model, one or more security policies corresponding to one or more entities of the computer system.\",\n \"18.The non-transitory computer-readable storage medium of claim 14, wherein the threat model is obtained by a software agent executing within an operating system of a virtual machine being monitored on the computing system.\",\n \"19.The non-transitory computer-readable storage medium of claim 14, wherein the executable instructions include executable instructions that, upon execution by the one or more processors of the computer system, cause the computer system to generate the threat model based at least in part on data received from elements of a distributed computing environment.\",\n \"20.The non-transitory computer-readable storage medium of claim 19, wherein the data received from elements of the distributed computing environment is a graph comprising a plurality of nodes representing the elements of the distributed computing environment, and edges indicating a plurality of relationships among the plurality of nodes.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>A distributed computing system includes a variety of resource types, such as software applications, data storage resources, and network resources.\",\n \"The interactions and relationships of these various resources with each other, and with resources external to the distributed computing system, can be difficult to track, which makes security vulnerabilities of the distributed computing system difficult to identify.\",\n \"Moreover, maintaining the security of the distributed computing system becomes increasingly challenging as applications are updated over time and as the complexity and usage of the system increases.\",\n \"Furthermore, it can also be difficult to isolate and troubleshoot issues with the system, and even when issues are identified, reliably securing the system may be challenging.\",\n \"Additionally, such distributed computing systems may not be configured to allow automated mitigation of such vulnerabilities.\"\n ],\n [\n \"<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>Various embodiments in accordance with the present disclosure will be described with reference to the drawings, in which: FIG.\",\n \"1 illustrates an example of a computing resource service provider environment with introspection points in accordance with an embodiment; FIG.\",\n \"2 illustrates an example of introspection of virtual computing network environments in accordance with an embodiment; FIG.\",\n \"3 illustrates an example of graph of resources in accordance with an embodiment; FIG.\",\n \"4 illustrates an example of an introspection agent in accordance with an embodiment; FIG.\",\n \"5 illustrates an example of an introspection agent in a virtualization layer in accordance with an embodiment; FIG.\",\n \"6 illustrates an example of computing resource service provider in accordance with an embodiment; FIG.\",\n \"7 is a flow chart that illustrates an example of generating a threat model from data collected at introspection points in accordance with an embodiment; FIG.\",\n \"8 is a flow chart that illustrates an example of determining potential vulnerabilities in a computing environment in accordance with an embodiment; and FIG.\",\n \"9 illustrates an environment in which various embodiments can be implemented.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/256,381, filed Sep. 2, 2016, entitled “THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION,” which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/673,642, filed Mar.\",\n \"30, 2015, now U.S. Pat.\",\n \"No.\",\n \"9,438,618, issued Sep. 6, 2016, entitled “THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION,” the disclosures of which are incorporated herein by reference for all purposes.\",\n \"BACKGROUND A distributed computing system includes a variety of resource types, such as software applications, data storage resources, and network resources.\",\n \"The interactions and relationships of these various resources with each other, and with resources external to the distributed computing system, can be difficult to track, which makes security vulnerabilities of the distributed computing system difficult to identify.\",\n \"Moreover, maintaining the security of the distributed computing system becomes increasingly challenging as applications are updated over time and as the complexity and usage of the system increases.\",\n \"Furthermore, it can also be difficult to isolate and troubleshoot issues with the system, and even when issues are identified, reliably securing the system may be challenging.\",\n \"Additionally, such distributed computing systems may not be configured to allow automated mitigation of such vulnerabilities.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Various embodiments in accordance with the present disclosure will be described with reference to the drawings, in which: FIG.\",\n \"1 illustrates an example of a computing resource service provider environment with introspection points in accordance with an embodiment; FIG.\",\n \"2 illustrates an example of introspection of virtual computing network environments in accordance with an embodiment; FIG.\",\n \"3 illustrates an example of graph of resources in accordance with an embodiment; FIG.\",\n \"4 illustrates an example of an introspection agent in accordance with an embodiment; FIG.\",\n \"5 illustrates an example of an introspection agent in a virtualization layer in accordance with an embodiment; FIG.\",\n \"6 illustrates an example of computing resource service provider in accordance with an embodiment; FIG.\",\n \"7 is a flow chart that illustrates an example of generating a threat model from data collected at introspection points in accordance with an embodiment; FIG.\",\n \"8 is a flow chart that illustrates an example of determining potential vulnerabilities in a computing environment in accordance with an embodiment; and FIG.\",\n \"9 illustrates an environment in which various embodiments can be implemented.\",\n \"DETAILED DESCRIPTION In the following description, various embodiments will be described.\",\n \"For purposes of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the embodiments.\",\n \"However, it will also be apparent to one skilled in the art that the embodiments may be practiced without the specific details.\",\n \"Furthermore, well-known features may be omitted or simplified in order not to obscure the embodiment being described.\",\n \"Techniques described and suggested include determining, by a computing resource service provider, a set of introspection points in a distributed computing system.\",\n \"The distributed computing system may include either or both physical and virtual computing systems.\",\n \"The distributed computing system may further include one or more computing network environments.\",\n \"The set of introspection points may be determined based on identifying characteristics that are accessible at the individual introspection points of the set of introspection points (e.g., network internet protocol addresses, encryption or decryption keys, software library versions, process names and identifiers, virtual machine identities, etc.).\",\n \"At the individual introspection points, the identifying characteristics may be measured, and a graph may be generated based on the measurements and/or configuration information of the distributed computing system.\",\n \"The generated graph may include a set of nodes representing elements (also referred to as resources or components) of the distributed computing system, with edges between the nodes indicating the relationships between the nodes.\",\n \"One or more rules may be evaluated against the graph; for example, a rule may specify that credentials should have no greater privileges than necessary for accessing requested resources, and, from the graph data, it may be determined that credentials used to access a certain resource have greater privileges than actually used.\",\n \"In such a case, the system may perform a security action, such as notifying an appropriate entity (e.g., network security personnel, an appropriate customer of the computing resource service provider, etc.)\",\n \"of the rule violation or automatically modifying a security policy to constrain the privileges of the respective credentials to the minimum necessary.\",\n \"In some embodiments, a threat model may be generated from the graph to illustrate the potential vulnerabilities and/or rule violations in the distributed computing system.\",\n \"The described and suggested techniques improve the field of computing in distributed systems, and specifically the field of threat detection and mitigation in distributed systems, by providing a new and useful system for detecting threats to a wide variety of resource types in large scale distributed computing systems.\",\n \"Additionally, the described and suggested techniques improve the functioning of computer systems by allowing automated updates in response to detected vulnerabilities and rule violations, thereby reducing the impact of a security breach of the system.\",\n \"Moreover, the described and suggested techniques offer meaningful advantages over general monitoring systems by providing the ability to customers of a computing resource service provider to monitor a wide variety of resource types in a computing network environment from locations in the computing network environment normally only accessible to the computing resource service provider itself.\",\n \"FIG.\",\n \"1 illustrates an aspect of an environment 100 in which an embodiment may be practiced.\",\n \"As illustrated in FIG.\",\n \"1, the environment 100 may include a computing resource service provider 102 having providing services supported by a distributed computing system.\",\n \"Such services may include, among others, a virtual computer system service 104 hosting a set of virtual machines 106, a data storage service 108 hosting a set of data storage resources 110, a policy management service 112 for managing a set of policies 114, and one or more other services 116.Resources within the environment 100, such as virtual machines of the set of virtual machines 106, may be accessible by users and customers via the Internet 118 through an application programming interface provided by the computing resource service provider 102.FIG.\",\n \"1 also illustrates a set of introspection points 120A-120E for collecting information about resource usage within the system.\",\n \"In embodiments of the present disclosure, a distributed computing environment, where a variety of resource types, hardware and software, are provided by the computing resource service provider 102, allows collection of information at a variety of introspection points within the overall system.\",\n \"In some examples, an “application system” may refer to a set of machines that execute a software application.\",\n \"In some cases, the set of machines may be multiple computing systems, such as servers, in communication with each other and/or in communication with other resources.\",\n \"In a virtual computer system environment, the configuration of all of the virtual machine instances in the environment, including which virtual machines are in use, firewall rules for each of the virtual machines, and type, amount, and location of storage for each of the virtual machines may be stored as configuration information.\",\n \"This configuration information may be stored in a form accessible to the computing resource service provider 102 of the virtual computer system service 104, such as in tables/records from a data store.\",\n \"Configuration information could include such information as a list of virtual machine instances (e.g., the set of virtual machine 106) ascribed to a customer owner, a number and identity of processors of a virtual machine instance, open and closed firewall ports of a virtual machine instance, internet protocol addresses for the virtual machine, and software applications running on the virtual machine and which credentials are in use by which software application.\",\n \"The computing resource service provider 102 may likewise detect and track each of the processes running in each virtual machine.\",\n \"In this manner, the computing resource service provider 102 may detect and flag when a previously undetected process launches within a virtual machine.\",\n \"Furthermore, the computing resource service provider 102 may also detect the software dependencies of processes installed in the virtual machine instance.\",\n \"Based on the data collected, the computing resource service provider 102 may create a threat model enumerating potential security threats within the monitored system.\",\n \"Analysis of the data may include walking each node/edge in the graph and determining, at each node, whether and what potential security risks exist (e.g., Ya, etc.\",\n \"), and determining whether the resource represented by each node is in compliance with rules specified by a customer and/or computing resource service provider.\",\n \"From this threat model a customer, the computing resource service provider 102, or other authorized entity (e.g., network security personnel), may implement a security rule to mitigate risks revealed by the threat model.\",\n \"For example, based on list of software dependencies of processes running within the environment, a rule could be implemented to perform a security action if a process is detected to run using a version of a software library that is not the most recent version available.\",\n \"The rule may be driven by the risk that older software libraries may contain security vulnerabilities that were fixed in a newer library.\",\n \"In some examples, a “security action” may refer to an action performed by a computing system of the computing resource service provider to notify or mitigate a detected violation or threat to one or more elements in a computing environment under the control of the computing resource service provider.\",\n \"Such security actions could include any of a variety of actions, such as preventing the process from running, logging the event (e.g., date, time, location of the process, virtual machine instance hosting the process, version of the software library, etc.\",\n \"), automatically updating the library to the most recent version, or sending an alert to the customer or to network security personnel.\",\n \"Other examples of security actions include updating one or more security policies (i.e., information defining permissions and constraints on users, applications, and other entities to access resources) corresponding to one or more entities (e.g., users, resources, applications, etc.)\",\n \"of the computing environment, sending notifications to a notification service of a computing resource service provider, and queuing a message in a message queue of a queue service.\",\n \"Still, other examples of security actions include causing a change to a network (e.g., change to a secure protocol) to which at least one network interface is attached, or triggering a forensics action (e.g., capturing network traffic, memory, or other state of a virtual machine).\",\n \"Security actions could also include terminating a virtual machine instance, isolating a process or virtual machine from a network for later analysis, rotating or blocking one or more security credentials, rotating one or more cryptographic keys, revoking a user's or other entity's access to a resource, or installing a software update.\",\n \"Still, other security actions could include capturing information (e.g., saving a snapshot) about the resource that potentially violates a rule, terminating and re-instantiating a virtual machine instance that appears to be behaving irregularly, storing a memory dump of a virtual machine instance, and/or reverting to a previous version of a data store.\",\n \"A security action may also include updating the configuration of a computer resource to comply with one or more specified rules (e.g., close specific network ports, refuse communications from certain internet protocol address ranges, etc.).\",\n \"Such rules may be implemented in a variety of ways, for example, by modifying firewall rules (e.g., allowing/blocking certain ports, internet protocol addresses, or network protocols), by updating a configuration corresponding to a virtual computing network environment and/or the set of virtual machines 106 running under a virtual computer system service.\",\n \"Various types of security actions are described in the present disclosure, and any reference to security actions in the present disclosure is contemplated to include other types of security actions not expressly mentioned.\",\n \"Likewise, the computing resource service provider 102 may track communications between processes and other entities internal or external to the local network of a virtual machine.\",\n \"Such tracked communications may allow a customer, the computing resource service provider 102, or other authorized entity to identify firewall vulnerabilities.\",\n \"For example, the computing resource service provider 102 may determine, based at least in part on the firewall configuration of a virtual machine, that a another computing system (virtual or physical) is allowed to communicate with the virtual machine.\",\n \"However, in this example, after a period of monitoring, no actual communication occurs between the first and second virtual machines.\",\n \"In this example, the computing resource service provider 102 may determine that, based at least in part on the lack of communication between the two virtual machine instances, that, even though permitted by the firewall, the communications channel between the first and second virtual machine instances should be closed.\",\n \"Based on this determination, the computing resource service provider 102 may perform a security action, such as automatically updating one or more firewall rules to block communication between the first and second virtual machine, or communicating the security concern to one or more customer owners of the virtual machine instances.\",\n \"Similarly, the computing resource service provider 102 may track requests (e.g., for access, for data, etc.)\",\n \"by users, virtual machines, and other entities, and may track the corresponding credentials used with those requests.\",\n \"By performing an analysis on the tracked requests after a period, the computing resource service provider 102 may determine that the credentials allow greater privileges than the privileges actually used.\",\n \"For example, the credentials may be associated with read and write permissions to a database, but the credentials are actually only used for reading from the database; in such a case, the write permission may be, at best, unnecessary, and, at worst, a security risk.\",\n \"In response, the computing resource service provider 102 may perform a security action, such as alerting the customer owner of a tracked virtual machine account for which the credentials are being used of the potential excess privileges associated with the credentials, or may, if directed to take such automatic actions, automatically reduce the privileges associated with the credentials only to those actually used/required by the requesting entity.\",\n \"Tracked information may further include which network connections are using an encrypted protocol versus an unencrypted protocol.\",\n \"Such information may be used to generate a threat model.\",\n \"For example, if the computing resource service provider 102 detects the virtual machine instance communicating with the other computing system under an unencrypted protocol, the computing resource service provider 102 may notify a customer owner of one of the virtual machine instance of the potential risk associated with the unsecured communication channel.\",\n \"Furthermore, data tracked at different times may be compared, such as to identify changes in behavior, performance, and security risks.\",\n \"As an example, a software application may be updated to a new version and implemented within one or more virtual machine instances within the virtual computer system environment.\",\n \"Information as described in the present disclosure may be tracked for a period of time and subsequently compared against information previously tracked when the software application was at a previous version.\",\n \"Such comparisons may allow the computing resource service provider 102 and/or customer owner of the virtual machine instances to identify anomalies and security risks.\",\n \"For example, using the case described above of a virtual machine and another computing system that had initially been allowed to communicate with each other but had never done so, upon a software update, the computing resource service provider 102 may detect that the virtual machine is now communicating with the other computing system (or vice versa).\",\n \"In some situations, this communication may be desired behavior (e.g., they may have been intended to communicate with each other, but due to some configuration or software error, were unable to do so), and the tracked information may serve as confirmation that the software update had a desired effect.\",\n \"In other situations, this communication may be unexpected; such as in a case where a software update contains a security vulnerability that some entity may be trying to exploit to gain access to the second virtual machine.\",\n \"In either case, the computing resource service provider 102 may perform a security action which may include alerting the customer owner of the virtual machine instances and/or blocking communication between the first and second virtual machine instances until receiving express confirmation from the customer owner that such communication is permitted.\",\n \"As illustrated in FIG.\",\n \"1, the computing resource service provider 102 may designate a set of introspection points 120A-120E for tracking the described information.\",\n \"The set of introspection points 120A-120E may be data collection points specified by a customer, computing resource service provider, or other authorized entity.\",\n \"Information may be collected at the introspection points by one or more introspection agents.\",\n \"Types of introspection points may include points between a web service request and the target of the request, locations in a network between an application and the endpoint of the communication, error logs and other various logs, infrastructure configuration information for the computing environment, security controls (e.g., users, credentials, permissions, etc.)\",\n \"and policies for the computing environment, database permissions, and/or billing records.\",\n \"Examples of types of information that may be collected at the set of introspection points 120A-120E include, requestor identifiers (ID), a service ID, date/time, application programming interface methods called, source and destination interne protocol addresses, cryptographic keys, hostnames, system process IDs, and/or user IDs.\",\n \"Information collected at the introspection points may serve to identify what application programming interfaces are being used in the environment 100 and to what extent, which credentials or cryptographic keys are being used, information about network traffic flow, hostnames, domain names, running system processes, or user IDs.\",\n \"For example, introspection point 120A illustrates an introspection point for collecting metadata about communications between one or more of the set of virtual machines 106.Similarly, introspection point 120B illustrates an introspection point for collecting metadata when a virtual machine of the set of virtual machines 106 attempts to access or receives data from one or more data storage resources of the set of data storage resources 110.For example, network communication monitored between a virtual machine and a data storage resource at the introspection point 120B may reveal whether the data passed between the virtual machine and the data storage resource is encrypted or not.\",\n \"Similarly, network communication monitored between the virtual machine and the data storage resource at the introspection point 120B may yield information about the identity of a logical storage container being accessed at the data storage resource, what credentials were used to access the data storage resource, etc.\",\n \"Likewise, introspection point 120C illustrates an introspection point for collecting metadata about credential usage and associated permissions, as defined within the set of policies 114.Additionally, introspection point 120C illustrates an introspection point for collecting metadata about communication between one or more computing devices communicating with a virtual machine of the set of virtual machines 106 through the Internet 118.Lastly, introspection point 120E illustrates an introspection point for collecting metadata about utilization of one or more of the other services 116 as may be provided by the computing resource service provider 102 to a virtual machine of the set of virtual machines 106 of the virtual computer system service 104.Note that although the set of introspection points 120A-120E are illustrated as individual points, it is understood that each of the set of introspection points 120A-120E may themselves be a subset of introspection points.\",\n \"In some examples, “introspection” may refer to an examination of states, system behavior, data, and information flows with and between processes in a distributed computing environment.\",\n \"In some examples, the term “introspection point” may refer to a data collection point, such as within a hypervisor, injection of executable code in application memory, or a software application with elevated access permissions (which may also be referred to as an “introspection agent”) executing on a computing system within the environment 100.The introspection point (or “sensor”) may be an endpoint of a network connection or may also include reading from logs generated through use of application programming interfaces of the computing resource service provider.\",\n \"An introspection point for a customer of a computing resource service provider could also include billing records, or a system or service with access to billing records; for example, a customer may request to be notified if charges for certain types of usage exceed a particular rate or amount, if charges accrue in any region of the computing environment that has not generated charges before, or if any cumulative charges are measured to surge above a norm or expected range.\",\n \"Introspection points may allow gathering of metadata from which may be determined the activity that is occurring at that point.\",\n \"For example, if an application utilizes a public-key cryptography system (PKCS) interface, such as an interface that complies with PKCS#11, and/or other suitable standards, or some other interface for digitally signing data, the interface may be designated as an introspection point.\",\n \"In this example, whenever the interface is called to sign data, metadata about the signing could be collected.\",\n \"Likewise, an introspection point may be designated at any similar interface within the environment 100 of the computing resource service provider 102.In some embodiments, a customer owner of one or more virtual machine instances can specify to the computing resource service provider 102, such as through a web interface, the set of introspection points 120A-120E (i.e., sensors) where an introspection agent is to take measurements (i.e., gather information).\",\n \"The customer owner may further specify a set of expected values or ranges for the measurements.\",\n \"Additionally, the customer owner may specify security actions for the introspection agent to take (or caused to be taken) if certain measurements fall outside expected values or ranges, and may specify for allowed/disallowed behavior by components of the customer owner's systems.\",\n \"For example, the customer owner may send a request to the computing resource service provider 102, such as through an application programming interface provided by the computing resource service provider 102, to implement a set of application agents responsible for monitoring software applications executing on the set of virtual machines 106 of the customer owner.\",\n \"In this example, the customer owner may provide, through the interface, the computing resource service provider 102 with a list of software applications the customer owner expects to be executing on the one or more virtual machines and may request to be notified if the computing resource service provider 102 detects any variance.\",\n \"In response to the request, in this example, the computing resource service provider 102 may configure the set of introspection agents to perform the security action of notifying the customer owner of any execution of a process not on the approved list in the set of virtual machines 106.In this manner, a customer owner may place (i.e., deploy), through the application programming interface, one or more sensors at specified locations in the customer owner's environment within the distributed computing system, if such sensors were not already deployed, without installing separate software applications and in locations within the distributed computing system that might otherwise be inaccessible to the customer owner.\",\n \"In some cases, a sensor may be able to determine whether a communication to/from a software application is encrypted or decrypted, but, if encrypted, may be otherwise unable to determine any information about the data within the encrypted communication.\",\n \"In some embodiments, however, upon instruction and consent from a customer, sensors may be inserted within an virtualization layer that is managing the execution of one or more of the customer's virtual machine instances, and instructed to detect an encryption protocol (e.g., transport Layer Security, Secure Sockets Layer (SSL), etc.)\",\n \"handshake and obtain a key for decrypting the data in the transmitted communications (e.g., PreMasterSecret, etc.).\",\n \"In this manner, such a sensor may be enabled to monitor data within encrypted communications.\",\n \"The set of virtual machines 106 may be one or more virtual machines configured to emulate computer system hardware.\",\n \"The set of virtual machines 106 may be implemented to run as a system virtual machine or as a process virtual machine (e.g., implemented to run under an operating system).\",\n \"In some implementations, the set of virtual machines 106 run under a virtualization layer.\",\n \"In some examples, a “virtualization layer” may refer to hardware or software that enables the physical hardware of the computing system to be used to provide computational resources upon which the set of virtual machines 106 may operate.\",\n \"The virtualization layer may be any device, software, or firmware used for providing a virtual computing platform for the set of virtual machines 106.The virtual computing platform may include various virtual computer components, such as one or more virtual processors, virtual memory and the like.\",\n \"The set of virtual machines 106 may be provided to customers of the computing service resource provider 102 and the customers may run an operating system or an application on virtual machines of the set of virtual machines 106.Further, the computing service resource provider 102 may use one or more of its own virtual machines for executing its applications.\",\n \"Examples of a virtualization layer include a hypervisor.\",\n \"In other embodiments, data collected at the introspection points 120A-120E is used to determine a set of reference/baseline values or ranges.\",\n \"In some of these embodiments, the set of reference values or ranges may be determined by measuring (i.e., collecting) data at designated introspection points for a period of time in a test environment.\",\n \"Thereafter, variance from the determined set of reference values or ranges in a live (i.e., production) environment may cause the computing resource service provider 102 to respond with a security action, such as requiring confirmation from a customer owner that the variance is acceptable before allowing the actions causing the variance to continue.\",\n \"For example, if the computing resource service provider 102 identified a set of software applications executing within the test environment, the set of software applications may be recorded as expected to execute in a live environment.\",\n \"However, if the computing resource service provider 102 subsequently identifies a software application, not on the list, executing in the live environment (e.g., different application or different version of an application observed to execute in the test environment), the computing resource service provider 102 may respond with a security action, such as notifying the customer owner (e.g., through a user interface alert, text message, e-mail message, etc.)\",\n \"of the unexpectedly executing software application.\",\n \"In some implementations, evaluation of the measurements taken at the introspection points 120A-120E and performance of security actions may occur in real-time.\",\n \"That is, as measurements are taken and threats to the computing environment are determined, security actions (e.g., notifying a customer, adding constraints to a configuration of the computing environment to ensure compliance with a set of rules, etc.)\",\n \"may be performed immediately.\",\n \"In other implementations, measurements may be logged for evaluation and threat determination later or upon request.\",\n \"In an example, a set of virtual machine instances of a customer may be configured and expected to execute the same set of software, execute the same set of resources, and perform in a similar manner.\",\n \"Introspection points may be specified for the set of virtual machine instances; e.g., within virtual memory, monitoring network communications, calls to application programming interfaces, etc.).\",\n \"After tracking information at these introspection points for a period, the computing resource service provider 102 may determine that a subset of the set of virtual machine instances exhibit a variance from expected values (e.g., executing a different version of a software application, attempting to access an unexpected resource, application errors, slower than expected performance, etc.).\",\n \"Based on this determination, the computing resource service provider 102 may perform any of a variety of security actions, such as notifying the customer about the unexpected behavior from the subset of the set of virtual machine instances, performing diagnostics on the physical host of the subset, terminating and reinstantiating the virtual machine instances of the subset, etc.).\",\n \"As noted, in some embodiments, an introspection point may be embodied by an introspection agent.\",\n \"The introspection agent may be implemented as a software application executing on the virtual or physical computing system with elevated access privileges (e.g., superuser/root access).\",\n \"The introspection agent may be implemented to execute within a virtualization layer (e.g., a hypervisor) or within a controlling domain of the virtualization layer.\",\n \"Additionally or alternatively, the introspection agent may be implemented in hardware, such as within a universal serial bus dongle device communicatively coupled to a physical system within the distributed computing system of the computing resource service provider 102.Alternatively or additionally, an introspection agent may be implemented within a kernel of an operating system of the physical or virtual computing system.\",\n \"The introspection agent may be configured to audit whenever a software process is launched, whenever a software process is stopped, and information about such software processes (e.g., file names, file locations, software dependencies, etc.).\",\n \"For example, the introspection agent may be configured to detect whenever a “process launched” event occurs, and, when such event occurs, gather a set of information about the software process (e.g., all libraries loaded by the process, checksum of the process, information on how the software process was compiled, parameters passed to the software process call, etc.).\",\n \"In some embodiments, the introspection agent may be loaded into virtual memory of a virtual machine running under a virtualization layer (e.g., a hypervisor) and caused to execute.\",\n \"In other embodiments, the introspection agent may execute within the virtualization layer, and, based on a query of a virtual method table, determine and monitor a process space of the software processes in a specified virtual machine instance designated to be monitored.\",\n \"Additionally or alternatively, in embodiments the introspection agent may hook into a syscall handler of the virtualization layer for the virtual machine instance being monitored.\",\n \"Within the computing resource service provider 102 environment, there may also be a data store containing a set of reference values representing expected values or expected ranges of values for the measurements being taken at designated introspection points.\",\n \"In response to variance from the expected value or range, the introspection agent may execute a security action, such as notifying a customer owner of a virtual machine instance that may be affected by the variance that the variance was observed.\",\n \"The introspection agent may access the data store containing the set of reference values and compare the set of reference values with information measured at the introspection points to determine whether variance from expected values or ranges has occurred.\",\n \"The computing resource service provider 102 may be a computing resource service provider, similar to the computing resource service provider 602 described in conjunction with FIG.\",\n \"6, and may provide one or more computing resource services to its customers individually or as a combination of services of a distributed computer system.\",\n \"The one or more computing resource services of the computing resource service provider 102 may be accessible over a network and may include services such as virtual computer system services, block-level data storage services, cryptography services, on-demand data storage services, notification services, authentication services, policy management services, task services, and/or other such services.\",\n \"Not all embodiments described include all of the services described and additional services may be provided in addition to, or as an alternative to, services explicitly described.\",\n \"Customers of the computing resource service provider 102 may communicate with one or more of the services via an interface, which may be a web services interface or any other type of customer interface.\",\n \"Each service provided by the computing resource service provider 102 may have its own interface and subsets of the services may have corresponding individual interfaces in addition to, or as an alternative to, a common interface.\",\n \"A customer may communicate with the computing resource service provider 102 through a network, whereby the network may be a communication network, such as the Internet 118, an intranet, an interne service provider (ISP) network and/or some other such network as described below.\",\n \"The virtual computer system service 104 may be used by the computing resource service provider 102 for providing computer system resources for customers.\",\n \"The virtual computer system service 104 may provide such computer system resources by instantiating virtual machine instances, such as the set of virtual machines 106, on physical hardware.\",\n \"The physical hardware may include physical hosts which may include any device or equipment configured to execute instructions for performing data computation, manipulation, or storage tasks, such as a computer or server similar to the electronic client device 902 and the application server 908 described in conjunction with FIG.\",\n \"9.The customer may interact with the virtual computer system service 104 to provision, place, and operate virtual machine instances.\",\n \"The virtual machine instances may be used for various purposes, such as to operate as servers supporting a website, to operate business applications or, generally, to serve as compute power for the customer.\",\n \"The data storage service 108 may provide a non-transitory persistent (non-volatile) storage for program and data files for use by computing systems, such as the set of virtual machines 106.Software applications executing within the set of virtual machines 106 may be stored within one or more data stores (also referred to as repositories) of the set of data storage resources 110.The data storage service 108 may additionally provide repositories for storing data used in accordance with the present disclosure.\",\n \"The set of data storage resources 110 may be one or more storage resources, such as databases or storage resources as might be provided by services, such as the block level data storage service 610 or the on-demand data storage service 614 of FIG.\",\n \"6.The policy management service 112 may be a service configured to authenticate users of the customer and manage policies on behalf of customers of the computing resource service provider 102, such as the policy management service 620 of FIG.\",\n \"6.The set of policies 114 may be security policies associated with roles and credentials of an entity (e.g., user, customer, application, resource, etc.)\",\n \"that specify the access privileges the entity may have to one or more resources.\",\n \"The one or more other services 116 may be any other service provided by the computing resource service provider, the resource usage of which may be tracked at an introspection point, such as the introspection point 120E.\",\n \"In an example, for a physical host of one or more virtual machines under the control of the computing resource service provider 102, the virtual memory of a virtual machine may be designated as an introspection point.\",\n \"To collect data within the virtual memory, the computing resource service provider 102 may grant direct memory access (DMA) to an introspection agent executing on the physical host for inspecting contents of at least portions of the virtual memory.\",\n \"Subsequently, the inspected contents of the virtual memory may be compared against reference values or ranges in order to detect any deviance from expected memory contents.\",\n \"As another example, network communication channels may be designated as introspection points, and an introspection agent for analyzing data packets and performing net flow analysis may be integrated into networking hardware.\",\n \"FIG.\",\n \"2 illustrates an aspect of an environment 200 in which an embodiment may be practiced.\",\n \"As illustrated in FIG.\",\n \"2, the environment 200 may include one or more virtual computing network environments 203A-203B in communication with one or more clients 210A-210C through a network connection, such as through the Internet 218, where each of the virtual computing network environments 203A-203B may be comprised of a set of computing systems 204A-204N, physical or virtual.\",\n \"Each of the set of computing systems 204A-204N, in turn, may include sets of various hardware and/or software components, such as a one or more processors 206A-206N and storage 208A-208N.\",\n \"In the environment 200, an introspection point 220 may be specified for collection of information associated with incoming and outgoing communications between the virtual computing network environments 203A-203B each other and between the virtual computing network environment and one or more clients 210A-210C via the Internet 218.The one or more virtual computing network environments 203A-203B may be configurable pools of shared computing resources of a customer of a computing resource service provider, isolated from other virtual computing network environments.\",\n \"Isolation of the virtual computing network environments may be achieved through allocation of a private interne protocol subnet, a virtual local area network, and/or encrypted communication channels between the shared resources within the virtual computing network environments.\",\n \"A virtual computing network environment may include a set of virtual machine instances, such as set of computing systems 204A-204N of the virtual computing network environment 203A.\",\n \"The set of computing systems 204A-204N may be a set of virtual machine instances.\",\n \"Each of the set of computing systems 204A-204N may comprise resources from multiple services of the computing resource service provider 202.For example, the computing resource service provider 202 may, for the computing system 204A, utilize a virtual computer system service to instantiate a virtual machine, similar to the set of virtual machines 106 of the virtual computer system service 104 in FIG.\",\n \"1, having one or more virtual processors 206A for the computing system 204A.\",\n \"The sets of one or more virtual processors 206A-206N may be emulations of physical processors for a set of computing systems 204A-204N.\",\n \"Likewise, the storage 208A-208N may be configured to emulate persistent storage (e.g., hard drives, network drives, databases, etc.).\",\n \"The storage 208A may be, for example, on-demand storage, block-level storage, or a database provided by a data storage service, similar to the set of data storage resources 110 of the data storage service 108 in FIG.\",\n \"1.Configuration information for each set of computing systems 204A-204N may be stored in a data store and accessible to the computing resource service provider 202.Each computing system of the set of computing systems 204A-204N may also have network ports for receiving requests from and establishing connections with computing systems internal and external to the respective virtual computing network environment 203A-203B.\",\n \"On the storage 208A-208N of the set of computing systems 204A-204N may be stored software library files, various configuration files, and/or digital certificates.\",\n \"As noted, the computing resource service provider 202 may be a computing resource service provider, similar to the computing resource service provider 602 described in conjunction with FIG.\",\n \"6, and may provide one or more computing resource services to its customers individually or as a combination of services of a distributed computer system.\",\n \"The one or more clients 210A-210C may be users or other entities attempting to access resources within one or more of the virtual computing network environments 203A-203B or may be customers of the computing resource service provider 202 attempting to access their own resources within their own virtual computing network environment.\",\n \"The introspection point 220 may be configured to monitor network communications between computing systems of virtual computing network environment 203A and virtual computing network environment 203B.\",\n \"Similarly, the introspection point may be configured to monitor network communications between the Internet 218 and virtual computing network environment 203A and/or virtual computing network environment 203B.\",\n \"Monitoring network traffic at the introspection point may include analyzing at least a portion of data packets passing through the network connection.\",\n \"As noted, the introspection point 220 depicted in FIG.\",\n \"2 may actually be a set of introspection points, implemented as hardware or software, assigned/deployed at various points of the network of the computing resource service provider 202.Note also that, besides the introspection point 220, there may be other active introspection points, such as introspection points within the virtual computing network environment and between the services providing the resources for the set of computing systems 204A-204N (as described in more detail in the description of FIG.\",\n \"1).\",\n \"FIG.\",\n \"3 illustrates an example visualization 300 of a graph of an embodiment of the present disclosure.\",\n \"Specifically, FIG.\",\n \"3 depicts a set of resources whose usage may be tracked at introspection points in the manner disclosed in the present disclosure.\",\n \"The set of resources may include any suitable resources that may be provided by a computing resource service provider, and, as an illustrative example, FIG.\",\n \"3 shows a set of processes 302A-302E executing within a distributed computing system environment, a set of network connections 304A-304D, a set of software libraries 306A-306B, and a service 308 of a set of services.\",\n \"Thus, the tracked data, collected in the manner detailed in the descriptions of FIGS.\",\n \"1 and 2, may be organized into a graph data structure.\",\n \"The graph may be generated as having nodes representing resources (e.g., software libraries, services of a computing resource service provider, network addresses and ports, processors of a virtual machine, software processes, etc.)\",\n \"and edges representing relationship (e.g., software library dependency, network connection, etc.)\",\n \"between those nodes.\",\n \"For example, information collected at introspection points may yield information linking processes to networks, processes to software libraries, networks to services, and other resources to other resources.\",\n \"A visual map (also referred to as a visualization) may further be generated from the graph.\",\n \"As an example, the visualization may be displayed using any suitable manner of displaying such a graph, such as through auto-generated JavaScript code provided to a web browser of a customer of the computing resource service provider.\",\n \"Each of the set of processes 302A-302E represent a running process in a distributed computing system.\",\n \"Examples of such processes include database applications, web servers, e-mail hosts, and video streaming software.\",\n \"The set of network connections 304A-304D represent network connections linking processes of the set of processes 302A-302E to other resources, such as to another process or to a service provided by the computing resource service provider.\",\n \"The network connections may be any suitable network and protocol for communication between computing devices and/or processes executing on computing devices.\",\n \"Examples of a network includes the Internet, a local area network, a wide area network and Wi-Fi.\",\n \"Information collected at an introspection point regarding a network may include a network address, network port, and a type of protocol being used.\",\n \"The set of software libraries 306A-306B may be files containing configuration data and/or pre-written executable code for use by one or more of the set of processes 302A-302E.\",\n \"As noted, the service 308 may be a service provided by the computing resource service provider, such as a policy management service, a data storage service, or any of the services 608-624 described in conjunction with FIG.\",\n \"6.Information about a service collected at an introspection point may include what operations are being performed by the service, whether communications are encrypted or unencrypted, and credentials being used for communication with the service.\",\n \"The service 308 may provide database services to a customer of the computing resource service provider.\",\n \"Thus, the database resource 312 may represent a particular database provided to the customer.\",\n \"The database may contain, tables, such as tables 316A-316B, for storing data records for the customer.\",\n \"The permissions 314A-314B (also referred to as rights) may represent access permissions a user or other identity has to the particular table.\",\n \"For example, permission 314A may be read/write access to the table 316A, whereas permission 314B may represent read-only access to the table 316B.\",\n \"By identifying common characteristics from information collected at introspection points, relationships between nodes may be determined.\",\n \"For example, information collected at an introspection point on a computing system executing the process 302A may reveal that the process 302A receives data from an internet protocol address/port identified as network 304B.\",\n \"Additional information associated with the network 304B may include a process identifier of a process associated with the network 304B (e.g., the process 302A), an identity of a user agent communicating through the network (e.g., Internet Explorer, Chrome, etc.\",\n \"), and/or an identity of a software application being communicated with (e.g., Apache HTTP Server, etc.).\",\n \"Such information may be stored in a database usable for introspection and other analysis.\",\n \"In embodiments of the present disclosure, the system may make conclusions about the relationships between the nodes.\",\n \"For example, information collected at an introspection point at service 308 would reveal that the service 308 communicates data through the network 304B.\",\n \"That is, by identifying that both the process 302A and the service 308 have the network 304B in common, the computing resource service provider can conclude that the process 302A is linked to the service 308 through the network 304B.\",\n \"Likewise, it is shown in FIG.\",\n \"3 that the process 302A communicates with process 302B through the network 304B.\",\n \"Additionally, it is shown that process 302C has attempted to communicate with the process 302B through network 304C, and also that the process 302B has not responded to the process 302C.\",\n \"It is also shown that process 302D also communicates with the service 308, but through network 304D.\",\n \"In an example, it may be that configurations for processes 302B and 302D indicate that they are meant to communicate with each other, but from the graph of FIG.\",\n \"3, it may be observed that said processes do not communicate directly with each other.\",\n \"By drawing attention to such a mismatch between a configuration and the graph, the computing resource service provider may identify potential errors with configurations that prevent the intended operations of processes running within the distributed computing system.\",\n \"As another example, it may be that there is nothing in a security policy or firewall configuration preventing communication between the processes 302B and 302D, but only that during the observational period, they have not done so.\",\n \"Based on information, the computing resource service provider may determine that the processes 302B and 302D are not intended to communicate with each other and implement a firewall rule preventing communication between the two processes to ensure that, should the security of the virtual machine upon which either the process 302B or the process 302D is running be compromised, that the firewall rule would prevent one of the processes from accessing the other without authorization.\",\n \"Alternatively, if two processes, such as the process 302B and the process 302D, are established as a baseline never to communicate with each other, and, subsequently they are observed to communicate with each other, the computing resource service provider may respond with a security action, such as alerting a customer owner or network security personnel.\",\n \"Once relationships between nodes are identified, rules may be implemented, such as by a customer owner through a user interface provided by the computing resource service provider, to specify acceptable behavior of the resources represented by the nodes.\",\n \"For example, a customer owner of a virtual machine upon which the process 302A is running may implement a rule specifying that communications between the process 302A and the service 308 must use an encrypted protocol.\",\n \"Based on this rule, the computing resource service provider may confirm that the network 304B does not use an unencrypted protocol.\",\n \"If the computing resource service provider detects that the protocol is unencrypted, the computing resource service provider may perform a security action, such as disallowing use of the network connection 304A to communicate with the service 308.Similarly, the customer owner may specify that all communications to/from the process 302A must be through an encrypted protocol, and the computing resource service provider may enforce this requirement on network 304A as well.\",\n \"Another example of a rule that may be implemented in the system of the present disclosure is a rule that specifies that, unless expressly allowed by the customer owner, no software applications within a set of virtual machine instances of the customer owner should execute with root/superuser privileges.\",\n \"Still another example of a rule is to specify that network port 22 of the set of virtual machine instances should be closed/blocked.\",\n \"Another example of a rule is to specify that credentials cannot be used to access more than one type of service (e.g., file storage service versus database service, etc.).\",\n \"Similarly, a rule could specify that certain credentials have write access to one service but only read access with a different service.\",\n \"Likewise, information collected at an introspection point at the process 302A may reveal that the process 302A has software dependencies of library 306A and 306B.\",\n \"Furthermore, information collected at introspection points at process 302C and process 302D reveal that they too depend on the library 306B.\",\n \"Based at least in part on this information, the computing resource service provider can quickly determine that, if a new version of the library 306B is made available, then the processes 302A, 302C, and 302D may be impacted or may need to be updated.\",\n \"Similarly, if the graph of the embodiment of the visualization represents a baseline (i.e., set of reference values or ranges), and/or if a subsequent generation of the graph reveals that the process 302A is using a different library than the library 306B, the computing resource service provider may respond by performing a security action.\",\n \"Such security action could include automatically updating the process 302C and the process 302D to use the different library (if it is determined to be a new, stable version of the library 306B), reverting the process 302A to use the library 306B instead of the different library, or sending an alert to the customer of the computing resource service provider responsible for virtual machine the process 302A is running on that the process 302A is using an unexpected library.\",\n \"The set of reference values or ranges as well as the appropriate security action to take could be specified by a customer owner of a virtual machine upon which the process is running.\",\n \"For example, the customer owner could specify that a specified library must be a specific version and for the computing resource service provider to halt/prevent any process with dependencies of a different library version from running.\",\n \"Configuration information associated with the resources, and the generated graph, a threat model describing potential security issues, such as threats to confidentiality, availability, and integrity of data and the applications, may be generated for customers of the computing resource service provider regarding their virtual computer system environment.\",\n \"In some implementations, a customer of the computing resource service provider may specify rules to apply to the customer's virtual computing system environment, and the computing resource service provider may compare the specified rules to a current graph of the virtual computing system environment.\",\n \"The computing resource service provider may provide, such as through a user interface, the results of the comparison to the customer, such as “The present configuration complies with the specified rule,” “The present configuration does not comply with the specified rule,” “Unable to evaluate the present configuration against the specified rule,” etc.\",\n \"The users 310A-310N may be an individual, virtual or physical computing device, software process, or other entity authorized to access resources of a customer account.\",\n \"Each of the users 310A-310N may have a unique name/identity within the account, and may present or otherwise prove the possession of security credentials, such as with a password, access key, and/or digital signature, to gain access to computing resources.\",\n \"The users 310A-310N may represent one or more users that authenticate with the service 308 through the network 304B.\",\n \"The other resources 318 include any of a variety of other resource types, including, but not limited to, files, credentials, or security policies.\",\n \"In some embodiments, resources of similar types may be combined into a single node.\",\n \"For example, in a distributed computing system there may be multiple identically configured web servers.\",\n \"Rather than generating a graph with a node for each such web server, in these embodiments, the web servers may be represented by a single web server node.\",\n \"Consequently, data collected at introspection points at or between any of the web servers may be used to generate links from the web server node to other resources accessed by any of the web servers.\",\n \"Likewise, in another example, a distributed computing system may have clusters of web servers, application servers, and database servers.\",\n \"For the graph in this example, the web servers may be “merged” (i.e., grouped together) to be represented by a single web server node, the database servers may merged to be represented by a single database server node, and the application servers may be merged to be represented by a single application server node.\",\n \"Alternatively, all three types of servers may be merged/grouped into a single server node.\",\n \"Thus, by analyzing data collected at the introspection points information may be gathered to determine if and which resources may be grouped/associated together.\",\n \"For example, the gathered information may detect that a child process was forked from a parent process at a first time and that a similar child process was forked from another instance of the parent process at a second time.\",\n \"Based on this information the two instances of the parent process may be merged into a node representing the unique parent process and the two child processes may be merged into a unique child process depending from the parent process, such as is illustrated by the process 302D (parent) and the process 302E (child).\",\n \"For example, a web server parent process may spawn a PHP Hypertext Preprocessor (PHP) child process, and rather than have a dozen web server processes linked to a dozen PHP child processes in the graph, the parent processes and child processes may be separately merged to have a single web server parent process linked to a single PHP child process.\",\n \"Merges may be additive; for example, if one of the aforementioned web server parent processes also spawns a second child process, that the other web servers do not, that second child process may still be linked to the merged web server parent node.\",\n \"Such determinations may be made based on common information obtained at the introspection points for each of those processes.\",\n \"These techniques may be applied to link and merge a variety of resource types.\",\n \"The logical grouping of resource types (i.e., the types of resources that may be merged) may be defined by the customer owner, such as through an application programming interface provided by the computing resource service provider.\",\n \"For example, customer owner may define five virtual machine instances belonging to the customer owner as “web servers” and may define seven other virtual machine instances and “application servers,” and so on.\",\n \"In some implementations, default logical groupings of resources are specified by the computing resource service provider, and the customer can modify the default groupings as needed.\",\n \"In some implementations, such logical groupings are automatically be determined by the computing resource service provider based on data collected at introspection points.\",\n \"For example, by collecting data at each machine and examining what processes run on each machine, certain machines may be probabilistically classified in a first group and other machines may be probabilistically classified into a second group (e.g., at least a 50% chance of being in the first group or at least a 50% chance of being in the second group, inferred by similarities between machines/processes, etc.).\",\n \"Note that the type and quantities of the sets of resources depicted in FIG.\",\n \"3 is only illustrative, and the visualization of an actual implementation may include many thousands of nodes and many more resource types than shown in FIG.\",\n \"3.FIG.\",\n \"4 illustrates an aspect of an environment 400 in which an embodiment may be practiced.\",\n \"Specifically, FIG.\",\n \"4 depicts an introspection agent 408 collecting data at an introspection point 420 between a first computing resource 406A and a second computing resource 406B, comparing the collected data against reference values 404 stored in a data store 410, and sending an alert 422 to a customer of a computing resource service provider if a variance between the collected data and the reference values 404 is found.\",\n \"Note that the embodiment depicted in FIG.\",\n \"4 is one of many possible examples, and that the introspection agent 408 could be executing at various locations in the system, including on either of resources 406A-406B, a virtualization layer (e.g., hypervisor), a controlling domain of a virtualization layer, or a third resource not depicted.\",\n \"The customer 402 may be a customer of the computing resource service provider that provides either or both of the resources 406A-406B for use by the customer 402.The reference values 404 may be one or more expected values or ranges for measurements at the introspection point 420.An example of reference values 404 may be a list of software applications running on resource 406A that have been approved to communicate with the resource 406B.\",\n \"The data store 410 may be any type of data storage configured to store the reference values 404 for the computing resource service provider.\",\n \"The resources 406A-406B are intended to represent any of a variety of computing resources, such as virtual machine instances, physical computing systems, on-demand data storage resources, archival data storage resources, or security policies.\",\n \"Either or both 406A-406B may be provided by the computing resource service provider, or one of the resources 406A-406B may be a computing resource external to the computing resource service provider environment.\",\n \"For example, resource 406A may be a computing resource within the environment of the computing resource service provider, while resource 406B may be computing system external to the computing resource service provider but accessible to the resource 406A through the Internet or other network.\",\n \"The communication channel 418 may be any type of communication channel by which two or more devices may communicate, including physical network cables, wireless communications, universal serial bus (USB), serial, parallel, and other conduits.\",\n \"The communication channel 418 may further be configured to communicate through, among others, the Internet, an intranet, wide area network (WAN), local area network (LAN), and direct connection.\",\n \"The communication channel 418 may further be configured to facilitate communications of any type of communication protocol, including a cellular wireless communications protocol, such as fourth generation (4G) communications or long term evolution (LTE™), a wireless local area network (WLAN) communications protocol, such as an Institute for Electrical and Electronics Engineers (IEEE) 802.11, 802.16 or 802.21 communication protocol, or short range communications protocol, among others.\",\n \"The introspection point 420 may be an introspection point similar to any of the introspection points 120A-120E described in conjunction with FIG.\",\n \"1.In FIG.\",\n \"4, the introspection point 420 is shown to be a data collection point for data flowing along the communication channel 418 between the resource 406A and the resource 406B.\",\n \"The introspection agent 408 may be executable code injected and executing in application memory of one of resources 406A-406B, a software application with elevated access permissions executing a computing system with access to read the data at the introspection point 420, or may be implemented in hardware of the communication channel 418.Upon detection of a variance between measured values at the introspection point 420 and the reference values 404, the introspection agent 408 may cause the alert 422 to be sent to the customer 402.For example, the introspection agent 408 may determine from the data at the introspection point 420 that the communications channel 418 is not encrypted, and therefore may be vulnerable to infiltration by unauthorized entities.\",\n \"The alert 422 may be an e-mail message, text message, message appearing in a popup window on a device of the customer, confirmation dialog, graphical indicator on a user interface provided by the computing resource service provider to the customer 402, or any other manner of notification to the customer 402 that a variance from expected values has been detected.\",\n \"The alert 422 provides notice that a potential violation has been detected, thereby allowing the customer 402 to determine whether the potential violation is an actual violation of a security rule and/or take action to mitigate the potential violation.\",\n \"For example, a customer of the computing resource service provider may specify a rule to take a security action to notify the customer if any month-to-date charges of the customer's virtual machine usage exceed an amount of two-hundred dollars.\",\n \"As another example, where a computing resource service provider provides virtual computer system services in different geographic regions and a customer employs services of the computing resource service provider in a first region but none in a second region, the customer may specify a security action to be notified if charges begin accruing to the customer from the second region.\",\n \"As still another example, if the system of an embodiment of the present disclosure determines, based on credential information collected at an introspection point of a customer computing environment, that a particular credential is being used insecurely, the alert 422 may provide notice to the customer that the particular credential may be in violation of a rule or may present a security vulnerability.\",\n \"In some implementations, the alert 422 may notify the customer 402 of actions to be taken by the computing resource service provider to mitigate the potential violation, such as changes to access permissions or firewall rules, and the customer 402 may be given the opportunity to confirm, deny, or undo the respective actions.\",\n \"FIG.\",\n \"5 illustrates an aspect of an environment 500 in which an embodiment may be practiced.\",\n \"Specifically, FIG.\",\n \"5 illustrates how an introspection agent 508 may be configured to run within a virtualization layer 530 managing the execution of one or more virtual machines 506A-506N or may be configured to run in a controlling domain 504 of the virtualization layer 530.The introspection agent 508 may be executable code executing in the controlling domain 504 of a virtualization layer 530 or within the virtualization layer 530 itself.\",\n \"The introspection agent 508 may be configured to monitor one or more introspection points 520A-520N of the virtual machines 506A-506N.\",\n \"Upon detection of a variance between measured values at the one or more introspection points 520A-520N and reference values, the introspection agent 508 may cause a security action to be performed, such as sending an alert to a customer owner of the one or more virtual machines 506A-506N, isolating the virtual machine exhibiting a variance from the reference values from the network, or terminating the virtual machine exhibiting the variance.\",\n \"The introspection points 520A-520N, as noted, may be a set of data collection points specified by a customer, computing resource service provider, or other authorized entity.\",\n \"Types of introspection points may include points at an incoming network port, log information regarding the virtual machines 506A-506N, and configuration files for the virtual machines 506A-506N.\",\n \"Collectable information at the introspection points 520A-520N may include credentials, whether communications are encrypted, security policies used, database permissions, and/or billing charges generated from usage of the virtual machines 506A-506N.\",\n \"The controlling domain 504 may be a privileged virtual machine instance from which the one or more virtual machines 506A-506N of the virtualization layer 530 may be managed.\",\n \"Unlike the one or more virtual machines 506A-506N, the controlling domain 504 may have direct access to the system hardware 528 (e.g., network interface controllers, hard drives, memory, etc.).\",\n \"The virtualization layer 530 may enable the system hardware 528 to be used to provide computational resources upon which the one or more virtual machines 506A-506N may operate.\",\n \"The virtualization layer 530 may be any device, software or firmware used for providing a virtual computer platform for the one or more virtual machines 506A-506N.\",\n \"An example of virtualization layer is a hypervisor.\",\n \"The virtual computer platform may include various virtual computer components, such as one or more virtual processors, virtual memory, virtual devices and the like.\",\n \"The one or more virtual machines 506A-506N may be provided to customers of the computing resource service provider, and the customers may run operating systems, applications and/or other such computer system entities on the one or more virtual machines 506A-506N.\",\n \"Thus, the introspection agent 508 running in either the controlling domain 504 or virtualization layer 530 may allow the introspection agent 508 to collect information at the introspection points 520A-520N of the virtual machines 506A-506N.\",\n \"Note too, that, although not illustrated as such in FIG.\",\n \"5, in some embodiments, the introspection agent 508 may additionally or alternatively execute in the system hardware 528, for example via an unified extensible firmware interface application or similar custom code on a peripheral hardware controller firmware of the system hardware 528.The system hardware 528 may include the hardware of a physical (i.e., non-virtual) computing device configured to execute instructions for performing data computation, manipulation, or storage tasks.\",\n \"The system hardware 528 may include one or more processors, such as a central processing unit (CPU), a graphics processing unit (GPU) or a digital signal processor (DSP), memory, including static and dynamic memory, buses, and input and output ports that are compliant with any handshaking, communications or data transfer protocol.\",\n \"The system hardware 528 may also include storage devices, such as storage disks and tapes, and/or networking equipment.\",\n \"The virtualization layer 530 may enable the system hardware 528 to be used to provide computational resources upon which the one or more virtual machines 506A-506N may operate.\",\n \"FIG.\",\n \"6 shows an example of a customer connected to a computing resource service provider in accordance with at least one embodiment.\",\n \"The computing resource service provider 602 may provide a variety of services to the customer 604 and the customer 604 may communicate with the computing resource service provider 602 via an interface 626, which may be a web services interface or any other type of customer interface.\",\n \"While FIG.\",\n \"6 shows one interface 626 for the services of the computing resource service provider 602, each service may have its own interface and, generally, subsets of the services may have corresponding interfaces in addition to or as an alternative to the interface 626.The customer 604 may be an organization that may utilize one or more of the services provided by the computing resource service provider 602 to maintain and deliver information to its employees, which may be located in various geographical locations.\",\n \"Additionally, the customer 604 may be an individual that utilizes the services of the computing resource service provider 602 to deliver content to a working group located remotely.\",\n \"As shown in FIG.\",\n \"6, the customer 604 may communicate with the computing resource service provider 602 through a network 606, whereby the network 606 may be a communication network, such as the Internet, an intranet or an Internet service provider (ISP) network.\",\n \"Some communications from the customer 604 to the computing resource service provider 602 may cause the computing resource service provider 602 to operate in accordance with one or more embodiments described or a variation thereof.\",\n \"The computing resource service provider 602 may provide various computing resource services to its customers.\",\n \"The services provided by the computing resource service provider 602, in this example, include a virtual computer system service 608, a block-level data storage service 610, a cryptography service 612, an on-demand data storage service 614, a notification service 616, an authentication system 618, a policy management service 620, a task service 622, and one or more other services 624.It is noted that not all embodiments described include the services 608-624 described with reference to FIG.\",\n \"6 and additional services may be provided in addition to or as an alternative to services explicitly described.\",\n \"As described, each of the services 608-624 may include one or more web service interfaces that enable the customer 604 to submit appropriately-configured API calls to the various services through web service requests.\",\n \"In addition, each of the services may include one or more service interfaces that enable the services to access each other (e.g., to enable a virtual computer system of the virtual computer system service 608 to store data in or retrieve data from the on-demand data storage service 614 and/or to access one or more block-level data storage devices provided by the block level data storage service 610).\",\n \"The virtual computer system service 608 may be a collection of computing resources configured to instantiate virtual machine instances on behalf of the customer 604.The customer 604 may interact with the virtual computer system service 608 (via appropriately configured and authenticated API calls) to provision and operate virtual computer systems that are instantiated on physical computing devices hosted and operated by the computing resource service provider 602.The virtual computer systems may be used for various purposes, such as to operate as servers supporting a website, to operate business applications or, generally, to serve as computing power for the customer.\",\n \"Other applications for the virtual computer systems may be to support database applications, electronic commerce applications, business applications, and/or other applications.\",\n \"Although the virtual computer system service 608 is shown in FIG.\",\n \"8, any other computer system or computer system service may be utilized by the computing resource service provider 602, such as a computer system or computer system service that does not employ virtualization or instantiation and instead provisions computing resources on dedicated or shared computers/servers and/or other physical devices.\",\n \"The block-level data storage service 610 may comprise one or more computing resources that collectively operate to store data for a customer 604 using block-level storage devices (and/or virtualizations thereof).\",\n \"The block-level storage devices of the block-level data storage service 610 may, for instance, be operationally attached to virtual computer systems provided by the virtual computer system service 608 to serve as logical units (e.g., virtual drives) for the computer systems.\",\n \"A block-level storage device may enable the persistent storage of data used/generated by a corresponding virtual computer system where the virtual computer system service 608 may only provide ephemeral data storage.\",\n \"The computing resource service provider 602 also includes a cryptography service 612.The cryptography service 612 may utilize one or more storage services of the computing resource service provider 602 to store keys of the customers in encrypted form, whereby the keys may be usable to decrypt customer 604 keys accessible only to particular devices of the cryptography service 612.The computing resource service provider 602 further includes an on-demand data storage service 614.The on-demand data storage service 614 may be a collection of computing resources configured to synchronously process requests to store and/or access data.\",\n \"The on-demand data storage service 614 may operate using computing resources (e.g., databases) that enable the on-demand data storage service 614 to locate and retrieve data quickly, to allow data to be provided in responses to requests for the data.\",\n \"For example, the on-demand data storage service 614 may maintain stored data in a manner such that, when a request for a data object is retrieved, the data object can be provided (or streaming of the data object can be initiated) in a response to the request.\",\n \"As noted, data stored in the on-demand data storage service 614 may be organized into data objects.\",\n \"The data objects may have arbitrary sizes except, perhaps, for certain constraints on size.\",\n \"Thus, the on-demand data storage service 614 may store numerous data objects of varying sizes.\",\n \"The on-demand data storage service 614 may operate as a key value store that associates data objects with identifiers of the data objects which may be used by the customer 604 to retrieve or perform other operations in connection with the data objects stored by the on-demand data storage service 614.In the environment illustrated in FIG.\",\n \"6, a notification service 616 is included.\",\n \"The notification service 616 may comprise a collection of computing resources collectively configured to provide a web service or other interface and browser-based management console.\",\n \"The management console can be used to configure topics for which customers seek to receive notifications, configure applications (or people), subscribe clients to the topics, publish messages, or configure delivery of the messages over clients' protocol of choice (i.e., hypertext transfer protocol (HTTP), e-mail and short message service (SMS), among others).\",\n \"The notification service 616 may provide notifications to clients using a “push” mechanism without the need to periodically check or “poll” for new information and updates.\",\n \"The notification service 616 may further be used for various purposes such as monitoring applications executing in the virtual computer system service 608, workflow systems, time-sensitive information updates, mobile applications, and many others.\",\n \"As illustrated in FIG.\",\n \"6, the computing resource service provider 602, in various embodiments, includes an authentication system 618 and a policy management service 620.The authentication system 618, in an embodiment, is a computer system (i.e., collection of computing resources) configured to perform operations involved in authentication of users of the customer.\",\n \"For instance, one of the services 608-616 and 620-624 may provide information from a user to the authentication system 618 to receive information in return that indicates whether the user requests are authentic.\",\n \"The policy management service 620, in an embodiment, is a computer system configured to manage policies on behalf of customers (such as customer 604) of the computing resource service provider 602.The policy management service 620 may include an interface that enables customers to submit requests related to the management of policy.\",\n \"Such requests, for instance, may be requests to add, delete, change, or otherwise modify policy for a customer or for other administrative actions, such as providing an inventory of existing policies and the like.\",\n \"The computing resource service provider 602, in various embodiments, is also equipped with a task service 622.The task service 622 is configured to receive a task package from the customer 604 and enable executing tasks as dictated by the task package.\",\n \"The task service 622 may be configured to use any resource of the computing resource service provider 602, such as one or more instantiated virtual machines or virtual hosts, for executing the task.\",\n \"The task service 623 may configure the one or more instantiated virtual machines or virtual hosts to operate using a selected operating system and/or a selected execution application in accordance with a requirement of the customer 604.The computing resource service provider 602 additionally maintains one or more other services 624 based at least in part on the needs of its customers 604.For instance, the computing resource service provider 602 may maintain a database service for its customers 604.A database service may be a collection of computing resources that collectively operate to run one or more databases for one or more customers 604.The customer 604 may operate and manage a database from the database service by utilizing appropriately configured API calls.\",\n \"This, in turn, may allow a customer 604 to maintain and potentially scale the operations in the database.\",\n \"Other services include, but are not limited to, object-level archival data storage services, services that manage and/or monitor other services.\",\n \"FIG.\",\n \"7 is a flow chart illustrating an example of a process 700 for generating a graph based at least in part on data collected at introspection points in accordance with various embodiments.\",\n \"The process 700 may be performed by any suitable system such as a server in a data center, multiple computing devices in a distributed system of a computing resource service provider, or any electronic client device, such as the electronic client device 902 described in conjunction with FIG.\",\n \"9.The process 700 includes a series of operations wherein introspection points are determined, data is collected at the introspection points, and a graph is generated from the collected data.\",\n \"In 702, an introspection point for obtaining measurements/collecting data about resources of a computing environment may be determined.\",\n \"For a given computing environment, there may be multiple resources with potentially several introspection points.\",\n \"Consequently, there may be multiple instances of the process 700 being performed in parallel by the system.\",\n \"The system performing the process 700 may initiate the operations of 702 in response to a request from a customer of a computing resource service provider.\",\n \"For example, the computing resource service provider may provide introspection of a set of the customer's virtual machine instances as a service.\",\n \"In other cases, the computing resource service provider may utilize introspection itself to analyze select sets of resources, select services, or the overall system.\",\n \"The identifying data collected may be used to identify threats to the computing environment and determine whether systems and resources within the computing environment are in compliance with rules and security policies.\",\n \"The introspection points may be determined based on identifying characteristics found in data that may be obtained at the introspection point.\",\n \"For example, an introspection point at a network connection may provide information regarding source and destination internet protocol addresses, process IDs, and whether or not communications are encrypted.\",\n \"In 704, measurements are taken at (i.e., information collected from) the introspection point.\",\n \"The measurements/information may be obtained at the introspection points by an introspection agent implemented in software or hardware.\",\n \"In some embodiments, the introspection agent may be running as part of a virtualization layer.\",\n \"In other embodiments, the introspection agent may be implemented as a system-level software process running in the operating system of a customer virtual machine being measured.\",\n \"In still other embodiments, the introspection agent may be implemented in hardware, such as networking hardware that analyzes data packets passing between devices in the computing environment.\",\n \"In 706, the measurements may be parsed to isolate and retrieve identifying information; that is, information from which the system may determine relationships between resources and characteristics of the computing environment usable for assessing security threats.\",\n \"As noted, such information may include identities of software processes, whether communications are encrypted, internet protocol addresses and ports, software dependencies, credentials, and access permissions.\",\n \"In 708, a graph representing a set of objects (e.g., resources) in the computing environment may be generated.\",\n \"The objects may be linked by common characteristics determined from the identifying information determined in 706 and configuration information.\",\n \"As an example, a computing resource service provider may host three different virtual computing network environments, each virtual computing network environment including a set of virtual machine instances.\",\n \"Each virtual computing network environment and/or set of virtual machine instances may have configuration information stored in a data store defining various aspects of the virtual computing network environments and their virtual machine instances, such as information specifying the operating systems running under each virtual machine, the data storage resources usable by each virtual machine, firewall settings, and/or internet protocol addresses of the virtual machines within each virtual computing network environment.\",\n \"With reference to the configuration information and the measurements of 704, a graph of the relationships between the resources of each virtual network computing environment to each other and to the resources of the other virtual network computing environments may be generated.\",\n \"In 710, the system performing the process 700 may determine whether additional data should be collected/measurements taken at the introspection points determined in 702.In some embodiments, measurements may be taken at intervals and compared with previous measurements.\",\n \"In cases where measurements taken at a first time and measurements taken at a second time do not differ from expected values (e.g., from a set of reference values), the system performing the process 700 may return to 704 to take additional measurements.\",\n \"On the other hand, if the measurements taken at the first time and the measurements taken at the second time unexpectedly differ (e.g., a software library has changed, a software process a previously unused port is being used, etc.\",\n \"), the system performing the process 700 may proceed to 712 to generate a threat model.\",\n \"In some embodiments, expected values and/or expected ranges of measurements may be specified by the computing resource service provider or by a customer of the computing resource service provider.\",\n \"In other embodiments, the expected values and/or expected ranges of measurements may be determined, at least initially, from a baseline measurement of an exemplary virtual computing network environment.\",\n \"Such expected values and ranges may be modified by the customer and/or computing resource service provider as needed.\",\n \"In 712, each node and edge in the graph may be walked to generate a threat model of the measured computing system.\",\n \"In some implementations, the threat model may be an interactive map/visualization of the computing system with various graphical indicators for drawing a user's attention to different potential threats and risk levels (e.g., “warning,” “error,” “secure,” “unsecure,” “unable to evaluate,” etc.).\",\n \"The threat model may provide information identifying possible ways the computing environment could be attacked, number, and type of actual attacks detected, probability of harm, levels of risk, and suggestions on mitigating threats.\",\n \"Note too that after 712, the operations of 702-712 may be repeated as often as required by the customer or computing resource service provider.\",\n \"Note too that one or more of the operations performed in 702-712 may be performed in various orders and combinations, including in parallel.\",\n \"FIG.\",\n \"8 is a flow chart illustrating an example of a process 800 for generating a graph and performing a security action in accordance with various embodiments.\",\n \"The process 800 may be performed by any suitable system such as a server in a data center, multiple computing devices in a distributed system of a computing resource service provider, or any electronic client device, such as the electronic client device 902 described in conjunction with FIG.\",\n \"9.The process 800 includes a series of operations wherein configuration information for a set of resources is obtained, usage of the set of resources is tracked, a graph is generated, and based on an analysis of the graph, potential vulnerabilities (also referred to as risks) are identified and addressed.\",\n \"In 802, configuration information for a set of resources (e.g., set of virtual machine instances, set of data storage resources in a distributed computing system, etc.)\",\n \"is obtained.\",\n \"Such configuration information may include firewall rules, identities of virtual machines running within the computing environment, access permissions for credentials used by users or virtual machines in the computing environment, and/or what databases are accessed by users and/or virtual machines in the computing environment.\",\n \"In some implementation, the configuration information may be stored in a data store or in various data files accessible to the computing resource service provider.\",\n \"In 804, information relating to usage of the set of resources (i.e., information is collected at introspection points, such as the introspection points set at 702 of FIG.\",\n \"7) is tracked/logged.\",\n \"As described in the present disclosure, such information may be tracked and logged by an introspection agent executing within the computing environment.\",\n \"In 806, a graph, as described in the present disclosure, may be generated based on tracked resource usage information and the obtained configuration information.\",\n \"In 808 and 810, the graph may be analyzed to assess the security state of the computing environment; i.e., to determine whether there are potential vulnerabilities within the computing environment.\",\n \"For example, if the system performing the process 800 determines that a first virtual machine has an open network communication channel to a second virtual machine, but in practice does not communicate with the second virtual machine, the system performing the process 800 may flag this as a potential violation.\",\n \"That is, should security of first virtual machine become compromised, the open communications channel may present a potential risk to the second virtual machine as well.\",\n \"Similarly, if a software application is detected as using an old version of a software library, this too may be flagged as a potential violation.\",\n \"In some implementations, analysis of the graph may include comparing the current generated graph to a previously generated graph to identify any differences, which may indicate potential vulnerabilities.\",\n \"Likewise, if measurements tracked by an introspection agent deviate from a set of reference values representing expected values or ranges of the measurements, such an anomaly may be flagged as a potential threat or violation.\",\n \"If no potential vulnerabilities are detected, the system performing the process 800 may return to 804 to continue to track resource usage.\",\n \"However, if potential vulnerabilities are identified in 812, the system performing the process 800 may perform a security action.\",\n \"Security actions may include notifying a customer owner of a virtual machine instance being monitored, or may additionally or alternatively include making changes to configuration information to mitigate the potential vulnerabilities (e.g., implementing firewall rules to close vulnerable ports, etc.).\",\n \"In the event configuration information changes, either by the system performing the process 800 or by a customer, the system performing the process 812 may return to 802 to repeat the process 800 to determine whether the configuration change affects the potential violation or introduces new potential vulnerabilities.\",\n \"Note that one or more of the operations performed in 802-812 may be performed in various orders and combinations, including in parallel.\",\n \"Note that, unless otherwise specified, use of expressions regarding executable instructions (also referred to as code, applications, agents, etc.)\",\n \"performing operations that instructions do not ordinarily perform unaided (e.g., transmission of data, calculations, etc.)\",\n \"in the context of describing disclosed embodiments denote that the instructions are being executed by a machine, thereby causing the machine to perform the specified operations.\",\n \"FIG.\",\n \"9 illustrates aspects of an example environment 900 for implementing aspects in accordance with various embodiments.\",\n \"As will be appreciated, although a web-based environment is used for purposes of explanation, different environments may be used, as appropriate, to implement various embodiments.\",\n \"The environment includes an electronic client device 902, which can include any appropriate device operable to send and/or receive requests, messages or information over an appropriate network 904 and, in some embodiments, convey information back to a user of the device.\",\n \"Examples of such client devices include personal computers, cell phones, handheld messaging devices, laptop computers, tablet computers, set-top boxes, personal data assistants, embedded computer systems, electronic book readers, and the like.\",\n \"The network 904 can include any appropriate network, including an intranet, the Internet, a cellular network, a local area network, a satellite network, or any other network and/or combination thereof.\",\n \"Components used for such a system can depend at least in part upon the type of network and/or environment selected.\",\n \"Protocols and components for communicating via such a network are well known and will not be discussed in detail.\",\n \"Communication over the network 904 can be enabled by wired or wireless connections and combinations thereof.\",\n \"In this example, the network 904 includes the Internet, as the environment includes a web server 906 for receiving requests and serving content in response thereto, although for other networks an alternative device serving a similar purpose could be used as would be apparent to one of ordinary skill in the art.\",\n \"The illustrative environment includes an application server 908 and a data store 910.It should be understood that there could be several application servers, layers, or other elements, processes, or components, which may be chained or otherwise configured, which can interact to perform tasks such as obtaining data from an appropriate data store.\",\n \"Servers, as used, may be implemented in various ways, such as hardware devices or virtual computer systems.\",\n \"In some contexts, servers may refer to a programming module being executed on a computer system.\",\n \"As used, unless otherwise stated or clear from context, the term “data store” refers to any device or combination of devices capable of storing, accessing, and retrieving data, which may include any combination and number of data servers, databases, data storage devices, and data storage media, in any standard, distributed, virtual, or clustered environment.\",\n \"The application server 908 can include any appropriate hardware, software, and firmware for integrating with the data store 910 as needed to execute aspects of one or more applications for the electronic client device 902, handling some or all of the data access and business logic for an application.\",\n \"The application server 908 may provide access control services in cooperation with the data store 910 and is able to generate content including, text, graphics, audio, video and/or other content usable to be provided to the user, which may be served to the user by the web server 906 in the form of HyperText Markup Language (“HTML”), Extensible Markup Language (“XML”), JavaScript, Cascading Style Sheets (“CSS”), or another appropriate client-side structured language.\",\n \"Content transferred to a client device may be processed by the electronic client device 902 to provide the content in one or more forms including, forms that are perceptible to the user audibly, visually, and/or through other senses including touch, taste, and/or smell.\",\n \"The handling of all requests and responses, as well as the delivery of content between the electronic client device 902 and the application server 908, can be handled by the web server 906 using PHP: Hypertext Preprocessor (“PHP”), Python, Ruby, Perl, Java, HTML, XML, or another appropriate server-side structured language in this example.\",\n \"It should be understood that the web server 906 and the application server 908 are not required and are merely example components, as structured code discussed can be executed on any appropriate device or host machine as discussed elsewhere.\",\n \"Further, operations described as being performed by a single device may, unless otherwise clear from context, be performed collectively by multiple devices, which may form a distributed and/or virtual system.\",\n \"The data store 910 can include several separate data tables, databases, data documents, dynamic data storage schemes, and/or other data storage mechanisms and media for storing data relating to a particular aspect of the present disclosure.\",\n \"For example, the data store 910 may include mechanisms for storing production data 912 and user information 916, which can be used to serve content for the production side.\",\n \"The data store 910 also is shown to include a mechanism for storing log data 914, which can be used for reporting, analysis, or other purposes.\",\n \"It should be understood that there can be many other aspects that may need to be stored in the data store 910, such as page image information and access rights information, which can be stored in any of the above listed mechanisms as appropriate or in additional mechanisms in the data store 910.The data store 910 is operable, through logic associated therewith, to receive instructions from the application server 908 and obtain, update, or otherwise process data in response thereto.\",\n \"The application server 908 may provide static, dynamic, or a combination of static and dynamic data in response to the received instructions.\",\n \"Dynamic data, such as data used in web logs (blogs), shopping applications, news services, and other applications may be generated by server-side structured languages as described or may be provided by a content management system (“CMS”) operating on, or under the control of, the application server 908.In one example, a user, through a device operated by the user, might submit a search request for a certain type of item.\",\n \"In this case, the data store 910 might access the user information 916 to verify the identity of the user and can access the catalog detail information to obtain information about items of that type.\",\n \"The information then can be returned to the user, such as in a results listing on a web page that the user is able to view via a browser on the electronic client device 902.Information for a particular item of interest can be viewed in a dedicated page or window of the browser.\",\n \"It should be noted, however, that embodiments of the present disclosure are not necessarily limited to the context of web pages, but may be more generally applicable to processing requests in general, where the requests are not necessarily requests for content.\",\n \"Each server typically will include an operating system that provides executable program instructions for the general administration and operation of that server and typically will include a computer-readable storage medium (e.g., a hard disk, random access memory, read only memory, etc.)\",\n \"storing instructions that, when executed by a processor of the server, allow the server to perform its intended functions.\",\n \"Suitable implementations for the operating system and general functionality of the servers are known or commercially available and are readily implemented by persons having ordinary skill in the art, particularly in light of the disclosure.\",\n \"The environment, in one embodiment, is a distributed and/or virtual computing environment utilizing several computer systems and components that are interconnected via communication links, using one or more computer networks or direct connections.\",\n \"However, it will be appreciated by those of ordinary skill in the art that such a system could operate equally well in a system having fewer or a greater number of components than are illustrated in FIG.\",\n \"9.Thus, the depiction of the example environment 900 in FIG.\",\n \"9 should be taken as being illustrative in nature and not limiting to the scope of the disclosure.\",\n \"The various embodiments further can be implemented in a wide variety of operating environments, which in some cases can include one or more user computers, computing devices, or processing devices that can be used to operate any of a number of applications.\",\n \"User or client devices can include any of a number of general purpose personal computers, such as desktop, laptop, or tablet computers running a standard operating system, as well as cellular, wireless, and handheld devices running mobile software and capable of supporting a number of networking and messaging protocols.\",\n \"Such a system also can include a number of workstations running any of a variety of commercially available operating systems and other known applications for purposes such as development and database management.\",\n \"These devices also can include other electronic devices, such as dummy terminals, thin-clients, gaming systems, and other devices capable of communicating via a network.\",\n \"These devices also can include virtual devices such as virtual machines, hypervisors, and other virtual devices capable of communicating via a network.\",\n \"Various embodiments of the present disclosure utilize a network that would be familiar to those skilled in the art for supporting communications using any of a variety of commercially available protocols, such as Transmission Control Protocol/Internet Protocol (“TCP/IP”), User Datagram Protocol (“UDP”), protocols operating in various layers of the Open System Interconnection (“OSI”) model, File Transfer Protocol (“FTP”), Universal Plug and Play (“UpnP”), Network File System (“NFS”), Common Internet File System (“CIFS”), and AppleTalk.\",\n \"The network 904 can be, for example, a local area network, a wide-area network, a virtual private network, the Internet, an intranet, an extranet, a public switched telephone network, an infrared network, a wireless network, a satellite network, and any combination thereof.\",\n \"In embodiments utilizing a web server, the web server can run any of a variety of server or mid-tier applications, including Hypertext Transfer Protocol (“HTTP”) servers, FTP servers, Common Gateway Interface (“CGP”) servers, data servers, Java servers, Apache servers, and business application servers.\",\n \"The server(s) also may be capable of executing programs or scripts in response to requests from user devices, such as by executing one or more web applications that may be implemented as one or more scripts or programs written in any programming language, such as Java®, C, C#, or C++, or any scripting language, such as Ruby, PHP, Perl, Python, or TCL, as well as combinations thereof.\",\n \"The server(s) may also include database servers, including those commercially available from Oracle®, Microsoft®, Sybase®, and IBM® as well as open-source servers such as MySQL, Postgres, SQLite, MongoDB, and any other server capable of storing, retrieving, and accessing structured or unstructured data.\",\n \"Database servers may include table-based servers, document-based servers, unstructured servers, relational servers, non-relational servers, or combinations of these and/or other database servers.\",\n \"The environment can include a variety of data stores and other memory and storage media as discussed above.\",\n \"These can reside in a variety of locations, such as on a storage medium local to (and/or resident in) one or more of the computers or remote from any or all of the computers across the network.\",\n \"In a particular set of embodiments, the information may reside in a storage-area network (“SAN”) familiar to those skilled in the art.\",\n \"Similarly, any necessary files for performing the functions attributed to the computers, servers or other network devices may be stored locally and/or remotely, as appropriate.\",\n \"Where a system includes computerized devices, each such device can include hardware elements that may be electrically coupled via a bus, the elements including, for example, a central processing unit (“CPU” or “processor”), an input device (e.g., a mouse, keyboard, controller, touch screen, or keypad), and an output device (e.g., a display device, printer, or speaker).\",\n \"Such a system may also include one or more storage devices, such as disk drives, optical storage devices, and solid-state storage devices, such as random access memory (“RAM”) or read-only memory (“ROM”), as well as removable media devices, memory cards, flash cards, etc.\",\n \"Such devices also can include a computer-readable storage media reader, a communications device (e.g., a modem, a wireless or wired network card, an infrared communication device, etc.\",\n \"), and working memory as described above.\",\n \"The computer-readable storage media reader can be connected with, or configured to receive, a computer-readable storage medium, representing remote, local, fixed, and/or removable storage devices as well as storage media for temporarily and/or more permanently containing, storing, transmitting, and retrieving computer-readable information.\",\n \"The system and various devices also typically will include a number of software applications, modules, services, or other elements located within a working memory device, including an operating system and application programs, such as a client application or web browser.\",\n \"It should be appreciated that alternate embodiments may have numerous variations from that described above.\",\n \"For example, customized hardware might also be used and/or particular elements might be implemented in hardware, software (including portable software, such as applets), or both.\",\n \"Further, connection to other computing devices such as network input/output devices may be employed.\",\n \"Storage media and computer readable media for containing code, or portions of code, can include any appropriate media known or used in the art, including storage media and communication media, such as volatile and non-volatile, removable and non-removable media implemented in any method or technology for storage and/or transmission of information such as computer readable instructions, data structures, program modules, or other data, including RAM, ROM, Electrically Erasable Programmable Read-Only Memory (“EEPROM”), flash memory, or other memory technology, Compact Disc Read-Only Memory (“CD-ROM”), digital versatile disk (DVD), or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices or any other medium which can be used to store the desired information and which can be accessed by the system device.\",\n \"Based on the disclosure and teachings provided, a person of ordinary skill in the art will appreciate other ways and/or methods to implement the various embodiments.\",\n \"The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.\",\n \"However, it will be evident that various modifications and changes may be made thereunto without departing from the broader spirit and scope of the invention as set forth in the claims.\",\n \"Other variations are within the spirit of the present disclosure.\",\n \"Thus, while the techniques are susceptible to various modifications and alternative constructions, certain illustrated embodiments thereof are shown in the drawings and have been described above in detail.\",\n \"It should be understood, however, that there is no intention to limit the invention to the specific form or forms disclosed, but on the contrary, the intention is to cover all modifications, alternative constructions and equivalents falling within the spirit and scope of the invention, as defined in the appended claims.\",\n \"The use of the terms “a,” “an,” and “the” and similar referents in the context of describing the embodiments (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated or clearly contradicted by context.\",\n \"The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted.\",\n \"The term “connected,” when unmodified and referring to physical connections, is to be construed as partly or wholly contained within, attached to or joined together, even if there is something intervening.\",\n \"Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated and each separate value is incorporated into the specification as if it were individually recited.\",\n \"The use of the term “set” (e.g., “a set of items”) or “subset” unless otherwise noted or contradicted by context, is to be construed as a nonempty collection comprising one or more members.\",\n \"Further, unless otherwise noted or contradicted by context, the term “subset” of a corresponding set does not necessarily denote a proper subset of the corresponding set, but the subset and the corresponding set may be equal.\",\n \"Conjunctive language, such as phrases of the form “at least one of A, B, and C,” or “at least one of A, B and C,” is understood with the context as used in general to present that an item, term, etc., may be either A or B or C, or any nonempty subset of the set of A and B and C, unless specifically stated otherwise or otherwise clearly contradicted by context.\",\n \"For instance, in the illustrative example of a set having three members, the conjunctive phrases “at least one of A, B, and C” and “at least one of A, B and C” refer to any of the following sets: {A}, {B}, {C}, {A, B}, {A, C}, {B, C}, {A, B, C}.\",\n \"Thus, such conjunctive language is not generally intended to imply that certain embodiments require at least one of A, at least one of B and at least one of C each to be present.\",\n \"Operations of processes described can be performed in any suitable order unless otherwise indicated or otherwise clearly contradicted by context.\",\n \"Processes described (or variations and/or combinations thereof) may be performed under the control of one or more computer systems configured with executable instructions and may be implemented as code (e.g., executable instructions, one or more computer programs or one or more applications) executing collectively on one or more processors, by hardware or combinations thereof.\",\n \"The code may be stored on a computer-readable storage medium, for example, in the form of a computer program comprising instructions executable by one or more processors.\",\n \"The computer-readable storage medium may be non-transitory.\",\n \"The use of any examples, or exemplary language (e.g., “such as”) provided, is intended merely to better illuminate embodiments of the invention and does not pose a limitation on the scope of the invention unless otherwise claimed.\",\n \"No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.\",\n \"Embodiments of this disclosure are described, including the best mode known to the inventors for carrying out the invention.\",\n \"Variations of those embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description.\",\n \"The inventors expect skilled artisans to employ such variations as appropriate and the inventors intend for embodiments of the present disclosure to be practiced otherwise than as specifically described.\",\n \"Accordingly, the scope of the present disclosure includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law.\",\n \"Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the scope of the present disclosure unless otherwise indicated or otherwise clearly contradicted by context.\",\n \"All references, including publications, patent applications, and patents, cited are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874771"}}},{"rowIdx":4494695,"cells":{"text":{"kind":"list like","value":[["DRYERS FOR REMOVING SOLVENT FROM A DRUG-ELUTING COATING APPLIED TO MEDICAL DEVICES","A coating device for coating a medical device with a drug-eluting material uses an in-process drying station between coats to improve a drug release profile.","The drying station includes a dryer having a telescoping plenum which provides a drying chamber for the stent or scaffold to reside while a heated gas is passed over the stent/scaffold.","The drying chamber improves efficiency in drying, predictability or drug release rate, uniformity of coating material properties lengthwise over the stent/scaffold and provides a platform that can effectively support stents that are over 40 mm in length."],["1-8.","(canceled) 9.An apparatus comprising, a dryer including a housing that forms a plenum; the housing comprising: a mouth from which a gas exits from the plenum, a shield having walls surrounding a drying region and the mouth, and an opening to the drying region defined by the shield walls, such that gas exiting from the mouth enters the drying region and exits the drying region through the opening, wherein the shield walls include a notch adapted to receive a mandrel supporting a stent at least partially within the drying region.","10-18.","(canceled) 19.An apparatus, comprising: a sprayer; a dryer; a linear actuator for moving a stent-supporting mandrel between the dryer and the sprayer; and a rotary actuator for rotating the stent-supporting mandrel during drying and spraying; wherein a plenum of the dryer is configured to expand when the stent-supporting mandrel is aligned with a mouth of the dryer.","20.","(canceled) 21.The apparatus of claim 19, wherein the dryer includes an actuator mechanism for extending a housing that forms the plenum, and wherein the housing comprises a shield that surrounds the mouth.","22.The apparatus of claim 19, further including a controller for controlling a gas supply temperature to the dryer, the controller configured for providing a steady state gas supply and switching between an idle state and an in-use state when the stent is being sprayed and dried, respectively.","23.The apparatus of claim 19, wherein the dryer includes means for both aligning the stent-supporting mandrel with the mouth and stabilizing the stent-supporting mandrel while a stent, mounted on the stent-supporting mandrel, is dried using the dryer.","24.A combination of a stent supported on a mandrel and the apparatus of claim 9, wherein a first end and a second end of the mandrel is received within the notch comprising respective first and second notches of the shield walls and the stent is disposed within the drying region.","25.The apparatus of claim 9, wherein the housing further comprises: a first housing, and a second housing comprising the shield, the second housing being coupled to the first housing and configured to extend from the first housing when the stent is aligned with the shield opening.","26.The dryer of claim 9, wherein the dryer is configured such that the plenum has a first size when the stent is in the drying region and a second size when the stent is not in the drying region, the first size being greater than the second size.","27.The apparatus of claim 9, wherein the dryer is a telescoping dryer.","28.The apparatus of claim 9, further comprising: a gripper, and an actuator mechanism adapted to cause the gripper to grab and release an end of the mandrel when the stent is in the drying region.","29.The apparatus of claim 28, wherein the gripper comprises arms having slots and the actuator mechanism is configured for moving the slots so as to form a passage for holding the end of the mandrel.","30.The apparatus of claim 28, wherein the actuator mechanism is one or more hydraulic actuators operated as part of a servomechanism controlled by a computer.","31.The apparatus of claim 28, wherein the gripper and actuator mechanism are connected to the housing.","32.The apparatus of claim 28, wherein the gripper forms a circular passage adapted to hold the end of the mandrel, wherein the circular passage is configured to hold the mandrel within the notch while permitting rotation of the mandrel about a longitudinal axis of the mandrel.","33.The apparatus of claim 28, wherein the actuator is configured to form a circular passage with the gripper and the circular passage is configured to align with the notch of the shield.","34.The apparatus of claim 9, wherein the housing includes a spacer and a screen disposed within the plenum.","35.The apparatus of claim 9, wherein the shield opening is elongate and the notch comprises a first notch and a second notch formed on the shield walls, the notches being located at the opening and configured to receive respective first and second portions of the mandrel therein.","36.An apparatus and stent, comprising: a dryer including a housing that forms a plenum; the housing comprising: a mouth from which a gas exits from the plenum, a shield having walls surrounding a drying region and the mouth, and an opening to the drying region defined by the shield walls, such that gas exiting from the mouth enters the drying region and exits the drying region through the opening; wherein the stent is disposed at least partially within the drying region.","37.The apparatus of claim 36, wherein the dryer is configured such that the plenum has a first size when the stent is in the drying chamber, and a second size when the stent is not in the drying region, the first size being greater than the second size.","38.The apparatus of claim 36, further comprising: a mandrel supporting the stent in the drying region; and a gripper coupled to the housing and located adjacent an end of the mandrel.","39.The apparatus of claim 36, wherein a first portion and a second portion of the mandrel are retained in a first notch and a second notch, respectively, of the shield walls and the stent is between the notches."],["<SOH> BACKGROUND OF THE INVENTION <EOH>"],["<SOH> SUMMARY OF THE INVENTION <EOH>The invention proposes an in-process dryer for maximizing in-process drying efficiency and uniformity for improving the product quality (e.g.","coating and its drug release consistency).","A dryer and associated process according to the invention can also obviate the need for an oven step which has been relied on to remove residual solvent, thereby streamlining the manufacturing process.","A dryer nozzle according to the invention has a wider mouth or exit from the plenum than previously proposed stent dryer designs.","With this design mean gas velocity at the dryer nozzle is reduced over earlier dryer designs, so that there is less or no influence by the surrounding ambient air and less oscillations of the stent during drying.","In a preferred embodiment the dryer is constructed as a telescoping dryer assembly, although other designs are contemplated, e.g., a dryer nozzle that is moved into and out of position as a single unit connected to a flexible gas supply.","A shield surrounds the drying region to isolate heated gas from surrounding cooler ambient air.","The stent (or scaffold) is disposed within this drying region during the drying step.","The dryer nozzle is retractable, which allows clearance for movement of the sent or scaffold between spraying and drying stations.","The feature of a retractable dryer nozzle also simplifies drying operations, such as concerns aligning the stent with the mouth or exit.","A dryer according to the invention addresses alignment issues and uneven drying seen in prior designs by ensuring full coverage and uniform heat application.","In addition, the influence of ambient air in the drying operation is effectively minimized or eliminated.","Tests have shown that the temperature within the shielded area of the drying region and just above it is at a constant temperature, indicating that no ambient air is drawn into the drying region.","Since the hot air within the drying region is at a slightly higher pressure than the surrounding ambient air, ambient air is prevented from being drawn into the drying region.","The dryer nozzle includes internal diffusers, e.g., stacked spacer and screen assemblies, to uniformly mix the heated drying gas, resulting in a temperature uniformity of within 1 degree C. across the stent drying area.","Accordingly, an inter-pass dryer, according to the invention, that is used in a stent coating process improves on the art by providing an apparatus and method for forming a drug-eluting coating that offers greater control over the release rate for a drug and less undesired interaction between residual solvent and the drug-polymer matrix in the coating.","The term “inter-pass drying” means drying, or removing solvent between one, two, three or more spray passes.","The weight of material per coat is in some embodiments are very light, about 5% of the total coating weight according to one embodiment.","This means, for this particular embodiment, 20 coats are needed to reach 100% of the coating weight.","In view of the foregoing, the invention provides one or more of the following additional improvements over the art.","According to one aspect of invention, a method for applying a composition to a stent, comprising the steps of spraying the composition on the stent; and drying the stent, including the steps of moving a shield, surrounding a drying region, over the stent, applying a drying gas to dry the stent, and after drying the stent, moving the shield away from the stent.","According to another aspect of invention, a dryer nozzle for drying a stent includes a first housing configured for being connected to a gas supply; a second housing movable within the first housing, the second housing including a drying region in fluid communication with a mouth of the dryer nozzle and configured to receive and support a mandrel, the mouth being located at a base of the drying region, and a diffusion chamber disposed below the mouth.","According to another aspect of invention, a stent coating system includes a sprayer; a telescoping dryer nozzle; and a linear actuator for moving a stent-supporting mandrel between the telescoping dryer nozzle and the sprayer.","The system may further include a rotary actuator for rotating the stent-supporting mandrel to improve consistency and uniformity of solvent removal."],["BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to drug-eluting medical devices; more particularly, this invention relates to processes for controlling the interaction among polymer, drug and solvent, and the release rate of a drug for drug eluting medical devices.","Background of the Invention Strict pharmacological and good mechanical integrity of a drug eluting medical device are required to assure a controlled drug release.","Significant technical challenges exist when developing an effective and versatile coating for a drug eluting medical device, such as a stent.","A coating may be applied by a spray coating process.","A drug-polymer composition dissolved in a solvent is applied to the surface of a medical device using this method.","The amount of drug-polymer to be applied has been expressed as a target coating weight, which corresponds to the weight of the coating after a substantial amount of the solvent is removed.","Previous efforts to produce a more consistent and stable drug release profile have been met with challenges.","Prior efforts have focused on the type or structure of the polymer carrier for a drug, and the type of solvent used.","However, these improvements have not been able to satisfactorily meet the needs for certain clinical applications, or provide a morphology that can be widely used.","A “drug release profile”, or “release profile” means the morphology, or characteristics of a drug-eluting matrix that delivers an expected therapeutic behavior after being placed within a body.","A drug release profile, or release profile therefore informs one of such things as the predictability of the release rate, variation, if any, in the release rate over time or on a per unit area basis across a drug-eluting surface.","It has been previously discovered that a significant improvement in the ability to tailor a drug release profile to suit a particular objective such as producing a specific release rate, uniformity in the release rate over a drug eluting surface, and/or uniformity in a production setting (high throughput) lay in obtaining more precise control over the amount of solvent present, or rate of solvent removal.","The criticality of solvent removal, distribution, etc.","generally depends on the drug-polymer-solvent formulation and particular objectives.","While it was already known that the morphology of a drug-polymer matrix is influenced by the presence of a solvent, it was later discovered that this interaction played a more significant role than previously thought.","Based on this conclusion, a more effective process for controlling the amount of solvent-polymer-drug interaction was sought.","It was found that the coating weight per spray cycle and manner in which solvent was removed, in connection with the coating thickness was an important consideration.","A relatively high coating weight per spray cycle has been sought in the past, because this minimizes process time and increases throughput.","Maintaining control over the amount or rate of solvent removal is, however, challenging unless an applied coating layer is relatively thin.","If the applied layer is too thick the removal of the solvent becomes more difficult to control or predict.","When the solvent is removed from a thick layer, therefore, the potential for undesired interaction among the solvent, polymer and drug, and related problems begin to impair the ability to retain control over the release profile.","Process conditions can affect the desired morphology.","For example, if there is excess residual solvent, i.e., solvent not removed between or after a spray cycle, the solvent can induce a plasticizing effect, which can significantly alter the release rate.","Therefore, it can be critically important to have a process that produces a coating with consistent properties—crystallinity, % solvent residue, % moisture content, etc.","If one or more of these parameters are not properly controlled, such that it varies over the thickness or across a surface of a drug-eluting device, then the release profile is affected.","One or more of these considerations can be more critical for some drug-polymer-solvent formulations than for other formulations.","To facilitate the incorporation of a drug on a stent, spraying a low solid percent polymer/drug solution over the stent followed by removing the solvent has become feasible in controlling the amount of drug (in micrograms range) deposited on the stent and the release profile.","A good coating quality benefits from using this spray technique, i.e., properties such as the crystallinity, % solvent residue, and % moisture content are more controllable as the coating weight is built up over several applied coatings.","Previous studies of the drying effect on drug release indicated a need for an optimal in-process or inter-pass drying technique to remove a solvent on the coated stent after each spray cycle.","This is a critical step in producing more stable products while retaining a high throughput.","The properties of a solvent, e.g., surface tension, vapor pressure or boiling point, viscosity, and dielectric constant, used in dissolving a polymer have a dominant effect on the coating quality, coating process throughput, drug stability, and the equipment required to process it.","A solvent can, of course, be removed by applying a heated gas over the stent.","However, this drying step must be carefully controlled in order to achieve the desired end result.","A uniform and efficient heat transfer from the gas to the coating surface must also take place.","The evaporation rate of a suitable solvent has an inverse relationship with the coating thickness (generally inversely proportional to the thickness) for a thin film coating.","And the resistance increases non-linearly as the coating thickness increases.","As alluded to earlier, this non-linearity should be avoided.","When the coating thickness is not too high more uniformity and control can be achieved in removing the solvent.","As a result, a more consistent drug release profile is obtained because there is the least drug-solvent-polymer interaction, solvent plasticizing and drug extraction rate.","It is therefore desired to achieve more control over, not only the uniformity of properties across the coating thickness and along the length of the stent, but also the ability to remove solvent.","This is because residual solvent on the drug eluting stent may induce adverse biological responses, compromise coating properties, induce drug degradation, and alter release profile.","Thus, it has been determined that a release rate can be better controlled by applying many coats of a low percentage solution, e.g., 5% of the final coating weight, with a drying step between each spray cycle.","Thus, in this example 20 coats are needed to produce the target coating weight.","In order to make this coating process more feasible as a production-level method, while maintaining control over the solvent and solvent-drug-polymer interaction, as just discussed, an efficient in-process drying step is needed.","Effective ways to remove residual solvent in the applied coating becomes more important for coating formulations that are more sensitive to a residual solvent level.","As explained above, excessive remaining solvent impacts the coating morphology and property.","For example, in the case of a coating formulation used for a polymer scaffold, e.g., PLLA, residual solvent left in the coating can induce phase separation between the drug and polymer because the drug and polymer are not miscible.","This can cause variation of the drug release rate and adversely impact the physical properties of the coating.","It is therefore desirable to achieve an optimized in-process dry nozzle design to ensure the removal of most of the residual solvent between successive spray cycles.","Examples of dryers seeking to achieve this objective are described in US20110059228 and US20110000427.For example, US20110000427 proposes using an external heat nozzle design having a narrow opening producing a drying gas exiting from the dryer plenum at relatively high velocity.","This arrangement requires precise alignment between the stent and heat nozzle for uniform drying.","The design can introduce extensive and interfering mixing of outside air into the gas stream before contacting the stent or scaffold; this mixing of outside air is uncontrolled and causes variation in the temperature across the drying area.","Additionally, the high velocity gas causes the stent to oscillate, which can be problematic for longer-length stents, such as those intended for peripheral vessels.","There is a continuing need for obtaining a better control over the drug-eluting product.","Specifically, there is a need to develop an inter-pass drying process that is better able to remove solvent to achieve improved rate of release of a drug, uniformity of release rate over the stent length and/or the effectiveness of a drug when released from the coating.","It is also desirable to reduce processing time when applying a drug-eluting coating.","SUMMARY OF THE INVENTION The invention proposes an in-process dryer for maximizing in-process drying efficiency and uniformity for improving the product quality (e.g.","coating and its drug release consistency).","A dryer and associated process according to the invention can also obviate the need for an oven step which has been relied on to remove residual solvent, thereby streamlining the manufacturing process.","A dryer nozzle according to the invention has a wider mouth or exit from the plenum than previously proposed stent dryer designs.","With this design mean gas velocity at the dryer nozzle is reduced over earlier dryer designs, so that there is less or no influence by the surrounding ambient air and less oscillations of the stent during drying.","In a preferred embodiment the dryer is constructed as a telescoping dryer assembly, although other designs are contemplated, e.g., a dryer nozzle that is moved into and out of position as a single unit connected to a flexible gas supply.","A shield surrounds the drying region to isolate heated gas from surrounding cooler ambient air.","The stent (or scaffold) is disposed within this drying region during the drying step.","The dryer nozzle is retractable, which allows clearance for movement of the sent or scaffold between spraying and drying stations.","The feature of a retractable dryer nozzle also simplifies drying operations, such as concerns aligning the stent with the mouth or exit.","A dryer according to the invention addresses alignment issues and uneven drying seen in prior designs by ensuring full coverage and uniform heat application.","In addition, the influence of ambient air in the drying operation is effectively minimized or eliminated.","Tests have shown that the temperature within the shielded area of the drying region and just above it is at a constant temperature, indicating that no ambient air is drawn into the drying region.","Since the hot air within the drying region is at a slightly higher pressure than the surrounding ambient air, ambient air is prevented from being drawn into the drying region.","The dryer nozzle includes internal diffusers, e.g., stacked spacer and screen assemblies, to uniformly mix the heated drying gas, resulting in a temperature uniformity of within 1 degree C. across the stent drying area.","Accordingly, an inter-pass dryer, according to the invention, that is used in a stent coating process improves on the art by providing an apparatus and method for forming a drug-eluting coating that offers greater control over the release rate for a drug and less undesired interaction between residual solvent and the drug-polymer matrix in the coating.","The term “inter-pass drying” means drying, or removing solvent between one, two, three or more spray passes.","The weight of material per coat is in some embodiments are very light, about 5% of the total coating weight according to one embodiment.","This means, for this particular embodiment, 20 coats are needed to reach 100% of the coating weight.","In view of the foregoing, the invention provides one or more of the following additional improvements over the art.","According to one aspect of invention, a method for applying a composition to a stent, comprising the steps of spraying the composition on the stent; and drying the stent, including the steps of moving a shield, surrounding a drying region, over the stent, applying a drying gas to dry the stent, and after drying the stent, moving the shield away from the stent.","According to another aspect of invention, a dryer nozzle for drying a stent includes a first housing configured for being connected to a gas supply; a second housing movable within the first housing, the second housing including a drying region in fluid communication with a mouth of the dryer nozzle and configured to receive and support a mandrel, the mouth being located at a base of the drying region, and a diffusion chamber disposed below the mouth.","According to another aspect of invention, a stent coating system includes a sprayer; a telescoping dryer nozzle; and a linear actuator for moving a stent-supporting mandrel between the telescoping dryer nozzle and the sprayer.","The system may further include a rotary actuator for rotating the stent-supporting mandrel to improve consistency and uniformity of solvent removal.","INCORPORATION BY REFERENCE All publications and patent applications mentioned in the present specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.","To the extent there are any inconsistent usages of words and/or phrases between an incorporated publication or patent and the present specification, these words and/or phrases will have a meaning that is consistent with the manner in which they are used in the present specification.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1A is side view of a dryer assembly in a first, retracted position according to one aspect of the disclosure.","FIG.","1B is side view of the dryer assembly in a second, expanded position according to another aspect of the disclosure.","FIG.","2 summarizes a process for coating a stent including a spraying step and in-process drying step using the dryer assembly of FIG.","1.FIG.","3 is a rear perspective view of the dryer assembly.","FIG.","4 is a front perspective, exploded assembly view of the dryer assembly showing component parts according to a preferred embodiment.","FIG.","5 is a perspective view of a base cap of the dryer assembly of FIG.","4.FIG.","6 is a perspective view of a diffuser housing of the dryer assembly of FIG.","4.FIGS.","7A and 7B are perspective views of left and right grippers of a mandrel gripper of the dryer assembly of FIG.","4.FIG.","8 is a perspective view of a base housing of the dryer assembly of FIG.","4.FIG.","9 is a schematic of a control system that may be used with the dryer assembly to minimize transient flow or wait time and conserve dryer resources while a coating is being applied to a stent.","DETAILED DESCRIPTION OF EMBODIMENTS According to a preferred implementation of the invention, a sprayer and dryer nozzle is used to form a drug-eluting coat on a surface of a stent.","A stent is an intravascular prosthesis that is delivered and implanted within a patient's vasculature or other bodily cavities and lumens by a balloon catheter for balloon expandable stents and by a catheter with an outer stent restraining sheath for self expanding stents.","The structure of a stent is typically composed of scaffolding, substrate, or base material that includes a pattern or network of interconnecting structural elements often referred to in the art as struts or bar arms.","A stent typically has a plurality of cylindrical elements having a radial stiffness and struts connecting the cylindrical elements.","Lengthwise the stent is supported mostly by only the flexural rigidity of slender-beam-like linking elements, which give the stent longitudinal flexibility.","Examples of the structure and surface topology of medical devices such as a stent and catheter are disclosed by U.S. Pat.","Nos.","4,733,665, 4,800,882, 4,886,062, 5,514,154, 5,569,295, and 5,507,768.As discussed earlier, one aspect of the stent coating process that has been simplified, or improved, as a result of the dryer according to the disclosure, is the ability to predict more consistently the rate of solvent removal and variation of that rate over the length of the stent.","Increasing the predictability of a solvent's presence in the applied coating, or remaining when determining a final weight can greatly increase the ability and/or efficiency in which a predictable release rate for a drug can be provided in a medical device, in the form of an applied coating.","Moreover, as the design or desired loading of polymer-drug on the stent is determined from the measured weight, it will be readily appreciated that there needs to be an accurate, reliable and repeatable process for being able to determine the amount and distribution of solvent remaining over the length of the stent.","This is especially true when less volatile solvents are used, e.g., DMAc as opposed to the more volatile solvent Acetone.","Since it is expected that a greater percentage of solvent will remain after drying for solvents having higher boiling points, the coating is more susceptible to variations in a solvent's presence over the stent surface and/or across the coating thickness.","Also when drying a polymer Acetone mixture, the rate and uniformity of drying affects the % crystallinity and thus the amount of locked in residual solvent.","The disclosure provides examples of spraying/drying components suited for addressing the previously discussed drawbacks and limitations in the art pertaining to a drug-eluting coating applied via a drug-polymer dissolved in a solvent.","FIGS.","1A-1B show side views of a telescoping dryer 10 (dryer 10) according to one aspect of the disclosure.","FIG.","2 shows a flow process for applying, via a spray apparatus, a composition, i.e., drug-polymer coating dissolved in a solvent, to a stent including applying one or more coats of the sprayed composition followed by a drying step that may include using dryer 10.Accordingly, the dryer 10 may be included as a component to a stent coating apparatus.","Such a stent coating apparatus implementing the process of FIG.","2 includes a sprayer, the dryer 10 and actuators for placing the stent between a spraying area or chamber and a drying area for performing a drying step, or solvent removal step, between each of several coatings of composition sprayed onto the stent.","Examples of a stent coating apparatus that may adopt principles of the disclosure are described in U.S. patent application Ser.","Nos.","12/497,133; 12/027,947 and 11/764,006.In these examples, the dryer(s) described therein may instead utilize a dryer according to the disclosure, as will be understood.","Referring, briefly, to side views of the dryer 10 as depicted in FIGS.","1A-1B, after one or more coatings are applied by a sprayer, the stent (supported on a mandrel 15) is moved into position over the dryer 10, as indicated in FIG.","1A.","Mandrel grippers 60 then engage a distal end 15a of the mandrel 15 to account for any slight misalignments of the stent position over the dryer exit or mouth and stabilize the stent as it rotates and is impacted by gas exiting from the dryer plenum.","A diffuser housing 30 telescopes or deploys from a base housing 20 (using a linear actuator mechanism 50) to place or enclose the stent within a shield 32, as indicated in FIG.","1B.","After the drying step is complete, the diffuser housing 30 retracts back into the base housing 20, the grippers 60 are released from the mandrel end 15a and the stent moved back to the spraying station to apply the next coating.","These steps of a stent coating process are summarized in FIG.","2.FIGS.","1A and 1B show the stent positioned above the dryer 10.However, the stent may alternatively be located below the dryer 10.In such an arrangement, the shield 32 would be placed above the stent and the drying gas directed downward, rather than placed below the stent and directed upward, respectively, as depicted in these drawings.","The stent, supported on the mandrel 15, is rotated by a rotary mechanism (not shown) coupled to the mandrel 15 as the sprayer applies a drug-polymer dissolved in a solvent, e.g., DMAc or Acetone, to the surface of the stent.","This rotary mechanism is also used to rotate the stent while it is disposed within the shield 32 to facilitate uniform removal of solvent about the circumference of the stent during drying.","A mass of heated gas exits from the mouth of the dryer (at a base of the shield 32) to accelerate the evaporation, or boiling-off of solvent from the coated stent surface.","In a preferred embodiment, this sprayer-dryer coating process is repeated until a final coating weight of drug-polymer and remaining solvent is measured.","During each drying stage the gas is capable of producing a uniform heat transfer across the surface of stents or scaffolds, even for stents or scaffolds having lengths of 100 mm, 150 mm, and 200 mm.","A coating process according to FIG.","2 may be preprogrammed, or programmed on the fly to adjust parameters such as number of coats, or passes with the sprayer between drying steps, number of cycles of spraying and drying, etc.","These and related parameters may be governed by the polymer-drug or solvent used, type of stent or medical device being coated, e.g., surface geometry.","In particular embodiments the protocol for coating a stent may be governed by a predetermined number of coating cycles, i.e., spraying then drying, based on an analytically determined final coating weight, or by intermittent weighing of the stent to determine the number of cycles needed to arrive at the target coating weight.","FIGS.","3 and 4 show an assembled rear perspective view and exploded front perspective assembly view, respectively, of the dryer 10.A mouth or exit of the dryer 10 is present at the base of the shield 32 and has dimensions the same as an opening of the shield 32; in other words, the walls forming the shield 32 are parallel to each other or the cross-sectional area of the entrance to the drying region surrounded by the shield 32 is the same as the cross-sectional area of the opening through which the stent passes when entering/exiting the drying region.","A gas supply is connected to an entrance of the dryer 10 provided by the base housing 20.The drying gas, e.g., heated nitrogen or air, is supplied through a gas supply 2b connected to a heater assembly 2.The heater assembly 2 includes a tubular conduit with heating coils exposed to the gas stream as it travels towards the dryer entrance 9.The coils are connected to a power source via a power connection.","A plenum of the dryer 10 is formed by internal volumes of the base housing 20, the diffuser housing 30 and a base cap 70.Perspective views of the base cap 70 and diffuser housing 30 are illustrated in FIGS.","5 and 6, respectively.","A hole in the dryer base housing 20 (hidden from view) is formed to co-align with a similar shaped hole in the base cap 70 (also hidden from view) to provide a passage for gas into the interior of the base cap 70.The hole or passage for gas through the base housing 20 includes a threading to sealingly engage a complimentary threaded fitting 2c of the heated gas supply.","Gas entering through this passage passes directly into the interior of the base cap 70, exits through a hole 72 formed at the top of the base cap 70 then passes up through the diffuser housing 30.The base cap 70 and diffuser housing 30 are contained within the base housing 20 when fully assembled.","To account for any thermal energy loss for gas near the walls of the housings 20, 30 one or more mixing regions are provided within the diffuser housing 30 so that the gas entering the drying region surrounded by the shield 32 has a more uniform heat transfer across the length of the stent.","Preferably three mixing regions are used for dryer 10.Each mixing region is formed by a diffuser screen 42 and spacer 40.Each screen and spacer are stacked on top of each other, as indicated in FIG.","4.From tests it was found that three spacers and screen assemblies were sufficient to cause no more than about a 1 degree Celsius temperature difference within the drying region during a drying step.","FIG.","4 indicates the order of assembly of the portions forming the plenum of the dryer 10, i.e., diffuser housing 30, base cap 70, base housing 20 and spacers and screens 40, 42.The three spacers and screens 40, 42 are placed inserted within the diffuser housing 30 and may be held in place by pins at the edge 31.The diffuser housing 30 is placed within the dryer base 20 through a bottom edge 24 thereof.","The dryer housing 20 and diffuser housing 30 are then placed on the base cap 70 such that a lower edge 24 of the dryer housing 20 rests on a lower flange 76 of the base cap 70.The lower spacer 40a rests on an upper surface 74 of the base cap 70.The base housing 20 is press-fit onto the base cap 70 to provide a fluid-tight seal between the walls of the two structures.","This assembled configuration of the dryer 10 is depicted in FIG.","1A.","As mentioned above, gas travels from the gas supply into the interior of the base cap 70, though the exit hole 72 and then through the diffuser housing 30.When the diffuser housing 30 is lifted up to position the stent within the drying region surrounded by the shield 32 (FIG.","1B), the spacer 40a lifts off the surface 74 of the base cap 70.To ensure gas passes directly from the base cap into the diffuser housing 30, a tight but slidable fit is formed between the interior walls of the housing 20 and a lower flange 31 of the diffuser housing 30.In essence, this fit maintains a desired gas pressure within the plenum while the dryer 10 is expanded (or housing 30 lifted) to receive the stent in the drying region, and while allowing the diffuser housing 30 to be moved up and down by the actuator 50 while the housing 20 and base cap 70 remain stationary (FIG.","1B).","The travel upwards of the diffuser housing 30 within the base housing 20 is limited by the flange 31.After the diffuser housing 30 has traveled a sufficient distance (to place the stent within the drying region) the flange 31 abuts an upper surface of the opening 22 of the diffuser housing 20, thereby preventing further upward movement.","To promote the seal between the interior walls of the housings 20, 30, therefore, the edge 31 slides against along the walls of the housing 20 as the diffuser housing 30 is being moved upwards and downwards within the housing 20 by the actuator 50.More generally, the sliding fit between these telescoping parts enables a plenum pressure to be achieved and maintained (no leaks) while the dryer 10 is retracted/shortened and expanded/lengthened.","As just alluded to, the aforementioned structure, i.e., housings 20, 30 and base cap 70, and mechanism 50 that form the plenum for the dryer 10 may be thought of as a telescoping dryer.","Prior to the stent being positioned over the drying region, the diffuser housing 30 is retracted within the base housing 20 to provide clearance for the stent and mandrel 15 to be linearly displaced from the spray station to a position over the drying region.","The dryer plenum is then essentially elongated or expanded to bring the stent into the drying region of the diffuser housing 30.Thus, a “telescoping dryer assembly” is intended to mean an arrangement of housings forming a plenum that slide inward and outward in overlapping fashion in a manner analogous to how a hand telescope slides inward and outward in an overlapping fashion, to thereby provide a variable length channel or internal passage for a pressurized fluid to pass through, i.e., a variable length plenum.","Referring to FIGS.","3 and 4, the dryer 10 components and actuating mechanisms 55 and 50 are secured to a plate 14, which is connected to a pair of blocks 16 and brackets 12.The actuating mechanism 55 is used to displace left and right grippers 62, 64 towards and away from each other to grip and release, respectively, the distal end 15a of the mandrel 15; this movement being indicated by the left and right arrows G in FIG.","3.A detailed view of each gripper 62, 64 is shown in FIGS.","7A-7B.","The actuating mechanism 50 (e.g., one or more hydraulic actuators, such as air cylinders, operated as part of a servomechanism pre-programmed or controlled by a computer processor to produce the desired movement in the housing 30 in accordance with a drying/spraying process as shown in FIG.","2) is used to raise and lower the diffuser housing 30; this movement indicated by the up and down arrows L in FIG.","3.A connecting plate 54 has a rim, which is placed over the diffusing housing and secured to a top ledge 34 of the diffuser housing 30, and a flange 54a that is secured to a platform 54b that is movable up and down by a pair of air cylinders 56a, 56b.","Thus, the actuator causes the plate 54 to pull up on the housing 30 when the plenum is being extended or lengthened (FIGS.","1B and 3), and push down on the housing 30 when the plenum is being retracted or shortened (FIG.","1A).","FIG.","3 shows the dryer 10 configuration with the housing 30 raised to position the stent within the drying region surrounded by the shield 32 and the gripper pair 62, 64 gripping the end 15a of the mandrel 15.This is also the configuration shown in FIG.","1B.","FIG.","5 shows a perspective view of the base cap 70, with the portions identified as previously described.","As can be appreciated by comparing the contours of the base cap top surface 74 and the housing 30 (FIG.","6), the dryer 10 preferably has an elongate shape with rounded ends, just as the shield 32 is shaped to receive the stent or scaffold.","The base cap 70 may be formed to have walls that are thicker than the housings 20, 30 (see FIG.","1A) to provide increased insulation capability.","Since the gas enters here and is redirected 90 degrees to exit from hole 72, there is a greater heat loss possibility than after the gas exits through hole 72.As such, the walls are made thicker and preferably they are made from PEEK.","As described earlier, a last step of the assembly for dryer 10 is to press fit the housing 20 (with diffuser housing 30 inside) onto the base cap 70.This last step essentially seals the dyer 10 and forms the interior space for the dryer plenum.","FIG.","6 shows a perspective view of the diffuser housing 30, with features of this structure as previously described.","The shield 32 is elongate with rounded ends to receive the stent or scaffold therein.","The shield 32 provides walls 30b that rise up from the ledge 34, which ledge 34 locates the exit opening from the plenum (the dryer mouth) into the drying region surrounded by the shield 32, thereby also reflecting a depth of the shield 32.Gas flowing near the stent and within the drying chamber 32 may exit from the plenum at a relatively low velocity which favorably limits the amount of regress or interference from ambient air.","As mentioned earlier, by providing a shield and gas at a lower exit velocity which maintains its heat when exposed to the stent, there is an alternative to the dryer assemblies described in US20110059228 and US20110000427.The mouth of the dryer is located at the base of the shield.","The opening provided for the stent is about the same size as the mouth size (not shown in the drawings).","FIGS.","7A and 7B show perspective views of grippers 62, 64, respectively.","Each has arms 58a, 58b that form holes 57a, 57a at lower ends thereof to secure the grippers 62, 64 to the actuator mechanism 55 (FIG.","4) using bolts.","At the head of the grippers 62, 64 are semicircular and complimentary slots 63a, 63b that are aligned to capture the distal end 15a of the mandrel 15 within a circular passage formed when the slots 63a, 63b are brought together by the actuator mechanism 55 (e.g., one or more hydraulic actuators, such as air cylinders, operated as part of a servomechanism pre-programmed or controlled by a computer processor to produce the desired movement in the grippers in accordance with a drying/spraying process as shown in FIG.","2).","V-shaped sections 66, 67, aligned with slots 63a, 63b, function as guiding surfaces to urge the mandrel 15 into the semicircular slots 63a, 63b (see FIGS.","1B and 3).","As can be appreciated by inspecting the spacing between the V-shaped section 66 and slot 63a of gripper 62, the closer spacing between the V-shaped section 67 and slot 63b of the gripper 64, the dimension G1 in FIGS.","7A-7B, and the interlocking manner in which the grippers engage the mandrel, as shown in FIG.","3, the V-shaped section 67 is disposed within the space 69 of the gripper 62 when the mandrel end 15a is engaged by the grippers 62, 64.When the stent is moved into position above the shield 32, the grippers 62, 64 come together.","Any misalignment of the mandrel end 15a is adjusted by the V-shaped sections engaging the mandrel end 15a and urging it towards alignment with the slots 63a, 63b.","When the grippers 62, 64 are moved into contact with each other, the mandrel end 15a is held in place within the circular passage formed by the slots 63a, 63b.","This ensures that the stent is being positioned properly within the shield 32 and held in position when the drying gas is passed over the stent.","The mandrel end 15a may rotate while it is disposed within the circular passage formed by the slots 63a, 63b.","The walls 30b forming the shield 32 include a first notch 36 disposed at one rounded end, and a second notch 38 disposed at a second or opposed rounded end.","These notches 36, 38 are used to allow the mandrel that the stent sits on to lower the stent to within the shield 32 during the drying.","When the gas exits, even at a low velocity the stent will oscillate since it rotates which presents a varying surface area to the gas exiting (in addition to the non-laminar or transient flow in and around the stent).","The problem of oscillations is especially noted for stents that are 40 mm and longer, e.g., stents (or scaffolds) intended for the superficial femoral artery.","To meet these needs the dryer 10 includes a support for the mandrel 15 distal end 15 a, i.e., mandrel grippers 60, in addition to the notches 36, 38.With the additional support provided by grippers 60 the stent becomes effectively fixed-supported at the mandrel distal end 15a when disposed over the dryer mouth (exit of the plenum), yet is still capable of being rotated about the mandrel axis by a rotary mechanism coupled to the mandrel.","This support may be achieved without interference with drying and prevents contact between the stent/scaffold and the walls 30b or mandrel 15 as the gas passes over the stent/scaffold.","The stent is mounted onto the mandrel 15 prior to the start of the stent coating process (FIG.","2).","The mandrel 15 controls the stent position during drying and spraying.","The mandrel 15 generally maintains axial alignment of the stent, and causes the stent to rotate at generally the same rate as the mandrel 15, which has a proximal end that fits into a chuck.","The chuck delivers a torque to the mandrel 15.The slots 36 and 38 provide a sufficient clearance to allow the mandrel 15 to rotate.","The mated grooves 63a, 63b (FIGS.","7A-7B) also provide this clearance for rotation.","Some heating gas will escape through the slots 36 and 38.FIG.","8 shows a perspective view of the base housing 20, with the portions identified as previously described.","As mentioned earlier, the base housing 20 includes a threaded fitting (hidden from view) that receives the fitting for the gas supply.","The diffuser housing 30 and spacers/screens 40, 42 are received in the base housing 20.The walls forming the shield 32 extend out from the opening 22 of the base housing 20 (see FIG.","1B).","For the drying systems described in US20110059228 and US20110000427 there is preferably an oven step for removing residual solvent from the stent or scaffold.","In an additional aspect of disclosure, the oven step may be skipped as tests show that the dryer 10 and process as shown and described may remove solvent at a sufficient rate during the process of FIG.","2 to obviate an oven step.","This is desirable as it reduces manufacturing time for the medical device.","Twelve as-coated samples were collected to assess efficiency of the dryer 10 with and without a later oven step.","Those samples were processed using inter pass dry temperature at 50 C. Those samples were divided into two groups—Group A and Group B.","The six group A samples were kept in a tightly sealed vial and in the refrigerator prior to residual solvent testing, and while the six group B samples proceeded with an additional oven dry at 50 C for 30 minutes immediately after the final coating step, then kept in the vial.","The residual acetone data for the two groups are listed in the TABLE 1.The data shows that there is not much different between the average of the residual acetone level between the two groups (between 1 to 2 micrograms).","This is because the actual amount of a residual solvent present in a coated stent can vary within a few micrograms of a measured amount, which is what TABLE 1 shows.","Moreover, in some applications up to 5 μg of residual solvent remaining in the coating is considered acceptable.","Accordingly, the test suggests there may be no need to have an oven bake step when using a dryer constructed in accordance with dryer 10.TABLE 1 residual acetone levels for Groups A vs. Group B (six 12 mm stents) Residual acetone μg/stent (12 mm) Group A Group B 100165795 100165796 Stent # without oven step with Oven step 1 1.17 1.66 2 1.06 1.29 3 1.06 1.48 4 0.88 1.37 5 5.20* (outlier) 1.04 6 1.14 1.04 Average 1.0 (does not include the outlier) or 1.8 1.3 (includes the outlier) A gas flow rate through the heater assembly 2 in FIG.","1 may be monitored/controlled by a commercially available mass flow regulator (not shown).","For example, such a mass flow regulator may be used to operate an adjustable valve coupling the gas supply line 2b to a gas source to produce the desired flow rate.","One example of a suitable mass flow regulator is the Aalborg GFCS series programmable mass flow regulator.","A use of a mass flow regulator and related control system suitable for use with aspects of the disclosure is described in U.S. application Ser.","No.","12/540,302.During a coating process, the dryer is not in use when the stent is being coated.","If the dryer is shut down or the flow rate reduced the temperature of the gas at the entrance to the plenum 10 of the dryer 1 will decrease.","If the stent is moved into position above the nozzle mouth for drying and the valve opened to increase the flow rate, there will be a period of transient flow.","It is desirable to avoid a period of solvent removal by transient gas flow, since the rate or amount of solvent removal by transient flow can be difficult to predict.","It is preferred, therefore, that the stent is dried only during steady state flow conditions.","If gas flow at the dryer is instead maintained at a constant rate, then the temperature may be maintained.","However, this wastes gas resources.","It would be desirable if the gas flow rate could be reduced when the dryer is not in use while holding the gas temperature at a constant value.","To meet this need, a closed loop control is preferably implemented with a stent dryer system according to the disclosure, so that the gas temperature may be maintained at variable flow rates.","Referring to FIG.","9, a schematic of this closed-loop control is illustrated.","A controller 300 continuously receives input temperatures at the entrance of the plenum from a thermocouple 302 and the gas flow rate upstream of the plenum entrance from a flow sensor 304.The controller 300 may be programmed to reduce the gas flow rate when the dryer is not in use, and increase the gas flow rate when the stent is ready to be moved into position above the dryer mouth.","As the flow rate is adjusted by opening/closing the adjustable valve 308, the controller senses a change in temperature from input received at the thermocouple 302, at which point it will increase/decrease the power delivered to the heating coils by affecting control 306 for power so that the temperature remains constant, regardless of the actual flow rate.","Thus, according to this aspect of the disclosure, a dryer system may be operated at variable flow rates during a coating process while maintaining a substantially steady state gas flow during the drying stage, or a minimal period of transient flow conditions until a steady state condition is reached.","This improves/maintains the predictability of solvent removal during drying, minimizes down time and allows gas resources to be conserved.","The coated stent is almost immediately subject to the drying step and dried in a manner that allows the improved prediction of solvent removal.","As discussed earlier, this is a critical step in the process of producing a predictable release rate for a drug-eluting stent and accurate assessment of whether the desired drug-polymer coating weight has been reached.","After, or just prior to completion of an application of coating composition on the stent, the controller 300 increases the gas flow temperature to the drying gas flow rate.","While the gas flow is being increased, the controller 300 monitors the temperature at the plenum entrance 2c by input received from the thermocouple 302 and the power increased to the heating coils as necessary to maintain the temperature of the exiting gas flow.","Once the gas flow has reached the operating flow rate and temperature, the stent is moved into position above the shield 32 and the housing 30 raised.","The stent is rotated.","After drying is complete, the gas flow is again returned to the idle state and the power to the heating coils decreased as necessary to maintain the same gas flow temperature (based on input received from the thermocouple 302) at/near location 2c.","The process repeats until the desired coating weight is obtained.","The above description of illustrated embodiments of the invention, including what is described in the Abstract, is not intended to be exhaustive or to limit the invention to the precise forms disclosed.","While specific embodiments of, and examples for, the invention are described herein for illustrative purposes, various modifications are possible within the scope of the invention, as those skilled in the relevant art will recognize.","These modifications can be made to the invention in light of the above detailed description.","The terms used in claims should not be construed to limit the invention to the specific embodiments disclosed in the specification.","Rather, the scope of the invention is to be determined entirely by claims, which are to be construed in accordance with established doctrines of claim interpretation."]],"string":"[\n [\n \"DRYERS FOR REMOVING SOLVENT FROM A DRUG-ELUTING COATING APPLIED TO MEDICAL DEVICES\",\n \"A coating device for coating a medical device with a drug-eluting material uses an in-process drying station between coats to improve a drug release profile.\",\n \"The drying station includes a dryer having a telescoping plenum which provides a drying chamber for the stent or scaffold to reside while a heated gas is passed over the stent/scaffold.\",\n \"The drying chamber improves efficiency in drying, predictability or drug release rate, uniformity of coating material properties lengthwise over the stent/scaffold and provides a platform that can effectively support stents that are over 40 mm in length.\"\n ],\n [\n \"1-8.\",\n \"(canceled) 9.An apparatus comprising, a dryer including a housing that forms a plenum; the housing comprising: a mouth from which a gas exits from the plenum, a shield having walls surrounding a drying region and the mouth, and an opening to the drying region defined by the shield walls, such that gas exiting from the mouth enters the drying region and exits the drying region through the opening, wherein the shield walls include a notch adapted to receive a mandrel supporting a stent at least partially within the drying region.\",\n \"10-18.\",\n \"(canceled) 19.An apparatus, comprising: a sprayer; a dryer; a linear actuator for moving a stent-supporting mandrel between the dryer and the sprayer; and a rotary actuator for rotating the stent-supporting mandrel during drying and spraying; wherein a plenum of the dryer is configured to expand when the stent-supporting mandrel is aligned with a mouth of the dryer.\",\n \"20.\",\n \"(canceled) 21.The apparatus of claim 19, wherein the dryer includes an actuator mechanism for extending a housing that forms the plenum, and wherein the housing comprises a shield that surrounds the mouth.\",\n \"22.The apparatus of claim 19, further including a controller for controlling a gas supply temperature to the dryer, the controller configured for providing a steady state gas supply and switching between an idle state and an in-use state when the stent is being sprayed and dried, respectively.\",\n \"23.The apparatus of claim 19, wherein the dryer includes means for both aligning the stent-supporting mandrel with the mouth and stabilizing the stent-supporting mandrel while a stent, mounted on the stent-supporting mandrel, is dried using the dryer.\",\n \"24.A combination of a stent supported on a mandrel and the apparatus of claim 9, wherein a first end and a second end of the mandrel is received within the notch comprising respective first and second notches of the shield walls and the stent is disposed within the drying region.\",\n \"25.The apparatus of claim 9, wherein the housing further comprises: a first housing, and a second housing comprising the shield, the second housing being coupled to the first housing and configured to extend from the first housing when the stent is aligned with the shield opening.\",\n \"26.The dryer of claim 9, wherein the dryer is configured such that the plenum has a first size when the stent is in the drying region and a second size when the stent is not in the drying region, the first size being greater than the second size.\",\n \"27.The apparatus of claim 9, wherein the dryer is a telescoping dryer.\",\n \"28.The apparatus of claim 9, further comprising: a gripper, and an actuator mechanism adapted to cause the gripper to grab and release an end of the mandrel when the stent is in the drying region.\",\n \"29.The apparatus of claim 28, wherein the gripper comprises arms having slots and the actuator mechanism is configured for moving the slots so as to form a passage for holding the end of the mandrel.\",\n \"30.The apparatus of claim 28, wherein the actuator mechanism is one or more hydraulic actuators operated as part of a servomechanism controlled by a computer.\",\n \"31.The apparatus of claim 28, wherein the gripper and actuator mechanism are connected to the housing.\",\n \"32.The apparatus of claim 28, wherein the gripper forms a circular passage adapted to hold the end of the mandrel, wherein the circular passage is configured to hold the mandrel within the notch while permitting rotation of the mandrel about a longitudinal axis of the mandrel.\",\n \"33.The apparatus of claim 28, wherein the actuator is configured to form a circular passage with the gripper and the circular passage is configured to align with the notch of the shield.\",\n \"34.The apparatus of claim 9, wherein the housing includes a spacer and a screen disposed within the plenum.\",\n \"35.The apparatus of claim 9, wherein the shield opening is elongate and the notch comprises a first notch and a second notch formed on the shield walls, the notches being located at the opening and configured to receive respective first and second portions of the mandrel therein.\",\n \"36.An apparatus and stent, comprising: a dryer including a housing that forms a plenum; the housing comprising: a mouth from which a gas exits from the plenum, a shield having walls surrounding a drying region and the mouth, and an opening to the drying region defined by the shield walls, such that gas exiting from the mouth enters the drying region and exits the drying region through the opening; wherein the stent is disposed at least partially within the drying region.\",\n \"37.The apparatus of claim 36, wherein the dryer is configured such that the plenum has a first size when the stent is in the drying chamber, and a second size when the stent is not in the drying region, the first size being greater than the second size.\",\n \"38.The apparatus of claim 36, further comprising: a mandrel supporting the stent in the drying region; and a gripper coupled to the housing and located adjacent an end of the mandrel.\",\n \"39.The apparatus of claim 36, wherein a first portion and a second portion of the mandrel are retained in a first notch and a second notch, respectively, of the shield walls and the stent is between the notches.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>The invention proposes an in-process dryer for maximizing in-process drying efficiency and uniformity for improving the product quality (e.g.\",\n \"coating and its drug release consistency).\",\n \"A dryer and associated process according to the invention can also obviate the need for an oven step which has been relied on to remove residual solvent, thereby streamlining the manufacturing process.\",\n \"A dryer nozzle according to the invention has a wider mouth or exit from the plenum than previously proposed stent dryer designs.\",\n \"With this design mean gas velocity at the dryer nozzle is reduced over earlier dryer designs, so that there is less or no influence by the surrounding ambient air and less oscillations of the stent during drying.\",\n \"In a preferred embodiment the dryer is constructed as a telescoping dryer assembly, although other designs are contemplated, e.g., a dryer nozzle that is moved into and out of position as a single unit connected to a flexible gas supply.\",\n \"A shield surrounds the drying region to isolate heated gas from surrounding cooler ambient air.\",\n \"The stent (or scaffold) is disposed within this drying region during the drying step.\",\n \"The dryer nozzle is retractable, which allows clearance for movement of the sent or scaffold between spraying and drying stations.\",\n \"The feature of a retractable dryer nozzle also simplifies drying operations, such as concerns aligning the stent with the mouth or exit.\",\n \"A dryer according to the invention addresses alignment issues and uneven drying seen in prior designs by ensuring full coverage and uniform heat application.\",\n \"In addition, the influence of ambient air in the drying operation is effectively minimized or eliminated.\",\n \"Tests have shown that the temperature within the shielded area of the drying region and just above it is at a constant temperature, indicating that no ambient air is drawn into the drying region.\",\n \"Since the hot air within the drying region is at a slightly higher pressure than the surrounding ambient air, ambient air is prevented from being drawn into the drying region.\",\n \"The dryer nozzle includes internal diffusers, e.g., stacked spacer and screen assemblies, to uniformly mix the heated drying gas, resulting in a temperature uniformity of within 1 degree C. across the stent drying area.\",\n \"Accordingly, an inter-pass dryer, according to the invention, that is used in a stent coating process improves on the art by providing an apparatus and method for forming a drug-eluting coating that offers greater control over the release rate for a drug and less undesired interaction between residual solvent and the drug-polymer matrix in the coating.\",\n \"The term “inter-pass drying” means drying, or removing solvent between one, two, three or more spray passes.\",\n \"The weight of material per coat is in some embodiments are very light, about 5% of the total coating weight according to one embodiment.\",\n \"This means, for this particular embodiment, 20 coats are needed to reach 100% of the coating weight.\",\n \"In view of the foregoing, the invention provides one or more of the following additional improvements over the art.\",\n \"According to one aspect of invention, a method for applying a composition to a stent, comprising the steps of spraying the composition on the stent; and drying the stent, including the steps of moving a shield, surrounding a drying region, over the stent, applying a drying gas to dry the stent, and after drying the stent, moving the shield away from the stent.\",\n \"According to another aspect of invention, a dryer nozzle for drying a stent includes a first housing configured for being connected to a gas supply; a second housing movable within the first housing, the second housing including a drying region in fluid communication with a mouth of the dryer nozzle and configured to receive and support a mandrel, the mouth being located at a base of the drying region, and a diffusion chamber disposed below the mouth.\",\n \"According to another aspect of invention, a stent coating system includes a sprayer; a telescoping dryer nozzle; and a linear actuator for moving a stent-supporting mandrel between the telescoping dryer nozzle and the sprayer.\",\n \"The system may further include a rotary actuator for rotating the stent-supporting mandrel to improve consistency and uniformity of solvent removal.\"\n ],\n [\n \"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to drug-eluting medical devices; more particularly, this invention relates to processes for controlling the interaction among polymer, drug and solvent, and the release rate of a drug for drug eluting medical devices.\",\n \"Background of the Invention Strict pharmacological and good mechanical integrity of a drug eluting medical device are required to assure a controlled drug release.\",\n \"Significant technical challenges exist when developing an effective and versatile coating for a drug eluting medical device, such as a stent.\",\n \"A coating may be applied by a spray coating process.\",\n \"A drug-polymer composition dissolved in a solvent is applied to the surface of a medical device using this method.\",\n \"The amount of drug-polymer to be applied has been expressed as a target coating weight, which corresponds to the weight of the coating after a substantial amount of the solvent is removed.\",\n \"Previous efforts to produce a more consistent and stable drug release profile have been met with challenges.\",\n \"Prior efforts have focused on the type or structure of the polymer carrier for a drug, and the type of solvent used.\",\n \"However, these improvements have not been able to satisfactorily meet the needs for certain clinical applications, or provide a morphology that can be widely used.\",\n \"A “drug release profile”, or “release profile” means the morphology, or characteristics of a drug-eluting matrix that delivers an expected therapeutic behavior after being placed within a body.\",\n \"A drug release profile, or release profile therefore informs one of such things as the predictability of the release rate, variation, if any, in the release rate over time or on a per unit area basis across a drug-eluting surface.\",\n \"It has been previously discovered that a significant improvement in the ability to tailor a drug release profile to suit a particular objective such as producing a specific release rate, uniformity in the release rate over a drug eluting surface, and/or uniformity in a production setting (high throughput) lay in obtaining more precise control over the amount of solvent present, or rate of solvent removal.\",\n \"The criticality of solvent removal, distribution, etc.\",\n \"generally depends on the drug-polymer-solvent formulation and particular objectives.\",\n \"While it was already known that the morphology of a drug-polymer matrix is influenced by the presence of a solvent, it was later discovered that this interaction played a more significant role than previously thought.\",\n \"Based on this conclusion, a more effective process for controlling the amount of solvent-polymer-drug interaction was sought.\",\n \"It was found that the coating weight per spray cycle and manner in which solvent was removed, in connection with the coating thickness was an important consideration.\",\n \"A relatively high coating weight per spray cycle has been sought in the past, because this minimizes process time and increases throughput.\",\n \"Maintaining control over the amount or rate of solvent removal is, however, challenging unless an applied coating layer is relatively thin.\",\n \"If the applied layer is too thick the removal of the solvent becomes more difficult to control or predict.\",\n \"When the solvent is removed from a thick layer, therefore, the potential for undesired interaction among the solvent, polymer and drug, and related problems begin to impair the ability to retain control over the release profile.\",\n \"Process conditions can affect the desired morphology.\",\n \"For example, if there is excess residual solvent, i.e., solvent not removed between or after a spray cycle, the solvent can induce a plasticizing effect, which can significantly alter the release rate.\",\n \"Therefore, it can be critically important to have a process that produces a coating with consistent properties—crystallinity, % solvent residue, % moisture content, etc.\",\n \"If one or more of these parameters are not properly controlled, such that it varies over the thickness or across a surface of a drug-eluting device, then the release profile is affected.\",\n \"One or more of these considerations can be more critical for some drug-polymer-solvent formulations than for other formulations.\",\n \"To facilitate the incorporation of a drug on a stent, spraying a low solid percent polymer/drug solution over the stent followed by removing the solvent has become feasible in controlling the amount of drug (in micrograms range) deposited on the stent and the release profile.\",\n \"A good coating quality benefits from using this spray technique, i.e., properties such as the crystallinity, % solvent residue, and % moisture content are more controllable as the coating weight is built up over several applied coatings.\",\n \"Previous studies of the drying effect on drug release indicated a need for an optimal in-process or inter-pass drying technique to remove a solvent on the coated stent after each spray cycle.\",\n \"This is a critical step in producing more stable products while retaining a high throughput.\",\n \"The properties of a solvent, e.g., surface tension, vapor pressure or boiling point, viscosity, and dielectric constant, used in dissolving a polymer have a dominant effect on the coating quality, coating process throughput, drug stability, and the equipment required to process it.\",\n \"A solvent can, of course, be removed by applying a heated gas over the stent.\",\n \"However, this drying step must be carefully controlled in order to achieve the desired end result.\",\n \"A uniform and efficient heat transfer from the gas to the coating surface must also take place.\",\n \"The evaporation rate of a suitable solvent has an inverse relationship with the coating thickness (generally inversely proportional to the thickness) for a thin film coating.\",\n \"And the resistance increases non-linearly as the coating thickness increases.\",\n \"As alluded to earlier, this non-linearity should be avoided.\",\n \"When the coating thickness is not too high more uniformity and control can be achieved in removing the solvent.\",\n \"As a result, a more consistent drug release profile is obtained because there is the least drug-solvent-polymer interaction, solvent plasticizing and drug extraction rate.\",\n \"It is therefore desired to achieve more control over, not only the uniformity of properties across the coating thickness and along the length of the stent, but also the ability to remove solvent.\",\n \"This is because residual solvent on the drug eluting stent may induce adverse biological responses, compromise coating properties, induce drug degradation, and alter release profile.\",\n \"Thus, it has been determined that a release rate can be better controlled by applying many coats of a low percentage solution, e.g., 5% of the final coating weight, with a drying step between each spray cycle.\",\n \"Thus, in this example 20 coats are needed to produce the target coating weight.\",\n \"In order to make this coating process more feasible as a production-level method, while maintaining control over the solvent and solvent-drug-polymer interaction, as just discussed, an efficient in-process drying step is needed.\",\n \"Effective ways to remove residual solvent in the applied coating becomes more important for coating formulations that are more sensitive to a residual solvent level.\",\n \"As explained above, excessive remaining solvent impacts the coating morphology and property.\",\n \"For example, in the case of a coating formulation used for a polymer scaffold, e.g., PLLA, residual solvent left in the coating can induce phase separation between the drug and polymer because the drug and polymer are not miscible.\",\n \"This can cause variation of the drug release rate and adversely impact the physical properties of the coating.\",\n \"It is therefore desirable to achieve an optimized in-process dry nozzle design to ensure the removal of most of the residual solvent between successive spray cycles.\",\n \"Examples of dryers seeking to achieve this objective are described in US20110059228 and US20110000427.For example, US20110000427 proposes using an external heat nozzle design having a narrow opening producing a drying gas exiting from the dryer plenum at relatively high velocity.\",\n \"This arrangement requires precise alignment between the stent and heat nozzle for uniform drying.\",\n \"The design can introduce extensive and interfering mixing of outside air into the gas stream before contacting the stent or scaffold; this mixing of outside air is uncontrolled and causes variation in the temperature across the drying area.\",\n \"Additionally, the high velocity gas causes the stent to oscillate, which can be problematic for longer-length stents, such as those intended for peripheral vessels.\",\n \"There is a continuing need for obtaining a better control over the drug-eluting product.\",\n \"Specifically, there is a need to develop an inter-pass drying process that is better able to remove solvent to achieve improved rate of release of a drug, uniformity of release rate over the stent length and/or the effectiveness of a drug when released from the coating.\",\n \"It is also desirable to reduce processing time when applying a drug-eluting coating.\",\n \"SUMMARY OF THE INVENTION The invention proposes an in-process dryer for maximizing in-process drying efficiency and uniformity for improving the product quality (e.g.\",\n \"coating and its drug release consistency).\",\n \"A dryer and associated process according to the invention can also obviate the need for an oven step which has been relied on to remove residual solvent, thereby streamlining the manufacturing process.\",\n \"A dryer nozzle according to the invention has a wider mouth or exit from the plenum than previously proposed stent dryer designs.\",\n \"With this design mean gas velocity at the dryer nozzle is reduced over earlier dryer designs, so that there is less or no influence by the surrounding ambient air and less oscillations of the stent during drying.\",\n \"In a preferred embodiment the dryer is constructed as a telescoping dryer assembly, although other designs are contemplated, e.g., a dryer nozzle that is moved into and out of position as a single unit connected to a flexible gas supply.\",\n \"A shield surrounds the drying region to isolate heated gas from surrounding cooler ambient air.\",\n \"The stent (or scaffold) is disposed within this drying region during the drying step.\",\n \"The dryer nozzle is retractable, which allows clearance for movement of the sent or scaffold between spraying and drying stations.\",\n \"The feature of a retractable dryer nozzle also simplifies drying operations, such as concerns aligning the stent with the mouth or exit.\",\n \"A dryer according to the invention addresses alignment issues and uneven drying seen in prior designs by ensuring full coverage and uniform heat application.\",\n \"In addition, the influence of ambient air in the drying operation is effectively minimized or eliminated.\",\n \"Tests have shown that the temperature within the shielded area of the drying region and just above it is at a constant temperature, indicating that no ambient air is drawn into the drying region.\",\n \"Since the hot air within the drying region is at a slightly higher pressure than the surrounding ambient air, ambient air is prevented from being drawn into the drying region.\",\n \"The dryer nozzle includes internal diffusers, e.g., stacked spacer and screen assemblies, to uniformly mix the heated drying gas, resulting in a temperature uniformity of within 1 degree C. across the stent drying area.\",\n \"Accordingly, an inter-pass dryer, according to the invention, that is used in a stent coating process improves on the art by providing an apparatus and method for forming a drug-eluting coating that offers greater control over the release rate for a drug and less undesired interaction between residual solvent and the drug-polymer matrix in the coating.\",\n \"The term “inter-pass drying” means drying, or removing solvent between one, two, three or more spray passes.\",\n \"The weight of material per coat is in some embodiments are very light, about 5% of the total coating weight according to one embodiment.\",\n \"This means, for this particular embodiment, 20 coats are needed to reach 100% of the coating weight.\",\n \"In view of the foregoing, the invention provides one or more of the following additional improvements over the art.\",\n \"According to one aspect of invention, a method for applying a composition to a stent, comprising the steps of spraying the composition on the stent; and drying the stent, including the steps of moving a shield, surrounding a drying region, over the stent, applying a drying gas to dry the stent, and after drying the stent, moving the shield away from the stent.\",\n \"According to another aspect of invention, a dryer nozzle for drying a stent includes a first housing configured for being connected to a gas supply; a second housing movable within the first housing, the second housing including a drying region in fluid communication with a mouth of the dryer nozzle and configured to receive and support a mandrel, the mouth being located at a base of the drying region, and a diffusion chamber disposed below the mouth.\",\n \"According to another aspect of invention, a stent coating system includes a sprayer; a telescoping dryer nozzle; and a linear actuator for moving a stent-supporting mandrel between the telescoping dryer nozzle and the sprayer.\",\n \"The system may further include a rotary actuator for rotating the stent-supporting mandrel to improve consistency and uniformity of solvent removal.\",\n \"INCORPORATION BY REFERENCE All publications and patent applications mentioned in the present specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.\",\n \"To the extent there are any inconsistent usages of words and/or phrases between an incorporated publication or patent and the present specification, these words and/or phrases will have a meaning that is consistent with the manner in which they are used in the present specification.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1A is side view of a dryer assembly in a first, retracted position according to one aspect of the disclosure.\",\n \"FIG.\",\n \"1B is side view of the dryer assembly in a second, expanded position according to another aspect of the disclosure.\",\n \"FIG.\",\n \"2 summarizes a process for coating a stent including a spraying step and in-process drying step using the dryer assembly of FIG.\",\n \"1.FIG.\",\n \"3 is a rear perspective view of the dryer assembly.\",\n \"FIG.\",\n \"4 is a front perspective, exploded assembly view of the dryer assembly showing component parts according to a preferred embodiment.\",\n \"FIG.\",\n \"5 is a perspective view of a base cap of the dryer assembly of FIG.\",\n \"4.FIG.\",\n \"6 is a perspective view of a diffuser housing of the dryer assembly of FIG.\",\n \"4.FIGS.\",\n \"7A and 7B are perspective views of left and right grippers of a mandrel gripper of the dryer assembly of FIG.\",\n \"4.FIG.\",\n \"8 is a perspective view of a base housing of the dryer assembly of FIG.\",\n \"4.FIG.\",\n \"9 is a schematic of a control system that may be used with the dryer assembly to minimize transient flow or wait time and conserve dryer resources while a coating is being applied to a stent.\",\n \"DETAILED DESCRIPTION OF EMBODIMENTS According to a preferred implementation of the invention, a sprayer and dryer nozzle is used to form a drug-eluting coat on a surface of a stent.\",\n \"A stent is an intravascular prosthesis that is delivered and implanted within a patient's vasculature or other bodily cavities and lumens by a balloon catheter for balloon expandable stents and by a catheter with an outer stent restraining sheath for self expanding stents.\",\n \"The structure of a stent is typically composed of scaffolding, substrate, or base material that includes a pattern or network of interconnecting structural elements often referred to in the art as struts or bar arms.\",\n \"A stent typically has a plurality of cylindrical elements having a radial stiffness and struts connecting the cylindrical elements.\",\n \"Lengthwise the stent is supported mostly by only the flexural rigidity of slender-beam-like linking elements, which give the stent longitudinal flexibility.\",\n \"Examples of the structure and surface topology of medical devices such as a stent and catheter are disclosed by U.S. Pat.\",\n \"Nos.\",\n \"4,733,665, 4,800,882, 4,886,062, 5,514,154, 5,569,295, and 5,507,768.As discussed earlier, one aspect of the stent coating process that has been simplified, or improved, as a result of the dryer according to the disclosure, is the ability to predict more consistently the rate of solvent removal and variation of that rate over the length of the stent.\",\n \"Increasing the predictability of a solvent's presence in the applied coating, or remaining when determining a final weight can greatly increase the ability and/or efficiency in which a predictable release rate for a drug can be provided in a medical device, in the form of an applied coating.\",\n \"Moreover, as the design or desired loading of polymer-drug on the stent is determined from the measured weight, it will be readily appreciated that there needs to be an accurate, reliable and repeatable process for being able to determine the amount and distribution of solvent remaining over the length of the stent.\",\n \"This is especially true when less volatile solvents are used, e.g., DMAc as opposed to the more volatile solvent Acetone.\",\n \"Since it is expected that a greater percentage of solvent will remain after drying for solvents having higher boiling points, the coating is more susceptible to variations in a solvent's presence over the stent surface and/or across the coating thickness.\",\n \"Also when drying a polymer Acetone mixture, the rate and uniformity of drying affects the % crystallinity and thus the amount of locked in residual solvent.\",\n \"The disclosure provides examples of spraying/drying components suited for addressing the previously discussed drawbacks and limitations in the art pertaining to a drug-eluting coating applied via a drug-polymer dissolved in a solvent.\",\n \"FIGS.\",\n \"1A-1B show side views of a telescoping dryer 10 (dryer 10) according to one aspect of the disclosure.\",\n \"FIG.\",\n \"2 shows a flow process for applying, via a spray apparatus, a composition, i.e., drug-polymer coating dissolved in a solvent, to a stent including applying one or more coats of the sprayed composition followed by a drying step that may include using dryer 10.Accordingly, the dryer 10 may be included as a component to a stent coating apparatus.\",\n \"Such a stent coating apparatus implementing the process of FIG.\",\n \"2 includes a sprayer, the dryer 10 and actuators for placing the stent between a spraying area or chamber and a drying area for performing a drying step, or solvent removal step, between each of several coatings of composition sprayed onto the stent.\",\n \"Examples of a stent coating apparatus that may adopt principles of the disclosure are described in U.S. patent application Ser.\",\n \"Nos.\",\n \"12/497,133; 12/027,947 and 11/764,006.In these examples, the dryer(s) described therein may instead utilize a dryer according to the disclosure, as will be understood.\",\n \"Referring, briefly, to side views of the dryer 10 as depicted in FIGS.\",\n \"1A-1B, after one or more coatings are applied by a sprayer, the stent (supported on a mandrel 15) is moved into position over the dryer 10, as indicated in FIG.\",\n \"1A.\",\n \"Mandrel grippers 60 then engage a distal end 15a of the mandrel 15 to account for any slight misalignments of the stent position over the dryer exit or mouth and stabilize the stent as it rotates and is impacted by gas exiting from the dryer plenum.\",\n \"A diffuser housing 30 telescopes or deploys from a base housing 20 (using a linear actuator mechanism 50) to place or enclose the stent within a shield 32, as indicated in FIG.\",\n \"1B.\",\n \"After the drying step is complete, the diffuser housing 30 retracts back into the base housing 20, the grippers 60 are released from the mandrel end 15a and the stent moved back to the spraying station to apply the next coating.\",\n \"These steps of a stent coating process are summarized in FIG.\",\n \"2.FIGS.\",\n \"1A and 1B show the stent positioned above the dryer 10.However, the stent may alternatively be located below the dryer 10.In such an arrangement, the shield 32 would be placed above the stent and the drying gas directed downward, rather than placed below the stent and directed upward, respectively, as depicted in these drawings.\",\n \"The stent, supported on the mandrel 15, is rotated by a rotary mechanism (not shown) coupled to the mandrel 15 as the sprayer applies a drug-polymer dissolved in a solvent, e.g., DMAc or Acetone, to the surface of the stent.\",\n \"This rotary mechanism is also used to rotate the stent while it is disposed within the shield 32 to facilitate uniform removal of solvent about the circumference of the stent during drying.\",\n \"A mass of heated gas exits from the mouth of the dryer (at a base of the shield 32) to accelerate the evaporation, or boiling-off of solvent from the coated stent surface.\",\n \"In a preferred embodiment, this sprayer-dryer coating process is repeated until a final coating weight of drug-polymer and remaining solvent is measured.\",\n \"During each drying stage the gas is capable of producing a uniform heat transfer across the surface of stents or scaffolds, even for stents or scaffolds having lengths of 100 mm, 150 mm, and 200 mm.\",\n \"A coating process according to FIG.\",\n \"2 may be preprogrammed, or programmed on the fly to adjust parameters such as number of coats, or passes with the sprayer between drying steps, number of cycles of spraying and drying, etc.\",\n \"These and related parameters may be governed by the polymer-drug or solvent used, type of stent or medical device being coated, e.g., surface geometry.\",\n \"In particular embodiments the protocol for coating a stent may be governed by a predetermined number of coating cycles, i.e., spraying then drying, based on an analytically determined final coating weight, or by intermittent weighing of the stent to determine the number of cycles needed to arrive at the target coating weight.\",\n \"FIGS.\",\n \"3 and 4 show an assembled rear perspective view and exploded front perspective assembly view, respectively, of the dryer 10.A mouth or exit of the dryer 10 is present at the base of the shield 32 and has dimensions the same as an opening of the shield 32; in other words, the walls forming the shield 32 are parallel to each other or the cross-sectional area of the entrance to the drying region surrounded by the shield 32 is the same as the cross-sectional area of the opening through which the stent passes when entering/exiting the drying region.\",\n \"A gas supply is connected to an entrance of the dryer 10 provided by the base housing 20.The drying gas, e.g., heated nitrogen or air, is supplied through a gas supply 2b connected to a heater assembly 2.The heater assembly 2 includes a tubular conduit with heating coils exposed to the gas stream as it travels towards the dryer entrance 9.The coils are connected to a power source via a power connection.\",\n \"A plenum of the dryer 10 is formed by internal volumes of the base housing 20, the diffuser housing 30 and a base cap 70.Perspective views of the base cap 70 and diffuser housing 30 are illustrated in FIGS.\",\n \"5 and 6, respectively.\",\n \"A hole in the dryer base housing 20 (hidden from view) is formed to co-align with a similar shaped hole in the base cap 70 (also hidden from view) to provide a passage for gas into the interior of the base cap 70.The hole or passage for gas through the base housing 20 includes a threading to sealingly engage a complimentary threaded fitting 2c of the heated gas supply.\",\n \"Gas entering through this passage passes directly into the interior of the base cap 70, exits through a hole 72 formed at the top of the base cap 70 then passes up through the diffuser housing 30.The base cap 70 and diffuser housing 30 are contained within the base housing 20 when fully assembled.\",\n \"To account for any thermal energy loss for gas near the walls of the housings 20, 30 one or more mixing regions are provided within the diffuser housing 30 so that the gas entering the drying region surrounded by the shield 32 has a more uniform heat transfer across the length of the stent.\",\n \"Preferably three mixing regions are used for dryer 10.Each mixing region is formed by a diffuser screen 42 and spacer 40.Each screen and spacer are stacked on top of each other, as indicated in FIG.\",\n \"4.From tests it was found that three spacers and screen assemblies were sufficient to cause no more than about a 1 degree Celsius temperature difference within the drying region during a drying step.\",\n \"FIG.\",\n \"4 indicates the order of assembly of the portions forming the plenum of the dryer 10, i.e., diffuser housing 30, base cap 70, base housing 20 and spacers and screens 40, 42.The three spacers and screens 40, 42 are placed inserted within the diffuser housing 30 and may be held in place by pins at the edge 31.The diffuser housing 30 is placed within the dryer base 20 through a bottom edge 24 thereof.\",\n \"The dryer housing 20 and diffuser housing 30 are then placed on the base cap 70 such that a lower edge 24 of the dryer housing 20 rests on a lower flange 76 of the base cap 70.The lower spacer 40a rests on an upper surface 74 of the base cap 70.The base housing 20 is press-fit onto the base cap 70 to provide a fluid-tight seal between the walls of the two structures.\",\n \"This assembled configuration of the dryer 10 is depicted in FIG.\",\n \"1A.\",\n \"As mentioned above, gas travels from the gas supply into the interior of the base cap 70, though the exit hole 72 and then through the diffuser housing 30.When the diffuser housing 30 is lifted up to position the stent within the drying region surrounded by the shield 32 (FIG.\",\n \"1B), the spacer 40a lifts off the surface 74 of the base cap 70.To ensure gas passes directly from the base cap into the diffuser housing 30, a tight but slidable fit is formed between the interior walls of the housing 20 and a lower flange 31 of the diffuser housing 30.In essence, this fit maintains a desired gas pressure within the plenum while the dryer 10 is expanded (or housing 30 lifted) to receive the stent in the drying region, and while allowing the diffuser housing 30 to be moved up and down by the actuator 50 while the housing 20 and base cap 70 remain stationary (FIG.\",\n \"1B).\",\n \"The travel upwards of the diffuser housing 30 within the base housing 20 is limited by the flange 31.After the diffuser housing 30 has traveled a sufficient distance (to place the stent within the drying region) the flange 31 abuts an upper surface of the opening 22 of the diffuser housing 20, thereby preventing further upward movement.\",\n \"To promote the seal between the interior walls of the housings 20, 30, therefore, the edge 31 slides against along the walls of the housing 20 as the diffuser housing 30 is being moved upwards and downwards within the housing 20 by the actuator 50.More generally, the sliding fit between these telescoping parts enables a plenum pressure to be achieved and maintained (no leaks) while the dryer 10 is retracted/shortened and expanded/lengthened.\",\n \"As just alluded to, the aforementioned structure, i.e., housings 20, 30 and base cap 70, and mechanism 50 that form the plenum for the dryer 10 may be thought of as a telescoping dryer.\",\n \"Prior to the stent being positioned over the drying region, the diffuser housing 30 is retracted within the base housing 20 to provide clearance for the stent and mandrel 15 to be linearly displaced from the spray station to a position over the drying region.\",\n \"The dryer plenum is then essentially elongated or expanded to bring the stent into the drying region of the diffuser housing 30.Thus, a “telescoping dryer assembly” is intended to mean an arrangement of housings forming a plenum that slide inward and outward in overlapping fashion in a manner analogous to how a hand telescope slides inward and outward in an overlapping fashion, to thereby provide a variable length channel or internal passage for a pressurized fluid to pass through, i.e., a variable length plenum.\",\n \"Referring to FIGS.\",\n \"3 and 4, the dryer 10 components and actuating mechanisms 55 and 50 are secured to a plate 14, which is connected to a pair of blocks 16 and brackets 12.The actuating mechanism 55 is used to displace left and right grippers 62, 64 towards and away from each other to grip and release, respectively, the distal end 15a of the mandrel 15; this movement being indicated by the left and right arrows G in FIG.\",\n \"3.A detailed view of each gripper 62, 64 is shown in FIGS.\",\n \"7A-7B.\",\n \"The actuating mechanism 50 (e.g., one or more hydraulic actuators, such as air cylinders, operated as part of a servomechanism pre-programmed or controlled by a computer processor to produce the desired movement in the housing 30 in accordance with a drying/spraying process as shown in FIG.\",\n \"2) is used to raise and lower the diffuser housing 30; this movement indicated by the up and down arrows L in FIG.\",\n \"3.A connecting plate 54 has a rim, which is placed over the diffusing housing and secured to a top ledge 34 of the diffuser housing 30, and a flange 54a that is secured to a platform 54b that is movable up and down by a pair of air cylinders 56a, 56b.\",\n \"Thus, the actuator causes the plate 54 to pull up on the housing 30 when the plenum is being extended or lengthened (FIGS.\",\n \"1B and 3), and push down on the housing 30 when the plenum is being retracted or shortened (FIG.\",\n \"1A).\",\n \"FIG.\",\n \"3 shows the dryer 10 configuration with the housing 30 raised to position the stent within the drying region surrounded by the shield 32 and the gripper pair 62, 64 gripping the end 15a of the mandrel 15.This is also the configuration shown in FIG.\",\n \"1B.\",\n \"FIG.\",\n \"5 shows a perspective view of the base cap 70, with the portions identified as previously described.\",\n \"As can be appreciated by comparing the contours of the base cap top surface 74 and the housing 30 (FIG.\",\n \"6), the dryer 10 preferably has an elongate shape with rounded ends, just as the shield 32 is shaped to receive the stent or scaffold.\",\n \"The base cap 70 may be formed to have walls that are thicker than the housings 20, 30 (see FIG.\",\n \"1A) to provide increased insulation capability.\",\n \"Since the gas enters here and is redirected 90 degrees to exit from hole 72, there is a greater heat loss possibility than after the gas exits through hole 72.As such, the walls are made thicker and preferably they are made from PEEK.\",\n \"As described earlier, a last step of the assembly for dryer 10 is to press fit the housing 20 (with diffuser housing 30 inside) onto the base cap 70.This last step essentially seals the dyer 10 and forms the interior space for the dryer plenum.\",\n \"FIG.\",\n \"6 shows a perspective view of the diffuser housing 30, with features of this structure as previously described.\",\n \"The shield 32 is elongate with rounded ends to receive the stent or scaffold therein.\",\n \"The shield 32 provides walls 30b that rise up from the ledge 34, which ledge 34 locates the exit opening from the plenum (the dryer mouth) into the drying region surrounded by the shield 32, thereby also reflecting a depth of the shield 32.Gas flowing near the stent and within the drying chamber 32 may exit from the plenum at a relatively low velocity which favorably limits the amount of regress or interference from ambient air.\",\n \"As mentioned earlier, by providing a shield and gas at a lower exit velocity which maintains its heat when exposed to the stent, there is an alternative to the dryer assemblies described in US20110059228 and US20110000427.The mouth of the dryer is located at the base of the shield.\",\n \"The opening provided for the stent is about the same size as the mouth size (not shown in the drawings).\",\n \"FIGS.\",\n \"7A and 7B show perspective views of grippers 62, 64, respectively.\",\n \"Each has arms 58a, 58b that form holes 57a, 57a at lower ends thereof to secure the grippers 62, 64 to the actuator mechanism 55 (FIG.\",\n \"4) using bolts.\",\n \"At the head of the grippers 62, 64 are semicircular and complimentary slots 63a, 63b that are aligned to capture the distal end 15a of the mandrel 15 within a circular passage formed when the slots 63a, 63b are brought together by the actuator mechanism 55 (e.g., one or more hydraulic actuators, such as air cylinders, operated as part of a servomechanism pre-programmed or controlled by a computer processor to produce the desired movement in the grippers in accordance with a drying/spraying process as shown in FIG.\",\n \"2).\",\n \"V-shaped sections 66, 67, aligned with slots 63a, 63b, function as guiding surfaces to urge the mandrel 15 into the semicircular slots 63a, 63b (see FIGS.\",\n \"1B and 3).\",\n \"As can be appreciated by inspecting the spacing between the V-shaped section 66 and slot 63a of gripper 62, the closer spacing between the V-shaped section 67 and slot 63b of the gripper 64, the dimension G1 in FIGS.\",\n \"7A-7B, and the interlocking manner in which the grippers engage the mandrel, as shown in FIG.\",\n \"3, the V-shaped section 67 is disposed within the space 69 of the gripper 62 when the mandrel end 15a is engaged by the grippers 62, 64.When the stent is moved into position above the shield 32, the grippers 62, 64 come together.\",\n \"Any misalignment of the mandrel end 15a is adjusted by the V-shaped sections engaging the mandrel end 15a and urging it towards alignment with the slots 63a, 63b.\",\n \"When the grippers 62, 64 are moved into contact with each other, the mandrel end 15a is held in place within the circular passage formed by the slots 63a, 63b.\",\n \"This ensures that the stent is being positioned properly within the shield 32 and held in position when the drying gas is passed over the stent.\",\n \"The mandrel end 15a may rotate while it is disposed within the circular passage formed by the slots 63a, 63b.\",\n \"The walls 30b forming the shield 32 include a first notch 36 disposed at one rounded end, and a second notch 38 disposed at a second or opposed rounded end.\",\n \"These notches 36, 38 are used to allow the mandrel that the stent sits on to lower the stent to within the shield 32 during the drying.\",\n \"When the gas exits, even at a low velocity the stent will oscillate since it rotates which presents a varying surface area to the gas exiting (in addition to the non-laminar or transient flow in and around the stent).\",\n \"The problem of oscillations is especially noted for stents that are 40 mm and longer, e.g., stents (or scaffolds) intended for the superficial femoral artery.\",\n \"To meet these needs the dryer 10 includes a support for the mandrel 15 distal end 15 a, i.e., mandrel grippers 60, in addition to the notches 36, 38.With the additional support provided by grippers 60 the stent becomes effectively fixed-supported at the mandrel distal end 15a when disposed over the dryer mouth (exit of the plenum), yet is still capable of being rotated about the mandrel axis by a rotary mechanism coupled to the mandrel.\",\n \"This support may be achieved without interference with drying and prevents contact between the stent/scaffold and the walls 30b or mandrel 15 as the gas passes over the stent/scaffold.\",\n \"The stent is mounted onto the mandrel 15 prior to the start of the stent coating process (FIG.\",\n \"2).\",\n \"The mandrel 15 controls the stent position during drying and spraying.\",\n \"The mandrel 15 generally maintains axial alignment of the stent, and causes the stent to rotate at generally the same rate as the mandrel 15, which has a proximal end that fits into a chuck.\",\n \"The chuck delivers a torque to the mandrel 15.The slots 36 and 38 provide a sufficient clearance to allow the mandrel 15 to rotate.\",\n \"The mated grooves 63a, 63b (FIGS.\",\n \"7A-7B) also provide this clearance for rotation.\",\n \"Some heating gas will escape through the slots 36 and 38.FIG.\",\n \"8 shows a perspective view of the base housing 20, with the portions identified as previously described.\",\n \"As mentioned earlier, the base housing 20 includes a threaded fitting (hidden from view) that receives the fitting for the gas supply.\",\n \"The diffuser housing 30 and spacers/screens 40, 42 are received in the base housing 20.The walls forming the shield 32 extend out from the opening 22 of the base housing 20 (see FIG.\",\n \"1B).\",\n \"For the drying systems described in US20110059228 and US20110000427 there is preferably an oven step for removing residual solvent from the stent or scaffold.\",\n \"In an additional aspect of disclosure, the oven step may be skipped as tests show that the dryer 10 and process as shown and described may remove solvent at a sufficient rate during the process of FIG.\",\n \"2 to obviate an oven step.\",\n \"This is desirable as it reduces manufacturing time for the medical device.\",\n \"Twelve as-coated samples were collected to assess efficiency of the dryer 10 with and without a later oven step.\",\n \"Those samples were processed using inter pass dry temperature at 50 C. Those samples were divided into two groups—Group A and Group B.\",\n \"The six group A samples were kept in a tightly sealed vial and in the refrigerator prior to residual solvent testing, and while the six group B samples proceeded with an additional oven dry at 50 C for 30 minutes immediately after the final coating step, then kept in the vial.\",\n \"The residual acetone data for the two groups are listed in the TABLE 1.The data shows that there is not much different between the average of the residual acetone level between the two groups (between 1 to 2 micrograms).\",\n \"This is because the actual amount of a residual solvent present in a coated stent can vary within a few micrograms of a measured amount, which is what TABLE 1 shows.\",\n \"Moreover, in some applications up to 5 μg of residual solvent remaining in the coating is considered acceptable.\",\n \"Accordingly, the test suggests there may be no need to have an oven bake step when using a dryer constructed in accordance with dryer 10.TABLE 1 residual acetone levels for Groups A vs. Group B (six 12 mm stents) Residual acetone μg/stent (12 mm) Group A Group B 100165795 100165796 Stent # without oven step with Oven step 1 1.17 1.66 2 1.06 1.29 3 1.06 1.48 4 0.88 1.37 5 5.20* (outlier) 1.04 6 1.14 1.04 Average 1.0 (does not include the outlier) or 1.8 1.3 (includes the outlier) A gas flow rate through the heater assembly 2 in FIG.\",\n \"1 may be monitored/controlled by a commercially available mass flow regulator (not shown).\",\n \"For example, such a mass flow regulator may be used to operate an adjustable valve coupling the gas supply line 2b to a gas source to produce the desired flow rate.\",\n \"One example of a suitable mass flow regulator is the Aalborg GFCS series programmable mass flow regulator.\",\n \"A use of a mass flow regulator and related control system suitable for use with aspects of the disclosure is described in U.S. application Ser.\",\n \"No.\",\n \"12/540,302.During a coating process, the dryer is not in use when the stent is being coated.\",\n \"If the dryer is shut down or the flow rate reduced the temperature of the gas at the entrance to the plenum 10 of the dryer 1 will decrease.\",\n \"If the stent is moved into position above the nozzle mouth for drying and the valve opened to increase the flow rate, there will be a period of transient flow.\",\n \"It is desirable to avoid a period of solvent removal by transient gas flow, since the rate or amount of solvent removal by transient flow can be difficult to predict.\",\n \"It is preferred, therefore, that the stent is dried only during steady state flow conditions.\",\n \"If gas flow at the dryer is instead maintained at a constant rate, then the temperature may be maintained.\",\n \"However, this wastes gas resources.\",\n \"It would be desirable if the gas flow rate could be reduced when the dryer is not in use while holding the gas temperature at a constant value.\",\n \"To meet this need, a closed loop control is preferably implemented with a stent dryer system according to the disclosure, so that the gas temperature may be maintained at variable flow rates.\",\n \"Referring to FIG.\",\n \"9, a schematic of this closed-loop control is illustrated.\",\n \"A controller 300 continuously receives input temperatures at the entrance of the plenum from a thermocouple 302 and the gas flow rate upstream of the plenum entrance from a flow sensor 304.The controller 300 may be programmed to reduce the gas flow rate when the dryer is not in use, and increase the gas flow rate when the stent is ready to be moved into position above the dryer mouth.\",\n \"As the flow rate is adjusted by opening/closing the adjustable valve 308, the controller senses a change in temperature from input received at the thermocouple 302, at which point it will increase/decrease the power delivered to the heating coils by affecting control 306 for power so that the temperature remains constant, regardless of the actual flow rate.\",\n \"Thus, according to this aspect of the disclosure, a dryer system may be operated at variable flow rates during a coating process while maintaining a substantially steady state gas flow during the drying stage, or a minimal period of transient flow conditions until a steady state condition is reached.\",\n \"This improves/maintains the predictability of solvent removal during drying, minimizes down time and allows gas resources to be conserved.\",\n \"The coated stent is almost immediately subject to the drying step and dried in a manner that allows the improved prediction of solvent removal.\",\n \"As discussed earlier, this is a critical step in the process of producing a predictable release rate for a drug-eluting stent and accurate assessment of whether the desired drug-polymer coating weight has been reached.\",\n \"After, or just prior to completion of an application of coating composition on the stent, the controller 300 increases the gas flow temperature to the drying gas flow rate.\",\n \"While the gas flow is being increased, the controller 300 monitors the temperature at the plenum entrance 2c by input received from the thermocouple 302 and the power increased to the heating coils as necessary to maintain the temperature of the exiting gas flow.\",\n \"Once the gas flow has reached the operating flow rate and temperature, the stent is moved into position above the shield 32 and the housing 30 raised.\",\n \"The stent is rotated.\",\n \"After drying is complete, the gas flow is again returned to the idle state and the power to the heating coils decreased as necessary to maintain the same gas flow temperature (based on input received from the thermocouple 302) at/near location 2c.\",\n \"The process repeats until the desired coating weight is obtained.\",\n \"The above description of illustrated embodiments of the invention, including what is described in the Abstract, is not intended to be exhaustive or to limit the invention to the precise forms disclosed.\",\n \"While specific embodiments of, and examples for, the invention are described herein for illustrative purposes, various modifications are possible within the scope of the invention, as those skilled in the relevant art will recognize.\",\n \"These modifications can be made to the invention in light of the above detailed description.\",\n \"The terms used in claims should not be construed to limit the invention to the specific embodiments disclosed in the specification.\",\n \"Rather, the scope of the invention is to be determined entirely by claims, which are to be construed in accordance with established doctrines of claim interpretation.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874772"}}},{"rowIdx":4494696,"cells":{"text":{"kind":"list like","value":[["TRANSFORMABLE SPEECH PROCESSOR MODULE FOR A HEARING PROSTHESIS","A method for operating an external component of a cochlear implant hearing system.","The external component includes a speech processor module operable in a stand-alone mode of operation and a body-worn mode of operation, and a protective case.","The method includes operating the speech processor module in the stand-alone mode, determining when the speech processor module is mounted in the case, and operating the speech processor module in the body-worn mode in response to determining that the speech processor module is mounted in the case."],["1.A device, comprising: a speech processor of a hearing prosthesis; and a barrier configured to protect the speech processor from water.","2.The device of claim 1, wherein: the barrier is a protective case; and the speech processor is removably received in the protective case.","3.The device of claim 2, wherein: the case includes an interior compartment in which is located the speech processor; and the case protects against ingress of water into the interior.","4.The device of claim 2, wherein the case includes two sections configured to be moved relative to one another, so that the case can be opened and closed so that the speech processor can be removed and installed therein, and wherein the device is configured such that when the two sections are brought into proximity with one another to protect the sound processor from water, a seal is established between the two sections preventing water from entering the case and reaching the sound processor.","5.The device of claim 2, further comprising: a transcutaneous transfer coil assembly including a transcutaneous transfer coil, a microphone and a cable, wherein, the device is configured to place the microphone and the transcutaneous transfer coil into signal communication with the speech processor via the cable.","6.The device of claim 2, wherein the speech processor is part of a behind the ear (BTE) device; at least a portion a body of the BTE device including the speech processor is removably received in the protective case; and wherein the case establishes a barrier protecting the at least a portion of the body of the BTE device in the case from water.","7.The device of claim 6, wherein: the case includes an interior compartment in which the least a portion of the body of the BTE device is located; and the case protects against ingress of water into the interior.","8.The device of claim 6, wherein: the case is configured to protect against substantially all fluid ingress into the case.","9.The device of claim 6, wherein the case includes two sections configured to be moved relative to one another, so that the case can be opened and closed so that the at least a portion of the body of the BTE device can be removed and installed therein, and wherein the device is configured such that when the two sections are brought into proximity with one another to protect the least a portion of the body of the BTE device from water, a seal is established between the two sections preventing water from entering the case and reaching the sound processor.","10.The device of claim 6, wherein: the case is configured to prevent substantially all fluid ingress at elevated atmospheric pressures.","11.The device of claim 6, further comprising: a transcutaneous transfer coil assembly including a transcutaneous transfer coil, a microphone and a cable, wherein, the device is configured to place the microphone and the transcutaneous transfer coil into signal communication with the speech processor via insertion of a connector at a distal end of the cable into the case.","12.The device of claim 1, further comprising: a transcutaneous transfer coil and a microphone, wherein the transcutaneous transfer coil assembly includes a housing that provides the same protection to the microphone from water as the case does to the sound processor.","13.The device of claim 6, wherein: the case includes a first portion of the case configured to move relative to the second portion of the case to open and close the case to enable installation and removal of the body of the BTE device, wherein the first portion and second portion of the case form an interior in which the speech processor is located protected by water by a seal between the first portion of the case and the second portion of the case.","14-29.","(canceled) 30.A protective case for a behind the ear (BTE) component including a speech processor of a hearing prosthesis, comprising: a base having a hollow portion configured to receive the speech processor; and a lid configured to extend over the hollow portion of the base, wherein the protective case is configured to removably receive the BTE component and protect the BTE component from water.","31.The protective case of claim 30, wherein: the case is configured to retain the BTE component one side of the hollow portion relative to an opposite side of the hollow portion.","32.The protective case of claim 30, wherein: the case is configured to enable a connector of a cable connected to a transcutaneous transfer coil to be inserted into the case to establish communication between the cable and a connector of a speech processor of the BTE component while protecting the BTE component from water such that a hearing percept can be evoked by an implanted component based on speech processed by the speech processor of the BTE component using the transcutaneous transfer coil via communication between the transcutaneous transfer coil and the speech processor while the BTE component is located in the case such that the BTE device is protected from water.","33.The protective case of claim 30, wherein: the case is configured to enable a connector of a cable to mate with the BTE component and the speech processor that is apart thereof while the BTE component is located in the case such that the BTE device is protected from water.","34.The protective case of claim 30, wherein: the case is configured to enable a connector of a cable to directly mate with the BTE component and the speech processor that is apart thereof while the BTE component is located in the case such that the BTE component is protected from water.","35.A device, comprising: the BTE component; and the protective case of claim 30, wherein the BTE component is removably received in the case, and wherein the case protects against substantially all fluid ingress into the case.","36.The protective case of claim 30, wherein: the case is configured to prevent substantially all fluid ingress at elevated atmospheric pressure when the case is closed.","37.The protective case of claim 30, wherein: case is configured to enable the lid to move relative to the base to open and close the case, wherein the base and lid form an interior in which, when the speech processor is removably received therein, is protected from water by a seal between the first portion of the case and the second portion of the case.","38.A method of utilizing an external component of a cochlear implant hearing system, the external component comprising a speech processor module operable in a stand-alone mode of operation and a external device controlled mode of operation; the method comprising: operating the speech processor module in the stand-alone mode; removably mounting the speech processor module in an external device including a case configured to have said speech processor module removably mounted therein and including external device user controls; determining whether or not to utilize an inputted external volume control setting inputted by a user to the external device user controls of the external device to control the speech processor module; and operating the speech processor in the external device controlled mode.","39.The method of claim 38, wherein: the action of determining whether or not to utilize an inputted external volume control setting inputted by a user to the external device user controls of the external device to control the speech processor module includes determining to utilize the inputted external volume control setting inputted by a user to the external device user controls of the external device to control the speech processor module; and the action of operating the speech processor in the external device controlled mode includes operating the speech processor in the external mode after the determination to use the inputted external volume control setting.","40-43.","(canceled) 44.The device of claim 6, wherein: the BTE device is configured to enable the evocation of a first hearing percept when the BTE device is located behind the ear of a recipient away from the protective case and when the BTE device is in signal communication with a transcutaneous transfer coil assembly including a transcutaneous transfer coil which is in signal communication with another coil of an implanted hearing prosthesis implanted in a recipient; and the at least a portion the body of the BTE device including the speech processor is configured to enable the evocation of a second hearing percept when the at least a portion of the BTE device is located in the case when the at least a portion of the BTE device is in signal communication with a transcutaneous transfer coil assembly including a transcutaneous transfer coil which is in signal communication with another coil of an implanted hearing prosthesis implanted in a recipient.","45.The device of claim 6, further comprising: a transcutaneous transfer coil assembly including a transcutaneous transfer coil, a microphone and a cable, wherein the microphone and the transcutaneous transfer coil is in signal communication with the speech processor via the cable, and the device is configured to enable the evocation of a hearing percept when the BTE device is located in the case when the at least a portion of the BTE device is in signal communication with the transcutaneous transfer coil assembly which is in signal communication with another coil of an implanted hearing prosthesis implanted in a recipient.","46.The device of claim 1 wherein: the device is an external component of a hearing prosthesis system in transcutaneous signal communication with an implantable component of the hearing prosthesis system.","47.The device of claim 1 wherein: the device is an external component of a cochlear implant hearing prosthesis system in transcutaneous signal communication with an implantable component of the cochlear implant hearing prosthesis system.","48.The device of claim 1 wherein: the device is an external component of a cochlear implant hearing prosthesis system in transcutaneous signal communication with an implantable component of the cochlear implant hearing prosthesis system.","49.The device of claim 1, wherein: the barrier is a protective case including a base housing and a cover, the cover including a gasket that seals the interior of the case from the exterior of the case; and the speech processor is removably received in the protective case and the gasket seals the case."],["<SOH> BACKGROUND <EOH>"],["<SOH> SUMMARY <EOH>In one aspect of the invention, a method for operating an external component of a cochlear implant hearing system is disclosed.","The external component comprises a speech processor module is operable in a stand-alone mode of operation and a body-worn mode of operation, and a protective case.","The method comprises operating the speech processor module in the stand-alone mode, determining when the speech processor module is mounted in the case, and operating the speech processor module in the body-worn mode in response to determining that the speech processor module is mounted in the case.","In another aspect of the invention, a method for operating a cochlear implant hearing system is disclosed.","The method comprises operating, in a stand-alone mode of operation, a speech processor module having processing circuitry disposed in a housing, determining, via an operational mode controller, when the speech processor module is mounted in a protective case, and operating the speech processor module in a body-worn mode of operation in response to determining that the speech processor module is mounted in the case."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation application of U.S. application Ser.","No.","13/729,485 filed Dec. 28, 2012, which is a continuation application of U.S. application Ser.","No.","12/703,160 filed Mar.","18, 2012, now U.S. Pat.","No.","8,352,037, which is a divisional of U.S. application Ser.","No.","10/586,524, filed Oct. 23, 2006, which is a National Stage application of International Application No.","PCT/US04/43288, filed Dec. 27, 2004, and which claims the benefit of Australian Provisional Patent Application No.","2003907138, filed Dec. 24, 2003.The content of these applications is hereby incorporated by reference herein.","BACKGROUND Field of the Invention The present invention relates to a hearing prosthesis and, more particularly, a transformable speech processor module for a hearing prosthesis.","Related Art The use of medical devices to provide therapy to individuals for various medical conditions has become more widespread as the advantages and benefits of such devices become more widely appreciated and accepted throughout the population.","In particular, devices such as implantable pacemakers, defibrillators, functional electrical stimulation devices such as hearing prostheses, organ assist or replacement devices, and other medical devices, have been successful in performing life saving and/or lifestyle enhancement functions for a number of individuals.","Many such medical devices often include one or more sensors, processors, controllers or other functional electrical components that are permanently or temporarily implanted in a patient.","Many such implantable devices require the transcutaneous transfer of power and/or information with external components that are part of, or operate in conjunction with, the implanted components of the medical device.","Such external components are typically removably attached to the body of the patient.","One such type of medical device is a cochlear implant system, also commonly referred to as a cochlear prosthesis.","Cochlear implant systems provide the benefit of hear to individuals suffering from severe to profound hearing loss.","Hearing loss in such individuals is due to the absence or destruction of the hair cells in the cochlea which transduce acoustic signals into nerve impulses.","Cochlear implants essentially simulate the cochlear hair cells by directly delivering electrical stimulation to the auditory nerve fibers.","This causes the brain to perceive a hearing sensation resembling the natural hearing sensation normally delivered to the auditory nerve.","Conventional cochlear implant systems primarily include an external assembly directly or indirectly attached to the body of the patient (referred to herein as the recipient), and an internal assembly which is implanted in the patient.","The external assembly typically comprises one or more microphones for detecting sound, a speech processing unit that converts detected sound, particularly speech, into an electrical coded signal, a power source, and an external transcutaneous transfer coil.","The internal assembly typically comprises an internal transcutaneous transfer coil, a stimulator unit located within a recess of the temporal bone of the recipient, and an electrode array positioned in the recipient's cochlear.","Collectively, the external coil and the internal coil form an inductively-coupled transcutaneous transfer system.","The transfer of energy via this system is controlled to effect the transmission of the electrical coded signals, referred to herein as stimulation signals, and power signals from the external speech processing unit to the implanted stimulator unit.","Similarly, the transcutaneous transfer system may be used to effect the transmission of telemetry data from the implanted stimulator unit to the exterior speech processing unit.","Conventionally, the communications link has been in the form of a radio frequency (RF) link, although other such links have been proposed and implemented.","Once a stimulation signal has been transmitted to the implanted transcutaneous transfer coil, it is provided to the implanted stimulator unit which processes the signal and outputs one or more signals to the intra-cochlear electrode assembly which applies the electrical stimulation directly to the auditory nerve of the recipient.","The speech processor unit has traditionally been worn on the body, such as by being attached to clothing, or by being supported on the ear of the recipient.","This latter configuration is commonly referred to as a BTE (behind the ear) configuration.","The speech processor unit is relatively expensive and susceptible to damage, especially in the hands of infants or small children, or when used in an unsuitable environment.","SUMMARY In one aspect of the invention, a method for operating an external component of a cochlear implant hearing system is disclosed.","The external component comprises a speech processor module is operable in a stand-alone mode of operation and a body-worn mode of operation, and a protective case.","The method comprises operating the speech processor module in the stand-alone mode, determining when the speech processor module is mounted in the case, and operating the speech processor module in the body-worn mode in response to determining that the speech processor module is mounted in the case.","In another aspect of the invention, a method for operating a cochlear implant hearing system is disclosed.","The method comprises operating, in a stand-alone mode of operation, a speech processor module having processing circuitry disposed in a housing, determining, via an operational mode controller, when the speech processor module is mounted in a protective case, and operating the speech processor module in a body-worn mode of operation in response to determining that the speech processor module is mounted in the case.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1A is a perspective view of one embodiment of a hearing prosthesis in which embodiments of the present invention may be advantageously implemented; FIG.","1B is a perspective view of one embodiment of a dual mode speech processing unit in accordance with one embodiment of the present invention; FIG.","2 is a perspective view of an external component system of a hearing prosthesis according to one embodiment of the present invention suitable for use with the speech processing unit illustrated in FIG.","1B; FIG.","3 is an exploded perspective view of the embodiment of illustrated in FIG.","2; FIG.","4 is an interface diagram of one embodiment of the speech processor module illustrated in FIG.","1B; FIG.","5 is a functional block of one embodiment of an aspect of the present invention; FIG.","6A is a schematic diagram of the relevant signal and electrical interfaces when the speech processor module shown in FIG.","1B is implemented in a stand-alone operational mode; and FIG.","6B is a schematic of the relevant signal and electrical interfaces when the speech processor module shown in FIG.","1B is implemented in a body-worn operational mode.","DETAILED DESCRIPTION Embodiments of the present invention are directed to a speech processor module which may be implemented in more than one mode of operation of a hearing prosthesis.","Specifically, certain embodiments of the present invention are directed to a speech processor module that can be implemented as a component of in a behind-the-ear (BTE) speech processing unit, and as a component of a body-worn speech processing unit.","The present invention is also directed to an external component system for a hearing prosthesis that enables the dual-mode speech processor module to be worn on the body of a recipient rather than behind the recipient's ear.","Advantageously, certain embodiments of certain aspects of the present invention can be implemented such that the dual-mode speech processor module is protected from adverse environmental conditions, including certain recipients.","For example, in some embodiments described herein, the external component system includes a protective case which protects the speech processor module from infants, small children, mentally handicapped, etc., and/or allows the use of the speech processor module in environments traditionally considered to be unsuitable for prosthetic hearing devices.","As a result, embodiments of the present invention enable hearing prostheses to be worn by a wide range of recipients in a wide range of environments.","Embodiments of the present invention are described below in connection with one embodiment of an exemplary hearing prosthesis, a cochlear prosthesis (also referred to as a cochlear implant system, cochlear prosthetic device and the like; “cochlear implant system” herein).","Cochlear implant systems use direct electrical stimulation of auditory nerve cells to bypass absent or defective hair cells that normally transducer acoustic vibrations into neural activity.","Such devices generally use multi-contact electrodes inserted into the scala tympani of the cochlea so that the electrodes may differentially activate auditory neurons that normally encode differential pitches of sound.","Such devices are also used to treat a smaller number of patients with bilateral degeneration of the auditory nerve.","For such patients, a cochlear implant system provides stimulation of the cochlear nucleus in the brainstem.","FIG.","1A is a schematic diagram of an exemplary cochlear implant system 100 in which embodiments of the present invention may advantageously be implemented.","Cochlear implant system 100 comprises external component assembly 142 which is directly or indirectly attached to the recipient, and an internal component assembly 144 which is temporarily or permanently implanted in the recipient.","External component assembly 142 typically comprises a microphone 120 for detecting sound, a speech processing unit 116, a power source (not shown), and an external transmitter unit 106.External transmitter unit 106 comprises an external coil 108, and preferably, an alignment magnet 110 secured directly or indirectly to external coil 108.Speech processing unit 116 processes the output of microphone 120 that are positioned, in the depicted example, by the ear 122 of the recipient.","Speech processing unit 116 generates coded signals, referred to herein as a stimulation data signals, which are provided to external transmitter unit 106 via cable 118.Internal components 144 comprise an internal receiver unit 112, a stimulator unit 126, and an electrode array 134.Internal receiver unit 112 comprises an internal transcutaneous transfer coil 124, and preferably, an alignment magnet 140 fixed relative to internal coil 124.Internal receiver unit 112 and stimulator unit 126 are hermetically sealed within a housing 128.Internal coil 124 receives power and data from external coil 108.A cable 130 extends from stimulator unit 126 to cochlea 132 and terminates in electrode array 134.Signals generated by stimulator unit 126 are applied by array 134 to the basilar membrane 136, thereby stimulating the auditory nerve 138.Collectively, external coil 108 and internal coil 124 form an inductively-coupled coil system of a transcutaneous transfer apparatus 102.In one embodiment, external coil 108 transmits and receives electrical signals to/from internal coil 124 via a radio frequency (RF) link 114.In use, implantable receiver unit 112 may be positioned in a recess of the temporal bone adjacent ear 122 of the recipient.","As noted, embodiments of the present invention are directed to a speech processor module which may be implemented in more than one mode of operation in a hearing prosthesis such as cochlear implant system 100.FIG.","1B is a perspective view of one embodiment of a dual-mode speech processor module of the present invention.","In this embodiment, the dual-mode speech processor module of the present invention is configured to be used in a behind-the-ear (BTE) speech processing unit 178, similar to speech processing unit 116 illustrated in FIG.","1A.","Behind the ear (BTE) speech processing unit 178 comprises a speech processor module 180 that contains signal processing circuitry (not shown).","A detachable ear hook 182 is provided at one end of speech processor module 180 so as to allow the speech processor to be supported behind the outer car of the recipient of the cochlear implant system.","A detachable power supply 184 comprising a rechargeable battery or other power source (not shown) is attached to speech processor module 180 to provide power to the module.","Speech processor module 180 utilizes a built-in microphone 186 that generates signals to the signal processing circuitry housed within the speech processor module.","Built-in microphone 186 is also referred to as internal microphone 186 herein.","Speech processor module 180 includes a headpiece connector 188 and an accessories connector 190 to connect to other components of the implementing cochlear implant system or other hearing prosthesis.","In operation, cables with an appropriately configured connector extends from speech processing module 180 to a headpiece and, possible, an accessory device, as described in detail below.","Speech processing unit 178 is configured to operate in a stand-alone manner; that is, as a behind-the-ear (BTE) speech processing unit.","However, speech processing unit 178 is susceptible to damage from rough handling, such as might be experienced when used by infants or small children.","It also may not be suitable for use in adverse environments, such as environments having airborne particulates or significant moisture.","To operate under such conditions, speech processor module 180 can operate in a body-worn mode of operation in an external component system.","One embodiment of an external component system 200 of a hearing prosthesis according to the present invention is depicted in FIGS.","2 and 3.External component system 200 operationally replaces external component assembly 142 of cochlear implant system 100 illustrated in FIG.","1A to convert the cochlear implant system from a prosthesis which may be readily damaged by the recipient and/or environment, to one which is more robust or rugged and, therefore, suitable for use by infants, children, mentally handicapped and other recipients, and/or worn by any recipient in one or more adverse environmental conditions.","In certain embodiments, external component system 200 provides protection for speech processor module 180.In the embodiment shown in FIG.","2, for example, a protective case 202 is included in external component system 200 to house speech processor module 180 and an on-board power supply 216.In certain embodiments, such protection includes protecting these components from ingress of fluid such as water.","In one embodiment, for example, protective case 202 is fluid resistant.","In another embodiment, protective case 202 prevents substantially all fluid ingress, even at elevated atmospheric pressure.","Similarly, in certain embodiments, protective case 202 is at least resistant to the ingress of dust or other particulates such as airborne fumes.","In other embodiments, protective case 202 is capable of providing protection against shocks and vibration, electromagnetic interference (EMI) and other environmental conditions which may adversely affect the operational performance, integrity, and/or lifespan of speech processor module 180.External component system 200 also comprises a one-piece headpiece 208 communicably coupled to speech processor module 180 via a cable 210.As will be described in greater detail below, headpiece 208 comprises the above-noted external transmitter unit 106 including external coil 108, and alignment magnet 110 mounted in a protective housing 220 that provides the same or similar protection of its components as protective case 202.Protective case 202 comprises a base member 204 and a cover member 206 which mechanically mate with each other to form a protective enclosure in which speech processor module 180 is secured.","Protective case 202 also comprises a tray 324 on which speech processor module 180 is removably mounted.","In addition, tray 324 is configured to have on-board power supply 216 mounted adjacent to speech processor module 180 to provide power to the speech processor module as described herein.","These and other components of protective case 202 are described in further detail below.","Referring again to FIG.","1B, speech processor module 180 is configured to be connected to a detachable power supply 184 when implemented in a stand-alone mode; here, as part of a behind the ear speech processing unit 178.When the recipient or their carer wishes speech processor module 180 to be protected by case 202, ear hook 182 and power supply 184 are detached from speech processor module 180, and the speech processor module is mounted on tray 324 of protective case 202.On-board power supply 216 is also mounted on tray 324.Cover member 206 is then secured to base member 204 to provide a sealed enclosure in which speech processor module 180 and on-board power supply 216 are protected.","The resulting external component system 200 is then used in place of the external component assembly 142 illustrated in FIG.","1A.","Protective case 202 is secured to the recipient using, for example, strap(s) threaded through brackets 218.As noted, in one embodiment, an on-board power supply 216 is included in protective case 202 to provide power to speech processor module 180 when the speech processor module is installed in protective case 202.Power supply 216 may be any suitable power supply now or later developed including but not limited to rechargeable batteries.","In one embodiment, on-board power supply 216 implements batteries which are conventional, commercially-available batteries, making them significantly less expensive than detachable power supply 184.Appropriate electrical connections are provided to transfer power from on-board power supply 216 to speech processor module 180.Referring to FIG.","3, speech processor module 180 has one or more connector pins 322 for connecting speech processor module 180 to detachable power supply 184 when implementing the stand-alone operational mode.","It should be appreciated that detachable power supply 184 has a connector (not shown) constructed and arranged to mate with the appropriate pin(s) 322 of speech processor module 180 to transfer power.","As shown in FIGS.","2 and 3, when speech processor module 180 is installed in protective case 202, on-board power supply 216 may not directly contact speech processor module 180.As a result, a connector similar to that implemented in detachable power supply 184 is not used in such embodiments to directly connect on-board power supply 216 to speech processor module 180.Rather, in the illustrative embodiment, a bridge connection is provided in protective case 202 to connect the appropriate pin(s) 322 of speech processor module 180 to terminals 328 of on-board power supply 216.In one embodiment, tray 324 provides the means to electrically connect on-board power supply 216 and speech processor module 180.Tray 324 also comprises apparatus to removably secure an installed power supply 216 and speech processor module 180 to prevent damage to themselves or the other components housed in protective case 202.In the embodiment shown in FIGS.","2 and 3, on-board power supply 216 is retained between a pair of vertical posts 326.Tray 324 also includes appropriately arranged contacts to electrically mate with terminals 328 on power supply 216 when the power supply is mounted on tray 324.In the embodiment shown, power supply 216 has terminals 328 disposed along a corner of the power supply.","Accordingly, tray 324 comprises contacts disposed at the junction of vertical columns 326 and the top surface of tray 324.It should be apparent to those of ordinary skill in the art that the contacts provided in tray 324 to electrically mate with terminals 328 of on-board power supply 216 may be located at any appropriate location and be configured in any way which will achieve a desired electrical connection.","As one of ordinary skill in the art would appreciate, the manner in which on-board power supply 216 is removably mounted on tray 324 can vary depending on a variety of factors including but not limited to the anticipated environment to which external component 200 and, in particular, protective case 202, will be exposed, the weight and mass of power supply 216, the weight distribution of the power supply, etc.","As noted, speech processor module 180 is removably mounted on tray 324.In the embodiment shown in FIG.","3 speech processor module 180 is shown detached from power supply 184 and ear hook 182, exposing pins 322 and raised guide surface 330.Raised guide surface 330 is received by a complementary channel in detachable power supply 184 to cause the power supply to properly mate with pins 322 when the power supply is attached to speech processor module 180.Tray 324 comprises a connector block 332 having in one embodiment, a mechanical and electrical interface similar to that of detachable power supply 184.That is, connector block 332 comprises a connector (not shown) constructed and arranged to mate with pins 322 when speech processor 180 is mounted on tray 324.In addition, connector block 332 has an integrated channel 320 configured to slidingly receive raised guide surface 330 of speech processor module 180.To mount speech processor module 180 on tray 324, the speech processor module is positioned such that raised guide surface 330 is aligned with an open end of channel 320.As speech processor module 180 is slid into position, channel 320 and raised guide surface 330 cooperate to facilitate the mating of speech processor module 180 and the connector of connector block 332.In addition, raised guide surface 330 and channel 320 cooperate to securely retain speech processor module 180 to tray 324 when the speech processor module is mounted in protective case 202.It should be appreciated, however, that additional or alternative means may be employed to removably secure speech processor module 180 to tray 324.Embodiments of tray 324 may also include other components to facilitate the removable mounting of speech processor 180.For example, in the embodiment illustrated in FIG.","3, a brace 318 which is curved to abut or be adjacent with a curved surface of speech processor module 180 is provided.","In alternative embodiments, speech processor 180 is securely retained in protective case 324 using other techniques now or later developed.","When speech processor module 180 and on-board power supply 216 are mounted on tray 324, they are electrically connected to each other.","In the embodiment shown in FIGS.","2 and 3, for example, such electrical connection is provided by tray 324 so that additional components need not be included in protective case 202, and additional steps beyond mounting speech processor 180 and power supply 216 are not necessary to attain an electrical connection.","Specifically, wiring connects the power supply contacts (not shown) on tray 324 and the connector (not shown) on connector block 332 which mates with speech processor module 180.Such wiring may be integrated, for example, into platform 336 of tray 324, or may extend below platform 336.In the latter embodiment, tray 324 preferably does not rest in the bottom surface of base member 204; rather, it rests on support members to provide a space between platform 336 and base member 204 when tray 324 is secured to the base member.","As one of ordinary skill in the art would appreciate, the type of electrical connection provided can vary depending on the particular application.","For example, the pins and sockets used to establish the battery connection can be replaced with any other type of electrical connectors.","Also, one pin 322 can provide both the positive and ground connections for transferring power to speech processor module 180.As noted, base member 204 and cover member 206 are attached to each other to provide a protective enclosure for speech processor module 180 and on-board power supply 216.Cover member 206 and base member 204 are configured also to provide the recipient or carer access the enclosure to install or remove speech processor module 180 and power supply 216.In the embodiment shown in FIGS.","2 and 3, for example, cover member 206 is removable; that is, cover member 206 and base member 204 separate from each other to expose the interior of base member 204.It should be appreciated, however, that a portion or all of cover member 206 may be configured, for example, to rotate away from base member 204 to create an aperture through which speech processor module 180 and on-board power supply 216 can be passed.","Such rotation can be provided, for example, with mechanical hinges.","There are, of course, a myriad of other arrangements that may be implemented to provide the noted access.","For example, one or more rotating, sliding, removable, or other types of doors, panels, sides, etc., may be implemented in either or both, cover member 206 and base member 204.Cover member 206 and base member 204 may be formed of any material or combination of materials suitable for the intended recipient and environment.","For example, cover and base members 206, 204 may be formed of metallic material, ceramic material, polymeric material, composites or any combination thereof.","In addition, cover and base members 206, 204 may be opaque, translucent, transparent, etc., to provide a desired view of a desired portion of the interior of protective case 202 from the recipient, carer or third party.","In the exemplary embodiment shown in FIG.","3, protective case 202 contains a gasket 302 to seal protective case 202 when cover member 206 is joined with base member 204.As noted, embodiments of protective case 202 protect components mounted therein from a variety of environmental elements such as fluids, dust, etc.","Gasket 302 is appropriately configured and formed of the appropriate material to provide the desired degree of protection from at least the environmental elements of concern.","In the embodiment shown in FIGS.","2 and 3, gasket 302 is shaped to be disposed between the mating surfaces of cover member 206 and base member 204 when the cover and base are brought together to form protective case 202.Accordingly, gasket 302 takes the shape of the perimeter of protective case 202 at the location that the cover and base members meet.","In one particular embodiment, gasket 302 provides additional protection.","As shown in FIGS.","2 and 3, gasket 302 includes a contiguous sheath 334 of fluid-impermeable, resiliently flexible material extending across the interior of the gasket.","When installed in protective case 202, this embodiment of gasket 302 seals with the perimeter wall of base member 204.This causes sheath 334 to cover speech processor module 180 and power supply 216 mounted in base member 204.Thus, in addition to preventing ingress of at least selected environmental elements, gasket 302 and sheath 334 also protect components from those environmental elements which manage to penetrate protective casing 202.Sheath 334 can be manufactured from polymeric, elastomeric or other suitable materials.","In one embodiment, sheath 334 is transparent.","Protective case 202 comprises a fixation device to removably secure cover member 206 to base member 204.In the embodiment illustrated in FIGS.","2 and 3, such a fixation device comprises a combination of an appropriately located screw and threaded hole.","Specifically, sheath 334 has an orifice 304 formed therein that is adapted to allow passage of a threaded shaft of fixation screw 214 through sheath 334.Similarly, cover member 206 has an orifice 308 adapted to allow passage of the threaded shaft of screw 214.When cover member 206 and sheath 334 are assembled with based member 204, orifice 308 and orifice 304 are aligned with each other.","Screw 214 may then pass through orifice 308 in cover member 206, and orifice 304 in sheath 334 to threadingly engage a threaded hole 310 of a post 312 on tray 324.It should be appreciated by those of ordinary skill in the art that the implemented fixation device should not degrade the integrity of the protective features implemented in protective case 202.For example, in the above embodiment in which a fixation screw 214 is implemented, at the location of screw 214, an elastomeric grommet 314 is provided to help prevent ingress of fluid into the protective case at the site of screw 214.Additionally washers, o-rings and the like may also be used as appropriate.","External component system 200 also comprises a one-piece headpiece 208 communicably coupled to speech processor module 180 via a cable 210.As noted, headpiece 208 comprises the above-noted external transmitter unit 106 including external coil 108, and magnet 110 mounted in a housing 220 that provides the same or similar protection of its components as protective case 202.In accordance with one embodiment of the present invention, headpiece 208 also comprises a second microphone 212 mounted thereon which is operable when speech processor module 180 is installed in protective case 202.When speech processor module 180 is installed in protective case 202, microphone 186 cannot be used since it will be enclosed with protective case 202.As such, external component system 200 provides an alternate or replacement microphone 212, referred to as external microphone 212.Protective case 202 has an additional orifice (not shown) provided in base member 204 to permit cable 210 to be inserted into the case.","Cable 210 extends from headpiece 208 into case 202 to mate with connector 188 of speech processor module 180.The orifice may be sealed, for example, by a grommet 316 provided around the distal end of cable 210.For example, in one embodiment, grommet 316 and orifice are constructed and arranged to prevent water from entering protective case 202.As noted, protective case 202 provides protection for speech processor module 180 and on-board power supply 216.In the embodiments described above, such protection includes protecting the components from ingress of fluid, dust or other particulates such as airborne fumes.","In other embodiments, protective case 202 is capable of providing protection against electromagnetic interference (EMI).","In such embodiments, the interior surfaces of cover member 206 and base member 204 are coated with a conformal EMI coating such as that used in cellular phones, computer systems and other electronic devices that emit or are sensitive to electromagnetic radiation.","In addition, in such embodiments gasket 302 is an EMI gasket suitable for preventing EMI from escaping through the joined surfaces of cover member 206 and base member 204.In other embodiments, protective case 202 protects the components mounted therein from vibration and/or shock.","In such embodiments, tray 324 may be suspended on a shock- and vibration-absorbing material or elements such as resilient posts or extensions disposed in or integrated with base member 204.In addition, the dimensions of tray 324 may be somewhat less than the interior dimensions of protective case 202 to reduce the likelihood of shocks to tray 324 and the components mounted thereon.","FIG.","4 is a schematic interface diagram of one embodiment of speech processor module 180 illustrated in FIGS.","2 and 3.In the embodiment shown in FIG.","4, speech processor module 180 comprises four (4) interfaces, a headpiece interface 402, an accessories interface 404, a power supply interface 406, and a clinical/diagnostic interface 408.Each of the interfaces 402-408 is supported by one or more connectors as described above with references to FIGS.","2 and 3.It should be appreciated by those of ordinary skill in the art, however, that interfaces 402-408 may be implemented in one or more connectors configured differently than that described herein.","Headpiece interface 402 comprises a microphone signal line 410, an RF/telemetry signal line 411, a voltage signal line 412 and a ground signal line 414.In the embodiment shown in FIGS.","2 and 3, these signal lines are included in cable 210 connecting headpiece 208 and speech processor module 180 via connector 188.Accessories interface 404 comprises an input audio signal line 418, an auxiliary voltage input signal line 420, an output audio signal line 422 and a ground signal line 424.These signal lines are transmitted between an accessory device (not shown) and accessories connector 190 of speech processor module 180.Power supply interface 406 comprises a power supply identifier (ID) signal line 426, a voltage signal line 428, and a ground signal line 430.These signal lines are transmitted between one or more pins 322 of speech processor module 180 and either power supply 184 or power supply 216.Clinical/diagnostic interface 408 comprises an alarm signal line 432, data in and out signal lines 434, 436, and a ground signal line 438.These signal lines are transmitted between one or more pins 322 of speech processor module 180 and a diagnostic device or display (not shown).","It should be appreciated that in the embodiment of external component system 200 illustrated in FIGS.","2 and 3, the apertures in protective case 202 which provide access by cables that connect to accessory connector 190 (providing accessory interface 404), and pin(s) 322 (providing clinical interface 408) are not shown.","Such apertures, however, are the same or similar to those described above.","In an alternative embodiment, such interfaces are available only when speech processor module 180 implements the stand-alone mode of operation.","FIG.","5 is a functional block diagram of these components of the present invention which enable speech processor module 180 to transition between stand-alone and a body-worn operational modes.","In FIG.","5 an operational mode controller 500 is implemented in speech processor module 180 to determine which operational mode speech processor module 180 is to implement, and to select the appropriate internal inputs and outputs (that is, provided as part of speech processor module 180) and external inputs and outputs (that is, provided as part of external component system 200) to enable speech processor module 180 to function in the desired operational mode.","FIGS.","6A and 6B are schematic diagrams showing a portion of the interfaces utilized by one embodiment of speech processor module 180 when implemented in both modes of operation.","In FIG.","6A, speech processor module 180 has ear hook 182 and power supply 184 attached to facilitate, in this embodiment, use as a stand-alone behind-the-ear (BTE) speech processing unit 178.Detachable power supply 184 is shown schematically, and contains a rechargeable battery 606 and an identifier resistor 604.Detachable power supply 184 is connected to speech processor module 180 via power supply interface 406.External coil 208, also shown schematically, is connected to speech processor module 180 via headpiece interface 402.It should be appreciated, however, that when in the BTE operating mode, speech processor module 180 does not utilize external microphone 212, and external transmitter unit 106 (FIG.","1A) may be used with speech processor module 180 rather than exterior component system 200.In FIG.","6B, speech processor module 180 is not attached to ear hook 182 and power supply 184.Rather, it is coupled to on-board power supply 216 and an alarm system 524.As will be described in detail below, speech processor module 180 may be connected to a variety of external components implemented in protective case 202 or other components of external component system 200 depending on the implemented functionality.","The embodiment shown in FIG.","6B is just one exemplary implementation.","In addition, external coil 208, also shown schematically, is connected to speech processor module 180 via headpiece interface 402 in the arrangement shown in FIG.","6B.","Returning to FIG.","5, in accordance with one embodiment of the present invention, operation mode controller 500 comprises an operational mode selector 502 that determines which operational mode speech processor module 180 is to implement.","As noted, in the exemplary embodiment described herein, speech processor module 180 may be implemented in a stand-alone mode as illustrated in FIG.","1B, or a body-worn mode of operation as illustrated in FIGS.","2 and 3.Operational mode selector 502 makes the noted determination based on settings or conditions sensed or received by either an external operational mode sensor 504 implemented in protective case 202, or an internal operational mode sensor 506 implemented in speech processor module 180.In one embodiment, the operational mode of speech processor module 180 is determined based on the identification of the power supply that is connected to the speech processor module.","In such an embodiment, each power supply which may be utilized in connection with speech processor module 180 includes some identifying feature.","Information regarding the identifying feature is communicated to speech processor module 180 via power supply identification (ID) signal line 426.In such embodiments, an internal operational mode sensor 506 is implemented to detect the particular identifying feature.","For example, in the embodiment illustrated in FIGS.","6A and 6B, the identifying feature is the value of a resistor included in each power supply.","Referring to FIG.","6A, detachable power supply 184 comprises a resistor 604 and, in this example, a rechargeable battery 606.Resistor 604 identifies power supply 184 as a type of detachable power supply suitable for use when speech processor module 180 implements the stand-alone mode of operation.","Referring to FIG.","6B, on-board power supply 216 comprises a resistor 654 and, in this example, a rechargeable battery 656.Resistor 654 identifies power supply 216 as a type of on-board power supply suitable for use when speech processor module 180 implements the body-worn mode of operation.","In such embodiments, internal operational mode sensor 506 measures the resistance between ID signal line 426 and ground signal line 430 to determine the resistance of resistor 604 or 654.Based on this information, the type of power supply (i.e.","one suitable for use in stand-alone mode verse one suitable for use in body-worn mode), and the desired mode of operation is determined by operational mode selector 502.The operational mode 501 is then distributed to other functional components of controller 500 as described herein.","It should also be appreciated that operational mode sensors 504, 506 may utilize other information to determine the operational mode of speech processor module 180.For example, an externally-accessible switch may be provided on speech processor unit 180 (as part of internal sensor 506) or protective case 202 (as part of external sensor 504) to enable the recipient or another to manually select the operational mode.","When implemented as part of external sensor 504, such a switch is preferably configured to prevent infants and children from changing the operational mode, as well as to prevent accidental changing of the operational mode during the intended use of the body-worn external component system 200.When implemented as part of internal sensor 506, such a switch is inaccessible once speech processor module 180 is mounted in protective case 202 making such safeguards optional.","In another embodiment, external operational mode sensor 504 includes an infrared or other sensor responsive to signals transmitted by a remote control device.","Such an embodiment allows the recipient or their carer to transmit appropriate signals to select the desired operational mode of speech processor module 180.Based on the selected mode of operation 501 generated by operational mode selector 502, a microphone selector 510 of controller 500 selects which microphone to use.","When in the stand-alone mode of operation, internal microphone 186 is utilized, as shown in FIG.","6A.","When implementing the body-worn mode of operation, microphone 212 on headpiece 208 is utilized, as shown in FIG.","6B.","Microphone selector 510 forwards, connects, routes or otherwise provides the selected microphone 511 to other components of speech processor module 180.As one of ordinary skill in the art would appreciate, external microphone 212 may be located elsewhere; however, it is preferable that the external microphone be integrated into headpiece 208 as described herein.","Such an embodiment reduces the quantity of components while also protecting the external microphone.","In the embodiment shown in FIG.","5, speech processor module 180 comprises internal alarm(s) 526 to provide the recipient or another with visual and/or audible indications of predetermined conditions occurring in the speech processor module when the speech processor module implements the stand-alone mode of operations.","Exterior alarm(s) 524 are provided in protective case 202 to provide the same or similar alarms to the recipient or another when speech processor module 180 implements the body-worn mode of operation.","In accordance with one embodiment, operational mode controller 500 comprises an alarm selector 520 that selects whether alarm conditions are to be broadcast using internal alarms 526 or external alarms 524 based on the selected operational mode 501.Referring to FIG.","6B, external alarm(s) 524 is/are implemented in protective case 202 and comprises a buzzer 662 that is actuated when an alarm condition 523 is detected.","External alarm(s) 524 incorporate a switch 658 that can be thrown by the recipient or another to generate a deactivate signal 521 to disable the alarm function.","Such a switch is preferably configured to prevent the unintended changing of the state of the alarm.","In one embodiment, external alarm 524 is implemented as part of connector block 332 on tray 324.In an alternative embodiment, external alarm 524 is implemented elsewhere on tray 324 or in protective case 202.It should be understood that the above embodiment of external alarm 524 is a buzzer.","Such an audible alarm may be located at the exterior surface of protective case 202, or may be located internal to protective case 202 with an adjacent aperture in the protective case to permit the sound to travel out of the case and be heard by the recipient.","In such alternative embodiments, such an aperture is constructed and arranged to provide a degree of protection analogous to that implemented in the other components and aspects of body-worn external components 200.It should also be appreciated that the type of alarm may include visual indicators in addition to or instead of the audible alarm noted above.","Alternatively, an audible sound may be injected into the audio path to be heard by only the recipient.","In one embodiment, the type of external alarm (indicator, enunciator, internal audio, etc.","), may be selected by the recipient or another, depending on the recipient and intended use of external components 200.As one of ordinary skill in the art would find apparent, any condition may be selected to be one which qualifies as an alarm condition.","For example, in one embodiment, alarm conditions include when the transcutaneous RF link fails such as by displacement of the external antenna.","In another embodiment, alarm conditions include when protective case 202 is opened.","It should also be appreciated that a hierarchical arrangement of alarm conditions may be established, each having a unique identifying alarm.","Speech processor module 180 comprises an internal display 536 comprising, for example, a liquid crystal display (LCD) and/or one or more LEDs that display performance criteria 531 of the module.","In one embodiment, performance criteria 531 comprises battery charge state, memory state, and/or other criteria.","In one embodiment, such performance criteria is not provided to the recipient when speech processor module 180 is mounted in protective case 202.In an alternative embodiment, a portion of cover member 206 and/or base member 204 are transparent to provide a view into a protective case 202 such that internal display 536 can be seen from a position external to protective case 202.In a further embodiment, illustrated in FIG.","5, protective case 202 provide an external display 534, for example, an LCD display located in cover member 206.A display selector 530 determines whether internal display 536 implemented in speech processor module 180 or external display 534 implemented in protective case 202 is to be used to provide the recipient or another with an indication of the noted performance criteria.","Such a determination is based on selected operational mode 501 generated by operational mode selector 501.Such information may be provided to external display 534 via, for example, data out signal line 436.Speech processor module 180 also comprises internal user controls 546 through which a recipient or another can program or otherwise select functional operating parameters in speech processor module 180.For example, in one embodiment, speech processor module 180 comprises internal user controls 546 which enable, for example, program selection, volume control, etc.","In one embodiment, such user controls are not provided to the recipient when speech processor module 180 is mounted in protective case 202.In a further embodiment, illustrated in FIG.","5, protective case 202 provides external user controls 544 located, for example, in cover member 206 and/or base member 204.A user controls selector 540 determines whether internal user controls 546 of speech processor module 180 or external user controls 544 in protective case 202 are to be utilized to provide the recipient or another with the ability to control speech processor module 180.Such a determination is made based on the operational mode 501 provided by operational mode selector 502.When external user controls 544 is selected (i.e.","speech processor module 180 implements the body-worn mode of operation), the transfer of information from the external interface is provided to selector 540 via, for example, data in signal line 434 (FIG.","4).","The user control inputs 541 generated by the selected user controls 544, 546 are forwarded, routed or otherwise provided to speech processor module 180 by selector 540.Speech processor module 180 includes internal on/off control 556, typically implemented as a manual switch in the housing of the speech processor module which can be manipulated by the recipient or another.","When speech processor module 180 is mounted in protective case 202, internal on/off control 556 is no longer accessible to control the power state of speech processor module 180.In one embodiment, no additional controls are provided.","In such an embodiment, protective case 202 must be opened to provide access to the above-noted on/off switch 556 on speech processor module 180.However, such an embodiment is inconvenient and time consuming to manage.","In addition, repeated access to protective case 202 will accelerate the wearing of gasket 302 or other seal implemented in protective case 202 to provide the above-noted protection.","In another embodiment, shown in FIG.","5, an external on/off control 554 is included in protective case 202 which can be activated without having to access the internal enclosure of the protective case.","In one embodiment, external on/off control 554 includes a reed switch or other magnetically-responsive component implemented in protective case 202.In the illustrated embodiment, the external on/off control 554 generates a signal which is forwarded, routed, passed, regenerated or otherwise provided to a power relay or other component speech processor module 180 to interrupt power to the module.","In an alternate embodiment, the magnetically-responsive component is electrically interposed between on-board power supply 216 and speech processor module 180.In this embodiment, speech processor module 180 is disconnected from the power supply when the magnetic field of a magnet such as alignment magnet 110 within headpiece 208 is brought to a location adjacent to the magnetically-responsive switch.","Other embodiments are also configured to cease operation when the transcutaneous RF link has been broken.","For example, in one embodiment, internal on/off control 556 causes speech processor module 180 to periodically transmit an RF signal to implantable components 144, and wait for a response.","When no response is present, speech processor module 180 enters a standby mode or turns off.","If a standby mode is implemented, speech processor module 180 periodically transmits an RF signal while in the standby mode.","If a response is received, speech processor module 180 then fully activates, starts processing sound and retransmits signals to implantable component 144.In another embodiment, external on/off control module 554 can include a manually-activated switch located on the exterior of protective case 202.Such a switch is preferably configured to prevent children from changing the power state, and from accidental changing of the power state during the intended use of the body-worn external components 200.In addition to one or more of the above embodiments, speech processor module 180 can also be adapted to shut down whenever on-board power supply 216 is being charged.","In such an embodiment, protective case 202 also comprises charging circuitry (not shown) to allow power supply 216 to be recharged when case 202 is not in use.","In another embodiment, external on/off control 554 includes an infrared or other sensor responsive to signals transmitted by a remote device operated by the recipient or their carer.","In the case of adults, the present invention provides a recipient with the flexibility of using their speech processor module 180 in a moist environment.","For infants and small children, the present invention also can be used in the comfort that the speech processor is less likely to be damaged than would be the case where the speech processor unit is used in the stand-alone mode.","The case 202 is also potentially advantageous in that it can serve to assist in preventing tampering of speech processor module 180 by a child recipient or a third party."]],"string":"[\n [\n \"TRANSFORMABLE SPEECH PROCESSOR MODULE FOR A HEARING PROSTHESIS\",\n \"A method for operating an external component of a cochlear implant hearing system.\",\n \"The external component includes a speech processor module operable in a stand-alone mode of operation and a body-worn mode of operation, and a protective case.\",\n \"The method includes operating the speech processor module in the stand-alone mode, determining when the speech processor module is mounted in the case, and operating the speech processor module in the body-worn mode in response to determining that the speech processor module is mounted in the case.\"\n ],\n [\n \"1.A device, comprising: a speech processor of a hearing prosthesis; and a barrier configured to protect the speech processor from water.\",\n \"2.The device of claim 1, wherein: the barrier is a protective case; and the speech processor is removably received in the protective case.\",\n \"3.The device of claim 2, wherein: the case includes an interior compartment in which is located the speech processor; and the case protects against ingress of water into the interior.\",\n \"4.The device of claim 2, wherein the case includes two sections configured to be moved relative to one another, so that the case can be opened and closed so that the speech processor can be removed and installed therein, and wherein the device is configured such that when the two sections are brought into proximity with one another to protect the sound processor from water, a seal is established between the two sections preventing water from entering the case and reaching the sound processor.\",\n \"5.The device of claim 2, further comprising: a transcutaneous transfer coil assembly including a transcutaneous transfer coil, a microphone and a cable, wherein, the device is configured to place the microphone and the transcutaneous transfer coil into signal communication with the speech processor via the cable.\",\n \"6.The device of claim 2, wherein the speech processor is part of a behind the ear (BTE) device; at least a portion a body of the BTE device including the speech processor is removably received in the protective case; and wherein the case establishes a barrier protecting the at least a portion of the body of the BTE device in the case from water.\",\n \"7.The device of claim 6, wherein: the case includes an interior compartment in which the least a portion of the body of the BTE device is located; and the case protects against ingress of water into the interior.\",\n \"8.The device of claim 6, wherein: the case is configured to protect against substantially all fluid ingress into the case.\",\n \"9.The device of claim 6, wherein the case includes two sections configured to be moved relative to one another, so that the case can be opened and closed so that the at least a portion of the body of the BTE device can be removed and installed therein, and wherein the device is configured such that when the two sections are brought into proximity with one another to protect the least a portion of the body of the BTE device from water, a seal is established between the two sections preventing water from entering the case and reaching the sound processor.\",\n \"10.The device of claim 6, wherein: the case is configured to prevent substantially all fluid ingress at elevated atmospheric pressures.\",\n \"11.The device of claim 6, further comprising: a transcutaneous transfer coil assembly including a transcutaneous transfer coil, a microphone and a cable, wherein, the device is configured to place the microphone and the transcutaneous transfer coil into signal communication with the speech processor via insertion of a connector at a distal end of the cable into the case.\",\n \"12.The device of claim 1, further comprising: a transcutaneous transfer coil and a microphone, wherein the transcutaneous transfer coil assembly includes a housing that provides the same protection to the microphone from water as the case does to the sound processor.\",\n \"13.The device of claim 6, wherein: the case includes a first portion of the case configured to move relative to the second portion of the case to open and close the case to enable installation and removal of the body of the BTE device, wherein the first portion and second portion of the case form an interior in which the speech processor is located protected by water by a seal between the first portion of the case and the second portion of the case.\",\n \"14-29.\",\n \"(canceled) 30.A protective case for a behind the ear (BTE) component including a speech processor of a hearing prosthesis, comprising: a base having a hollow portion configured to receive the speech processor; and a lid configured to extend over the hollow portion of the base, wherein the protective case is configured to removably receive the BTE component and protect the BTE component from water.\",\n \"31.The protective case of claim 30, wherein: the case is configured to retain the BTE component one side of the hollow portion relative to an opposite side of the hollow portion.\",\n \"32.The protective case of claim 30, wherein: the case is configured to enable a connector of a cable connected to a transcutaneous transfer coil to be inserted into the case to establish communication between the cable and a connector of a speech processor of the BTE component while protecting the BTE component from water such that a hearing percept can be evoked by an implanted component based on speech processed by the speech processor of the BTE component using the transcutaneous transfer coil via communication between the transcutaneous transfer coil and the speech processor while the BTE component is located in the case such that the BTE device is protected from water.\",\n \"33.The protective case of claim 30, wherein: the case is configured to enable a connector of a cable to mate with the BTE component and the speech processor that is apart thereof while the BTE component is located in the case such that the BTE device is protected from water.\",\n \"34.The protective case of claim 30, wherein: the case is configured to enable a connector of a cable to directly mate with the BTE component and the speech processor that is apart thereof while the BTE component is located in the case such that the BTE component is protected from water.\",\n \"35.A device, comprising: the BTE component; and the protective case of claim 30, wherein the BTE component is removably received in the case, and wherein the case protects against substantially all fluid ingress into the case.\",\n \"36.The protective case of claim 30, wherein: the case is configured to prevent substantially all fluid ingress at elevated atmospheric pressure when the case is closed.\",\n \"37.The protective case of claim 30, wherein: case is configured to enable the lid to move relative to the base to open and close the case, wherein the base and lid form an interior in which, when the speech processor is removably received therein, is protected from water by a seal between the first portion of the case and the second portion of the case.\",\n \"38.A method of utilizing an external component of a cochlear implant hearing system, the external component comprising a speech processor module operable in a stand-alone mode of operation and a external device controlled mode of operation; the method comprising: operating the speech processor module in the stand-alone mode; removably mounting the speech processor module in an external device including a case configured to have said speech processor module removably mounted therein and including external device user controls; determining whether or not to utilize an inputted external volume control setting inputted by a user to the external device user controls of the external device to control the speech processor module; and operating the speech processor in the external device controlled mode.\",\n \"39.The method of claim 38, wherein: the action of determining whether or not to utilize an inputted external volume control setting inputted by a user to the external device user controls of the external device to control the speech processor module includes determining to utilize the inputted external volume control setting inputted by a user to the external device user controls of the external device to control the speech processor module; and the action of operating the speech processor in the external device controlled mode includes operating the speech processor in the external mode after the determination to use the inputted external volume control setting.\",\n \"40-43.\",\n \"(canceled) 44.The device of claim 6, wherein: the BTE device is configured to enable the evocation of a first hearing percept when the BTE device is located behind the ear of a recipient away from the protective case and when the BTE device is in signal communication with a transcutaneous transfer coil assembly including a transcutaneous transfer coil which is in signal communication with another coil of an implanted hearing prosthesis implanted in a recipient; and the at least a portion the body of the BTE device including the speech processor is configured to enable the evocation of a second hearing percept when the at least a portion of the BTE device is located in the case when the at least a portion of the BTE device is in signal communication with a transcutaneous transfer coil assembly including a transcutaneous transfer coil which is in signal communication with another coil of an implanted hearing prosthesis implanted in a recipient.\",\n \"45.The device of claim 6, further comprising: a transcutaneous transfer coil assembly including a transcutaneous transfer coil, a microphone and a cable, wherein the microphone and the transcutaneous transfer coil is in signal communication with the speech processor via the cable, and the device is configured to enable the evocation of a hearing percept when the BTE device is located in the case when the at least a portion of the BTE device is in signal communication with the transcutaneous transfer coil assembly which is in signal communication with another coil of an implanted hearing prosthesis implanted in a recipient.\",\n \"46.The device of claim 1 wherein: the device is an external component of a hearing prosthesis system in transcutaneous signal communication with an implantable component of the hearing prosthesis system.\",\n \"47.The device of claim 1 wherein: the device is an external component of a cochlear implant hearing prosthesis system in transcutaneous signal communication with an implantable component of the cochlear implant hearing prosthesis system.\",\n \"48.The device of claim 1 wherein: the device is an external component of a cochlear implant hearing prosthesis system in transcutaneous signal communication with an implantable component of the cochlear implant hearing prosthesis system.\",\n \"49.The device of claim 1, wherein: the barrier is a protective case including a base housing and a cover, the cover including a gasket that seals the interior of the case from the exterior of the case; and the speech processor is removably received in the protective case and the gasket seals the case.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>\"\n ],\n [\n \"<SOH> SUMMARY <EOH>In one aspect of the invention, a method for operating an external component of a cochlear implant hearing system is disclosed.\",\n \"The external component comprises a speech processor module is operable in a stand-alone mode of operation and a body-worn mode of operation, and a protective case.\",\n \"The method comprises operating the speech processor module in the stand-alone mode, determining when the speech processor module is mounted in the case, and operating the speech processor module in the body-worn mode in response to determining that the speech processor module is mounted in the case.\",\n \"In another aspect of the invention, a method for operating a cochlear implant hearing system is disclosed.\",\n \"The method comprises operating, in a stand-alone mode of operation, a speech processor module having processing circuitry disposed in a housing, determining, via an operational mode controller, when the speech processor module is mounted in a protective case, and operating the speech processor module in a body-worn mode of operation in response to determining that the speech processor module is mounted in the case.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation application of U.S. application Ser.\",\n \"No.\",\n \"13/729,485 filed Dec. 28, 2012, which is a continuation application of U.S. application Ser.\",\n \"No.\",\n \"12/703,160 filed Mar.\",\n \"18, 2012, now U.S. Pat.\",\n \"No.\",\n \"8,352,037, which is a divisional of U.S. application Ser.\",\n \"No.\",\n \"10/586,524, filed Oct. 23, 2006, which is a National Stage application of International Application No.\",\n \"PCT/US04/43288, filed Dec. 27, 2004, and which claims the benefit of Australian Provisional Patent Application No.\",\n \"2003907138, filed Dec. 24, 2003.The content of these applications is hereby incorporated by reference herein.\",\n \"BACKGROUND Field of the Invention The present invention relates to a hearing prosthesis and, more particularly, a transformable speech processor module for a hearing prosthesis.\",\n \"Related Art The use of medical devices to provide therapy to individuals for various medical conditions has become more widespread as the advantages and benefits of such devices become more widely appreciated and accepted throughout the population.\",\n \"In particular, devices such as implantable pacemakers, defibrillators, functional electrical stimulation devices such as hearing prostheses, organ assist or replacement devices, and other medical devices, have been successful in performing life saving and/or lifestyle enhancement functions for a number of individuals.\",\n \"Many such medical devices often include one or more sensors, processors, controllers or other functional electrical components that are permanently or temporarily implanted in a patient.\",\n \"Many such implantable devices require the transcutaneous transfer of power and/or information with external components that are part of, or operate in conjunction with, the implanted components of the medical device.\",\n \"Such external components are typically removably attached to the body of the patient.\",\n \"One such type of medical device is a cochlear implant system, also commonly referred to as a cochlear prosthesis.\",\n \"Cochlear implant systems provide the benefit of hear to individuals suffering from severe to profound hearing loss.\",\n \"Hearing loss in such individuals is due to the absence or destruction of the hair cells in the cochlea which transduce acoustic signals into nerve impulses.\",\n \"Cochlear implants essentially simulate the cochlear hair cells by directly delivering electrical stimulation to the auditory nerve fibers.\",\n \"This causes the brain to perceive a hearing sensation resembling the natural hearing sensation normally delivered to the auditory nerve.\",\n \"Conventional cochlear implant systems primarily include an external assembly directly or indirectly attached to the body of the patient (referred to herein as the recipient), and an internal assembly which is implanted in the patient.\",\n \"The external assembly typically comprises one or more microphones for detecting sound, a speech processing unit that converts detected sound, particularly speech, into an electrical coded signal, a power source, and an external transcutaneous transfer coil.\",\n \"The internal assembly typically comprises an internal transcutaneous transfer coil, a stimulator unit located within a recess of the temporal bone of the recipient, and an electrode array positioned in the recipient's cochlear.\",\n \"Collectively, the external coil and the internal coil form an inductively-coupled transcutaneous transfer system.\",\n \"The transfer of energy via this system is controlled to effect the transmission of the electrical coded signals, referred to herein as stimulation signals, and power signals from the external speech processing unit to the implanted stimulator unit.\",\n \"Similarly, the transcutaneous transfer system may be used to effect the transmission of telemetry data from the implanted stimulator unit to the exterior speech processing unit.\",\n \"Conventionally, the communications link has been in the form of a radio frequency (RF) link, although other such links have been proposed and implemented.\",\n \"Once a stimulation signal has been transmitted to the implanted transcutaneous transfer coil, it is provided to the implanted stimulator unit which processes the signal and outputs one or more signals to the intra-cochlear electrode assembly which applies the electrical stimulation directly to the auditory nerve of the recipient.\",\n \"The speech processor unit has traditionally been worn on the body, such as by being attached to clothing, or by being supported on the ear of the recipient.\",\n \"This latter configuration is commonly referred to as a BTE (behind the ear) configuration.\",\n \"The speech processor unit is relatively expensive and susceptible to damage, especially in the hands of infants or small children, or when used in an unsuitable environment.\",\n \"SUMMARY In one aspect of the invention, a method for operating an external component of a cochlear implant hearing system is disclosed.\",\n \"The external component comprises a speech processor module is operable in a stand-alone mode of operation and a body-worn mode of operation, and a protective case.\",\n \"The method comprises operating the speech processor module in the stand-alone mode, determining when the speech processor module is mounted in the case, and operating the speech processor module in the body-worn mode in response to determining that the speech processor module is mounted in the case.\",\n \"In another aspect of the invention, a method for operating a cochlear implant hearing system is disclosed.\",\n \"The method comprises operating, in a stand-alone mode of operation, a speech processor module having processing circuitry disposed in a housing, determining, via an operational mode controller, when the speech processor module is mounted in a protective case, and operating the speech processor module in a body-worn mode of operation in response to determining that the speech processor module is mounted in the case.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1A is a perspective view of one embodiment of a hearing prosthesis in which embodiments of the present invention may be advantageously implemented; FIG.\",\n \"1B is a perspective view of one embodiment of a dual mode speech processing unit in accordance with one embodiment of the present invention; FIG.\",\n \"2 is a perspective view of an external component system of a hearing prosthesis according to one embodiment of the present invention suitable for use with the speech processing unit illustrated in FIG.\",\n \"1B; FIG.\",\n \"3 is an exploded perspective view of the embodiment of illustrated in FIG.\",\n \"2; FIG.\",\n \"4 is an interface diagram of one embodiment of the speech processor module illustrated in FIG.\",\n \"1B; FIG.\",\n \"5 is a functional block of one embodiment of an aspect of the present invention; FIG.\",\n \"6A is a schematic diagram of the relevant signal and electrical interfaces when the speech processor module shown in FIG.\",\n \"1B is implemented in a stand-alone operational mode; and FIG.\",\n \"6B is a schematic of the relevant signal and electrical interfaces when the speech processor module shown in FIG.\",\n \"1B is implemented in a body-worn operational mode.\",\n \"DETAILED DESCRIPTION Embodiments of the present invention are directed to a speech processor module which may be implemented in more than one mode of operation of a hearing prosthesis.\",\n \"Specifically, certain embodiments of the present invention are directed to a speech processor module that can be implemented as a component of in a behind-the-ear (BTE) speech processing unit, and as a component of a body-worn speech processing unit.\",\n \"The present invention is also directed to an external component system for a hearing prosthesis that enables the dual-mode speech processor module to be worn on the body of a recipient rather than behind the recipient's ear.\",\n \"Advantageously, certain embodiments of certain aspects of the present invention can be implemented such that the dual-mode speech processor module is protected from adverse environmental conditions, including certain recipients.\",\n \"For example, in some embodiments described herein, the external component system includes a protective case which protects the speech processor module from infants, small children, mentally handicapped, etc., and/or allows the use of the speech processor module in environments traditionally considered to be unsuitable for prosthetic hearing devices.\",\n \"As a result, embodiments of the present invention enable hearing prostheses to be worn by a wide range of recipients in a wide range of environments.\",\n \"Embodiments of the present invention are described below in connection with one embodiment of an exemplary hearing prosthesis, a cochlear prosthesis (also referred to as a cochlear implant system, cochlear prosthetic device and the like; “cochlear implant system” herein).\",\n \"Cochlear implant systems use direct electrical stimulation of auditory nerve cells to bypass absent or defective hair cells that normally transducer acoustic vibrations into neural activity.\",\n \"Such devices generally use multi-contact electrodes inserted into the scala tympani of the cochlea so that the electrodes may differentially activate auditory neurons that normally encode differential pitches of sound.\",\n \"Such devices are also used to treat a smaller number of patients with bilateral degeneration of the auditory nerve.\",\n \"For such patients, a cochlear implant system provides stimulation of the cochlear nucleus in the brainstem.\",\n \"FIG.\",\n \"1A is a schematic diagram of an exemplary cochlear implant system 100 in which embodiments of the present invention may advantageously be implemented.\",\n \"Cochlear implant system 100 comprises external component assembly 142 which is directly or indirectly attached to the recipient, and an internal component assembly 144 which is temporarily or permanently implanted in the recipient.\",\n \"External component assembly 142 typically comprises a microphone 120 for detecting sound, a speech processing unit 116, a power source (not shown), and an external transmitter unit 106.External transmitter unit 106 comprises an external coil 108, and preferably, an alignment magnet 110 secured directly or indirectly to external coil 108.Speech processing unit 116 processes the output of microphone 120 that are positioned, in the depicted example, by the ear 122 of the recipient.\",\n \"Speech processing unit 116 generates coded signals, referred to herein as a stimulation data signals, which are provided to external transmitter unit 106 via cable 118.Internal components 144 comprise an internal receiver unit 112, a stimulator unit 126, and an electrode array 134.Internal receiver unit 112 comprises an internal transcutaneous transfer coil 124, and preferably, an alignment magnet 140 fixed relative to internal coil 124.Internal receiver unit 112 and stimulator unit 126 are hermetically sealed within a housing 128.Internal coil 124 receives power and data from external coil 108.A cable 130 extends from stimulator unit 126 to cochlea 132 and terminates in electrode array 134.Signals generated by stimulator unit 126 are applied by array 134 to the basilar membrane 136, thereby stimulating the auditory nerve 138.Collectively, external coil 108 and internal coil 124 form an inductively-coupled coil system of a transcutaneous transfer apparatus 102.In one embodiment, external coil 108 transmits and receives electrical signals to/from internal coil 124 via a radio frequency (RF) link 114.In use, implantable receiver unit 112 may be positioned in a recess of the temporal bone adjacent ear 122 of the recipient.\",\n \"As noted, embodiments of the present invention are directed to a speech processor module which may be implemented in more than one mode of operation in a hearing prosthesis such as cochlear implant system 100.FIG.\",\n \"1B is a perspective view of one embodiment of a dual-mode speech processor module of the present invention.\",\n \"In this embodiment, the dual-mode speech processor module of the present invention is configured to be used in a behind-the-ear (BTE) speech processing unit 178, similar to speech processing unit 116 illustrated in FIG.\",\n \"1A.\",\n \"Behind the ear (BTE) speech processing unit 178 comprises a speech processor module 180 that contains signal processing circuitry (not shown).\",\n \"A detachable ear hook 182 is provided at one end of speech processor module 180 so as to allow the speech processor to be supported behind the outer car of the recipient of the cochlear implant system.\",\n \"A detachable power supply 184 comprising a rechargeable battery or other power source (not shown) is attached to speech processor module 180 to provide power to the module.\",\n \"Speech processor module 180 utilizes a built-in microphone 186 that generates signals to the signal processing circuitry housed within the speech processor module.\",\n \"Built-in microphone 186 is also referred to as internal microphone 186 herein.\",\n \"Speech processor module 180 includes a headpiece connector 188 and an accessories connector 190 to connect to other components of the implementing cochlear implant system or other hearing prosthesis.\",\n \"In operation, cables with an appropriately configured connector extends from speech processing module 180 to a headpiece and, possible, an accessory device, as described in detail below.\",\n \"Speech processing unit 178 is configured to operate in a stand-alone manner; that is, as a behind-the-ear (BTE) speech processing unit.\",\n \"However, speech processing unit 178 is susceptible to damage from rough handling, such as might be experienced when used by infants or small children.\",\n \"It also may not be suitable for use in adverse environments, such as environments having airborne particulates or significant moisture.\",\n \"To operate under such conditions, speech processor module 180 can operate in a body-worn mode of operation in an external component system.\",\n \"One embodiment of an external component system 200 of a hearing prosthesis according to the present invention is depicted in FIGS.\",\n \"2 and 3.External component system 200 operationally replaces external component assembly 142 of cochlear implant system 100 illustrated in FIG.\",\n \"1A to convert the cochlear implant system from a prosthesis which may be readily damaged by the recipient and/or environment, to one which is more robust or rugged and, therefore, suitable for use by infants, children, mentally handicapped and other recipients, and/or worn by any recipient in one or more adverse environmental conditions.\",\n \"In certain embodiments, external component system 200 provides protection for speech processor module 180.In the embodiment shown in FIG.\",\n \"2, for example, a protective case 202 is included in external component system 200 to house speech processor module 180 and an on-board power supply 216.In certain embodiments, such protection includes protecting these components from ingress of fluid such as water.\",\n \"In one embodiment, for example, protective case 202 is fluid resistant.\",\n \"In another embodiment, protective case 202 prevents substantially all fluid ingress, even at elevated atmospheric pressure.\",\n \"Similarly, in certain embodiments, protective case 202 is at least resistant to the ingress of dust or other particulates such as airborne fumes.\",\n \"In other embodiments, protective case 202 is capable of providing protection against shocks and vibration, electromagnetic interference (EMI) and other environmental conditions which may adversely affect the operational performance, integrity, and/or lifespan of speech processor module 180.External component system 200 also comprises a one-piece headpiece 208 communicably coupled to speech processor module 180 via a cable 210.As will be described in greater detail below, headpiece 208 comprises the above-noted external transmitter unit 106 including external coil 108, and alignment magnet 110 mounted in a protective housing 220 that provides the same or similar protection of its components as protective case 202.Protective case 202 comprises a base member 204 and a cover member 206 which mechanically mate with each other to form a protective enclosure in which speech processor module 180 is secured.\",\n \"Protective case 202 also comprises a tray 324 on which speech processor module 180 is removably mounted.\",\n \"In addition, tray 324 is configured to have on-board power supply 216 mounted adjacent to speech processor module 180 to provide power to the speech processor module as described herein.\",\n \"These and other components of protective case 202 are described in further detail below.\",\n \"Referring again to FIG.\",\n \"1B, speech processor module 180 is configured to be connected to a detachable power supply 184 when implemented in a stand-alone mode; here, as part of a behind the ear speech processing unit 178.When the recipient or their carer wishes speech processor module 180 to be protected by case 202, ear hook 182 and power supply 184 are detached from speech processor module 180, and the speech processor module is mounted on tray 324 of protective case 202.On-board power supply 216 is also mounted on tray 324.Cover member 206 is then secured to base member 204 to provide a sealed enclosure in which speech processor module 180 and on-board power supply 216 are protected.\",\n \"The resulting external component system 200 is then used in place of the external component assembly 142 illustrated in FIG.\",\n \"1A.\",\n \"Protective case 202 is secured to the recipient using, for example, strap(s) threaded through brackets 218.As noted, in one embodiment, an on-board power supply 216 is included in protective case 202 to provide power to speech processor module 180 when the speech processor module is installed in protective case 202.Power supply 216 may be any suitable power supply now or later developed including but not limited to rechargeable batteries.\",\n \"In one embodiment, on-board power supply 216 implements batteries which are conventional, commercially-available batteries, making them significantly less expensive than detachable power supply 184.Appropriate electrical connections are provided to transfer power from on-board power supply 216 to speech processor module 180.Referring to FIG.\",\n \"3, speech processor module 180 has one or more connector pins 322 for connecting speech processor module 180 to detachable power supply 184 when implementing the stand-alone operational mode.\",\n \"It should be appreciated that detachable power supply 184 has a connector (not shown) constructed and arranged to mate with the appropriate pin(s) 322 of speech processor module 180 to transfer power.\",\n \"As shown in FIGS.\",\n \"2 and 3, when speech processor module 180 is installed in protective case 202, on-board power supply 216 may not directly contact speech processor module 180.As a result, a connector similar to that implemented in detachable power supply 184 is not used in such embodiments to directly connect on-board power supply 216 to speech processor module 180.Rather, in the illustrative embodiment, a bridge connection is provided in protective case 202 to connect the appropriate pin(s) 322 of speech processor module 180 to terminals 328 of on-board power supply 216.In one embodiment, tray 324 provides the means to electrically connect on-board power supply 216 and speech processor module 180.Tray 324 also comprises apparatus to removably secure an installed power supply 216 and speech processor module 180 to prevent damage to themselves or the other components housed in protective case 202.In the embodiment shown in FIGS.\",\n \"2 and 3, on-board power supply 216 is retained between a pair of vertical posts 326.Tray 324 also includes appropriately arranged contacts to electrically mate with terminals 328 on power supply 216 when the power supply is mounted on tray 324.In the embodiment shown, power supply 216 has terminals 328 disposed along a corner of the power supply.\",\n \"Accordingly, tray 324 comprises contacts disposed at the junction of vertical columns 326 and the top surface of tray 324.It should be apparent to those of ordinary skill in the art that the contacts provided in tray 324 to electrically mate with terminals 328 of on-board power supply 216 may be located at any appropriate location and be configured in any way which will achieve a desired electrical connection.\",\n \"As one of ordinary skill in the art would appreciate, the manner in which on-board power supply 216 is removably mounted on tray 324 can vary depending on a variety of factors including but not limited to the anticipated environment to which external component 200 and, in particular, protective case 202, will be exposed, the weight and mass of power supply 216, the weight distribution of the power supply, etc.\",\n \"As noted, speech processor module 180 is removably mounted on tray 324.In the embodiment shown in FIG.\",\n \"3 speech processor module 180 is shown detached from power supply 184 and ear hook 182, exposing pins 322 and raised guide surface 330.Raised guide surface 330 is received by a complementary channel in detachable power supply 184 to cause the power supply to properly mate with pins 322 when the power supply is attached to speech processor module 180.Tray 324 comprises a connector block 332 having in one embodiment, a mechanical and electrical interface similar to that of detachable power supply 184.That is, connector block 332 comprises a connector (not shown) constructed and arranged to mate with pins 322 when speech processor 180 is mounted on tray 324.In addition, connector block 332 has an integrated channel 320 configured to slidingly receive raised guide surface 330 of speech processor module 180.To mount speech processor module 180 on tray 324, the speech processor module is positioned such that raised guide surface 330 is aligned with an open end of channel 320.As speech processor module 180 is slid into position, channel 320 and raised guide surface 330 cooperate to facilitate the mating of speech processor module 180 and the connector of connector block 332.In addition, raised guide surface 330 and channel 320 cooperate to securely retain speech processor module 180 to tray 324 when the speech processor module is mounted in protective case 202.It should be appreciated, however, that additional or alternative means may be employed to removably secure speech processor module 180 to tray 324.Embodiments of tray 324 may also include other components to facilitate the removable mounting of speech processor 180.For example, in the embodiment illustrated in FIG.\",\n \"3, a brace 318 which is curved to abut or be adjacent with a curved surface of speech processor module 180 is provided.\",\n \"In alternative embodiments, speech processor 180 is securely retained in protective case 324 using other techniques now or later developed.\",\n \"When speech processor module 180 and on-board power supply 216 are mounted on tray 324, they are electrically connected to each other.\",\n \"In the embodiment shown in FIGS.\",\n \"2 and 3, for example, such electrical connection is provided by tray 324 so that additional components need not be included in protective case 202, and additional steps beyond mounting speech processor 180 and power supply 216 are not necessary to attain an electrical connection.\",\n \"Specifically, wiring connects the power supply contacts (not shown) on tray 324 and the connector (not shown) on connector block 332 which mates with speech processor module 180.Such wiring may be integrated, for example, into platform 336 of tray 324, or may extend below platform 336.In the latter embodiment, tray 324 preferably does not rest in the bottom surface of base member 204; rather, it rests on support members to provide a space between platform 336 and base member 204 when tray 324 is secured to the base member.\",\n \"As one of ordinary skill in the art would appreciate, the type of electrical connection provided can vary depending on the particular application.\",\n \"For example, the pins and sockets used to establish the battery connection can be replaced with any other type of electrical connectors.\",\n \"Also, one pin 322 can provide both the positive and ground connections for transferring power to speech processor module 180.As noted, base member 204 and cover member 206 are attached to each other to provide a protective enclosure for speech processor module 180 and on-board power supply 216.Cover member 206 and base member 204 are configured also to provide the recipient or carer access the enclosure to install or remove speech processor module 180 and power supply 216.In the embodiment shown in FIGS.\",\n \"2 and 3, for example, cover member 206 is removable; that is, cover member 206 and base member 204 separate from each other to expose the interior of base member 204.It should be appreciated, however, that a portion or all of cover member 206 may be configured, for example, to rotate away from base member 204 to create an aperture through which speech processor module 180 and on-board power supply 216 can be passed.\",\n \"Such rotation can be provided, for example, with mechanical hinges.\",\n \"There are, of course, a myriad of other arrangements that may be implemented to provide the noted access.\",\n \"For example, one or more rotating, sliding, removable, or other types of doors, panels, sides, etc., may be implemented in either or both, cover member 206 and base member 204.Cover member 206 and base member 204 may be formed of any material or combination of materials suitable for the intended recipient and environment.\",\n \"For example, cover and base members 206, 204 may be formed of metallic material, ceramic material, polymeric material, composites or any combination thereof.\",\n \"In addition, cover and base members 206, 204 may be opaque, translucent, transparent, etc., to provide a desired view of a desired portion of the interior of protective case 202 from the recipient, carer or third party.\",\n \"In the exemplary embodiment shown in FIG.\",\n \"3, protective case 202 contains a gasket 302 to seal protective case 202 when cover member 206 is joined with base member 204.As noted, embodiments of protective case 202 protect components mounted therein from a variety of environmental elements such as fluids, dust, etc.\",\n \"Gasket 302 is appropriately configured and formed of the appropriate material to provide the desired degree of protection from at least the environmental elements of concern.\",\n \"In the embodiment shown in FIGS.\",\n \"2 and 3, gasket 302 is shaped to be disposed between the mating surfaces of cover member 206 and base member 204 when the cover and base are brought together to form protective case 202.Accordingly, gasket 302 takes the shape of the perimeter of protective case 202 at the location that the cover and base members meet.\",\n \"In one particular embodiment, gasket 302 provides additional protection.\",\n \"As shown in FIGS.\",\n \"2 and 3, gasket 302 includes a contiguous sheath 334 of fluid-impermeable, resiliently flexible material extending across the interior of the gasket.\",\n \"When installed in protective case 202, this embodiment of gasket 302 seals with the perimeter wall of base member 204.This causes sheath 334 to cover speech processor module 180 and power supply 216 mounted in base member 204.Thus, in addition to preventing ingress of at least selected environmental elements, gasket 302 and sheath 334 also protect components from those environmental elements which manage to penetrate protective casing 202.Sheath 334 can be manufactured from polymeric, elastomeric or other suitable materials.\",\n \"In one embodiment, sheath 334 is transparent.\",\n \"Protective case 202 comprises a fixation device to removably secure cover member 206 to base member 204.In the embodiment illustrated in FIGS.\",\n \"2 and 3, such a fixation device comprises a combination of an appropriately located screw and threaded hole.\",\n \"Specifically, sheath 334 has an orifice 304 formed therein that is adapted to allow passage of a threaded shaft of fixation screw 214 through sheath 334.Similarly, cover member 206 has an orifice 308 adapted to allow passage of the threaded shaft of screw 214.When cover member 206 and sheath 334 are assembled with based member 204, orifice 308 and orifice 304 are aligned with each other.\",\n \"Screw 214 may then pass through orifice 308 in cover member 206, and orifice 304 in sheath 334 to threadingly engage a threaded hole 310 of a post 312 on tray 324.It should be appreciated by those of ordinary skill in the art that the implemented fixation device should not degrade the integrity of the protective features implemented in protective case 202.For example, in the above embodiment in which a fixation screw 214 is implemented, at the location of screw 214, an elastomeric grommet 314 is provided to help prevent ingress of fluid into the protective case at the site of screw 214.Additionally washers, o-rings and the like may also be used as appropriate.\",\n \"External component system 200 also comprises a one-piece headpiece 208 communicably coupled to speech processor module 180 via a cable 210.As noted, headpiece 208 comprises the above-noted external transmitter unit 106 including external coil 108, and magnet 110 mounted in a housing 220 that provides the same or similar protection of its components as protective case 202.In accordance with one embodiment of the present invention, headpiece 208 also comprises a second microphone 212 mounted thereon which is operable when speech processor module 180 is installed in protective case 202.When speech processor module 180 is installed in protective case 202, microphone 186 cannot be used since it will be enclosed with protective case 202.As such, external component system 200 provides an alternate or replacement microphone 212, referred to as external microphone 212.Protective case 202 has an additional orifice (not shown) provided in base member 204 to permit cable 210 to be inserted into the case.\",\n \"Cable 210 extends from headpiece 208 into case 202 to mate with connector 188 of speech processor module 180.The orifice may be sealed, for example, by a grommet 316 provided around the distal end of cable 210.For example, in one embodiment, grommet 316 and orifice are constructed and arranged to prevent water from entering protective case 202.As noted, protective case 202 provides protection for speech processor module 180 and on-board power supply 216.In the embodiments described above, such protection includes protecting the components from ingress of fluid, dust or other particulates such as airborne fumes.\",\n \"In other embodiments, protective case 202 is capable of providing protection against electromagnetic interference (EMI).\",\n \"In such embodiments, the interior surfaces of cover member 206 and base member 204 are coated with a conformal EMI coating such as that used in cellular phones, computer systems and other electronic devices that emit or are sensitive to electromagnetic radiation.\",\n \"In addition, in such embodiments gasket 302 is an EMI gasket suitable for preventing EMI from escaping through the joined surfaces of cover member 206 and base member 204.In other embodiments, protective case 202 protects the components mounted therein from vibration and/or shock.\",\n \"In such embodiments, tray 324 may be suspended on a shock- and vibration-absorbing material or elements such as resilient posts or extensions disposed in or integrated with base member 204.In addition, the dimensions of tray 324 may be somewhat less than the interior dimensions of protective case 202 to reduce the likelihood of shocks to tray 324 and the components mounted thereon.\",\n \"FIG.\",\n \"4 is a schematic interface diagram of one embodiment of speech processor module 180 illustrated in FIGS.\",\n \"2 and 3.In the embodiment shown in FIG.\",\n \"4, speech processor module 180 comprises four (4) interfaces, a headpiece interface 402, an accessories interface 404, a power supply interface 406, and a clinical/diagnostic interface 408.Each of the interfaces 402-408 is supported by one or more connectors as described above with references to FIGS.\",\n \"2 and 3.It should be appreciated by those of ordinary skill in the art, however, that interfaces 402-408 may be implemented in one or more connectors configured differently than that described herein.\",\n \"Headpiece interface 402 comprises a microphone signal line 410, an RF/telemetry signal line 411, a voltage signal line 412 and a ground signal line 414.In the embodiment shown in FIGS.\",\n \"2 and 3, these signal lines are included in cable 210 connecting headpiece 208 and speech processor module 180 via connector 188.Accessories interface 404 comprises an input audio signal line 418, an auxiliary voltage input signal line 420, an output audio signal line 422 and a ground signal line 424.These signal lines are transmitted between an accessory device (not shown) and accessories connector 190 of speech processor module 180.Power supply interface 406 comprises a power supply identifier (ID) signal line 426, a voltage signal line 428, and a ground signal line 430.These signal lines are transmitted between one or more pins 322 of speech processor module 180 and either power supply 184 or power supply 216.Clinical/diagnostic interface 408 comprises an alarm signal line 432, data in and out signal lines 434, 436, and a ground signal line 438.These signal lines are transmitted between one or more pins 322 of speech processor module 180 and a diagnostic device or display (not shown).\",\n \"It should be appreciated that in the embodiment of external component system 200 illustrated in FIGS.\",\n \"2 and 3, the apertures in protective case 202 which provide access by cables that connect to accessory connector 190 (providing accessory interface 404), and pin(s) 322 (providing clinical interface 408) are not shown.\",\n \"Such apertures, however, are the same or similar to those described above.\",\n \"In an alternative embodiment, such interfaces are available only when speech processor module 180 implements the stand-alone mode of operation.\",\n \"FIG.\",\n \"5 is a functional block diagram of these components of the present invention which enable speech processor module 180 to transition between stand-alone and a body-worn operational modes.\",\n \"In FIG.\",\n \"5 an operational mode controller 500 is implemented in speech processor module 180 to determine which operational mode speech processor module 180 is to implement, and to select the appropriate internal inputs and outputs (that is, provided as part of speech processor module 180) and external inputs and outputs (that is, provided as part of external component system 200) to enable speech processor module 180 to function in the desired operational mode.\",\n \"FIGS.\",\n \"6A and 6B are schematic diagrams showing a portion of the interfaces utilized by one embodiment of speech processor module 180 when implemented in both modes of operation.\",\n \"In FIG.\",\n \"6A, speech processor module 180 has ear hook 182 and power supply 184 attached to facilitate, in this embodiment, use as a stand-alone behind-the-ear (BTE) speech processing unit 178.Detachable power supply 184 is shown schematically, and contains a rechargeable battery 606 and an identifier resistor 604.Detachable power supply 184 is connected to speech processor module 180 via power supply interface 406.External coil 208, also shown schematically, is connected to speech processor module 180 via headpiece interface 402.It should be appreciated, however, that when in the BTE operating mode, speech processor module 180 does not utilize external microphone 212, and external transmitter unit 106 (FIG.\",\n \"1A) may be used with speech processor module 180 rather than exterior component system 200.In FIG.\",\n \"6B, speech processor module 180 is not attached to ear hook 182 and power supply 184.Rather, it is coupled to on-board power supply 216 and an alarm system 524.As will be described in detail below, speech processor module 180 may be connected to a variety of external components implemented in protective case 202 or other components of external component system 200 depending on the implemented functionality.\",\n \"The embodiment shown in FIG.\",\n \"6B is just one exemplary implementation.\",\n \"In addition, external coil 208, also shown schematically, is connected to speech processor module 180 via headpiece interface 402 in the arrangement shown in FIG.\",\n \"6B.\",\n \"Returning to FIG.\",\n \"5, in accordance with one embodiment of the present invention, operation mode controller 500 comprises an operational mode selector 502 that determines which operational mode speech processor module 180 is to implement.\",\n \"As noted, in the exemplary embodiment described herein, speech processor module 180 may be implemented in a stand-alone mode as illustrated in FIG.\",\n \"1B, or a body-worn mode of operation as illustrated in FIGS.\",\n \"2 and 3.Operational mode selector 502 makes the noted determination based on settings or conditions sensed or received by either an external operational mode sensor 504 implemented in protective case 202, or an internal operational mode sensor 506 implemented in speech processor module 180.In one embodiment, the operational mode of speech processor module 180 is determined based on the identification of the power supply that is connected to the speech processor module.\",\n \"In such an embodiment, each power supply which may be utilized in connection with speech processor module 180 includes some identifying feature.\",\n \"Information regarding the identifying feature is communicated to speech processor module 180 via power supply identification (ID) signal line 426.In such embodiments, an internal operational mode sensor 506 is implemented to detect the particular identifying feature.\",\n \"For example, in the embodiment illustrated in FIGS.\",\n \"6A and 6B, the identifying feature is the value of a resistor included in each power supply.\",\n \"Referring to FIG.\",\n \"6A, detachable power supply 184 comprises a resistor 604 and, in this example, a rechargeable battery 606.Resistor 604 identifies power supply 184 as a type of detachable power supply suitable for use when speech processor module 180 implements the stand-alone mode of operation.\",\n \"Referring to FIG.\",\n \"6B, on-board power supply 216 comprises a resistor 654 and, in this example, a rechargeable battery 656.Resistor 654 identifies power supply 216 as a type of on-board power supply suitable for use when speech processor module 180 implements the body-worn mode of operation.\",\n \"In such embodiments, internal operational mode sensor 506 measures the resistance between ID signal line 426 and ground signal line 430 to determine the resistance of resistor 604 or 654.Based on this information, the type of power supply (i.e.\",\n \"one suitable for use in stand-alone mode verse one suitable for use in body-worn mode), and the desired mode of operation is determined by operational mode selector 502.The operational mode 501 is then distributed to other functional components of controller 500 as described herein.\",\n \"It should also be appreciated that operational mode sensors 504, 506 may utilize other information to determine the operational mode of speech processor module 180.For example, an externally-accessible switch may be provided on speech processor unit 180 (as part of internal sensor 506) or protective case 202 (as part of external sensor 504) to enable the recipient or another to manually select the operational mode.\",\n \"When implemented as part of external sensor 504, such a switch is preferably configured to prevent infants and children from changing the operational mode, as well as to prevent accidental changing of the operational mode during the intended use of the body-worn external component system 200.When implemented as part of internal sensor 506, such a switch is inaccessible once speech processor module 180 is mounted in protective case 202 making such safeguards optional.\",\n \"In another embodiment, external operational mode sensor 504 includes an infrared or other sensor responsive to signals transmitted by a remote control device.\",\n \"Such an embodiment allows the recipient or their carer to transmit appropriate signals to select the desired operational mode of speech processor module 180.Based on the selected mode of operation 501 generated by operational mode selector 502, a microphone selector 510 of controller 500 selects which microphone to use.\",\n \"When in the stand-alone mode of operation, internal microphone 186 is utilized, as shown in FIG.\",\n \"6A.\",\n \"When implementing the body-worn mode of operation, microphone 212 on headpiece 208 is utilized, as shown in FIG.\",\n \"6B.\",\n \"Microphone selector 510 forwards, connects, routes or otherwise provides the selected microphone 511 to other components of speech processor module 180.As one of ordinary skill in the art would appreciate, external microphone 212 may be located elsewhere; however, it is preferable that the external microphone be integrated into headpiece 208 as described herein.\",\n \"Such an embodiment reduces the quantity of components while also protecting the external microphone.\",\n \"In the embodiment shown in FIG.\",\n \"5, speech processor module 180 comprises internal alarm(s) 526 to provide the recipient or another with visual and/or audible indications of predetermined conditions occurring in the speech processor module when the speech processor module implements the stand-alone mode of operations.\",\n \"Exterior alarm(s) 524 are provided in protective case 202 to provide the same or similar alarms to the recipient or another when speech processor module 180 implements the body-worn mode of operation.\",\n \"In accordance with one embodiment, operational mode controller 500 comprises an alarm selector 520 that selects whether alarm conditions are to be broadcast using internal alarms 526 or external alarms 524 based on the selected operational mode 501.Referring to FIG.\",\n \"6B, external alarm(s) 524 is/are implemented in protective case 202 and comprises a buzzer 662 that is actuated when an alarm condition 523 is detected.\",\n \"External alarm(s) 524 incorporate a switch 658 that can be thrown by the recipient or another to generate a deactivate signal 521 to disable the alarm function.\",\n \"Such a switch is preferably configured to prevent the unintended changing of the state of the alarm.\",\n \"In one embodiment, external alarm 524 is implemented as part of connector block 332 on tray 324.In an alternative embodiment, external alarm 524 is implemented elsewhere on tray 324 or in protective case 202.It should be understood that the above embodiment of external alarm 524 is a buzzer.\",\n \"Such an audible alarm may be located at the exterior surface of protective case 202, or may be located internal to protective case 202 with an adjacent aperture in the protective case to permit the sound to travel out of the case and be heard by the recipient.\",\n \"In such alternative embodiments, such an aperture is constructed and arranged to provide a degree of protection analogous to that implemented in the other components and aspects of body-worn external components 200.It should also be appreciated that the type of alarm may include visual indicators in addition to or instead of the audible alarm noted above.\",\n \"Alternatively, an audible sound may be injected into the audio path to be heard by only the recipient.\",\n \"In one embodiment, the type of external alarm (indicator, enunciator, internal audio, etc.\",\n \"), may be selected by the recipient or another, depending on the recipient and intended use of external components 200.As one of ordinary skill in the art would find apparent, any condition may be selected to be one which qualifies as an alarm condition.\",\n \"For example, in one embodiment, alarm conditions include when the transcutaneous RF link fails such as by displacement of the external antenna.\",\n \"In another embodiment, alarm conditions include when protective case 202 is opened.\",\n \"It should also be appreciated that a hierarchical arrangement of alarm conditions may be established, each having a unique identifying alarm.\",\n \"Speech processor module 180 comprises an internal display 536 comprising, for example, a liquid crystal display (LCD) and/or one or more LEDs that display performance criteria 531 of the module.\",\n \"In one embodiment, performance criteria 531 comprises battery charge state, memory state, and/or other criteria.\",\n \"In one embodiment, such performance criteria is not provided to the recipient when speech processor module 180 is mounted in protective case 202.In an alternative embodiment, a portion of cover member 206 and/or base member 204 are transparent to provide a view into a protective case 202 such that internal display 536 can be seen from a position external to protective case 202.In a further embodiment, illustrated in FIG.\",\n \"5, protective case 202 provide an external display 534, for example, an LCD display located in cover member 206.A display selector 530 determines whether internal display 536 implemented in speech processor module 180 or external display 534 implemented in protective case 202 is to be used to provide the recipient or another with an indication of the noted performance criteria.\",\n \"Such a determination is based on selected operational mode 501 generated by operational mode selector 501.Such information may be provided to external display 534 via, for example, data out signal line 436.Speech processor module 180 also comprises internal user controls 546 through which a recipient or another can program or otherwise select functional operating parameters in speech processor module 180.For example, in one embodiment, speech processor module 180 comprises internal user controls 546 which enable, for example, program selection, volume control, etc.\",\n \"In one embodiment, such user controls are not provided to the recipient when speech processor module 180 is mounted in protective case 202.In a further embodiment, illustrated in FIG.\",\n \"5, protective case 202 provides external user controls 544 located, for example, in cover member 206 and/or base member 204.A user controls selector 540 determines whether internal user controls 546 of speech processor module 180 or external user controls 544 in protective case 202 are to be utilized to provide the recipient or another with the ability to control speech processor module 180.Such a determination is made based on the operational mode 501 provided by operational mode selector 502.When external user controls 544 is selected (i.e.\",\n \"speech processor module 180 implements the body-worn mode of operation), the transfer of information from the external interface is provided to selector 540 via, for example, data in signal line 434 (FIG.\",\n \"4).\",\n \"The user control inputs 541 generated by the selected user controls 544, 546 are forwarded, routed or otherwise provided to speech processor module 180 by selector 540.Speech processor module 180 includes internal on/off control 556, typically implemented as a manual switch in the housing of the speech processor module which can be manipulated by the recipient or another.\",\n \"When speech processor module 180 is mounted in protective case 202, internal on/off control 556 is no longer accessible to control the power state of speech processor module 180.In one embodiment, no additional controls are provided.\",\n \"In such an embodiment, protective case 202 must be opened to provide access to the above-noted on/off switch 556 on speech processor module 180.However, such an embodiment is inconvenient and time consuming to manage.\",\n \"In addition, repeated access to protective case 202 will accelerate the wearing of gasket 302 or other seal implemented in protective case 202 to provide the above-noted protection.\",\n \"In another embodiment, shown in FIG.\",\n \"5, an external on/off control 554 is included in protective case 202 which can be activated without having to access the internal enclosure of the protective case.\",\n \"In one embodiment, external on/off control 554 includes a reed switch or other magnetically-responsive component implemented in protective case 202.In the illustrated embodiment, the external on/off control 554 generates a signal which is forwarded, routed, passed, regenerated or otherwise provided to a power relay or other component speech processor module 180 to interrupt power to the module.\",\n \"In an alternate embodiment, the magnetically-responsive component is electrically interposed between on-board power supply 216 and speech processor module 180.In this embodiment, speech processor module 180 is disconnected from the power supply when the magnetic field of a magnet such as alignment magnet 110 within headpiece 208 is brought to a location adjacent to the magnetically-responsive switch.\",\n \"Other embodiments are also configured to cease operation when the transcutaneous RF link has been broken.\",\n \"For example, in one embodiment, internal on/off control 556 causes speech processor module 180 to periodically transmit an RF signal to implantable components 144, and wait for a response.\",\n \"When no response is present, speech processor module 180 enters a standby mode or turns off.\",\n \"If a standby mode is implemented, speech processor module 180 periodically transmits an RF signal while in the standby mode.\",\n \"If a response is received, speech processor module 180 then fully activates, starts processing sound and retransmits signals to implantable component 144.In another embodiment, external on/off control module 554 can include a manually-activated switch located on the exterior of protective case 202.Such a switch is preferably configured to prevent children from changing the power state, and from accidental changing of the power state during the intended use of the body-worn external components 200.In addition to one or more of the above embodiments, speech processor module 180 can also be adapted to shut down whenever on-board power supply 216 is being charged.\",\n \"In such an embodiment, protective case 202 also comprises charging circuitry (not shown) to allow power supply 216 to be recharged when case 202 is not in use.\",\n \"In another embodiment, external on/off control 554 includes an infrared or other sensor responsive to signals transmitted by a remote device operated by the recipient or their carer.\",\n \"In the case of adults, the present invention provides a recipient with the flexibility of using their speech processor module 180 in a moist environment.\",\n \"For infants and small children, the present invention also can be used in the comfort that the speech processor is less likely to be damaged than would be the case where the speech processor unit is used in the stand-alone mode.\",\n \"The case 202 is also potentially advantageous in that it can serve to assist in preventing tampering of speech processor module 180 by a child recipient or a third party.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874774"}}},{"rowIdx":4494697,"cells":{"text":{"kind":"list like","value":[["GROOVE PATTERN FOR A PUTTER HEAD","A putter head is provided.","The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.","The groove pattern includes multiple sets of grooves spaced apart from one another in a vertical direction of the putter face.","The sets of grooves have different cross-sectional configurations to adjust a launch angle of a golf ball based on an impact location of the golf ball along the vertical direction of the putter face."],["1.A putter head, comprising: a putter face defining: a first set of grooves located in an upper region or a lower region of the putter face and including multiple vertically-adjacent grooves extending in a heel-to-toe direction of the putter head, each groove of the first set of grooves having a non-symmetrical cross-sectional configuration; and a second set of grooves located in a middle region of the putter face, the second set of grooves including one or more grooves extending in the heel-to-toe direction of the putter head, each groove of the second set of grooves having a symmetrical cross-sectional configuration; wherein the non-symmetrical cross-sectional configurations of the grooves of the first set of grooves gradually transition into the symmetrical cross-sectional configuration of the one or more grooves of the second set of grooves to provide a varying launch angle along a vertical direction of the first set of grooves.","2.The putter head according to claim 1, wherein each groove of the second set of grooves comprises a substantially square groove.","3.The putter head according to claim 1, wherein each groove of the second set of grooves is defined by an upper wall surface and a lower wall surface that each extend inwardly into the putter head and are connected together by a substantially flat surface located at a bottom of the groove.","4.The putter head according to claim 1, wherein the grooves of the first set of grooves are separated from one another by intermediate surfaces that are coplanar with the putter face.","5.The putter head according to claim 1, wherein the depth of the grooves of the first set of grooves varies along the vertical direction of the putter face.","6.The putter head according to claim 1, wherein the depth of the grooves of the first set of grooves increases along the vertical direction of the putter face.","7.The putter head according to claim 1, wherein the depth of the grooves of the first set of grooves decreases along the vertical direction of the putter face.","8.The putter head according to claim 1, wherein each groove of the first set of grooves has a different depth.","9.The putter head according to claim 1, wherein: each groove of the first set of grooves includes an upper wall surface and a lower wall surface; one of the upper wall surfaces or the lower wall surfaces extend inwardly into the putter head at an angle that varies along the vertical direction of the putter face; and the other of the upper wall surfaces or the lower wall surfaces extend inwardly into the putter head at substantially the same angle along the vertical direction of the putter face.","10.The putter head according to claim 9, wherein the upper wall surfaces and the lower wall surfaces intersect at a bottom of the respective grooves.","11.The putter head according to claim 9, wherein: the first set of grooves is located in the lower region of the putter face; the upper wall surfaces extend inwardly into the putter head at substantially the same angle along the vertical direction of the putter face; and the lower wall surfaces extend upwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face.","12.The putter head according to claim 11, wherein the upper wall surfaces extend substantially perpendicular to the putter face.","13.The putter head according to claim 9, wherein: the first set of grooves is located in the upper region of the putter face; the upper wall surfaces extend downwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face; and the lower wall surfaces extend inwardly into the putter head at substantially the same angle along the vertical direction of the putter face.","14.The putter head according to claim 13, wherein the lower wall surfaces extend substantially perpendicular to the putter face.","15.The putter head according to claim 1, wherein the first set of grooves is located in the lower region of the putter face; and further comprising a third set of grooves located in the upper region of the putter face and including multiple vertically-adjacent grooves extending in the heel-to-toe direction of the putter head, each groove of the third set of grooves having a non-symmetrical cross-sectional configuration.","16.The putter head according to claim 15, wherein the non-symmetrical cross-sectional configurations of the grooves of the third set of grooves gradually transition into the symmetrical cross-sectional configuration of the one or more grooves of the second set of grooves to provide a varying launch angle along a vertical direction of the third set of grooves.","17.The putter head according to claim 16, wherein: the depth of the grooves of the first set of grooves varies along the vertical direction of the putter face; and the depth of the grooves of the third set of grooves varies along the vertical direction of the putter face.","18.The putter head according to claim 17, wherein the depth of the grooves of the first set of grooves and of the grooves of the third set of grooves increases as the first set of grooves and the third set of grooves approach the second set of grooves.","19.The putter head according to claim 17, wherein the depth of the grooves of the first set of grooves and of the grooves of the third set of grooves decreases as the first set of grooves and the third set of grooves approach the second set of grooves.","20.The putter head according to claim 16, wherein: each groove of the first set of grooves includes an upper wall surface and a lower wall surface; the upper wall surfaces of the grooves of the first set of grooves extend substantially perpendicular to the putter face; the lower wall surfaces of the grooves of the first set of grooves extend upwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face; each groove of the third set of grooves includes an upper wall surface and a lower wall surface; the upper wall surfaces of the grooves of the third set of grooves extend downwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face; and the lower wall surfaces of the grooves of the third set of grooves extend substantially perpendicular to the putter face."],["<SOH> BACKGROUND <EOH>Generally, when a golfer putts a ball, it initially skids along the ground before it begins to roll in a forward direction.","Minimizing the amount of skid increases the golfer's control of the ball.","The quicker the ball achieves true forward roll or rotation (the moment that the ball achieves forward or over spin without skidding or retaining backspin), the more control the golfer has over the distance and the path the golf ball travels along the green surface.","When a golf ball is struck by a putter head at a bottom of the golfer's swing, generally the static loft of the putter face lifts the ball out of a small depression in the green surface caused by the ball, and the ball reaches a forward roll quickly along the green surface.","However, golfers typically are not consistent in their swing, which generally reduces the control the golfer has over the distance and the path the golf ball travels along the green surface.","For example, if a golf ball is struck by a putter during an upward motion of the putter head, the putter head typically launches the ball off the ground, and the ball bounces and/or skids when it hits the green surface, thereby reducing a golfer's control over the distance and the path of the putt.","Alternatively, if a golf ball is struck by a putter during a downward motion of the putter head, the putter head typically drives the ball into the ground, causing the ball to bounce and/or skid, thereby reducing a golfer's control over the distance and the path of the putt.","For at least these reasons, it is difficult to fit a particular golfer with a putter."],["<SOH> SUMMARY <EOH>Embodiments of the disclosure generally provide a putter head that improves accuracy and consistency of putts, regardless of variations in a golfer's swing.","The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.","The groove pattern includes multiple sets, regions, or zones of grooves spaced apart from one another in a vertical direction of the putter face.","The sets of grooves have different cross-sectional configurations to adjust a launch angle of a golf ball based on an impact location of the golf ball along the vertical direction of the putter face.","In some embodiments, the putter head includes a putter face defining a first set of grooves and a second set of grooves extending in a heel-to-toe direction of the putter head.","The second set of grooves may be positioned apart from the first set of grooves in the vertical direction of the putter face.","The first and second sets of grooves may have different cross-sectional configurations.","The putter head may include a third set of grooves extending in the heel-to-toe direction and positioned apart from the first and second sets of grooves in the vertical direction of the putter face.","Each groove of the first and third sets of grooves may have a non-symmetrical cross-sectional configuration, whereas each groove of the second set of grooves may have a symmetrical cross-sectional configuration.","This summary of the disclosure is given to aid understanding, and one of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances.","Accordingly, while the disclosure is presented in terms of embodiments, it should be appreciated that individual aspects of any embodiment can be claimed separately or in combination with aspects and features of that embodiment or any other embodiment.","The present disclosure is set forth in various levels of detail in this application and no limitation as to the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, or the like in this summary.","In certain instances, details that are not necessary for an understanding of the disclosure or that render other details difficult to perceive may have been omitted.","It should be understood that the claimed subject matter is not necessarily limited to the particular embodiments or arrangements illustrated herein."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","15/292,412, filed Oct. 13, 2016, and entitled “Groove Pattern for a Putter Head,” which claims the benefit of priority under 35 U.S.C.","§ 119(e) of U.S. provisional patent application Ser.","No.","62/247,688, filed Oct. 28, 2015, and entitled “Groove Pattern for a Putter Head,” and of U.S. provisional patent application Ser.","No.","62/326,247, filed Apr.","22, 2016, and entitled “Groove Pattern for a Putter Head,” which are hereby incorporated herein in their entireties.","FIELD The present disclosure relates generally to golf clubs, and more particularly to a groove pattern for a putter head.","BACKGROUND Generally, when a golfer putts a ball, it initially skids along the ground before it begins to roll in a forward direction.","Minimizing the amount of skid increases the golfer's control of the ball.","The quicker the ball achieves true forward roll or rotation (the moment that the ball achieves forward or over spin without skidding or retaining backspin), the more control the golfer has over the distance and the path the golf ball travels along the green surface.","When a golf ball is struck by a putter head at a bottom of the golfer's swing, generally the static loft of the putter face lifts the ball out of a small depression in the green surface caused by the ball, and the ball reaches a forward roll quickly along the green surface.","However, golfers typically are not consistent in their swing, which generally reduces the control the golfer has over the distance and the path the golf ball travels along the green surface.","For example, if a golf ball is struck by a putter during an upward motion of the putter head, the putter head typically launches the ball off the ground, and the ball bounces and/or skids when it hits the green surface, thereby reducing a golfer's control over the distance and the path of the putt.","Alternatively, if a golf ball is struck by a putter during a downward motion of the putter head, the putter head typically drives the ball into the ground, causing the ball to bounce and/or skid, thereby reducing a golfer's control over the distance and the path of the putt.","For at least these reasons, it is difficult to fit a particular golfer with a putter.","SUMMARY Embodiments of the disclosure generally provide a putter head that improves accuracy and consistency of putts, regardless of variations in a golfer's swing.","The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.","The groove pattern includes multiple sets, regions, or zones of grooves spaced apart from one another in a vertical direction of the putter face.","The sets of grooves have different cross-sectional configurations to adjust a launch angle of a golf ball based on an impact location of the golf ball along the vertical direction of the putter face.","In some embodiments, the putter head includes a putter face defining a first set of grooves and a second set of grooves extending in a heel-to-toe direction of the putter head.","The second set of grooves may be positioned apart from the first set of grooves in the vertical direction of the putter face.","The first and second sets of grooves may have different cross-sectional configurations.","The putter head may include a third set of grooves extending in the heel-to-toe direction and positioned apart from the first and second sets of grooves in the vertical direction of the putter face.","Each groove of the first and third sets of grooves may have a non-symmetrical cross-sectional configuration, whereas each groove of the second set of grooves may have a symmetrical cross-sectional configuration.","This summary of the disclosure is given to aid understanding, and one of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances.","Accordingly, while the disclosure is presented in terms of embodiments, it should be appreciated that individual aspects of any embodiment can be claimed separately or in combination with aspects and features of that embodiment or any other embodiment.","The present disclosure is set forth in various levels of detail in this application and no limitation as to the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, or the like in this summary.","In certain instances, details that are not necessary for an understanding of the disclosure or that render other details difficult to perceive may have been omitted.","It should be understood that the claimed subject matter is not necessarily limited to the particular embodiments or arrangements illustrated herein.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated into and constitute a part of the specification, illustrate embodiments of the disclosure and, together with the general description given above and the detailed description given below, serve to explain the principles of these embodiments.","FIG.","1 is a front isometric view of a putter head in accordance with some embodiments of the present disclosure.","FIG.","2 is a side elevation view of the putter head of FIG.","1 in accordance with some embodiments of the present disclosure.","FIG.","3 is a front elevation view of the putter head of FIG.","1 in accordance with some embodiments of the present disclosure.","FIG.","4 is a cross-sectional view of the putter head of FIG.","1 taken along sectional line 4-4 of FIG.","3 in accordance with some embodiments of the present disclosure.","FIG.","5 is an enlarged, fragmentary view of a middle region of the putter face shown in the cross-sectional view of FIG.","4 in accordance with some embodiments of the present disclosure.","FIG.","6 is an enlarged, fragmentary view of a lower region of a putter face shown in the cross-sectional view of FIG.","4 in accordance with some embodiments of the present disclosure.","FIG.","7 is an enlarged, fragmentary view of an upper region of the putter face shown in the cross-sectional view of FIG.","4 in accordance with some embodiments of the present disclosure.","FIG.","8 is a front isometric, exploded view of a putter head in accordance with some embodiments of the present disclosure.","FIG.","9 is a cross-sectional view of the putter head of FIG.","1 taken along sectional line 4-4 of FIG.","3 with a middle region of the putter face in contact with a golf ball in accordance with some embodiments of the present disclosure.","FIG.","10 is a cross-sectional view of the putter head of FIG.","1 taken along sectional line 4-4 of FIG.","3 with a lower region of the putter face in contact with a golf ball in accordance with some embodiments of the present disclosure.","FIG.","11 is a cross-sectional view of the putter head of FIG.","1 taken along sectional line 4-4 of FIG.","3 with an upper region of the putter face in contact with a golf ball in accordance with some embodiments of the present disclosure.","FIG.","12 is a view of a putter head including a different groove configuration relative to FIG.","4 in accordance with some embodiments of the present disclosure.","FIG.","13 is a view of a putter head including a different groove configuration relative to FIGS.","4 and 12 in accordance with some embodiments of the present disclosure.","DETAILED DESCRIPTION Embodiments of the present disclosure generally provide a putter head including grooves located in different regions on a putter face for improving the accuracy and consistency of putts, regardless of variations in the golfer's swing.","The applicant uses the term “groove” in this description broadly to include cuts, crevices, depressions, recesses, troughs, or other voids that are associated with a putter face.","In a preferred embodiment, the grooves are substantially parallel to one another and are arranged generally horizontally in a heel-to-toe direction on the putter face.","An example embodiment of a putter head is shown and described below with respect to FIGS.","1-11.Although in each of these figures the putter head is shown with three regions of grooves, the putter head may include two, three, or more regions of grooves.","The grooves may be used with any type of putter head or shaft, whether currently known or later developed.","Referring to FIG.","1, a front isometric view of an illustrative embodiment of a putter head formed in accordance with some embodiments of the present disclosure is provided.","Putter head 100, illustrated in FIG.","1, includes a top surface 102, a bottom surface or sole 104, a heel 106, a toe 108, and a hosel 110.The top surface 102 is directed generally towards the sky and the bottom surface 104 is directed generally toward the ground when the golfer addresses the golf ball.","The heel 106 is generally directed towards the golfer and the toe 108 is generally directed away from the golfer when the golfer addresses the golf ball.","The hosel 110 generally extends upwardly from the top surface 102, typically proximate to the heel 106, and is the portion of the putter head 100 to which a shaft is attached.","The respective top surface 102, bottom surface 104, heel 106, toe 108, and hosel 110 may be formed in various shapes and sizes.","With continued reference to FIG.","1, the putter head 100 includes a face 112 that is directed generally towards a golf ball when the golfer addresses the golf ball.","The putter face 112 generally extends between the top surface 102, the bottom surface 104, the heel 106, and the toe 108.As shown in FIG.","2, the putter face 112 may be substantially flat and planar.","As further shown in FIG.","2, the putter face 112 may be lofted in order to lift the ball up onto the top of the green surface from a slight depression in which it rests.","As the loft angle of the putter face 112 (generally referred to as static loft) increases, more lift will be imparted to the ball.","The putter face 112 may have some degree of static loft.","For example, the loft angle of the putter face 112 may range from about 1 degree to about 5 degrees.","In some embodiments, the putter face 112 has a loft angle of about 3 degrees.","With continued reference to FIG.","2, a lower, front edge 114 of the putter head 100 may be rounded to allow the putter face 112 to glide better through taller grass when used in the fringe of the green surface and to reduce the likelihood that the putter face 112 catches or grabs on the green surface during the course of play.","Referring back to FIG.","1, the putter face 112 includes a groove pattern 116.The groove pattern 116 may be cut, etched, molded, or otherwise formed in the putter face 112.The groove pattern 116 may be formed directly into a face of the putter head 100 (e.g., milled into the putter head), or, as shown in FIGS.","1 and 3-11, the groove pattern 116 may be formed in a putter face insert 118 that is attached to the putter head 100.As shown in FIG.","8, the putter head 100 may define a cavity 119 opening through the bottom surface 104 of the putter head 100 that receives the insert 118.By inserting the insert 118 through the opening in the bottom surface 104, the insert 118 may provide a softer feel when a ball is struck low on the putter face 112 in embodiments where the insert 118 is made from a softer material than the body of the putter head 100.The insert 118 also does not visually disturb the top surface 102 of the putter head 100, which may distract the golfer during putting.","Although not shown, the cavity 119 may open through the top surface 102 of the putter head 100, or may not open through either the top surface 102 or the bottom surface 104.The insert 118 may be formed in a trapezoidal shape as shown in FIGS.","1, 3, and 8, a conic shape, a rectangular shape, or any other shape.","With continued reference to FIG.","1, the groove pattern 116 generally extends in a heel-to-toe direction 119 along the face 112 of the putter head 100.The groove pattern 116 generally increases the time the ball spends in contact with the putter face 112, generally referred to as dwell time, by reducing the surface area of the putter face 112 in contact with the ball, thereby providing the putter head 100 with a soft feel upon contact with the ball.","The groove pattern 116 may be formed in a trapezoidal shaped perimeter as shown in FIG.","1, a conic shaped perimeter, a rectangular shaped perimeter, or any other shaped perimeter.","The groove pattern 116 may extend partially across the putter face 112, for example as shown in FIG.","1, or may extend across the entire putter face 112 from the heel 106 to the toe 108.Referring to FIGS.","3 and 4, the groove pattern 116 includes multiple sets, regions, or zones of different grooves extending in a heel-to-toe direction 119 of the putter head 100 and spaced apart from one another in a vertical direction 121 of the putter face 112.The groove pattern 116 is configured to provide a golfer a relatively large margin of error in the angle of impact between the putter head 100 and the golf ball so that the ball travels straighter with a desired distance regardless of the golfer's variation in their swing from one putt to another putt.","The groove pattern 116 generally improves the forward roll or rotation of the golf ball when the ball is struck off-center up and down the putter face 112.In FIGS.","3 and 4, the putter face 112 defines three sets of grooves.","However, it should be appreciated the putter face 112 may include two, three, or more sets of grooves.","With continued reference to FIGS.","3 and 4, the putter face 112 includes a first set, region, or zone of grooves 120 (hereinafter “first set of grooves” for the sake of convenience without intent to limit) and a second set, region, or zone of grooves 122 (hereinafter “second set of grooves” for the sake of convenience without intent to limit).","The first and second set of grooves 120, 122 extend in the heel-to-toe direction 119 of the putter head 100 and are spaced apart from each other in the vertical direction 121 of the putter face 112.The vertical direction 121 of the putter face 112 is oriented generally perpendicular to the heel-to-toe direction 119 of the putter head 100 and generally parallel to the putter face 112.As shown in FIGS.","3 and 4, the putter face 112 may include a third set, region, or zone of grooves 126 (hereinafter “third set of grooves” for the sake of convenience without intent to limit) extending in the heel-to-toe direction 119 of the putter head 100.The third set of grooves 126 may be spaced apart from the first and second set of grooves 120, 122 in the vertical direction 121.Referring still to FIGS.","3 and 4, the second set of grooves 122 may be located vertically between the first set of grooves 120 and the third set of grooves 126.The first set of grooves 120, the second set of grooves 122, and the third set of grooves 126 may extend parallel to one another along the putter face 112.The first set of grooves 120 may be located in a lower region 130 of the putter face 112 generally below a center of gravity of the putter head 100.The third set of grooves 126 may be located in an upper region 134 of the putter face 112 generally above a center of gravity of the putter head 100.The second set of grooves 122 may be located in a middle region 132 of the putter face 112 generally in front of a center of gravity of the putter head 100.The lower region 130 may be located near the bottom surface 104 of the putter head 100 in a lower one-third portion of the putter face 112, the upper region 134 be located near the top surface 102 of the putter head 100 in an upper one-third portion of the putter face 112, and the middle region 132 may be located between the lower and upper regions 130, 134 in a middle one-third portion of the putter face 112.Referring to FIG.","5, an enlarged cross-sectional view of the middle region 132 of the putter face 112 is provided.","The middle region 132, as shown in FIG.","5, may include the second set of grooves 122.The second set of grooves 122 generally contacts the golf ball when the putter head 100 strikes the ball near the vertical center of the putter face 112 and/or center of gravity of the putter head 100.In FIG.","5, the second set of grooves 122 includes five grooves formed in the putter face 112.It should be understood that the second set of grooves 122 may include more or less than five grooves.","For example, in some configurations, the second set of grooves 122 includes a single groove.","In some configurations, the second set of grooves 122 includes two or more grooves.","Referring still to FIG.","5, each groove 138 of the second set of grooves 122 may have a symmetrical cross-sectional configuration or shape.","In FIG.","5, each groove 138 of the illustrative embodiment has a substantially square cross-sectional configuration including an upper or first wall surface 140 and a lower or second wall surface 142 that each extend inwardly into the putter head 100 and are connected together by a substantially flat surface 144 located at a bottom of the groove 138.The upper and lower walls surfaces 140, 142 may extend substantially perpendicularly (e.g., at a ninety degree angle) to the putter face 112 and the substantially flat surfaces 144.In some embodiments, the upper and lower wall surfaces 140, 142 may extend toward one another as they extend inwardly into the putter head 100.In some embodiments, the upper and lower wall surfaces 140, 142 have about a 10 degree draft angle, and the depth of each respective groove 138 is about 0.015 inches.","Although the grooves 138 shown in FIG.","5 have a substantially square cross-sectional configuration, in some embodiments the grooves 138 have other symmetrical cross-sectional configurations, such as a V-shaped cross-sectional configuration having upper and lower wall surfaces 140, 142 intersect at a bottom of the respective grooves 138 or a parallelogram configuration.","With continued reference to FIG.","5, adjacent grooves 138 of the second set of grooves 122 may be separated from each other by intermediate surfaces 146 of the putter face 112.The intermediate surfaces 146 may be flat and coplanar with the putter face 112.The intersection of the upper wall surface 140 and a respective superjacent intermediate surface 146 may form an upper or first groove edge 148a, and the intersection of the lower wall surface 142 and a respective subjacent intermediate surface 146 may form a lower or second groove edge 148b for each groove 138.The upper and lower groove edges 148a, 148b generally have the same angle or sharpness.","The upper and lower groove edges 148a, 148b may be formed by substantially right angles (e.g., about seventy-five to one-hundred and five degree angles) defined by the intersections of the upper and lower wall surfaces 140, 142, and the intermediate surfaces 146.The upper and lower edges 148a, 148b may be coplanar with the putter face 112.The distance between the upper and lower edges 148a, 148b generally defines the opening or mouth of each groove 138, which may be greater in dimension than the respective intermediate surfaces 146 in the vertical direction 119 of the putter face 112.Referring to FIG.","9, when a golf ball 149 is struck near the vertical center of the putter face 112 and/or center of gravity of the putter head 100, the intermediate surfaces 146 generally strike the back of the ball 149 with little or no need for modulation of the launch angle by the groove edges 148a, 148b since the static loft angle of the putter face 112 imparts a desired launch angle to the ball 149, causing the ball 149 to roll forward in a desired path, with the static loft angle of the putter face 112 slightly lifting the ball 149 out of a depression in which it rests.","To the extent the ball is struck in the middle region 132 of the putter head 100 but the putter face 112 is angled forwardly or rearwardly of the desired static loft angle, one or more of the upper and lower groove edges 148a, 148b engage the outer surface of the ball 149, thereby altering the launch angle of the ball 149 to counteract the misalignment of the putter face 112 relative to the ball 149, resulting in improved putting performance.","The launch angle is the angle at which the golf ball is launched into the air after contacting the putter face 112, and generally is measured between a projected path of the golf ball and a horizontal or ground plane.","Both dynamic loft angle and static loft angle affect the launch angle.","Dynamic loft angle generally is a combination of the static loft angle, the lean of the shaft, and the path of the club head as the golfer swings and addresses the ball.","Static loft angle generally is defined by the plane in which the putter face lies.","Many other factors may also affect the degree of launch angle.","Referring to FIG.","6, an enlarged cross-sectional view of the lower region 130 of the putter face 112 is provided.","The lower region 130, as shown in FIG.","6, may include the first set of grooves 120.The first set of grooves 122 generally contacts the golf ball when the putter head 100 strikes the ball below the vertical center of the putter face 112 and/or center of gravity of the putter head 100.In FIG.","6, the first set of grooves 120 includes four grooves formed in the putter face 112.It should be understood that the first set of grooves 120 may include more or less than four grooves.","For example, in some configurations, the first set of grooves 120 includes a single groove.","In some configurations, the first set of grooves 120 includes two or more grooves.","Referring to FIGS.","5 and 6, the first and second set of grooves 120, 122 have different cross-sectional configurations.","Referring specifically to FIG.","6, each groove 150 of the first set of grooves 120 has a non-symmetrical cross-sectional configuration or shape.","In FIG.","6, each groove 150 of the illustrative embodiment extends upwardly into the putter head 100.Each groove 150 may be defined by a lower or first wall surface 152 and an upper or second wall surface 154.The lower wall surface 152 may extend upwardly and inwardly into the putter head 100 at a first angle α1 relative to the putter face 112, and the upper wall surface 154 may extend inwardly into the putter head 100 at a second angle α2 relative to the putter face 112 that is greater than the first angle α1.The upper wall surface 154 may extend downwardly into the putter head 100 at the second angle α2.In some embodiments, the first angle α1 is about 20 degrees, and the second angle α2 is about 80 degrees, although other angles are contemplated.","The lower and upper wall surfaces 152, 154 may extend toward one another as they extend inwardly into the putter head 100 and may intersect at a bottom 155 of a respective groove 150.With continued reference to FIG.","6, adjacent grooves 150 of the first set of grooves 120 may be separated from each other by intermediate surfaces 156.The intermediate surfaces 156 may be flat and coplanar with the putter face 112.The intersection of the upper wall surface 154 and a respective superjacent intermediate surface 156 may form an upper or first groove edge 158a, and the intersection of the lower wall surface 152 and a respective subjacent intermediate surface 156 may form a lower or second groove edge 158b for each groove 150.The upper groove edges 158a are sharper (e.g., have sharper angles) than the lower grooves edges 158b based on the different angles α2, α1 of the upper and lower wall surfaces 154, 152, respectively.","The upper groove edges 158a may be formed by substantially right angles (e.g., about seventy-five to one-hundred and five degree angles) defined by the intersections of the upper wall surfaces 154 and the intermediate surfaces 156, whereas the lower groove edges 158b may be formed by substantially obtuse angles (i.e., greater than ninety degree angles) defined by the intersections of the lower wall surfaces 152 and the intermediate surfaces 156.The upper and lower edges 158a, 158b may be coplanar with the putter face 112.The distance between the upper and lower edges 158a, 158b generally defines the opening or mouth of each groove 150, which may be greater in dimension than the respective intermediate surfaces 156 in the vertical direction 119 of the putter face 112.Generally, when a golf ball is struck below a vertical center of a putter face and/or center of gravity of a putter head, the shaft and the putter face typically are tilted rearwardly, causing more loft to be presented at the point of impact.","This increased loft typically causes the ball to launch higher than desired, resulting in decreased distance and accuracy.","Referring to FIGS.","6 and 10, the first set of grooves 120 modulates this undesired loft angle to improve putter performance.","When the putter face 112 is tilted backwards and the lower region 120 of the putter face 112 impacts the golf ball 149, one or more of the upper and lower groove edges 158a, 158b engage the outer surface of the ball 149.The sharper angle of the upper groove edges 158a relative to the lower groove edges 158b reduces the launch angle of the ball 149, thereby lifting the ball on top of the green surface without launching the ball into the air, resulting in reduced bouncing and backspin and improved putting performance.","Referring to FIG.","7, an enlarged cross-sectional view of the upper region 134 of the putter face 112 is provided.","The upper region 134, as shown in FIG.","7, may include the third set of grooves 126.The third set of grooves 126 generally contacts the golf ball when the putter head 100 strikes the ball above the vertical center of the putter face 112 and/or center of gravity of the putter head 100.In FIG.","7, the third set of grooves 126 includes four grooves formed in the putter face 112.It should be understood that the third set of grooves 126 may include more or less than four grooves.","For example, in some configurations, the third set of grooves 126 includes a single groove.","In some configurations, the third set of grooves 126 includes two or more grooves.","Referring to FIGS.","5 and 7, the second and third set of grooves 122, 126 have different cross-sectional configurations.","Referring to FIGS.","4-7, the first and third set of grooves 120, 126 may be symmetrical about a plane that is oriented parallel to the sole 104 of the putter head 100, extends in the heel-to-toe direction 119, and bisects the second set of grooves 122.Referring specifically to FIG.","7, each groove 160 of the third set of grooves 126 has a non-symmetrical cross-sectional configuration or shape.","In FIG.","7, each groove 160 of the illustrative embodiment extends downwardly into the putter head 100.Each groove 160 may be defined by an upper or first wall surface 162 and a lower or second wall surface 164.The upper wall surface 162 may extend downwardly and inwardly into the putter head 100 at a first angle α3 relative to the putter face 112, and the lower wall surface 164 may extend inwardly into the putter head 100 at a second angle α4 relative to the putter face 112 that is greater than the first angle α3.The lower wall surface 164 may extend upwardly into the putter head 100 at the second angle α4.In some embodiments, the first angle α3 is about 20 degrees, and the second angle α4 is about 80 degrees, although other angles are contemplated.","The upper and lower wall surfaces 162, 164 may extend toward one another as they extend inwardly into the putter head 100 and may intersect at a bottom 165 of the respective groove 160.With continued reference to FIG.","7, adjacent grooves 160 of the third set of grooves 126 may be separated from each other by intermediate surfaces 166.The intermediate surfaces 166 may be flat and coplanar with the putter face 112.The intersection of the upper wall surface 162 and a respective superjacent intermediate surface 166 may form an upper or first groove edge 168a, and the intersection of the lower wall surface 164 and a respective subjacent intermediate surface 166 may form a lower or second groove edge 168b for each groove 160.The lower groove edges 168b are sharper (e.g., have sharper angles) than the upper grooves edges 168a based on the different angles α4, α3 of the lower and upper wall surfaces 164, 162, respectively.","The upper groove edges 168a may be formed by substantially obtuse angles (i.e., greater than ninety degree angles) defined by the intersections of the upper wall surfaces 162 and the intermediate surfaces 166, whereas the lower groove edges 168b may be formed by substantially right angles (e.g., about seventy-five to one-hundred and five degree angles) defined by the intersections of the lower wall surfaces 164 and the intermediate surfaces 166.The upper and lower edges 168a, 168b may be coplanar with the putter face 112.The distance between the upper and lower edges 168a, 168b generally defines the opening or mouth of each groove 160, which may be greater in dimension than the respective intermediate surfaces 166 in the vertical direction 119 of the putter face 112.Generally, when a golf ball is struck above a vertical center of a putter face and/or center of gravity of the putter head, the shaft and the putter face typically are tilted forwardly, causing decreased loft to be presented at the point of ball impact.","This decreased loft typically causes the ball to launch into the ground, resulting in decreased distance and accuracy.","Referring to FIGS.","7 and 11, the third set of grooves 126 modulates this undesired loft angle to improve putter performance.","When the putter face 112 is tilted forwards and the upper region 126 of the putter face 112 impacts the golf ball 149, one or more of the upper and lower groove edges 156a, 168b engage the outer surface of the ball 149.The sharper angle of the lower groove edges 168b relative to the upper groove edges 168a increases the launch angle of the ball 149, thereby lifting the ball on top of the green surface, rather than driving the ball into the ground, resulting in improved putting performance.","With reference to FIGS.","1-12, the putter head 100 may be formed of various materials, including metallic materials, non-metallic materials, or a combination of both.","In some embodiments, the putter head 100 is formed of a stainless steel material, such as 303 and/or 304 stainless steel, which is forged steel that provides a softer feel at impact because of the density of the material.","Referring to FIGS.","1 and 3-11, if the putter head 100 includes a putter face insert 118, the insert 118 may be formed of a polymer, for example.","Golfers generally prefer a softer feeling putter, and polymer inserts have a much softer durometer measurement than a steel face insert.","The softer durometer measurement of the polymer insert also increases the dwell time of the ball, resulting in increased friction between the ball and the putter face 112, and thereby improving ball roll and launch conditions measured by how quickly and consistently the ball begins forward rotation.","In some embodiments, the insert 118 may be formed of polyurethane, which is easy to manufacture and allows the manufacturer to select different hardness factors for the insert 118, which impacts the feel of the putter.","In some groove pattern configurations, the first and third set of grooves 120, 126 may gradually transition into the second set of grooves 122.For example, the non-symmetrical cross-sectional configurations of the first and third set of grooves 120, 126 may gradually transition into the symmetrical cross-sectional configuration of the second set of grooves 122, which may include one or more substantially square grooves.","In other words, the cross-sectional configurations of the first and third set of grooves 120, 126 may gradually become more symmetrical as they approach the second set of grooves 122 so that the first and third set of grooves 120, 126 gradually transition into the second set of grooves 122.By gradually transitioning the first and third set of grooves 120, 126 into the second set of grooves 122, the groove pattern 116 provides a continuously varying launch angle modulation along the vertical direction 119 of the putter face 112.With the exception of the groove patterns 216, 316 illustrated in FIGS.","12 and 13, respectively, the putter heads 200 and 300 illustrated in FIGS.","12 and 13, respectively, have the same features and operation as the putter head 100 depicted in FIGS.","1-11.Accordingly, the preceding discussion of the features and operation of the putter head 100 should be considered equally applicable to the putter heads 200 and 300 illustrated in FIGS.","12 and 13, except as noted in the following discussion pertaining to the groove patterns 216 and 316.Referring to FIG.","12, the groove pattern 216 includes a first set, region, or zone of grooves 220 (hereinafter “first set of grooves” for the sake of convenience without intent to limit), a second set, region, or zone of grooves 222 (hereinafter “second set of grooves” for the sake of convenience without intent to limit), and a third set, region, or zone of grooves 226 (hereinafter “third set of grooves” for the sake of convenience without intent to limit).","In FIG.","12, the first set of grooves 220 includes seven grooves formed in the putter face 212, the second set of grooves 222 includes a single groove formed in the putter face 212, and the third set of grooves 226 includes seven grooves formed in the putter face 212.It should be understood that the first set of grooves 220, the second set of grooves 222, and the third set of grooves 226 may include more or less than the grooves illustrated in FIG.","12.The first set of grooves 220 may extend at an incline from the putter face 212 into the putter head 200, and the third set of grooves 226 may extend at a decline from the putter face 212 into the putter head 200.The groove pattern 216 may exhibit a gradual change in the pitch of the groove angles in the first set of grooves 220 and the third set of grooves 226 along the vertical profile of the putter face 212.Each groove in the first set of grooves 220 and in the third set of grooves 226 may have a unique pitch.","The pitch of adjacent grooves in the first set of grooves 220 and in the third set of grooves 226 along the vertical profile of the putter face 212 may differ by a delta amount, such as about 5 degrees.","The delta amount may vary depending on the putter.","Referring still to FIG.","12, each groove 250 of the first set of grooves 220 may have a non-symmetrical cross-sectional configuration or shape.","In FIG.","12, each groove 250 may extend upwardly into the putter head 200.Each groove 250 may be defined by a lower or first wall surface 252 and an upper or second wall surface 254, which may intersect each other to define a bottom or vertex 255 of the respective groove 250.The lower wall surface 252 may extend at an incline angle or pitch from the putter face 212 into the putter head 200, and the upper wall surface 254 may extend substantially perpendicular to the putter face 212 into the putter head 200.The first set of grooves 220 may exhibit a gradual change in the incline angle or pitch of the lower wall surfaces 252 along the vertical profile of the putter face 212, while the angle or pitch of the upper wall surfaces 254 may be substantially the same.","In other words, each lower wall surface 252 may have a unique pitch that differs by a delta amount from adjacent lower wall surfaces 252.In some arrangements, the pitch of adjacent lower wall surfaces 252 may differ by a delta amount of about 5 degrees.","The delta amount may vary depending on the putter.","In FIG.","12, a lowermost groove 250a of the first set of grooves 220 includes a lower wall surface 252a having a first inclined pitch, an uppermost groove 250b of the first set of grooves 220 includes a lower wall surface 252b having a second inclined pitch that is less than the first inclined pitch, and the lower wall surfaces 252 of the grooves 250 located between the lowermost groove 250a and the uppermost groove 250b gradually decrease in their inclined pitch from the lowermost groove 250a to the uppermost groove 250b along the vertical profile of the putter face 212.Referring still to FIG.","12, each groove 260 of the third set of grooves 226 may have a non-symmetrical cross-sectional configuration or shape.","In FIG.","12, each groove 260 of the third set of grooves 226 may extend downwardly into the putter head 200.Each groove 260 may be defined by an upper or first wall surface 262 and a lower or second wall surface 264, which may intersect each other to define a bottom or vertex 265 of the respective groove 260.The upper wall surface 262 may extend at a decline angle or pitch from the putter face 212 into the putter head 200, and the lower wall surface 264 may extend substantially perpendicular to the putter face 212 into the putter head 200.The third set of grooves 226 may exhibit a gradual change in the decline angle or pitch of the upper wall surfaces 262 along the vertical profile of the putter face 212, while the angle or pitch of the lower wall surfaces 264 may be substantially the same.","In other words, each upper wall surface 262 may have a unique pitch that differs by a delta amount from adjacent upper wall surfaces 262.In some arrangements, the pitch of adjacent upper wall surfaces 262 may differ by a delta amount of about 5 degrees.","The delta amount may vary depending on the putter.","In FIG.","12, a lowermost groove 260a of the third set of grooves 226 includes an upper wall surface 262a having a first declined pitch, an uppermost groove 260b includes an upper wall surface 262b having a second declined pitch that is greater than the first declined pitch, and the upper wall surfaces 262 of the grooves 260 located between the lowermost groove 260a and the uppermost groove 260b gradually increase in their declined pitch from the lowermost groove 260a to the uppermost groove 260b along the vertical profile of the putter face 212.With continued reference to FIG.","12, the second set of grooves 222 generally is located at the center of the putter face 212 near the vertical center of gravity (center of mass) of the putter head 200, where the ball is ideally struck.","In FIG.","12, a single groove 238 is included in the second set of grooves 222, although more than one groove may be included in the second set of grooves 222.The one or more grooves of the second set of grooves 222 may be located near the center of the putter face 212 and may include upper and lower wall surfaces oriented substantially perpendicular to the putter face 212, as illustrated in FIG.","12.The upper and lower wall surfaces may be connected together by a substantially flat surface located at a bottom of the respective groove and oriented substantially parallel to the putter face 212, as illustrated in FIG.","12.Referring to FIG.","13, the groove pattern 316 includes a first set, region, or zone of grooves 320 (hereinafter “first set of grooves” for the sake of convenience without intent to limit), a second set, region, or zone of grooves 322 (hereinafter “second set of grooves” for the sake of convenience without intent to limit), and a third set, region, or zone of grooves 326 (hereinafter “third set of grooves” for the sake of convenience without intent to limit).","In FIG.","13, the first set of grooves 320 includes seven grooves formed in the putter face 312, the second set of grooves 322 includes a single groove formed in the putter face 312, and the third set of grooves 326 includes seven grooves formed in the putter face 312.It should be understood that the first set of grooves 320, the second set of grooves 322, and the third set of grooves 326 may include more or less than the grooves illustrated in FIG.","13.The first set of grooves 320 may extend at an incline from the putter face 312 into the putter head 300, and the third set of grooves 326 may extend at a decline from the putter face 312 into the putter head 300.The groove pattern 316 may exhibit a gradual change in the pitch of the groove angles in the first set of grooves 320 and the third set of grooves 326 along the vertical profile of the putter face 312.Each groove in the first set of grooves 320 and in the third set of grooves 326 may have a unique pitch.","The pitch of adjacent grooves in the first set of grooves 320 and in the third set of grooves 326 along the vertical profile of the putter face 312 may differ by a delta amount, such as about 5 degrees.","The delta amount may vary depending on the putter.","Referring still to FIG.","13, each groove 350 of the first set of grooves 320 may have a non-symmetrical cross-sectional configuration or shape.","In FIG.","13, each groove 350 may extend upwardly into the putter head 300.Each groove 350 may be defined by a lower or first wall surface 352 and an upper or second wall surface 354, which may intersect each other to define a bottom or vertex 355 of the respective groove 350.The lower wall surface 352 may extend at an incline angle or pitch from the putter face 312 into the putter head 300, and the upper wall surface 354 may extend substantially perpendicular to the putter face 312 into the putter head 300.The first set of grooves 320 may exhibit a gradual change in the incline angle or pitch of the lower wall surfaces 352 along the vertical profile of the putter face 312, while the angle or pitch of the upper wall surfaces 354 may be substantially the same.","In other words, each lower wall surface 352 may have a unique pitch that differs by a delta amount from adjacent lower wall surfaces 352.In some arrangements, the pitch of adjacent lower wall surfaces 352 may differ by a delta amount of about 5 degrees.","The delta amount may vary depending on the putter.","In FIG.","13, a lowermost groove 350a of the first set of grooves 320 includes a lower wall surface 352a having a first inclined pitch, an uppermost groove 350b of the first set of grooves 320 includes a lower wall surface 352b having a second inclined pitch that is greater than the first inclined pitch, and the lower wall surfaces 352 of the grooves 350 located between the lowermost groove 350a and the uppermost groove 350b gradually increase in their inclined pitch from the lowermost groove 350a to the uppermost groove 350b along the vertical profile of the putter face 312.Referring still to FIG.","13, each groove 360 of the third set of grooves 326 may have a non-symmetrical cross-sectional configuration or shape.","In FIG.","13, each groove 360 of the third set of grooves 326 may extend downwardly into the putter head 300.Each groove 360 may be defined by an upper or first wall surface 362 and a lower or second wall surface 364, which may intersect each other to define a bottom or vertex 365 of the respective groove 360.The upper wall surface 362 may extend at a decline angle or pitch from the putter face 312 into the putter head 300, and the lower wall surface 364 may extend substantially perpendicular to the putter face 312 into the putter head 300.The third set of grooves 326 may exhibit a gradual change in the decline angle or pitch of the upper wall surfaces 362 along the vertical profile of the putter face 312, while the angle or pitch of the lower wall surfaces 364 may be substantially the same.","In other words, each upper wall surface 362 may have a unique pitch that differs by a delta amount from adjacent upper wall surfaces 362.In some arrangements, the pitch of adjacent upper wall surfaces 362 may differ by a delta amount of about 5 degrees.","The delta amount may vary depending on the putter.","In FIG.","13, a lowermost groove 360a of the third set of grooves 326 includes an upper wall surface 362a having a first declined pitch, an uppermost groove 360b includes an upper wall surface 362b having a second declined pitch that is less than the first declined pitch, and the upper wall surfaces 362 of the grooves 360 located between the lowermost groove 360a and the uppermost groove 360b gradually decrease in their declined pitch from the lowermost groove 360a to the uppermost groove 360b along the vertical profile of the putter face 312.With continued reference to FIG.","13, the second set of grooves 322 generally is located at the center of the putter face 312 near the vertical center of gravity (center of mass) of the putter head 300, where the ball is ideally struck.","In FIG.","13, a single groove 338 is included in the second set of grooves 322, although more than one groove may be included in the second set of grooves 322.The one or more grooves of the second set of grooves 322 may be located near the center of the putter face 312 and may include upper and lower wall surfaces oriented substantially perpendicular to the putter face 312, as illustrated in FIG.","13.The upper and lower wall surfaces may be connected together by a substantially flat surface located at a bottom of the respective groove and oriented substantially parallel to the putter face 312, as illustrated in FIG.","13.Referring to FIGS.","12 and 13, the depth of the grooves in the first set of grooves 220, 320 and the third set of grooves 226, 326 may change along the vertical profile of the putter face 212, 312, because the pitch or pitch angles of the respective grooves change along the vertical profile of the putter face 212, 312.The groove pattern 216 of FIG.","12 includes deeper grooves in the first set of grooves 220 and the third set of grooves 226 near the center of the putter face 212 adjacent the second set of grooves 222.In contrast, the groove pattern 316 of FIG.","13 includes deeper grooves in the first set of grooves 320 and the third set of grooves 326 near the top and bottom of the putter face 312 distal to the second set of grooves 322.With continued reference to FIGS.","12 and 13, the gradual pitch change in the groove patterns 216 and 316 along the vertical profile of the putter faces 212 and 312, respectively, influences the amount the groove edges interact with the surface of the ball.","The amount of interaction required to influence ball roll performance diminishes the closer the ball is struck to the center of mass of the putter head because, as previously described, a ball that is struck near the center of mass of the putter head generally achieves forward roll in an efficient manner based on the static loft angle of the putter face.","The groove patterns 216 and 316 generally create a modulated groove effect depending on how far off-center the ball is struck along the face 212, 312 of the putter head 200, 300, respectively.","The more vertically off-center the ball is struck along the face 212, 312 of the putter head 200, 300, the more influence the groove patterns 216 and 316 impart on the ball to compensate for the misalignment of the ball's center of mass with the putter's center of mass.","The foregoing description has broad application.","It should be appreciated that the concepts disclosed herein may apply to many different styles and types of putters, in addition to the putter described and depicted herein.","The discussion of any embodiment is meant only to be explanatory and is not intended to suggest that the scope of the disclosure, including the claims, is limited to these embodiments.","In other words, while illustrative embodiments of the disclosure have been described in detail herein, it is to be understood that the inventive concepts may be otherwise variously embodied and employed, and that the appended claims are intended to be construed to include such variations, except as limited by the prior art.","The foregoing discussion has been presented for purposes of illustration and description and is not intended to limit the disclosure to the form or forms disclosed herein.","For example, the preceding discussion refers to first, second, and third sets of grooves.","The first, second, and third identifiers are used in the preceding discussion to distinguish one set of grooves from another for convenience purposes.","In the following claims, the first, second, and third identifiers may be used to refer to any one of the sets of grooves previously described.","As another example, various features of the disclosure are grouped together in one or more aspects, embodiments, or configurations for the purpose of streamlining the disclosure.","However, it should be understood that various features of the certain aspects, embodiments, or configurations of the disclosure may be combined in alternate aspects, embodiments, or configurations.","Moreover, the following claims are hereby incorporated into this Detailed Description by this reference, with each claim standing on its own as a separate embodiment of the present disclosure.","The phrases “at least one”, “one or more”, and “and/or”, as used herein, are open-ended expressions that are both conjunctive and disjunctive in operation.","The term “a” or “an” entity, as used herein, refers to one or more of that entity.","As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein.","All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, longitudinal, front, back, top, bottom, above, below, vertical, horizontal, radial, axial, clockwise, and counterclockwise) are only used for identification purposes to aid the reader's understanding of the present disclosure, and do not create limitations, particularly as to the position, orientation, or use of this disclosure.","Connection references (e.g., attached, coupled, connected, and joined) are to be construed broadly and may include intermediate members between a collection of elements and relative movement between elements unless otherwise indicated.","As such, connection references do not necessarily infer that two elements are directly connected and in fixed relation to each other.","Identification references (e.g., primary, secondary, first, second, third, fourth, etc.)","are not intended to connote importance or priority, but are used to distinguish one feature from another.","The drawings are for purposes of illustration only and the dimensions, positions, order and relative sizes reflected in the drawings attached hereto may vary."]],"string":"[\n [\n \"GROOVE PATTERN FOR A PUTTER HEAD\",\n \"A putter head is provided.\",\n \"The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.\",\n \"The groove pattern includes multiple sets of grooves spaced apart from one another in a vertical direction of the putter face.\",\n \"The sets of grooves have different cross-sectional configurations to adjust a launch angle of a golf ball based on an impact location of the golf ball along the vertical direction of the putter face.\"\n ],\n [\n \"1.A putter head, comprising: a putter face defining: a first set of grooves located in an upper region or a lower region of the putter face and including multiple vertically-adjacent grooves extending in a heel-to-toe direction of the putter head, each groove of the first set of grooves having a non-symmetrical cross-sectional configuration; and a second set of grooves located in a middle region of the putter face, the second set of grooves including one or more grooves extending in the heel-to-toe direction of the putter head, each groove of the second set of grooves having a symmetrical cross-sectional configuration; wherein the non-symmetrical cross-sectional configurations of the grooves of the first set of grooves gradually transition into the symmetrical cross-sectional configuration of the one or more grooves of the second set of grooves to provide a varying launch angle along a vertical direction of the first set of grooves.\",\n \"2.The putter head according to claim 1, wherein each groove of the second set of grooves comprises a substantially square groove.\",\n \"3.The putter head according to claim 1, wherein each groove of the second set of grooves is defined by an upper wall surface and a lower wall surface that each extend inwardly into the putter head and are connected together by a substantially flat surface located at a bottom of the groove.\",\n \"4.The putter head according to claim 1, wherein the grooves of the first set of grooves are separated from one another by intermediate surfaces that are coplanar with the putter face.\",\n \"5.The putter head according to claim 1, wherein the depth of the grooves of the first set of grooves varies along the vertical direction of the putter face.\",\n \"6.The putter head according to claim 1, wherein the depth of the grooves of the first set of grooves increases along the vertical direction of the putter face.\",\n \"7.The putter head according to claim 1, wherein the depth of the grooves of the first set of grooves decreases along the vertical direction of the putter face.\",\n \"8.The putter head according to claim 1, wherein each groove of the first set of grooves has a different depth.\",\n \"9.The putter head according to claim 1, wherein: each groove of the first set of grooves includes an upper wall surface and a lower wall surface; one of the upper wall surfaces or the lower wall surfaces extend inwardly into the putter head at an angle that varies along the vertical direction of the putter face; and the other of the upper wall surfaces or the lower wall surfaces extend inwardly into the putter head at substantially the same angle along the vertical direction of the putter face.\",\n \"10.The putter head according to claim 9, wherein the upper wall surfaces and the lower wall surfaces intersect at a bottom of the respective grooves.\",\n \"11.The putter head according to claim 9, wherein: the first set of grooves is located in the lower region of the putter face; the upper wall surfaces extend inwardly into the putter head at substantially the same angle along the vertical direction of the putter face; and the lower wall surfaces extend upwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face.\",\n \"12.The putter head according to claim 11, wherein the upper wall surfaces extend substantially perpendicular to the putter face.\",\n \"13.The putter head according to claim 9, wherein: the first set of grooves is located in the upper region of the putter face; the upper wall surfaces extend downwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face; and the lower wall surfaces extend inwardly into the putter head at substantially the same angle along the vertical direction of the putter face.\",\n \"14.The putter head according to claim 13, wherein the lower wall surfaces extend substantially perpendicular to the putter face.\",\n \"15.The putter head according to claim 1, wherein the first set of grooves is located in the lower region of the putter face; and further comprising a third set of grooves located in the upper region of the putter face and including multiple vertically-adjacent grooves extending in the heel-to-toe direction of the putter head, each groove of the third set of grooves having a non-symmetrical cross-sectional configuration.\",\n \"16.The putter head according to claim 15, wherein the non-symmetrical cross-sectional configurations of the grooves of the third set of grooves gradually transition into the symmetrical cross-sectional configuration of the one or more grooves of the second set of grooves to provide a varying launch angle along a vertical direction of the third set of grooves.\",\n \"17.The putter head according to claim 16, wherein: the depth of the grooves of the first set of grooves varies along the vertical direction of the putter face; and the depth of the grooves of the third set of grooves varies along the vertical direction of the putter face.\",\n \"18.The putter head according to claim 17, wherein the depth of the grooves of the first set of grooves and of the grooves of the third set of grooves increases as the first set of grooves and the third set of grooves approach the second set of grooves.\",\n \"19.The putter head according to claim 17, wherein the depth of the grooves of the first set of grooves and of the grooves of the third set of grooves decreases as the first set of grooves and the third set of grooves approach the second set of grooves.\",\n \"20.The putter head according to claim 16, wherein: each groove of the first set of grooves includes an upper wall surface and a lower wall surface; the upper wall surfaces of the grooves of the first set of grooves extend substantially perpendicular to the putter face; the lower wall surfaces of the grooves of the first set of grooves extend upwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face; each groove of the third set of grooves includes an upper wall surface and a lower wall surface; the upper wall surfaces of the grooves of the third set of grooves extend downwardly into the putter head at an angle that either increases or decreases along the vertical direction of the putter face; and the lower wall surfaces of the grooves of the third set of grooves extend substantially perpendicular to the putter face.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>Generally, when a golfer putts a ball, it initially skids along the ground before it begins to roll in a forward direction.\",\n \"Minimizing the amount of skid increases the golfer's control of the ball.\",\n \"The quicker the ball achieves true forward roll or rotation (the moment that the ball achieves forward or over spin without skidding or retaining backspin), the more control the golfer has over the distance and the path the golf ball travels along the green surface.\",\n \"When a golf ball is struck by a putter head at a bottom of the golfer's swing, generally the static loft of the putter face lifts the ball out of a small depression in the green surface caused by the ball, and the ball reaches a forward roll quickly along the green surface.\",\n \"However, golfers typically are not consistent in their swing, which generally reduces the control the golfer has over the distance and the path the golf ball travels along the green surface.\",\n \"For example, if a golf ball is struck by a putter during an upward motion of the putter head, the putter head typically launches the ball off the ground, and the ball bounces and/or skids when it hits the green surface, thereby reducing a golfer's control over the distance and the path of the putt.\",\n \"Alternatively, if a golf ball is struck by a putter during a downward motion of the putter head, the putter head typically drives the ball into the ground, causing the ball to bounce and/or skid, thereby reducing a golfer's control over the distance and the path of the putt.\",\n \"For at least these reasons, it is difficult to fit a particular golfer with a putter.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>Embodiments of the disclosure generally provide a putter head that improves accuracy and consistency of putts, regardless of variations in a golfer's swing.\",\n \"The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.\",\n \"The groove pattern includes multiple sets, regions, or zones of grooves spaced apart from one another in a vertical direction of the putter face.\",\n \"The sets of grooves have different cross-sectional configurations to adjust a launch angle of a golf ball based on an impact location of the golf ball along the vertical direction of the putter face.\",\n \"In some embodiments, the putter head includes a putter face defining a first set of grooves and a second set of grooves extending in a heel-to-toe direction of the putter head.\",\n \"The second set of grooves may be positioned apart from the first set of grooves in the vertical direction of the putter face.\",\n \"The first and second sets of grooves may have different cross-sectional configurations.\",\n \"The putter head may include a third set of grooves extending in the heel-to-toe direction and positioned apart from the first and second sets of grooves in the vertical direction of the putter face.\",\n \"Each groove of the first and third sets of grooves may have a non-symmetrical cross-sectional configuration, whereas each groove of the second set of grooves may have a symmetrical cross-sectional configuration.\",\n \"This summary of the disclosure is given to aid understanding, and one of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances.\",\n \"Accordingly, while the disclosure is presented in terms of embodiments, it should be appreciated that individual aspects of any embodiment can be claimed separately or in combination with aspects and features of that embodiment or any other embodiment.\",\n \"The present disclosure is set forth in various levels of detail in this application and no limitation as to the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, or the like in this summary.\",\n \"In certain instances, details that are not necessary for an understanding of the disclosure or that render other details difficult to perceive may have been omitted.\",\n \"It should be understood that the claimed subject matter is not necessarily limited to the particular embodiments or arrangements illustrated herein.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/292,412, filed Oct. 13, 2016, and entitled “Groove Pattern for a Putter Head,” which claims the benefit of priority under 35 U.S.C.\",\n \"§ 119(e) of U.S. provisional patent application Ser.\",\n \"No.\",\n \"62/247,688, filed Oct. 28, 2015, and entitled “Groove Pattern for a Putter Head,” and of U.S. provisional patent application Ser.\",\n \"No.\",\n \"62/326,247, filed Apr.\",\n \"22, 2016, and entitled “Groove Pattern for a Putter Head,” which are hereby incorporated herein in their entireties.\",\n \"FIELD The present disclosure relates generally to golf clubs, and more particularly to a groove pattern for a putter head.\",\n \"BACKGROUND Generally, when a golfer putts a ball, it initially skids along the ground before it begins to roll in a forward direction.\",\n \"Minimizing the amount of skid increases the golfer's control of the ball.\",\n \"The quicker the ball achieves true forward roll or rotation (the moment that the ball achieves forward or over spin without skidding or retaining backspin), the more control the golfer has over the distance and the path the golf ball travels along the green surface.\",\n \"When a golf ball is struck by a putter head at a bottom of the golfer's swing, generally the static loft of the putter face lifts the ball out of a small depression in the green surface caused by the ball, and the ball reaches a forward roll quickly along the green surface.\",\n \"However, golfers typically are not consistent in their swing, which generally reduces the control the golfer has over the distance and the path the golf ball travels along the green surface.\",\n \"For example, if a golf ball is struck by a putter during an upward motion of the putter head, the putter head typically launches the ball off the ground, and the ball bounces and/or skids when it hits the green surface, thereby reducing a golfer's control over the distance and the path of the putt.\",\n \"Alternatively, if a golf ball is struck by a putter during a downward motion of the putter head, the putter head typically drives the ball into the ground, causing the ball to bounce and/or skid, thereby reducing a golfer's control over the distance and the path of the putt.\",\n \"For at least these reasons, it is difficult to fit a particular golfer with a putter.\",\n \"SUMMARY Embodiments of the disclosure generally provide a putter head that improves accuracy and consistency of putts, regardless of variations in a golfer's swing.\",\n \"The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.\",\n \"The groove pattern includes multiple sets, regions, or zones of grooves spaced apart from one another in a vertical direction of the putter face.\",\n \"The sets of grooves have different cross-sectional configurations to adjust a launch angle of a golf ball based on an impact location of the golf ball along the vertical direction of the putter face.\",\n \"In some embodiments, the putter head includes a putter face defining a first set of grooves and a second set of grooves extending in a heel-to-toe direction of the putter head.\",\n \"The second set of grooves may be positioned apart from the first set of grooves in the vertical direction of the putter face.\",\n \"The first and second sets of grooves may have different cross-sectional configurations.\",\n \"The putter head may include a third set of grooves extending in the heel-to-toe direction and positioned apart from the first and second sets of grooves in the vertical direction of the putter face.\",\n \"Each groove of the first and third sets of grooves may have a non-symmetrical cross-sectional configuration, whereas each groove of the second set of grooves may have a symmetrical cross-sectional configuration.\",\n \"This summary of the disclosure is given to aid understanding, and one of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances.\",\n \"Accordingly, while the disclosure is presented in terms of embodiments, it should be appreciated that individual aspects of any embodiment can be claimed separately or in combination with aspects and features of that embodiment or any other embodiment.\",\n \"The present disclosure is set forth in various levels of detail in this application and no limitation as to the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, or the like in this summary.\",\n \"In certain instances, details that are not necessary for an understanding of the disclosure or that render other details difficult to perceive may have been omitted.\",\n \"It should be understood that the claimed subject matter is not necessarily limited to the particular embodiments or arrangements illustrated herein.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated into and constitute a part of the specification, illustrate embodiments of the disclosure and, together with the general description given above and the detailed description given below, serve to explain the principles of these embodiments.\",\n \"FIG.\",\n \"1 is a front isometric view of a putter head in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"2 is a side elevation view of the putter head of FIG.\",\n \"1 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"3 is a front elevation view of the putter head of FIG.\",\n \"1 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"4 is a cross-sectional view of the putter head of FIG.\",\n \"1 taken along sectional line 4-4 of FIG.\",\n \"3 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"5 is an enlarged, fragmentary view of a middle region of the putter face shown in the cross-sectional view of FIG.\",\n \"4 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"6 is an enlarged, fragmentary view of a lower region of a putter face shown in the cross-sectional view of FIG.\",\n \"4 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"7 is an enlarged, fragmentary view of an upper region of the putter face shown in the cross-sectional view of FIG.\",\n \"4 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"8 is a front isometric, exploded view of a putter head in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"9 is a cross-sectional view of the putter head of FIG.\",\n \"1 taken along sectional line 4-4 of FIG.\",\n \"3 with a middle region of the putter face in contact with a golf ball in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"10 is a cross-sectional view of the putter head of FIG.\",\n \"1 taken along sectional line 4-4 of FIG.\",\n \"3 with a lower region of the putter face in contact with a golf ball in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"11 is a cross-sectional view of the putter head of FIG.\",\n \"1 taken along sectional line 4-4 of FIG.\",\n \"3 with an upper region of the putter face in contact with a golf ball in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"12 is a view of a putter head including a different groove configuration relative to FIG.\",\n \"4 in accordance with some embodiments of the present disclosure.\",\n \"FIG.\",\n \"13 is a view of a putter head including a different groove configuration relative to FIGS.\",\n \"4 and 12 in accordance with some embodiments of the present disclosure.\",\n \"DETAILED DESCRIPTION Embodiments of the present disclosure generally provide a putter head including grooves located in different regions on a putter face for improving the accuracy and consistency of putts, regardless of variations in the golfer's swing.\",\n \"The applicant uses the term “groove” in this description broadly to include cuts, crevices, depressions, recesses, troughs, or other voids that are associated with a putter face.\",\n \"In a preferred embodiment, the grooves are substantially parallel to one another and are arranged generally horizontally in a heel-to-toe direction on the putter face.\",\n \"An example embodiment of a putter head is shown and described below with respect to FIGS.\",\n \"1-11.Although in each of these figures the putter head is shown with three regions of grooves, the putter head may include two, three, or more regions of grooves.\",\n \"The grooves may be used with any type of putter head or shaft, whether currently known or later developed.\",\n \"Referring to FIG.\",\n \"1, a front isometric view of an illustrative embodiment of a putter head formed in accordance with some embodiments of the present disclosure is provided.\",\n \"Putter head 100, illustrated in FIG.\",\n \"1, includes a top surface 102, a bottom surface or sole 104, a heel 106, a toe 108, and a hosel 110.The top surface 102 is directed generally towards the sky and the bottom surface 104 is directed generally toward the ground when the golfer addresses the golf ball.\",\n \"The heel 106 is generally directed towards the golfer and the toe 108 is generally directed away from the golfer when the golfer addresses the golf ball.\",\n \"The hosel 110 generally extends upwardly from the top surface 102, typically proximate to the heel 106, and is the portion of the putter head 100 to which a shaft is attached.\",\n \"The respective top surface 102, bottom surface 104, heel 106, toe 108, and hosel 110 may be formed in various shapes and sizes.\",\n \"With continued reference to FIG.\",\n \"1, the putter head 100 includes a face 112 that is directed generally towards a golf ball when the golfer addresses the golf ball.\",\n \"The putter face 112 generally extends between the top surface 102, the bottom surface 104, the heel 106, and the toe 108.As shown in FIG.\",\n \"2, the putter face 112 may be substantially flat and planar.\",\n \"As further shown in FIG.\",\n \"2, the putter face 112 may be lofted in order to lift the ball up onto the top of the green surface from a slight depression in which it rests.\",\n \"As the loft angle of the putter face 112 (generally referred to as static loft) increases, more lift will be imparted to the ball.\",\n \"The putter face 112 may have some degree of static loft.\",\n \"For example, the loft angle of the putter face 112 may range from about 1 degree to about 5 degrees.\",\n \"In some embodiments, the putter face 112 has a loft angle of about 3 degrees.\",\n \"With continued reference to FIG.\",\n \"2, a lower, front edge 114 of the putter head 100 may be rounded to allow the putter face 112 to glide better through taller grass when used in the fringe of the green surface and to reduce the likelihood that the putter face 112 catches or grabs on the green surface during the course of play.\",\n \"Referring back to FIG.\",\n \"1, the putter face 112 includes a groove pattern 116.The groove pattern 116 may be cut, etched, molded, or otherwise formed in the putter face 112.The groove pattern 116 may be formed directly into a face of the putter head 100 (e.g., milled into the putter head), or, as shown in FIGS.\",\n \"1 and 3-11, the groove pattern 116 may be formed in a putter face insert 118 that is attached to the putter head 100.As shown in FIG.\",\n \"8, the putter head 100 may define a cavity 119 opening through the bottom surface 104 of the putter head 100 that receives the insert 118.By inserting the insert 118 through the opening in the bottom surface 104, the insert 118 may provide a softer feel when a ball is struck low on the putter face 112 in embodiments where the insert 118 is made from a softer material than the body of the putter head 100.The insert 118 also does not visually disturb the top surface 102 of the putter head 100, which may distract the golfer during putting.\",\n \"Although not shown, the cavity 119 may open through the top surface 102 of the putter head 100, or may not open through either the top surface 102 or the bottom surface 104.The insert 118 may be formed in a trapezoidal shape as shown in FIGS.\",\n \"1, 3, and 8, a conic shape, a rectangular shape, or any other shape.\",\n \"With continued reference to FIG.\",\n \"1, the groove pattern 116 generally extends in a heel-to-toe direction 119 along the face 112 of the putter head 100.The groove pattern 116 generally increases the time the ball spends in contact with the putter face 112, generally referred to as dwell time, by reducing the surface area of the putter face 112 in contact with the ball, thereby providing the putter head 100 with a soft feel upon contact with the ball.\",\n \"The groove pattern 116 may be formed in a trapezoidal shaped perimeter as shown in FIG.\",\n \"1, a conic shaped perimeter, a rectangular shaped perimeter, or any other shaped perimeter.\",\n \"The groove pattern 116 may extend partially across the putter face 112, for example as shown in FIG.\",\n \"1, or may extend across the entire putter face 112 from the heel 106 to the toe 108.Referring to FIGS.\",\n \"3 and 4, the groove pattern 116 includes multiple sets, regions, or zones of different grooves extending in a heel-to-toe direction 119 of the putter head 100 and spaced apart from one another in a vertical direction 121 of the putter face 112.The groove pattern 116 is configured to provide a golfer a relatively large margin of error in the angle of impact between the putter head 100 and the golf ball so that the ball travels straighter with a desired distance regardless of the golfer's variation in their swing from one putt to another putt.\",\n \"The groove pattern 116 generally improves the forward roll or rotation of the golf ball when the ball is struck off-center up and down the putter face 112.In FIGS.\",\n \"3 and 4, the putter face 112 defines three sets of grooves.\",\n \"However, it should be appreciated the putter face 112 may include two, three, or more sets of grooves.\",\n \"With continued reference to FIGS.\",\n \"3 and 4, the putter face 112 includes a first set, region, or zone of grooves 120 (hereinafter “first set of grooves” for the sake of convenience without intent to limit) and a second set, region, or zone of grooves 122 (hereinafter “second set of grooves” for the sake of convenience without intent to limit).\",\n \"The first and second set of grooves 120, 122 extend in the heel-to-toe direction 119 of the putter head 100 and are spaced apart from each other in the vertical direction 121 of the putter face 112.The vertical direction 121 of the putter face 112 is oriented generally perpendicular to the heel-to-toe direction 119 of the putter head 100 and generally parallel to the putter face 112.As shown in FIGS.\",\n \"3 and 4, the putter face 112 may include a third set, region, or zone of grooves 126 (hereinafter “third set of grooves” for the sake of convenience without intent to limit) extending in the heel-to-toe direction 119 of the putter head 100.The third set of grooves 126 may be spaced apart from the first and second set of grooves 120, 122 in the vertical direction 121.Referring still to FIGS.\",\n \"3 and 4, the second set of grooves 122 may be located vertically between the first set of grooves 120 and the third set of grooves 126.The first set of grooves 120, the second set of grooves 122, and the third set of grooves 126 may extend parallel to one another along the putter face 112.The first set of grooves 120 may be located in a lower region 130 of the putter face 112 generally below a center of gravity of the putter head 100.The third set of grooves 126 may be located in an upper region 134 of the putter face 112 generally above a center of gravity of the putter head 100.The second set of grooves 122 may be located in a middle region 132 of the putter face 112 generally in front of a center of gravity of the putter head 100.The lower region 130 may be located near the bottom surface 104 of the putter head 100 in a lower one-third portion of the putter face 112, the upper region 134 be located near the top surface 102 of the putter head 100 in an upper one-third portion of the putter face 112, and the middle region 132 may be located between the lower and upper regions 130, 134 in a middle one-third portion of the putter face 112.Referring to FIG.\",\n \"5, an enlarged cross-sectional view of the middle region 132 of the putter face 112 is provided.\",\n \"The middle region 132, as shown in FIG.\",\n \"5, may include the second set of grooves 122.The second set of grooves 122 generally contacts the golf ball when the putter head 100 strikes the ball near the vertical center of the putter face 112 and/or center of gravity of the putter head 100.In FIG.\",\n \"5, the second set of grooves 122 includes five grooves formed in the putter face 112.It should be understood that the second set of grooves 122 may include more or less than five grooves.\",\n \"For example, in some configurations, the second set of grooves 122 includes a single groove.\",\n \"In some configurations, the second set of grooves 122 includes two or more grooves.\",\n \"Referring still to FIG.\",\n \"5, each groove 138 of the second set of grooves 122 may have a symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"5, each groove 138 of the illustrative embodiment has a substantially square cross-sectional configuration including an upper or first wall surface 140 and a lower or second wall surface 142 that each extend inwardly into the putter head 100 and are connected together by a substantially flat surface 144 located at a bottom of the groove 138.The upper and lower walls surfaces 140, 142 may extend substantially perpendicularly (e.g., at a ninety degree angle) to the putter face 112 and the substantially flat surfaces 144.In some embodiments, the upper and lower wall surfaces 140, 142 may extend toward one another as they extend inwardly into the putter head 100.In some embodiments, the upper and lower wall surfaces 140, 142 have about a 10 degree draft angle, and the depth of each respective groove 138 is about 0.015 inches.\",\n \"Although the grooves 138 shown in FIG.\",\n \"5 have a substantially square cross-sectional configuration, in some embodiments the grooves 138 have other symmetrical cross-sectional configurations, such as a V-shaped cross-sectional configuration having upper and lower wall surfaces 140, 142 intersect at a bottom of the respective grooves 138 or a parallelogram configuration.\",\n \"With continued reference to FIG.\",\n \"5, adjacent grooves 138 of the second set of grooves 122 may be separated from each other by intermediate surfaces 146 of the putter face 112.The intermediate surfaces 146 may be flat and coplanar with the putter face 112.The intersection of the upper wall surface 140 and a respective superjacent intermediate surface 146 may form an upper or first groove edge 148a, and the intersection of the lower wall surface 142 and a respective subjacent intermediate surface 146 may form a lower or second groove edge 148b for each groove 138.The upper and lower groove edges 148a, 148b generally have the same angle or sharpness.\",\n \"The upper and lower groove edges 148a, 148b may be formed by substantially right angles (e.g., about seventy-five to one-hundred and five degree angles) defined by the intersections of the upper and lower wall surfaces 140, 142, and the intermediate surfaces 146.The upper and lower edges 148a, 148b may be coplanar with the putter face 112.The distance between the upper and lower edges 148a, 148b generally defines the opening or mouth of each groove 138, which may be greater in dimension than the respective intermediate surfaces 146 in the vertical direction 119 of the putter face 112.Referring to FIG.\",\n \"9, when a golf ball 149 is struck near the vertical center of the putter face 112 and/or center of gravity of the putter head 100, the intermediate surfaces 146 generally strike the back of the ball 149 with little or no need for modulation of the launch angle by the groove edges 148a, 148b since the static loft angle of the putter face 112 imparts a desired launch angle to the ball 149, causing the ball 149 to roll forward in a desired path, with the static loft angle of the putter face 112 slightly lifting the ball 149 out of a depression in which it rests.\",\n \"To the extent the ball is struck in the middle region 132 of the putter head 100 but the putter face 112 is angled forwardly or rearwardly of the desired static loft angle, one or more of the upper and lower groove edges 148a, 148b engage the outer surface of the ball 149, thereby altering the launch angle of the ball 149 to counteract the misalignment of the putter face 112 relative to the ball 149, resulting in improved putting performance.\",\n \"The launch angle is the angle at which the golf ball is launched into the air after contacting the putter face 112, and generally is measured between a projected path of the golf ball and a horizontal or ground plane.\",\n \"Both dynamic loft angle and static loft angle affect the launch angle.\",\n \"Dynamic loft angle generally is a combination of the static loft angle, the lean of the shaft, and the path of the club head as the golfer swings and addresses the ball.\",\n \"Static loft angle generally is defined by the plane in which the putter face lies.\",\n \"Many other factors may also affect the degree of launch angle.\",\n \"Referring to FIG.\",\n \"6, an enlarged cross-sectional view of the lower region 130 of the putter face 112 is provided.\",\n \"The lower region 130, as shown in FIG.\",\n \"6, may include the first set of grooves 120.The first set of grooves 122 generally contacts the golf ball when the putter head 100 strikes the ball below the vertical center of the putter face 112 and/or center of gravity of the putter head 100.In FIG.\",\n \"6, the first set of grooves 120 includes four grooves formed in the putter face 112.It should be understood that the first set of grooves 120 may include more or less than four grooves.\",\n \"For example, in some configurations, the first set of grooves 120 includes a single groove.\",\n \"In some configurations, the first set of grooves 120 includes two or more grooves.\",\n \"Referring to FIGS.\",\n \"5 and 6, the first and second set of grooves 120, 122 have different cross-sectional configurations.\",\n \"Referring specifically to FIG.\",\n \"6, each groove 150 of the first set of grooves 120 has a non-symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"6, each groove 150 of the illustrative embodiment extends upwardly into the putter head 100.Each groove 150 may be defined by a lower or first wall surface 152 and an upper or second wall surface 154.The lower wall surface 152 may extend upwardly and inwardly into the putter head 100 at a first angle α1 relative to the putter face 112, and the upper wall surface 154 may extend inwardly into the putter head 100 at a second angle α2 relative to the putter face 112 that is greater than the first angle α1.The upper wall surface 154 may extend downwardly into the putter head 100 at the second angle α2.In some embodiments, the first angle α1 is about 20 degrees, and the second angle α2 is about 80 degrees, although other angles are contemplated.\",\n \"The lower and upper wall surfaces 152, 154 may extend toward one another as they extend inwardly into the putter head 100 and may intersect at a bottom 155 of a respective groove 150.With continued reference to FIG.\",\n \"6, adjacent grooves 150 of the first set of grooves 120 may be separated from each other by intermediate surfaces 156.The intermediate surfaces 156 may be flat and coplanar with the putter face 112.The intersection of the upper wall surface 154 and a respective superjacent intermediate surface 156 may form an upper or first groove edge 158a, and the intersection of the lower wall surface 152 and a respective subjacent intermediate surface 156 may form a lower or second groove edge 158b for each groove 150.The upper groove edges 158a are sharper (e.g., have sharper angles) than the lower grooves edges 158b based on the different angles α2, α1 of the upper and lower wall surfaces 154, 152, respectively.\",\n \"The upper groove edges 158a may be formed by substantially right angles (e.g., about seventy-five to one-hundred and five degree angles) defined by the intersections of the upper wall surfaces 154 and the intermediate surfaces 156, whereas the lower groove edges 158b may be formed by substantially obtuse angles (i.e., greater than ninety degree angles) defined by the intersections of the lower wall surfaces 152 and the intermediate surfaces 156.The upper and lower edges 158a, 158b may be coplanar with the putter face 112.The distance between the upper and lower edges 158a, 158b generally defines the opening or mouth of each groove 150, which may be greater in dimension than the respective intermediate surfaces 156 in the vertical direction 119 of the putter face 112.Generally, when a golf ball is struck below a vertical center of a putter face and/or center of gravity of a putter head, the shaft and the putter face typically are tilted rearwardly, causing more loft to be presented at the point of impact.\",\n \"This increased loft typically causes the ball to launch higher than desired, resulting in decreased distance and accuracy.\",\n \"Referring to FIGS.\",\n \"6 and 10, the first set of grooves 120 modulates this undesired loft angle to improve putter performance.\",\n \"When the putter face 112 is tilted backwards and the lower region 120 of the putter face 112 impacts the golf ball 149, one or more of the upper and lower groove edges 158a, 158b engage the outer surface of the ball 149.The sharper angle of the upper groove edges 158a relative to the lower groove edges 158b reduces the launch angle of the ball 149, thereby lifting the ball on top of the green surface without launching the ball into the air, resulting in reduced bouncing and backspin and improved putting performance.\",\n \"Referring to FIG.\",\n \"7, an enlarged cross-sectional view of the upper region 134 of the putter face 112 is provided.\",\n \"The upper region 134, as shown in FIG.\",\n \"7, may include the third set of grooves 126.The third set of grooves 126 generally contacts the golf ball when the putter head 100 strikes the ball above the vertical center of the putter face 112 and/or center of gravity of the putter head 100.In FIG.\",\n \"7, the third set of grooves 126 includes four grooves formed in the putter face 112.It should be understood that the third set of grooves 126 may include more or less than four grooves.\",\n \"For example, in some configurations, the third set of grooves 126 includes a single groove.\",\n \"In some configurations, the third set of grooves 126 includes two or more grooves.\",\n \"Referring to FIGS.\",\n \"5 and 7, the second and third set of grooves 122, 126 have different cross-sectional configurations.\",\n \"Referring to FIGS.\",\n \"4-7, the first and third set of grooves 120, 126 may be symmetrical about a plane that is oriented parallel to the sole 104 of the putter head 100, extends in the heel-to-toe direction 119, and bisects the second set of grooves 122.Referring specifically to FIG.\",\n \"7, each groove 160 of the third set of grooves 126 has a non-symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"7, each groove 160 of the illustrative embodiment extends downwardly into the putter head 100.Each groove 160 may be defined by an upper or first wall surface 162 and a lower or second wall surface 164.The upper wall surface 162 may extend downwardly and inwardly into the putter head 100 at a first angle α3 relative to the putter face 112, and the lower wall surface 164 may extend inwardly into the putter head 100 at a second angle α4 relative to the putter face 112 that is greater than the first angle α3.The lower wall surface 164 may extend upwardly into the putter head 100 at the second angle α4.In some embodiments, the first angle α3 is about 20 degrees, and the second angle α4 is about 80 degrees, although other angles are contemplated.\",\n \"The upper and lower wall surfaces 162, 164 may extend toward one another as they extend inwardly into the putter head 100 and may intersect at a bottom 165 of the respective groove 160.With continued reference to FIG.\",\n \"7, adjacent grooves 160 of the third set of grooves 126 may be separated from each other by intermediate surfaces 166.The intermediate surfaces 166 may be flat and coplanar with the putter face 112.The intersection of the upper wall surface 162 and a respective superjacent intermediate surface 166 may form an upper or first groove edge 168a, and the intersection of the lower wall surface 164 and a respective subjacent intermediate surface 166 may form a lower or second groove edge 168b for each groove 160.The lower groove edges 168b are sharper (e.g., have sharper angles) than the upper grooves edges 168a based on the different angles α4, α3 of the lower and upper wall surfaces 164, 162, respectively.\",\n \"The upper groove edges 168a may be formed by substantially obtuse angles (i.e., greater than ninety degree angles) defined by the intersections of the upper wall surfaces 162 and the intermediate surfaces 166, whereas the lower groove edges 168b may be formed by substantially right angles (e.g., about seventy-five to one-hundred and five degree angles) defined by the intersections of the lower wall surfaces 164 and the intermediate surfaces 166.The upper and lower edges 168a, 168b may be coplanar with the putter face 112.The distance between the upper and lower edges 168a, 168b generally defines the opening or mouth of each groove 160, which may be greater in dimension than the respective intermediate surfaces 166 in the vertical direction 119 of the putter face 112.Generally, when a golf ball is struck above a vertical center of a putter face and/or center of gravity of the putter head, the shaft and the putter face typically are tilted forwardly, causing decreased loft to be presented at the point of ball impact.\",\n \"This decreased loft typically causes the ball to launch into the ground, resulting in decreased distance and accuracy.\",\n \"Referring to FIGS.\",\n \"7 and 11, the third set of grooves 126 modulates this undesired loft angle to improve putter performance.\",\n \"When the putter face 112 is tilted forwards and the upper region 126 of the putter face 112 impacts the golf ball 149, one or more of the upper and lower groove edges 156a, 168b engage the outer surface of the ball 149.The sharper angle of the lower groove edges 168b relative to the upper groove edges 168a increases the launch angle of the ball 149, thereby lifting the ball on top of the green surface, rather than driving the ball into the ground, resulting in improved putting performance.\",\n \"With reference to FIGS.\",\n \"1-12, the putter head 100 may be formed of various materials, including metallic materials, non-metallic materials, or a combination of both.\",\n \"In some embodiments, the putter head 100 is formed of a stainless steel material, such as 303 and/or 304 stainless steel, which is forged steel that provides a softer feel at impact because of the density of the material.\",\n \"Referring to FIGS.\",\n \"1 and 3-11, if the putter head 100 includes a putter face insert 118, the insert 118 may be formed of a polymer, for example.\",\n \"Golfers generally prefer a softer feeling putter, and polymer inserts have a much softer durometer measurement than a steel face insert.\",\n \"The softer durometer measurement of the polymer insert also increases the dwell time of the ball, resulting in increased friction between the ball and the putter face 112, and thereby improving ball roll and launch conditions measured by how quickly and consistently the ball begins forward rotation.\",\n \"In some embodiments, the insert 118 may be formed of polyurethane, which is easy to manufacture and allows the manufacturer to select different hardness factors for the insert 118, which impacts the feel of the putter.\",\n \"In some groove pattern configurations, the first and third set of grooves 120, 126 may gradually transition into the second set of grooves 122.For example, the non-symmetrical cross-sectional configurations of the first and third set of grooves 120, 126 may gradually transition into the symmetrical cross-sectional configuration of the second set of grooves 122, which may include one or more substantially square grooves.\",\n \"In other words, the cross-sectional configurations of the first and third set of grooves 120, 126 may gradually become more symmetrical as they approach the second set of grooves 122 so that the first and third set of grooves 120, 126 gradually transition into the second set of grooves 122.By gradually transitioning the first and third set of grooves 120, 126 into the second set of grooves 122, the groove pattern 116 provides a continuously varying launch angle modulation along the vertical direction 119 of the putter face 112.With the exception of the groove patterns 216, 316 illustrated in FIGS.\",\n \"12 and 13, respectively, the putter heads 200 and 300 illustrated in FIGS.\",\n \"12 and 13, respectively, have the same features and operation as the putter head 100 depicted in FIGS.\",\n \"1-11.Accordingly, the preceding discussion of the features and operation of the putter head 100 should be considered equally applicable to the putter heads 200 and 300 illustrated in FIGS.\",\n \"12 and 13, except as noted in the following discussion pertaining to the groove patterns 216 and 316.Referring to FIG.\",\n \"12, the groove pattern 216 includes a first set, region, or zone of grooves 220 (hereinafter “first set of grooves” for the sake of convenience without intent to limit), a second set, region, or zone of grooves 222 (hereinafter “second set of grooves” for the sake of convenience without intent to limit), and a third set, region, or zone of grooves 226 (hereinafter “third set of grooves” for the sake of convenience without intent to limit).\",\n \"In FIG.\",\n \"12, the first set of grooves 220 includes seven grooves formed in the putter face 212, the second set of grooves 222 includes a single groove formed in the putter face 212, and the third set of grooves 226 includes seven grooves formed in the putter face 212.It should be understood that the first set of grooves 220, the second set of grooves 222, and the third set of grooves 226 may include more or less than the grooves illustrated in FIG.\",\n \"12.The first set of grooves 220 may extend at an incline from the putter face 212 into the putter head 200, and the third set of grooves 226 may extend at a decline from the putter face 212 into the putter head 200.The groove pattern 216 may exhibit a gradual change in the pitch of the groove angles in the first set of grooves 220 and the third set of grooves 226 along the vertical profile of the putter face 212.Each groove in the first set of grooves 220 and in the third set of grooves 226 may have a unique pitch.\",\n \"The pitch of adjacent grooves in the first set of grooves 220 and in the third set of grooves 226 along the vertical profile of the putter face 212 may differ by a delta amount, such as about 5 degrees.\",\n \"The delta amount may vary depending on the putter.\",\n \"Referring still to FIG.\",\n \"12, each groove 250 of the first set of grooves 220 may have a non-symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"12, each groove 250 may extend upwardly into the putter head 200.Each groove 250 may be defined by a lower or first wall surface 252 and an upper or second wall surface 254, which may intersect each other to define a bottom or vertex 255 of the respective groove 250.The lower wall surface 252 may extend at an incline angle or pitch from the putter face 212 into the putter head 200, and the upper wall surface 254 may extend substantially perpendicular to the putter face 212 into the putter head 200.The first set of grooves 220 may exhibit a gradual change in the incline angle or pitch of the lower wall surfaces 252 along the vertical profile of the putter face 212, while the angle or pitch of the upper wall surfaces 254 may be substantially the same.\",\n \"In other words, each lower wall surface 252 may have a unique pitch that differs by a delta amount from adjacent lower wall surfaces 252.In some arrangements, the pitch of adjacent lower wall surfaces 252 may differ by a delta amount of about 5 degrees.\",\n \"The delta amount may vary depending on the putter.\",\n \"In FIG.\",\n \"12, a lowermost groove 250a of the first set of grooves 220 includes a lower wall surface 252a having a first inclined pitch, an uppermost groove 250b of the first set of grooves 220 includes a lower wall surface 252b having a second inclined pitch that is less than the first inclined pitch, and the lower wall surfaces 252 of the grooves 250 located between the lowermost groove 250a and the uppermost groove 250b gradually decrease in their inclined pitch from the lowermost groove 250a to the uppermost groove 250b along the vertical profile of the putter face 212.Referring still to FIG.\",\n \"12, each groove 260 of the third set of grooves 226 may have a non-symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"12, each groove 260 of the third set of grooves 226 may extend downwardly into the putter head 200.Each groove 260 may be defined by an upper or first wall surface 262 and a lower or second wall surface 264, which may intersect each other to define a bottom or vertex 265 of the respective groove 260.The upper wall surface 262 may extend at a decline angle or pitch from the putter face 212 into the putter head 200, and the lower wall surface 264 may extend substantially perpendicular to the putter face 212 into the putter head 200.The third set of grooves 226 may exhibit a gradual change in the decline angle or pitch of the upper wall surfaces 262 along the vertical profile of the putter face 212, while the angle or pitch of the lower wall surfaces 264 may be substantially the same.\",\n \"In other words, each upper wall surface 262 may have a unique pitch that differs by a delta amount from adjacent upper wall surfaces 262.In some arrangements, the pitch of adjacent upper wall surfaces 262 may differ by a delta amount of about 5 degrees.\",\n \"The delta amount may vary depending on the putter.\",\n \"In FIG.\",\n \"12, a lowermost groove 260a of the third set of grooves 226 includes an upper wall surface 262a having a first declined pitch, an uppermost groove 260b includes an upper wall surface 262b having a second declined pitch that is greater than the first declined pitch, and the upper wall surfaces 262 of the grooves 260 located between the lowermost groove 260a and the uppermost groove 260b gradually increase in their declined pitch from the lowermost groove 260a to the uppermost groove 260b along the vertical profile of the putter face 212.With continued reference to FIG.\",\n \"12, the second set of grooves 222 generally is located at the center of the putter face 212 near the vertical center of gravity (center of mass) of the putter head 200, where the ball is ideally struck.\",\n \"In FIG.\",\n \"12, a single groove 238 is included in the second set of grooves 222, although more than one groove may be included in the second set of grooves 222.The one or more grooves of the second set of grooves 222 may be located near the center of the putter face 212 and may include upper and lower wall surfaces oriented substantially perpendicular to the putter face 212, as illustrated in FIG.\",\n \"12.The upper and lower wall surfaces may be connected together by a substantially flat surface located at a bottom of the respective groove and oriented substantially parallel to the putter face 212, as illustrated in FIG.\",\n \"12.Referring to FIG.\",\n \"13, the groove pattern 316 includes a first set, region, or zone of grooves 320 (hereinafter “first set of grooves” for the sake of convenience without intent to limit), a second set, region, or zone of grooves 322 (hereinafter “second set of grooves” for the sake of convenience without intent to limit), and a third set, region, or zone of grooves 326 (hereinafter “third set of grooves” for the sake of convenience without intent to limit).\",\n \"In FIG.\",\n \"13, the first set of grooves 320 includes seven grooves formed in the putter face 312, the second set of grooves 322 includes a single groove formed in the putter face 312, and the third set of grooves 326 includes seven grooves formed in the putter face 312.It should be understood that the first set of grooves 320, the second set of grooves 322, and the third set of grooves 326 may include more or less than the grooves illustrated in FIG.\",\n \"13.The first set of grooves 320 may extend at an incline from the putter face 312 into the putter head 300, and the third set of grooves 326 may extend at a decline from the putter face 312 into the putter head 300.The groove pattern 316 may exhibit a gradual change in the pitch of the groove angles in the first set of grooves 320 and the third set of grooves 326 along the vertical profile of the putter face 312.Each groove in the first set of grooves 320 and in the third set of grooves 326 may have a unique pitch.\",\n \"The pitch of adjacent grooves in the first set of grooves 320 and in the third set of grooves 326 along the vertical profile of the putter face 312 may differ by a delta amount, such as about 5 degrees.\",\n \"The delta amount may vary depending on the putter.\",\n \"Referring still to FIG.\",\n \"13, each groove 350 of the first set of grooves 320 may have a non-symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"13, each groove 350 may extend upwardly into the putter head 300.Each groove 350 may be defined by a lower or first wall surface 352 and an upper or second wall surface 354, which may intersect each other to define a bottom or vertex 355 of the respective groove 350.The lower wall surface 352 may extend at an incline angle or pitch from the putter face 312 into the putter head 300, and the upper wall surface 354 may extend substantially perpendicular to the putter face 312 into the putter head 300.The first set of grooves 320 may exhibit a gradual change in the incline angle or pitch of the lower wall surfaces 352 along the vertical profile of the putter face 312, while the angle or pitch of the upper wall surfaces 354 may be substantially the same.\",\n \"In other words, each lower wall surface 352 may have a unique pitch that differs by a delta amount from adjacent lower wall surfaces 352.In some arrangements, the pitch of adjacent lower wall surfaces 352 may differ by a delta amount of about 5 degrees.\",\n \"The delta amount may vary depending on the putter.\",\n \"In FIG.\",\n \"13, a lowermost groove 350a of the first set of grooves 320 includes a lower wall surface 352a having a first inclined pitch, an uppermost groove 350b of the first set of grooves 320 includes a lower wall surface 352b having a second inclined pitch that is greater than the first inclined pitch, and the lower wall surfaces 352 of the grooves 350 located between the lowermost groove 350a and the uppermost groove 350b gradually increase in their inclined pitch from the lowermost groove 350a to the uppermost groove 350b along the vertical profile of the putter face 312.Referring still to FIG.\",\n \"13, each groove 360 of the third set of grooves 326 may have a non-symmetrical cross-sectional configuration or shape.\",\n \"In FIG.\",\n \"13, each groove 360 of the third set of grooves 326 may extend downwardly into the putter head 300.Each groove 360 may be defined by an upper or first wall surface 362 and a lower or second wall surface 364, which may intersect each other to define a bottom or vertex 365 of the respective groove 360.The upper wall surface 362 may extend at a decline angle or pitch from the putter face 312 into the putter head 300, and the lower wall surface 364 may extend substantially perpendicular to the putter face 312 into the putter head 300.The third set of grooves 326 may exhibit a gradual change in the decline angle or pitch of the upper wall surfaces 362 along the vertical profile of the putter face 312, while the angle or pitch of the lower wall surfaces 364 may be substantially the same.\",\n \"In other words, each upper wall surface 362 may have a unique pitch that differs by a delta amount from adjacent upper wall surfaces 362.In some arrangements, the pitch of adjacent upper wall surfaces 362 may differ by a delta amount of about 5 degrees.\",\n \"The delta amount may vary depending on the putter.\",\n \"In FIG.\",\n \"13, a lowermost groove 360a of the third set of grooves 326 includes an upper wall surface 362a having a first declined pitch, an uppermost groove 360b includes an upper wall surface 362b having a second declined pitch that is less than the first declined pitch, and the upper wall surfaces 362 of the grooves 360 located between the lowermost groove 360a and the uppermost groove 360b gradually decrease in their declined pitch from the lowermost groove 360a to the uppermost groove 360b along the vertical profile of the putter face 312.With continued reference to FIG.\",\n \"13, the second set of grooves 322 generally is located at the center of the putter face 312 near the vertical center of gravity (center of mass) of the putter head 300, where the ball is ideally struck.\",\n \"In FIG.\",\n \"13, a single groove 338 is included in the second set of grooves 322, although more than one groove may be included in the second set of grooves 322.The one or more grooves of the second set of grooves 322 may be located near the center of the putter face 312 and may include upper and lower wall surfaces oriented substantially perpendicular to the putter face 312, as illustrated in FIG.\",\n \"13.The upper and lower wall surfaces may be connected together by a substantially flat surface located at a bottom of the respective groove and oriented substantially parallel to the putter face 312, as illustrated in FIG.\",\n \"13.Referring to FIGS.\",\n \"12 and 13, the depth of the grooves in the first set of grooves 220, 320 and the third set of grooves 226, 326 may change along the vertical profile of the putter face 212, 312, because the pitch or pitch angles of the respective grooves change along the vertical profile of the putter face 212, 312.The groove pattern 216 of FIG.\",\n \"12 includes deeper grooves in the first set of grooves 220 and the third set of grooves 226 near the center of the putter face 212 adjacent the second set of grooves 222.In contrast, the groove pattern 316 of FIG.\",\n \"13 includes deeper grooves in the first set of grooves 320 and the third set of grooves 326 near the top and bottom of the putter face 312 distal to the second set of grooves 322.With continued reference to FIGS.\",\n \"12 and 13, the gradual pitch change in the groove patterns 216 and 316 along the vertical profile of the putter faces 212 and 312, respectively, influences the amount the groove edges interact with the surface of the ball.\",\n \"The amount of interaction required to influence ball roll performance diminishes the closer the ball is struck to the center of mass of the putter head because, as previously described, a ball that is struck near the center of mass of the putter head generally achieves forward roll in an efficient manner based on the static loft angle of the putter face.\",\n \"The groove patterns 216 and 316 generally create a modulated groove effect depending on how far off-center the ball is struck along the face 212, 312 of the putter head 200, 300, respectively.\",\n \"The more vertically off-center the ball is struck along the face 212, 312 of the putter head 200, 300, the more influence the groove patterns 216 and 316 impart on the ball to compensate for the misalignment of the ball's center of mass with the putter's center of mass.\",\n \"The foregoing description has broad application.\",\n \"It should be appreciated that the concepts disclosed herein may apply to many different styles and types of putters, in addition to the putter described and depicted herein.\",\n \"The discussion of any embodiment is meant only to be explanatory and is not intended to suggest that the scope of the disclosure, including the claims, is limited to these embodiments.\",\n \"In other words, while illustrative embodiments of the disclosure have been described in detail herein, it is to be understood that the inventive concepts may be otherwise variously embodied and employed, and that the appended claims are intended to be construed to include such variations, except as limited by the prior art.\",\n \"The foregoing discussion has been presented for purposes of illustration and description and is not intended to limit the disclosure to the form or forms disclosed herein.\",\n \"For example, the preceding discussion refers to first, second, and third sets of grooves.\",\n \"The first, second, and third identifiers are used in the preceding discussion to distinguish one set of grooves from another for convenience purposes.\",\n \"In the following claims, the first, second, and third identifiers may be used to refer to any one of the sets of grooves previously described.\",\n \"As another example, various features of the disclosure are grouped together in one or more aspects, embodiments, or configurations for the purpose of streamlining the disclosure.\",\n \"However, it should be understood that various features of the certain aspects, embodiments, or configurations of the disclosure may be combined in alternate aspects, embodiments, or configurations.\",\n \"Moreover, the following claims are hereby incorporated into this Detailed Description by this reference, with each claim standing on its own as a separate embodiment of the present disclosure.\",\n \"The phrases “at least one”, “one or more”, and “and/or”, as used herein, are open-ended expressions that are both conjunctive and disjunctive in operation.\",\n \"The term “a” or “an” entity, as used herein, refers to one or more of that entity.\",\n \"As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein.\",\n \"All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, longitudinal, front, back, top, bottom, above, below, vertical, horizontal, radial, axial, clockwise, and counterclockwise) are only used for identification purposes to aid the reader's understanding of the present disclosure, and do not create limitations, particularly as to the position, orientation, or use of this disclosure.\",\n \"Connection references (e.g., attached, coupled, connected, and joined) are to be construed broadly and may include intermediate members between a collection of elements and relative movement between elements unless otherwise indicated.\",\n \"As such, connection references do not necessarily infer that two elements are directly connected and in fixed relation to each other.\",\n \"Identification references (e.g., primary, secondary, first, second, third, fourth, etc.)\",\n \"are not intended to connote importance or priority, but are used to distinguish one feature from another.\",\n \"The drawings are for purposes of illustration only and the dimensions, positions, order and relative sizes reflected in the drawings attached hereto may vary.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874776"}}},{"rowIdx":4494698,"cells":{"text":{"kind":"list like","value":[["DUAL ANTI-PLATELET MEDICATION/ASPIRIN RESPONSE AND REACTIVITY TEST USING SYNTHETIC COLLAGEN","The present invention provides tests that measures functional platelet aggregation such as by using Light Transmission Aggregometry Assays (LTAAs) or flow cytometry, using synthetic, self-assembling human type I collagen, methods of predicting and measuring an individual's platelet anti-platelet medication sensitivity and residual platelet activity status when the individual is on a dual anti-platelet therapy of aspirin and anti-platelet medication and kits useful in the assays and methods."],["1.A platelet aggregation assay comprising a light transmission aggregometry assay for determining an individual's anti-platelet medication sensitivity status, when the individual is on a dual therapy of aspirin and an anti-platelet medication that is not aspirin, the assay comprising the use of synthetic collagen at a final concentration in the light transmission aggregometry assay from about 40 ng/mL to about 500 ng/mL, wherein the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) -(Pro-X-Gly)n (I) wherein X represents Hyp; and n represents an integer of from 20 to 250.2.The method of claim 1 wherein platelet aggregation is analyzed with light transmission aggregometry assays and wherein the patient sample is platelet rich plasma."],["<SOH> BACKGROUND OF THE INVENTION <EOH>The conventional, primary need for an effective assessment of platelet response and reactivity is in the field of cardiology.","The public health incidence and burden of heart attack, stroke and related cardiovascular and thrombotic diseases are well known.","The medical community has long recommended the use of aspirin in primary care to reduce cardiovascular, stroke and certain other risks.","The use of Aspirin in other area such as DVT prophylaxis, oncology, orthopedics and prevention is driving a renewed interest in and use of Aspirin alone or in combination with other drugs.","Additionally compliance testing and personalized medicine initiatives increase the unmet medical need for a test which can provide Aspirin presence and response, presence and efficacy of a second antiplatelet drug and the residual reactivity of a patient's platelet reactivity.","Aspirin (salicylate based compounds) ingestion or exposure inhibits the COX 1 pathway and modifies COX 2 enzymatic processes, which then precludes all subsequent events necessary for platelet aggregation.","Since the ingestion of or exposure to aspirin can inhibit platelet aggregation, it has been given as a therapy to prevent undesired platelet aggregation, which can be a source of many heart attacks, strokes and other thrombotic events.","Despite the benefits of aspirin therapy in many individuals, aspirin therapy is not effective enough in some individuals as it does not cause the desired inhibition of platelet aggregation or its effect is shorter than the dosing interval (some patients may only get 6 to 12 hours of protection rather than 24 hours resulting in an above baseline risk for the patient in the time between doses).","In these individuals the residual platelet reactivity is high and the patient's risk is not mitigated.","In other individuals, aspirin therapy can be harmful as it creates an increased risk of unwanted bleeding complications because the aspirin seems to block platelet activity altogether so that the blood does not clot when physiologically necessary.","Recently, two elements of Aspirin's pharmacodynamic behavior have entered the clinical mindset: Aspirin must be taken at the same time every day to maintain its antiplatelet effectiveness; and the thrombotic risk from failure to keep this schedule is greater than the patient's baseline risk.","Thus, physicians often prescribe a course of treatment involving both low dose aspirin and an anti-platelet medication to inhibit unwanted platelet aggregation.","This is often called a “dual therapy.” Not all patients will respond to the dual therapy or the individual anti-platelet medication in the same way.","Selecting and monitoring Aspirin in dual treatment protocols is also necessary because certain antiplatelet drugs like ticagrelor lose their effectiveness if the Aspirin dose is greater than 100 mg.","There currently is not an effective way to measure a patient's response to dual anti-platelet medication therapy or to determine the patient's residual platelet reactivity.","Thus, there is an unmet need for a reliable tool to assess and manage the anti-platelet medication response and reactivity on platelet aggregation when a patient is on a dual anti-platelet medication therapy, as well as checking patient compliance with the treatment regimen.","Traditionally, a patient's response to aspirin and other anti-platelet medication therapy is assessed by testing platelet activity using a series of platelet aggregation test.","The “gold standard” of platelet aggregation tests, light transmission aggregometry (LTA), utilizes collagen from biological sources as the agonist to bring about platelet aggregation, as a measure of the degree or extent of platelet response or inhibition to aggregation.","However, there are multiple issues as well as the risk of infectious disease transmission when using biological material.","Biologically derived products, whether ‘natural,’ processed, manufactured by fermentation, cell culture or similar processes, or recombinant, all share the following drawbacks: carry a risk of infectious disease transmission; have lot to lot variability (regarding the ratio of active materials, performance, chemical characteristics, solubility, stability, moisture content, and process contaminants); differing bio-profiles depending upon the location the product was made; differences caused by processing; and environment, geographic and dietary differences affecting the source animal or culture.","Biological collagens cannot be diluted to enhance sensitivity or to generate dilution profiles, both of which easily performed with synthetic collagen.","It is widely believed that anti-platelet therapy contributes to the reduction of major atherothrombotic complications in cardiovascular, neurovascular and other diseases.","In the treatment of percutaneous coronary intervention and acute coronary syndromes, dual anti-platelet therapy when performed at optimal dosing and timing has significantly lowered the risk of thrombotic complications and contributed to positive outcomes.","However, an important clinical problem of increased incidence of major adverse clinical events (“MACE”) and confounding differences in patient outcomes relates to the variability in patient response to anti-platelet treatments, especially in a dual antiplatelet therapy (a combination of Aspirin and a second agent such as clopidogrel or ticagrelor).","Understanding the mechanisms underlying this phenomenon is important to individualizing and improving patient care, long term (maintenance—sometimes referred to as chronic therapy in the literature) therapy and consistent (positive) outcomes.","However, a clear and reliable predictive model for responsiveness to anti-platelet therapy is currently not available.","Attempts have been made to characterize the efficacy of anti-platelet therapy using platelet function testing but based on current information, and dependence on biological agonists, its routine use is not recommended particularly as costs, complexities and cost effectiveness have not been established, and lack of correlation, standardization and agreement between laboratory methods, and their respective results, is well documented in the literature.","Tobias Geislera et al., Circulation 2010; 122:1049-1052.In addition, the inhibitory effects of aspirin on platelets decreases over time in patients on long term or chronic therapy.","Violi, F. et al., J Am Cardio, Vol.","43, No.","6, 2004.Further, as evidenced in AstraZeneca's complete prescribing information on ticagrelor (trade name Brilinta® in the US, Brilique® and Possia® in Europe), Aspirin doses greater than 100 mg reduce the ability of ticagrelor to inhibit platelet aggregation.","This conflicts with current clinical care guidelines in which increasing doses of Aspirin to ‘overcome’ Aspirin resistance is recommended.","Thus, there remains a need for a quantitative, functional platelet activity test that does not use an animal derived collagen as the agonist.","There remains a need for a test that is able to measure the platelet response to an anti-platelet medication when the patient is on a dual therapy of aspirin and an anti-platelet medication, as well as a test to monitor patient compliance with the dual therapy regimen.","Dual antiplatelet therapy is the global practice standard.","There is also a need for a test that can measure residual platelet activity (that is the platelet activity that remains even while the patient is on a dual anti-platelet medication therapy) rather than platelet inhibition, which is the result for currently available tests.","Platelet inhibition does not equal residual platelet reactivity.","Residual platelet reactivity is what determines patient outcome and thus is the better measurement.","The present invention meets these needs."],["<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provide tests for determining a donor's platelet combined sensitivity status when the individual is on a dual therapy of aspirin and an anti-platelet medication comprising the use of synthetic collagen.","Exemplary tests include the use of platelet aggregation studies using for example, light transmission aggregation assays (LTAAs) and flow Cytometry, and to a lesser degree, methods based on measuring aggregation by impedance or whole blood aggregometry.","The tests of the present invention use synthetic collagen as the agonist.","Tests of the invention provide assays that “discount” or “ignore” the effect of the aspirin on platelet aggregation, but still measure the effect of the anti-platelet medication on the platelet aggregation.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.","Further, the invention provides tests that “discount” or “ignore” the effect of the anti-platelet medication, but still measure the effect of the aspirin on platelet aggregation.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.","The methods of the present invention are able to test the ability of the individual's platelets to aggregate after the individual has ingested an anti-platelet medication and aspirin.","In other words, this tests the residual platelet activity—how reactive are the platelets (likely to aggregate) after the patient has ingested the dual therapy of an anti-platelet medication and aspirin.","In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.","Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 to 12.5 ng/mL; or ranges from about 2.0 to about 25 ng/mL; or ranges from about 2.0 to about 35 ng/mL; or ranges from about 2.0 to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 to about 25 ng/mL; or ranges from about 12.5 to about 35 ng/mL; or ranges from about 12.5 to about 39.0 ng/mL; or ranges from about 25 to about 39 ng/mL.","The literature shows that 30-70% of patients do not comply with taking their medication or taking it as directed, and there is no current compliance test.","There is developing thought that ‘resistance’ may be due, at least in part, to non-compliance.","The present invention also provides a method of testing patient compliance, with the dual therapy regimen.","The DAPT results will show noncompliance for Aspirin therapy as well as deviation from the scheduled dosing window.","The present invention also provides a method of testing patient compliance for the aspirin therapy aspect while on a dual therapy, or testing patient compliance for the anti-platelet medication aspect while on a dual therapy.","The present invention also provides methods of predicting the effectiveness of aspirin therapy, of an anti-platelet medication therapy, or a dual therapy.","In certain embodiments, the synthetic collagen is a synthetic collagen that has the ability to self-assemble into a triple helix to form fibrils and which mimics human type I collagen.","In certain embodiments the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) in-line-formulae description=\"In-line Formulae\" end=\"lead\"?","-(Pro-X-Gly) n (I) in-line-formulae description=\"In-line Formulae\" end=\"tail\"?","wherein X represents Hyp; and n represents an integer of from 20 to 5,000; and wherein the polypeptide has a molecular weight at a range of from 10,000 to 500,000.In certain embodiments, n=20-250.The present invention also provides kits for testing platelet aggregation in a light transmission assay, comprising a vial of synthetic collagen; and instructions for use of the synthetic collagen in the dual anti-platelet therapy test (DAPT) of the present invention.","In certain embodiments (including the methods described herein and the kits), the synthetic collagen is supplied and/or stored in a polypropylene homomer container.","In certain embodiments, the cap is the same material as the vial/tube.","In certain embodiments, the container has an additional internal seal or a cap having a secondary seal molded therein.","In certain embodiments, the container contains all of the above described characteristics"],["This application is a divisional of U.S. patent application Ser.","No.","14/419,880 filed on Feb. 5, 2015 (pending), which is a U.S. National Phase under 35 U.S.C.","§ 371 of International Application PCT/US2013/053612, filed on Aug. 5, 2013, which claims priority to U.S.","Provisional Application 61/680,111, filed on Aug. 6, 2012, and U.S.","Provisional Applications 61/681,485 filed on Aug. 9, 2012, which are incorporated herein in their entirety.","This application also claims priority to PCT application, PCT/US13/49418, filed on Jul.","5, 2013.All publications, patents, patent applications, databases and other references cited in this application, all related applications referenced herein, and all references cited therein, are incorporated by reference in their entirety as if restated here in full and as if each individual publication, patent, patent application, database or other reference were specifically and individually indicated to be incorporated by reference.","BACKGROUND OF THE INVENTION The conventional, primary need for an effective assessment of platelet response and reactivity is in the field of cardiology.","The public health incidence and burden of heart attack, stroke and related cardiovascular and thrombotic diseases are well known.","The medical community has long recommended the use of aspirin in primary care to reduce cardiovascular, stroke and certain other risks.","The use of Aspirin in other area such as DVT prophylaxis, oncology, orthopedics and prevention is driving a renewed interest in and use of Aspirin alone or in combination with other drugs.","Additionally compliance testing and personalized medicine initiatives increase the unmet medical need for a test which can provide Aspirin presence and response, presence and efficacy of a second antiplatelet drug and the residual reactivity of a patient's platelet reactivity.","Aspirin (salicylate based compounds) ingestion or exposure inhibits the COX 1 pathway and modifies COX 2 enzymatic processes, which then precludes all subsequent events necessary for platelet aggregation.","Since the ingestion of or exposure to aspirin can inhibit platelet aggregation, it has been given as a therapy to prevent undesired platelet aggregation, which can be a source of many heart attacks, strokes and other thrombotic events.","Despite the benefits of aspirin therapy in many individuals, aspirin therapy is not effective enough in some individuals as it does not cause the desired inhibition of platelet aggregation or its effect is shorter than the dosing interval (some patients may only get 6 to 12 hours of protection rather than 24 hours resulting in an above baseline risk for the patient in the time between doses).","In these individuals the residual platelet reactivity is high and the patient's risk is not mitigated.","In other individuals, aspirin therapy can be harmful as it creates an increased risk of unwanted bleeding complications because the aspirin seems to block platelet activity altogether so that the blood does not clot when physiologically necessary.","Recently, two elements of Aspirin's pharmacodynamic behavior have entered the clinical mindset: Aspirin must be taken at the same time every day to maintain its antiplatelet effectiveness; and the thrombotic risk from failure to keep this schedule is greater than the patient's baseline risk.","Thus, physicians often prescribe a course of treatment involving both low dose aspirin and an anti-platelet medication to inhibit unwanted platelet aggregation.","This is often called a “dual therapy.” Not all patients will respond to the dual therapy or the individual anti-platelet medication in the same way.","Selecting and monitoring Aspirin in dual treatment protocols is also necessary because certain antiplatelet drugs like ticagrelor lose their effectiveness if the Aspirin dose is greater than 100 mg.","There currently is not an effective way to measure a patient's response to dual anti-platelet medication therapy or to determine the patient's residual platelet reactivity.","Thus, there is an unmet need for a reliable tool to assess and manage the anti-platelet medication response and reactivity on platelet aggregation when a patient is on a dual anti-platelet medication therapy, as well as checking patient compliance with the treatment regimen.","Traditionally, a patient's response to aspirin and other anti-platelet medication therapy is assessed by testing platelet activity using a series of platelet aggregation test.","The “gold standard” of platelet aggregation tests, light transmission aggregometry (LTA), utilizes collagen from biological sources as the agonist to bring about platelet aggregation, as a measure of the degree or extent of platelet response or inhibition to aggregation.","However, there are multiple issues as well as the risk of infectious disease transmission when using biological material.","Biologically derived products, whether ‘natural,’ processed, manufactured by fermentation, cell culture or similar processes, or recombinant, all share the following drawbacks: carry a risk of infectious disease transmission; have lot to lot variability (regarding the ratio of active materials, performance, chemical characteristics, solubility, stability, moisture content, and process contaminants); differing bio-profiles depending upon the location the product was made; differences caused by processing; and environment, geographic and dietary differences affecting the source animal or culture.","Biological collagens cannot be diluted to enhance sensitivity or to generate dilution profiles, both of which easily performed with synthetic collagen.","It is widely believed that anti-platelet therapy contributes to the reduction of major atherothrombotic complications in cardiovascular, neurovascular and other diseases.","In the treatment of percutaneous coronary intervention and acute coronary syndromes, dual anti-platelet therapy when performed at optimal dosing and timing has significantly lowered the risk of thrombotic complications and contributed to positive outcomes.","However, an important clinical problem of increased incidence of major adverse clinical events (“MACE”) and confounding differences in patient outcomes relates to the variability in patient response to anti-platelet treatments, especially in a dual antiplatelet therapy (a combination of Aspirin and a second agent such as clopidogrel or ticagrelor).","Understanding the mechanisms underlying this phenomenon is important to individualizing and improving patient care, long term (maintenance—sometimes referred to as chronic therapy in the literature) therapy and consistent (positive) outcomes.","However, a clear and reliable predictive model for responsiveness to anti-platelet therapy is currently not available.","Attempts have been made to characterize the efficacy of anti-platelet therapy using platelet function testing but based on current information, and dependence on biological agonists, its routine use is not recommended particularly as costs, complexities and cost effectiveness have not been established, and lack of correlation, standardization and agreement between laboratory methods, and their respective results, is well documented in the literature.","Tobias Geislera et al., Circulation 2010; 122:1049-1052.In addition, the inhibitory effects of aspirin on platelets decreases over time in patients on long term or chronic therapy.","Violi, F. et al., J Am Cardio, Vol.","43, No.","6, 2004.Further, as evidenced in AstraZeneca's complete prescribing information on ticagrelor (trade name Brilinta® in the US, Brilique® and Possia® in Europe), Aspirin doses greater than 100 mg reduce the ability of ticagrelor to inhibit platelet aggregation.","This conflicts with current clinical care guidelines in which increasing doses of Aspirin to ‘overcome’ Aspirin resistance is recommended.","Thus, there remains a need for a quantitative, functional platelet activity test that does not use an animal derived collagen as the agonist.","There remains a need for a test that is able to measure the platelet response to an anti-platelet medication when the patient is on a dual therapy of aspirin and an anti-platelet medication, as well as a test to monitor patient compliance with the dual therapy regimen.","Dual antiplatelet therapy is the global practice standard.","There is also a need for a test that can measure residual platelet activity (that is the platelet activity that remains even while the patient is on a dual anti-platelet medication therapy) rather than platelet inhibition, which is the result for currently available tests.","Platelet inhibition does not equal residual platelet reactivity.","Residual platelet reactivity is what determines patient outcome and thus is the better measurement.","The present invention meets these needs.","SUMMARY OF THE INVENTION The present invention provide tests for determining a donor's platelet combined sensitivity status when the individual is on a dual therapy of aspirin and an anti-platelet medication comprising the use of synthetic collagen.","Exemplary tests include the use of platelet aggregation studies using for example, light transmission aggregation assays (LTAAs) and flow Cytometry, and to a lesser degree, methods based on measuring aggregation by impedance or whole blood aggregometry.","The tests of the present invention use synthetic collagen as the agonist.","Tests of the invention provide assays that “discount” or “ignore” the effect of the aspirin on platelet aggregation, but still measure the effect of the anti-platelet medication on the platelet aggregation.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.","Further, the invention provides tests that “discount” or “ignore” the effect of the anti-platelet medication, but still measure the effect of the aspirin on platelet aggregation.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.","The methods of the present invention are able to test the ability of the individual's platelets to aggregate after the individual has ingested an anti-platelet medication and aspirin.","In other words, this tests the residual platelet activity—how reactive are the platelets (likely to aggregate) after the patient has ingested the dual therapy of an anti-platelet medication and aspirin.","In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.","Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 to 12.5 ng/mL; or ranges from about 2.0 to about 25 ng/mL; or ranges from about 2.0 to about 35 ng/mL; or ranges from about 2.0 to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 to about 25 ng/mL; or ranges from about 12.5 to about 35 ng/mL; or ranges from about 12.5 to about 39.0 ng/mL; or ranges from about 25 to about 39 ng/mL.","The literature shows that 30-70% of patients do not comply with taking their medication or taking it as directed, and there is no current compliance test.","There is developing thought that ‘resistance’ may be due, at least in part, to non-compliance.","The present invention also provides a method of testing patient compliance, with the dual therapy regimen.","The DAPT results will show noncompliance for Aspirin therapy as well as deviation from the scheduled dosing window.","The present invention also provides a method of testing patient compliance for the aspirin therapy aspect while on a dual therapy, or testing patient compliance for the anti-platelet medication aspect while on a dual therapy.","The present invention also provides methods of predicting the effectiveness of aspirin therapy, of an anti-platelet medication therapy, or a dual therapy.","In certain embodiments, the synthetic collagen is a synthetic collagen that has the ability to self-assemble into a triple helix to form fibrils and which mimics human type I collagen.","In certain embodiments the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) -(Pro-X-Gly)n (I) wherein X represents Hyp; and n represents an integer of from 20 to 5,000; and wherein the polypeptide has a molecular weight at a range of from 10,000 to 500,000.In certain embodiments, n=20-250.The present invention also provides kits for testing platelet aggregation in a light transmission assay, comprising a vial of synthetic collagen; and instructions for use of the synthetic collagen in the dual anti-platelet therapy test (DAPT) of the present invention.","In certain embodiments (including the methods described herein and the kits), the synthetic collagen is supplied and/or stored in a polypropylene homomer container.","In certain embodiments, the cap is the same material as the vial/tube.","In certain embodiments, the container has an additional internal seal or a cap having a secondary seal molded therein.","In certain embodiments, the container contains all of the above described characteristics BRIEF DESCRIPTION OF THE FIGURES FIG.","1 provides graphs showing the use of a high concentration of synthetic collagen, which shows at high concentrations, the synthetic collagen has no sensitivity to aspirin.","FIG.","2 provides graphs showing the use of a low concentration of synthetic collagen, which shows that at low concentrations synthetic collagen is sensitive to aspirin.","It is this unique property of the synthetic collagen that is the basis for responsiveness and residual reactivity determinations as well as the concurrent assessment of multiple classes of anti-platelet medications.","FIG.","3 shows the results of LTAs run using synthetic collagen.","This figure shows that synthetic collagen provides the ability to measure the effect of other anti-platelet medications in patients on a dual anti-platelet therapy (when one medication is aspirin).","FIG.","4 provides a graph of test (with the readout as area under the curve (“AUC”)) run on an individual known to be aspirin resistant before and after aspirin ingestion.","The tests were run over various dilutions of synthetic collagen.","A “bounce back” is seen between 1.0 ng/mL and 0.1 ng/mL.","This bounce back is where the line showing the AUC should be decreasing down to correspond with the decreasing concentration of synthetic collagen, but instead bounces up and then bounces down to where it should be (decreasing).","FIG.","5 provides a graph of test (with the readout as area under the curve (“AUC”)) run on an individual known to be a normal or average aspirin responder before and after aspirin ingestion.","The tests were run over various dilutions of synthetic collagen.","As expected the AUC decreases as the concentration of synthetic collagen decreases.","There is no pronounced “bounce back” as seen in the aspirin resistant individual.","FIG.","6 provides the test results shown as AUC on a known normal/average aspirin responder using Chrono-Log (Horm) collagen before and after aspirin ingestion.","This figure shows that the Chrono-Log (Horm) collagen is insensitive to aspirin because the pre-aspirin and post aspirin AUCs are very similar and would be difficult if not impossible to distinguish.","This insensitivity to aspirin in one reason why Chrono-Log (Horm) collagen could not be used to determine the combined effect of aspirin and an anti-platelet medication on platelet activity/aggregation.","Further, the non dilutability of biological collagen limits its sensitivity and usefulness in assessing anti-platelet medication effectiveness.","FIG.","7 provides a block diagram of a dual anti-platelet medication therapy test.","FIGS.","8-13 show the results of tests where synthetic collagen was used to detect anti-platelet activity of various anti-platelet medications.","In these tests, light transmission assays using Bio/Data's PAP 8E platelet aggregometer was used.","The ICHOR II impedance cell counter was used to count the platelets.","See Example 1.FIG.","8 shows the effect of ticagrelor on agonist-induced platelet aggregation.","FIG.","9 shows the effect of ticagrelor on agonist-induced platelet aggregation in aspirinized plasma.","FIG.","10 shows the effect of cilostazol on agonist-induced platelet aggregation.","FIG.","11 shows the effect of cilostazol on agonist-induced platelet aggregation in aspirinized plasma.","FIG.","12 shows the effect of abciximab on agonist-induced platelet aggregation.","FIG.","13 shows the effect of abciximab on agonist-induced platelet aggregation in aspirinized plasma.","FIG.","14 shows biological collagen at 5 and 2 μg/mL.","In using the whole blood mode of the Chrono Log aggregometer, a test measuring platelet aggregation on whole blood (impedance aggregation), at 5 μg/mL, the biological collagen gets a response.","At 2 μg/mL, there is no response.","As an aside, even though called “whole blood mode” by the manufacture, most often whole blood is actually diluted whole blood (usually a 1:1 or greater dilution).","FIG.","15 shows that synthetic collagen can be diluted from 100 ng/mL to 12.5 ng/mL and still elicit the same response using the whole blood mode of the Chrono Log aggregometer, a test measuring platelet aggregation on whole blood (impedance aggregation).","DETAILED DESCRIPTION OF THE INVENTION The present invention provides dual anti-platelet therapy tests (“DAPT™”).","The DAPT™ test is a unique, quantitative, functional test, based on different synthetic collagen concentrations, that measures the patient's response to different classes of anti-platelet medications administered concurrently with aspirin, as well as the combined residual platelet reactivity of the aspirin and anti-platelet medication inhibited patient platelets.","The test results provide the physician with information about the patient's response to the combination of aspiring and anti-platelet medication as well as discreet and combined residual platelet activity.","The dual anti-platelet therapy tests of the present invention use platelet aggregation assays to measure platelet aggregation or inhibition of platelet aggregation, which include, but are not limited to light transmission aggregometry (LTA) (which uses platelet rich plasma (“PRP”)); flow cytometry (which uses whole blood); whole blood impedance aggregometry.","The present invention also provides a method for testing a patient's compliance with a dual therapy regimen by monitoring the patient's platelet response over time.","Compliance with the dual therapy means both taking both the medications (aspirin and an anti-platelet medication), and taking them at the proper time to maintain its risk-reducing anti-platelet effect.","It is also known that tailoring the second drug (the anti-platelet medication) in dual therapy is important because the pathways that process the anti-platelet drugs also process other drugs.","For example, in a patient on dual anti-platelet therapy in which one drug is ticagrelor, the plasma level of statins is increased and may be above the therapeutic level.","High dose statin therapy avoidance is recommended by the FDA.","Other drugs, such as digoxin, must be regularly monitored when a patient is on dual antiplatelet therapy.","Incidentally, the aspirin dose must not go over 100 mg, or ticagrelor effectiveness decreases and MACE risk increases.","Residual platelet activity is the activity (functionality) of the platelets after they have been exposed to the dual anti-platelet medication therapy.","No therapeutic dose will impair 100% of the platelets, nor would any combination reach 100% (nor would this be desirable).","In this case the major adverse clinical event (MACE) would be severe bleeding.","However, the reactivity of these non-impaired platelets is a key factor in understanding the individual's complete platelet response and MACE risk.","For instance if the dual anti-platelet medication therapy were to impair 80% of the platelets (keep 80% platelets from aggregation), there is still 20% of the individual's platelets that could cause thrombotic risk if they were to be extremely active or alternatively, could pose a risk of bleeding to death if the platelets were not active and would not aggregate (and thus would not clot).","The present invention provides a method for determining an individual's functional response to an anti-platelet medication when the individual is on, or is a candidate for a dual anti-platelet medication therapy regimen.","A dual anti-platelet therapy regimen means an anti-platelet aggregation regimen involving the administration of a low or patient specific dose of aspirin and at least one other anti-platelet medication, typically a first generation thienopyridine such as clopidogrel or increasingly, ticagrelor—a cyclopentyltriazolopyrimidine.","Aspirin is a common drug whose active ingredient is acetylsalicylic acid (ASA or ASS).","It is a weak acid that is absorbed across the mucosal lining of the stomach and small intestine.","After absorption, ASA is (metabolized) hydrolyzed to acetic acid and salicylic acid.","In most individuals, aspirin causes inhibition of platelet aggregation and thus, aspirin is used in many therapies where it is desired to minimize platelet aggregation.","These individuals are sometimes referred to as normal or average aspirin sensitive.","However, in some individuals, even after taking aspirin, the platelets will still aggregate, and hence aspirin therapy would not be beneficial or at the very least would not be beneficial alone.","These individuals are often referred to as aspirin resistant or aspirin non-responsive, or high on treatment platelet reactivity (platelets are still highly reactive while patient is on therapy).","In this situation, it is important for the physician to know if the patient is compliant or non-compliant in their therapy regimen rather than being non-responsive to aspirin.","Several studies report patient noncompliance to range from 30-70%.","Noncompliance, which is currently only documented by patient interviews, may be a major reason for outcome variability.","In yet other individuals, even very small doses of aspirin cause a severe inhibition of platelet aggregation that could lead to serious bleeding issues.","These individuals can be called aspirin hypersensitive.","For these individuals aspirin therapy may cause more harm than good because of the increased bleeding risk.","In other individuals, aspirin administration causes a life threatening anaphylactic reaction.","These individuals are said to be aspirin intolerant.","Thus, it is very desirable to be able to test a patient/donor for their response to aspirin to see what effects the aspirin will have on the patient's platelet aggregation to determine whether the aspirin therapy will be useful for preventing unwanted platelet aggregation or whether aspirin therapy should be avoided altogether or perhaps instead be used with another drug to enhance the aspirin effect.","Low-dose aspirin (81 mg) is the most common dose used as a preventative regimen against a heart attack or a stroke.","However, the dose for daily aspirin can range from 81 mg to 500 mg. Tablets marketed as “low-dose aspirin” contain 81 mg aspirin.","One adult-strength tablet contains about 325 mg aspirin, and “advanced” extra strength contains 500 mg.","Patient specific aspirin doses can vary from 81 mg to 500 mg. Resistance or insensitivity can occur at any of these doses.","Antiplatelet medications are known and include, but are not limited to, abciximab (Reopro®), anagrelide (Agrylin®), apixoban (Eliquis®), clopidogrel bisulfate (Plavix®), eptifabatide (Integrilin®), tirofiban (Aggrastat®), dipyridamole/aspirin (ASA) (Aggrenox®), cilostazol (Pletal®); dipyridamole (Persantine®), ticlopidine (Ticlid®), ticagrelor (Brilinta®), Aloxiprin (aluminum acetylsalicylate), Carbasalate calcium (mixture of calcium acetylsalicylate and urea), Cloricromen, Clorindione, Ditazole, Indobufen, Picotamide, Ramatroban, Terbogrel, Terutroban, and triflusal, as well as those in similar drug classes that are in various stages of development like cangrelor, elinogrel, prasugrel, and others.","Aspirin is also considered an anti-platelet medication.","For purposes of this application, when referring to a “dual therapy” it is meant as a therapy that includes aspirin and an anti-platelet medication (that is not aspirin).","The methods of the present invention are able to test the ability of the individual's platelets to aggregate after the individual has ingested an anti-platelet medication and aspirin.","In addition, methods of the invention provide assays that “discount” or “ignore” the effect of the aspirin on platelet aggregation, but still measure the effect of the anti-platelet medication on the platelet aggregation.","Further, the invention provides assays that “discount” or “ignore” the effect of the anti-platelet medication, but still measure the effect of the aspirin on platelet aggregation.","In most individuals, various anti-platelet medications will cause a variable degree of inhibition of platelet aggregation.","These individuals are sometimes referred to as having an average/normal response or “low on therapy platelet reactivity.” However, in some individuals, even after taking the standard dose of anti-platelet medication, the platelets will still aggregate, and hence the particular anti-platelet medication would not be beneficial, but rather detrimental since the thrombotic risk would not be controlled, reduced or evident to the clinician.","These individuals are often referred to being non-responsive.","In such individuals, the clinician might change medication doses, try another drug class or even add a third drug to the anti-platelet regimen if the bleeding risk is reasonable.","In yet other individuals, even very small doses of anti-platelet medication causes a severe inhibition of platelet aggregation that could lead to bleeding issues, which in some cases are life threatening or life ending.","These individuals can be called hypersensitive.","For these individuals a particular anti-platelet medication therapy may cause more harm than good because of the known bleeding risk attendant to the use of these types of medications.","Thus, it is very desirable to be able to test a patient/individual for their response to a particular anti-platelet medication to see what effects the anti-platelet medications will have on the patient's platelet aggregation and residual platelet reactivity to determine whether the anti-platelet medication therapy will be useful for preventing unwanted platelet aggregation or whether the particular anti-platelet medication therapy should be avoided because of bleeding, interference with other drug therapies, or other serious risks.","In addition, the tests can be used to monitor patient compliance in taking the prescribed anti-platelet medication.","Non-compliance has been identified in multiple studies as a significant occurrence and carries a very high risk for the patient.","The preceding is the basis for the increasing shift to a personalized medicine focus, a key element of selecting the right drug or combination of drugs for the individual patient.","The DAPT meets this currently unmet need.","Embodiments of the invention can test for platelet aggregation using methods known in the art, including, but not limited to flow cytometery and light transmission aggregometry (LTA) and whole blood impedance aggregometry.","Flow cytometry uses whole blood and can be used to detect platelet aggregation.","Light Transmission Aggregometry (LTA) studies, which are known as the “gold standard” in testing platelet aggregation.","Light Transmission Aggregometry (LTA) is an in vitro diagnostic functional assay that measures quantitatively multiple optical parameters from changes in light transmission through Platelet Rich Plasma (PRP) following the addition of an agonist (such as, collagen, ADP, epinephrine, Ristocetin, Arachidonic Acid, thrombin and TRAP) (e.g.","more light passes through a sample where there has been platelet aggregation as compared to a sample with no platelet aggregation).","Often a blank is used for the comparison, which is the donor's plasma with no platelets present, which is often called “platelet poor plasma” (“PPP”).","An agonist is a material that when added to platelet rich plasma, causes the platelets to aggregate.","In the methods of the present invention the agonist is synthetic collagen.","In LTAA, the PRP is usually stirred in a cuvette at 37° C., and the cuvette sits between a light course and a photocell.","After an agonist is added to platelet rich plasma (PRP), the platelets aggregate and absorb less light, so the light transmission increases and is detected by the photocell.","LTAAs generate data in the form of aggregation patterns.","The LTAA generates parameters plotted on an x/y grid.","The x axis is usually a linear time base (typically—minutes).","The y axis is a logarithmic scale based upon light transmittance.","This light transmittance is equated to percent (%) aggregation.","As the LTAA pattern or curve is generated (primary data), various derived measurements are calculated, including Slope (Sa); Maximum Aggregation; Final Aggregation; Area Under the Curve (AUC), Area Under the Slope (AUS) and others.","In some embodiments of the present invention AUC is a preferred measurement aspect, because it appears more sensitive than the others.","Slope of aggregation (Sa) is a measurement of the rate at which the reaction is proceeding.","Dilution profile (DUP) is an incremental change in concentration of the reactants in a test mixture.","In collagen testing, the DUP is comprised of the changes to the concentration of the collagen reagent used.","Other dilution profiles may be defined and used in analyses.","Slope of the dilution Profile (Sd) is generally the regression analysis of the change in concentration.","Slope of the reaction profile (Sr) is generally the regression analysis of the change of reaction to change of dilution.","The regression analysis may be linear, polynomial or other models.","Area under the curve (AUC) is a receiver operating curve that is the calculated graphical volume from the start of the reaction to the end of the reaction as defined by the aggregation and slope of aggregation (Sa).","The use of the AUC parameter increases the sensitivity of the DAPT assay(s).","This may be considered as the “Power” generated by the reaction.","The present invention utilizes synthetic collagen, which it turns out is much more sensitive, potent, predictive and precise than biological collagen, and further is dilutable, which allows extremely low amounts of synthetic collagen to be used.","Using synthetic collagen, the methods of the present invention are able measure the degree to which the patient's platelets resist aggregation after the patient has ingested aspirin and an anti-platelet medication.","This is a key element, which permits the clinician to accurately assess thrombotic risk avoid MACE and improve patient outcome.","In addition, as will be described below in more detail, because the synthetic collagen is dilutable and can be used at many different concentrations, (thereby the right concentration for maximum sensitivity) the tests can be manipulated using different concentrations of the collagen to test for residual platelet activity, to test the effect the anti-platelet medication is having on platelet activity, and to test the effect that the aspirin is having on platelet activity.","Further, synthetic collagen provides a means of quantitatively assessing residual platelet reactivity, which is the key indicator of prognostic risk, and is, therefore, more useful information than the currently available, qualitative and highly variable parameter called platelet inhibition.","It is important to note that inhibition of aggregation does not equal residual platelet reactivity.","Until recently, “platelet inhibition” was the global term and test parameter that was accepted for understanding how platelets behaved when exposed to an anti-platelet drug.","The percent aggregation or percent inhibition of aggregation was simply adopted because that is how platelet aggregation was reported.","So, inhibition was simply the difference between the patient's original aggregation result and the post treatment result.","If the patient's original aggregation result was 82% and the post treatment aggregation result was, 23%, the percent inhibition was reported as 59%.","It was then assumed that the other 41% of the platelets were not inhibited.","The target was to get the percentage of inhibition between 60 and 80% because that would mean the patient would neither clot nor bleed (ideal outcome).","However, it has now been determined that this simplistic construct or understanding does not tell the whole story and thus not work because it does nothing to aid in the understanding of the residual platelet reactivity (that is, the reactivity of the platelets that did not respond to the ingested medicine).","There simply is no direct, measurable or predictable relationship between percent inhibition and residual platelet reactivity.","Physicians have discovered that patient outcomes to various treatments would vary even when they shared the same percent inhibition.","For example, two patients who showed 41 percent inhibition (and thus had 59% aggregation) in an LTA might respond very differently (one may still have problems with unwanted clotting and the other may have problems with bleeding).","This observation has slowly led to the realization that although the percent inhibition number (the number of remaining or uninhibited platelets) could be identical, the patient responses could be very different.","This has recently spawned the use of terms such as hyper and hypoactive, hyper and hypo-responders, platelet reactivity, residual platelet reactivity, and High on Treatment Platelet Reactivity.","The point is that percent inhibition is not the same as residual platelet reactivity.","It is clear that platelet response is the measurable effect of a challenge on platelet function, i.e., how a particular drug interferes with a platelet function pathway (platelet and metabolic genetics, drug action and pharmacokinetics, and other factors all come in to play for residual platelet reactivity).","The present invention can measure residual platelet reactivity, which is a combination of three things wrapped up into basically a single measurement.","The first component is a dose response based on the primary drug (e.g.","an anti-platelet medication) to show what portion of the patient's platelets are rendered partially or non-functional based on the that particular patient's individual response to that drug and dose.","The second component relates to how reactive the remaining platelets are.","These platelets, like the ones that are inhibited, could be hyperactive, hypoactive or anywhere on the continuum between those two points to a different medicine.","The third component provides information about the effect of the second drug (e.g.","aspirin), which has all the same considerations of the first drug.","Synthetic collagen has a unique ability to be insensitive to aspirin at certain concentrations, which allows for the assessment of the second anti-platelet medication, along with its residual platelet reactivity and yet can be used at extremely low concentrations to allow assessment of aspirin sensitivity alone (see FIGS.","1 and 2) and further, at other concentrations, can be used to assess residual platelet activity (the activity of the platelets remaining in response to both the anti-platelet medication and the aspirin.","FIG.","1 shows no aspirin sensitivity when the synthetic collagen concentration is high.","FIG.","2 shows aspirin sensitivity when the synthetic collagen is low.","The insensitivity to aspirin is a key factor in measuring the second anti-platelet drug while the sensitivity to aspirin is needed to assess the residual platelet activity (the activity remaining despite the separate effects of the two drugs).","In one aspect, the synthetic collagen is used at a concentration that causes the test to ignore or discount the effect that that aspirin might be having on platelet activity, but still allows one to measure the effect of the anti-platelet medication on platelet activity.","In this aspect, the concentration is greater than 40 ng/mL and preferably greater than 50 ng/mL.","In another aspect, the synthetic collagen is used at a concentration that causes the test to ignore or discount the effect that the anti-platelet medication might be having on the platelets but still allows one to measure the effect of the aspirin on platelet activity.","In another aspect, the amount of synthetic collagen is used at a concentration that tests the residual activity of the platelets after being exposed to the aspirin and the anti-platelet medication.","In this aspect, the concentration of synthetic collagen is between about 25 ng/mL to about 35 ng/mL.","There are ranges of platelet aggregation that occur after an individual consumes an anti-platelet medication and these ranges can be used to characterize an individual as having a hypersensitive response, a normal/average response, or having a non-response to the anti-platelet medication.","Different individuals respond to a particular anti platelet medications differently, so the present invention provides a way of measuring the response to the anti-platelet medication as well as residual platelet reactivity.","If the individual does not respond to the medication as desired, the physician can then change the dose, prescribe a different anti-platelet medication or even add a third drug.","The present invention also provides embodiments that capitalize on the repeatability and sensitivity of the synthetic collagen as well as its ability to be reproducibly diluted over a range of concentrations and thus, employs multiple dilutions of synthetic collagen (referred to herein as “dilution profiles”) to aid a physician in determining not only whether an individual is sensitive to the anti-platelet medication and/or aspirin, but to further understand an individual's anti-platelet medication and/or aspirin sensitivity status (e.g.","the degree to which an individual is anti-platelet medication and/or aspirin sensitive, non-responsive or hypersensitive).","This information may be useful for the physician to determine an appropriate dose (patient specific) of anti-platelet medication and/or aspirin in the prescribed therapeutic regimen, or perhaps whether a second or third therapeutic medicine is required, or whether to consider abandoning the use of the anti-platelet medication and/or aspirin altogether for an alternative therapy.","Further capitalizing on the sensitivity of synthetic collagen and further using the dilution profile concept, the present invention also provides embodiments where an individual's anti-platelet medication and/or aspirin sensitivity can be predicted even before the donor ingests the anti-platelet medication.","Aspirin and anti-platelet medication non-responder (resistant) donors have a distinct response (referred to herein as the “bounce back”) to LTAAs run over varying concentrations of synthetic collagen, which can be used to diagnose a donor's response to the aspirin and the anti-platelet medication.","This and other embodiments are discussed more fully herein below.","As mentioned above, LTAAs use Platelet Rich Plasma (PRP), which is prepared from properly anti-coagulated whole blood.","The individual's blood is collected and spun down to obtain the PRP.","Since platelets are very sensitive and can be readily activated during the preparation of PRP, the individual's blood is usually collected in a tube containing a particular anticoagulant.","For example, venous blood is obtained and collected into 3.2% sodium citrate in a ratio of 1:9 (1 part anticoagulant to 9 parts blood).","Whole blood samples should be processed within 4 hours of collection and blood samples for platelet aggregation testing must be stored at room temperature as cooling the platelets can lead to activation and erroneous test results.","PRP is usually prepared by centrifugation at 20° C. for 10-15 minutes at 150-200 g, or, with platelet function centrifuge such as the PDQ companion centrifuge for the PAP 8E, PRP can be prepared in under 4 minutes.","The PRP is carefully removed and placed into a stoppered plastic tube.","PRP must be stored at room temperature.","Platelet poor plasma (PPP) can be then prepared by further centrifugation of the remaining plasma at 2700 g for 15 minutes.","Platelet poor plasma (PPP) contains no platelets or other cellular material, and is often used as a blank in LTA sample analyses.","By using the PDQ platelet function centrifuge, this time can be reduced to about three minutes.","In certain embodiments a special centrifuge that can repeatedly generate PRP and PPP in about 5 minutes instead of the typical 45-60 minutes is employed.","This makes the LTAA even more practical for emergency and critical care situations or for a high throughput clinical setting.","In addition to the rapid sample preparation, the use of certain concentrations of synthetic collagen can be used to generate the patient's global residual platelet reactivity on an emergency basis.","Addition of a platelet agonist to the PRP usually leads to platelet activation, and leads to a change in their shape from discoid to spiny spheres, which is associated with a transient increase in optical density.","Exceptions to this are epinephrine in which there is no shape change, and ristocetin, which causes platelet agglutination rather than aggregation, i.e.","there is no binding of fibrinogen.","Agonists are usually classified as strong agonists or weak agonists.","Strong Agonists (e.g.","Collagen, thrombin, TRAP, high concentration ADP, and U46619 (an analog of TxA2)) directly induce platelet aggregation, TxA2 synthesis and platelet granule secretion.","Weak Agonists (e.g.","low concentration ADP & epinephrine) induce platelet aggregation without inducing secretion.","In general, LTAs are performed at 37° C. The aggregometer is calibrated by: 1) a cuvette containing PRP, which equates to 0% light transmission; and 2) a second cuvette containing PPP, which equates to 100% light transmission.","Since platelets will normally only aggregate if they are activated (with an agonist) and in contact with each other, they must be stirred whilst testing is taking place.","Absence of stirring will lead to an absence of, or at least a significant reduction in, aggregation.","The present invention utilizes synthetic collagen as the agonist instead of collagen obtained from biological sources in the light transmission aggregometry (“LTA”).","The use of synthetic collagen provides many unexpected benefits over the use of biological collagen, which is described herein.","In certain embodiments, Bio/Data's PAP 8E LTA is employed (See U.S. Pat.","No.","7,453,555) as the LTA used in the LTAAs of the present invention.","Normally a test for spontaneous platelet aggregation (“SPA”) is performed.","SPA is rare in healthy individuals, but occurs in people with hyperactive platelets and is also recognized as an independent marker for some pro-thrombotic conditions, in some cases of von Willebrand Disease (vWD), in some patients with diabetes, in some lipid disorders and in a variety of other disorders.","The presence of SPA is tested by placing undiluted PRP in the aggregometer and stirring for 15 minutes.","In cases of SPA, dilution of the PRP may abolish this and if the platelet count remains >200×109/L then aggregation testing can proceed.","In general, about 225 μL of PRP is added to the aggregometry test cuvette and warmed at 37° C. Then 25 μL of the agonist is added and the response recorded.","The typical readouts or responses recorded include primary aggregation (“PA”) (which usually provides a value indicating the amount of aggregation), primary slope (“PS”)(which usually provides a value relating to the speed of aggregation) and area under the curve (“AUC”)(which generally provides a value relating to a combination of PA and PS).","Aggregometry analyzers used in the field typically will provide these readouts along with a pictorial graph of the aggregation.","Each aggregometer or system calculates the values a bit differently and may use a proprietary formulae embedded in the system software.","For example, % maximal aggregation may be calculated by measuring the distance between the baseline [0% aggregation−platelet rich plasma] and platelet poor plasma [100% aggregation] [Y] and dividing this number by the maximal aggregation [X].","So if the Y=100 mm and X=89 mm then percentage maximal aggregation=X/Y=89%.","In the methods/assays of the present invention, instead of having the patient ingest aspirin and thereafter take a blood sample, a sample of blood can be taken before any aspirin is ingested and the sample can be “aspirinated” (or “aspirinized”)(that is, an aspirin solution (may also be the lysine salt of aspirin or Aspisol®) is added to the PRP and then tested).","It has been determined that in the all of the methods/assays of the present, either the patient can ingest the aspirin or the sample can be aspirinated.","This can speed up the testing because the patient does not need to ingest the aspirin and have time pass to allow the aspirin to get into the patient's system.","Instead, the blood is drawn and a PRP sample is obtained, and one part is aspirinated and the other part is not, thus also allowing the two samples to be tested side by side.","A.","Testing for Platelet Sensitivity to Anti-Platelet Medication in an Individual on Dual Anti-Platelet Medication Therapy (Ignoring the Effect of Aspirin at this Stage of the Assay, but can be Measured at Another Stage) One embodiment of the present invention provides tests that can determine the individual's platelet sensitivity to an anti-platelet medication when the individual is on a dual anti-platelet medication therapy (i.e.","on aspirin and an anti-platelet medication).","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.","This method involves performing one or more platelet aggregation assays, such as light transmission assays or flow cytometry whereby a first platelet rich sample or whole blood sample is obtained from an individual and is combined with synthetic collagen to form a first treated sample.","For the first treated sample, the individual has not ingested the anti-platelet medication for a time period of about 24 hours, preferably 72-96 hours.","The idea is to make sure that the individual will not have any anti-platelet medication in his system to affect the platelet aggregation tests.","The first treated sample is tested/measured for platelet aggregation to get a first readout to determine the individual's baseline level of platelet aggregation in the absence of ingested anti-platelet medication.","If LTA is used, the sample is placed into a LTA aggregometer and light transmission through the first treated sample is obtained to get the first readout.","In certain embodiments, an initial LTAA or other platelet aggregation assay may be performed to check for spontaneous aggregation to test for whether the platelets have any inherent hyperactivity.","Then the individual is given the anti-platelet medication (presumably the individual is already on aspirin therapy and has ingested aspirin) and a time period sufficient to allow the anti-platelet medication to be metabolized (e.g.","at least about 2 hours to about 16 hours) is allowed to pass before a second platelet rich plasma sample is obtained from the donor.","Another platelet aggregation assay such as LTAA is performed on the second platelet rich plasma sample by treating it with synthetic collagen to form a second treated sample.","Platelet aggregation is measured to obtain a second readout.","If LTAA is the assay used to measure platelet aggregation, light transmission through the second sample is measured to obtain the second readout.","It is preferred that the same type of platelet aggregation assay is used throughout the process.","For example, if LTAA is used for the first treated sample, then preferably LTAA is used for the second treated sample.","The baseline level readout of platelet aggregation in the absence of ingested anti-platelet medication is compared with the second treated sample readout (obtained after the anti-platelet medication ingestion) and the results of this comparison will determine the individual's anti-platelet medication response status.","For example, if the individual shows a significant reduction in platelet aggregation after the anti-platelet medication ingestion (in the second sample) as compared to the baseline sample, then the individual may be characterized as normal or having an average anti-platelet medication sensitivity.","If the individual shows very little difference in the platelet aggregation after taking the anti-platelet medication (i.e.","the platelets still aggregated after the individual ingested the anti-platelet medication), then the individual may be characterized as being anti-platelet medication non-responsive.","If the individual showed an almost complete lack of platelet aggregation after ingesting the anti-platelet medication, then the individual may be characterized as being anti-platelet medication hypersensitive, which itself is a very high risk state for the patient.","In certain embodiments, the test uses LTAA for platelet aggregation measurements.","The readout from the LTAA may be slope, primary aggregation, area under the curve, lag phase disaggregation or a combination thereof.","For example, when using the Bio/Data's PAP 8E aggregometer, and when using an “in-test” concentration of 50 ng/mL of synthetic collagen, for an anti-platelet medication hypersensitive individual, the baseline for PA will range from 40% to 100%.","The baseline for PS will range from 20 to 60.The baseline for AUC will range from 300 to 700.After the anti-platelet medication, the AUC will range from 100 to 400.PS, PA and LP, will be different from their respective baselines.","The anti-platelet medication sensitive and the anti-platelet medication non-responders will show differences from baselines; sensitive individuals will show less aggregation.","In certain embodiments, an algorithm that combines and categorizes this data, into an actionable form useful to the physician is.","In these tests, the individual may or may not have also consumed aspirin for the test.","In one embodiment, the individual does not consume aspirin before the first platelet sample is obtained for the baseline readout, but then ingests aspirin before the second assay is run.","In another embodiment, the individual was already on aspirin therapy and had ingested aspirin before the baseline readout was obtained and continued taking the aspirin during the testing.","Since this test uses synthetic collagen at a range where it is insensitive to the effects of aspirin on platelets, it does not matter for the test results if the individual consumes aspirin.","The beauty of the test is that any inhibition of platelet aggregation seen in the test occurs because of the effect of the anti-platelet medication on the platelet activity and not the aspirin.","In another embodiment, no baseline readout is obtained.","In this situation, it may be desirable, but is not necessary, to use a previous test run for this individual before the individual started the dual anti-platelet medication therapy as the baseline readout.","In the situation where no baseline was obtained, the assay involves performing one or more tests, such as light transmission assays, whereby a first platelet rich sample is obtained from an individual and is combined with synthetic collagen to form a treated sample.","The sample is tested and in the case of LTAA is placed into a LTA aggregometer and the light transmission through the treated sample is obtained to get a readout to determine the individual's level of platelet aggregation.","In certain embodiments, an initial test may be performed to check for spontaneous aggregation.","The results of this treated sample assay are used to determine the individual's anti-platelet medication response status.","For example, if the individual shows a significant reduction in platelet aggregation, then the individual may be characterized as normal or having an average anti-platelet medication sensitivity.","If the individual shows very little inhibition of platelet aggregation after taking the anti-platelet medication (i.e.","the platelets still aggregated after the individual ingested the anti-platelet medication), then the individual may be characterized as being anti-platelet medication non-responsive.","If the individual showed an almost complete lack of platelet aggregation after ingesting the anti-platelet medication, then the individual may be characterized as being anti-platelet medication hypersensitive.","If the test used LTAAs then the readout of platelet aggregation from the LTAA may be slope, primary aggregation, area under the curve, lag phase, disaggregation, final aggregation or a combination thereof.","B.","Testing for Platelet Sensitivity to an Anti-Platelet Medication in an Individual on Dual Anti-Platelet Medication Therapy Using a Dilution Profile (Ignoring the Effect of Aspirin on the Platelets) In another embodiment, a dilution profile of synthetic collagen is utilized across a number of different platelet aggregation tests run on an individual's whole blood or PRP sample.","In this embodiment of the invention, more than two reactions (more than just the baseline test before the anti-platelet medication ingestion and the test after the anti-platelet medication) are run.","A series of platelet aggregation tests, such as a series of LTAAs, are run using multiple differing amounts of synthetic collagen.","This is referred to herein as the “dilution profile assays” or “dilution profiles.” In this embodiment, multiple different whole blood or PRP samples are obtained from the individual before the anti-platelet medication ingestion (to obtain a baseline dilution profile) and after the anti-platelet medication ingestion (to obtain a post anti-platelet medication dilution profile).","Each individual pre-anti-platelet medication platelet sample is mixed with a different amount of synthetic collagen and a platelet aggregation assay, such as LTAA, is performed on each sample to obtain a baseline dilution profile over the range of concentrations.","Then the individual is given the anti-platelet medication and sufficient time is allowed to pass to ensure the anti-platelet medication has been metabolized.","Multiple whole blood or PRP samples are obtained from the individual post anti-platelet medication ingestion and mixed with different amounts of synthetic collagen.","Platelet aggregation tests, such as LTAAs, are performed on each different sample to obtain a post-anti-platelet medication dilution profile.","The same concentrations of synthetic collagen that were used in the pre-anti-platelet medication baseline platelet aggregation tests are preferably used in the post-anti-platelet medication platelet aggregation tests.","The results are analyzed and the change in platelet aggregation between the pre- and post-anti-platelet medication tests as well as the change of aggregation over the differing amounts of synthetic collagen are studied to determine the individual's anti-platelet medication sensitivity response (whether the individual is anti-platelet medication hypersensitive, average anti-platelet medication sensitive or anti-platelet medication non-responsive and the degree of sensitivity therein).","If the tests utilized LTAAs then the PA, PS or AUC or a combination thereof between the pre- and post-anti-platelet medication LTAs, as well as changes in the PA, PS or AUC or a combination thereof over the differing amounts of synthetic collagen, are studied (often using an algorithm that categorizes the data or information and reports the data) to determine the individual's anti-platelet medication sensitivity response (whether the individual is anti-platelet medication hypersensitive, average anti-platelet medication sensitive or anti-platelet medication non-responsive and the degree of sensitivity therein).","In certain embodiments, the results are characterized using the aggregometer's proprietary algorithm embedded in system software, which makes the analysis easier for the diagnostician to understand and make appropriate clinical decisions.","In other embodiments, the pre-anti-platelet medication baseline is established with one platelet aggregation test (such as an LTAA) performed using one concentration of synthetic collagen (such as 50 ng/mL) in the LTAA on an individual pre-anti-platelet medication platelet sample, whereas multiple different concentrations of synthetic collagen are still used in different post anti-platelet medication platelet aggregation tests, such as LTAAs, to create the post-anti-platelet medication dilution profile.","In this case, the results are analyzed and the change in platelet aggregation seen in the different amounts of synthetic collagen are studied, and compared against each other as well as to against the baseline (pre-anti-platelet medication) to determine the donor's anti-platelet medication sensitivity response (whether anti-platelet medication hypersensitive, normal/average anti-platelet medication sensitive or anti-platelet medication non-responsive and the degree of sensitivity therein).","When the platelet aggregation tests use LTAAs, the PA, PS, AUC, or a combination thereof from differing amounts of synthetic collagen are studied, and compared against each other as well as to against the baseline (pre-anti-platelet medication) LTAA to determine the donor's anti-platelet medication sensitivity response.","In other embodiments, a pre-anti-platelet medication baseline or pre-anti-platelet medication dilution profile is not obtained.","This may be useful in the emergency clinical setting when it is not feasible to obtain a pre-anti-platelet medication baseline or whether one cannot determine from the patient whether he or she has been on anti-platelet medication therapy.","In this embodiment, multiple different platelet rich plasma samples or whole blood samples are obtained from the individual and each are mixed independently with a different synthetic collagen concentration to obtain multiple different treated samples for the dilution profile tests.","Platelet aggregation tests, such as LTAAs, are performed for each of these samples to obtain a dilution profile over the range of different concentrations.","The data is obtained and measured.","When the platelet aggregation tests are LTAAs, the AUC, PA, and/or PS or combination therefore are obtained and analyzed over the different ranges of synthetic collagen.","In certain embodiments, the results are analyzed using the aggregometer's proprietary algorithm embedded in system software.","The inventors have determined that this embodiment can be used to predict the donor's platelet the anti-platelet medication response.","For individuals having an average or “normal” anti-platelet medication sensitivity, when looking at the slope, percentage aggregation and/or the AUC, over the dilution profile, the slope, percentage aggregation and/or the AUC will show a corresponding decrease along with the decrease in the amount of synthetic collagen used.","Thus, for example, within a given range of various dilutions of synthetic collagen, as the concentration goes down, so will the slope, percentage aggregation, and the AUC.","There seems to be an almost linear decrease in slope, percentage aggregation and AUC that runs almost parallel or has almost a direct correlation with the concentration of synthetic collagen.","On the other hand, for individuals who are anti-platelet medication non-responders, instead of having a slope, percentage aggregation, and/or the AUC that has a linear-like decrease that corresponds with the decrease in synthetic collagen, there is a point along the dilution profile where there is an increase in slope, an unexpected temporary increase in percentage aggregation and/or a temporary increase in AUC when there should be a decrease (because the concentration of synthetic collagen decreases).","Then, as the dilution profile continues to decrease, the slope and AUC “bounce back” down to where it should be (based on the dilution of synthetic collagen) and where it was before the temporary increase and then continues along decreasing.","The point at which the bounce back will occur will be at different concentrations of synthetic collagen, and will depend upon the medication class and dose, as well as the patient's metabolic and platelet receptor genetics.","Anti-platelet medication hypersensitive individuals will show increases in PA, PS and AUC compared to expected/normal results.","In certain embodiments of the invention utilizing the dilution profile concept, a series of 7, 6 or 5 different concentrations are used to develop a dilution profile, and in other embodiments, 4 different concentrations are used and yet in other embodiments, 3 or 2 different concentrations are used.","Using too many different concentrations can make the test cumbersome and time consuming, whereas using too few concentrations reduces the amount of data obtained and limits the sensitivity analysis.","The range of synthetic collagen used is the dilution profile is preferably within the “anti-platelet medication sensitive range,” which is defined herein as the range of concentrations in which in an average anti-platelet medication sensitive individual the measured platelet activity/aggregation is reduced corresponding with decreasing amounts of synthetic collagen concentrations (e.g.","the AUC and/or the slope decreases with the concentration of collagen).","In these embodiments the final in-test concentration of synthetic collagen used in the dilution profiles tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.","In certain embodiments the different synthetic collagen dilution amounts comprise multiple different synthetic collagen amounts chosen from within the concentration range from about 50 ng/mL to about 500 ng/mL or the range from about 50 ng/mL to about 250 ng/mL.","For example, in certain embodiments there are seven different synthetic collagen amounts as the final “in test” concentration as follows: 500 ng/mL; 325 ng/mL; 250 ng/mL; 150 ng/mL; 100 ng/mL; 75 ng/mL; and 50 ng/mL.","In other embodiments, there are different synthetic collagen amounts (2, 3, 4, 5, 6 or 7 different dilutions) each chosen from within the range of about 50 ng/mL to about 500 ng/mL or each chosen from within the range of about 50 ng/mL to about about 250 ng/mL, or chosen within the range of about 40 ng/mL to about 500 ng/mL.","As some non-limiting examples, in certain embodiments, there are 7 different concentrations (50 ng/mL, 75 ng/mL, 100 ng/mL, 150 ng/mL, 250 ng/mL, 325 ng/mL, and 500 ng/mL).","In certain embodiments there are 6 different concentrations (50 ng/mL, 100 ng/mL, 150 ng/mL, 200 ng/mL, 250 ng/mL, and 300 ng/mL).","In certain embodiments, there are 5 different concentrations (100 ng/mL, 200 ng/mL, 300 ng/mL, 400 ng/mL, and 500 ng/mL).","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.","C. Testing for Platelet Sensitivity to Aspirin in an Individual on Dual Anti-Platelet Medication Therapy (Ignoring Effect of Anti-Platelet Medication) One method of the present invention provides tests that can determine an individual's platelet sensitivity to aspirin when the individual is on a dual anti-platelet medication therapy.","In this embodiment, the concentration of synthetic collagen is low enough to be insensitive to the effects of the antiplatelet medication on platelet activity but high enough to be sensitive to the effects of aspirin on platelet activity.","In other words, in these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.","The concentration of synthetic collagen in this is aspect is a low range and is actually so low that a biological collagen could not be diluted to this low concentration.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","This method involves performing one or more platelet aggregation tests, such as light transmission assays, whereby a first platelet rich sample or whole blood sample is obtained from an individual and is combined with synthetic collagen to form a first treated sample.","For this first treated sample, the individual has not ingested the aspirin for a time period of about 24 hours, preferably 72-96 hours (presumably the patient is on an anti-platelet medication).","The idea is to make sure that the individual will not have any aspirin in his system to affect the platelet aggregation tests.","The sample is measured, such as by placing into a LTA aggregometer and the light transmission through the first treated sample is obtained, to get a first readout to determine the individual's baseline level in the absence of ingested aspirin.","In certain embodiments, an initial platelet aggregation assay may be performed to check for spontaneous aggregation to test for whether the platelets have any inherent hyperactivity.","Then the individual's is given the aspirin and a time period sufficient to allow the aspirin to be metabolized (e.g.","at least about 2 hours to about 16 hours) is allowed to pass before a second platelet rich plasma sample or whole blood sample is obtained from the donor.","A platelet aggregation study, such as LTAA, is performed on the second platelet rich plasma sample by treating it with synthetic collagen to form a second treated sample.","The second sample is assayed such as in an LTAA by measuring light transmission through the second treated sample to obtain a second readout.","The baseline level readout in the absence of ingested aspirin is compared with the second treated sample readout (obtained after the aspirin ingestion) and the results of this comparison will determine the individual's aspirin response status.","For example, if the individual shows a significant reduction in platelet aggregation after the aspirin ingestion (in the second sample) as compared to the baseline sample, then the individual may be characterized as normal or having an average aspirin sensitivity.","If the individual shows very little difference in the platelet aggregation after taking the aspirin (i.e.","the platelets still aggregated after the individual ingested the aspirin), then the individual may be characterized as being aspirin non-responsive.","If the individual showed an almost complete lack of platelet aggregation after ingesting the aspirin, then the individual may be characterized as being aspirin hypersensitive.","Instead of having the patient ingest the aspirin, the sample can be aspirinated (a solution of aspirin is added to the PRP sample (or whole blood sample).","If the platelet aggregation tests used LTAAs, then the readout from the LTA may be slope, primary aggregation, area under the curve, or a combination thereof.","The aspirin sensitive and the aspirin non-responders will show differences from baselines; sensitive individuals will show less aggregation.","In certain embodiments, an algorithm that combines and categorizes this data, into an actionable form useful to the physician is employed.","During these tests the individual is also preferably taking an anti-platelet medication.","Because the amount of synthetic collagen used is so low, the test is insensitive to any action of the anti-platelet medication on the platelets.","This allows the tester to analyze the effects of the aspirin on platelet activity, while the individual is on the dual anti-platelet medication therapy.","This can provide useful information, for example, in cases where the individual turns out to be an aspirin non-responder.","In this case, the physician might take the patient off of the aspirin altogether and might prescribe a second anti-platelet medication.","Or it could turn out that the patient is hypersensitive to aspirin, which may render the patient at a high risk to unwanted bleeding complications.","In this case, the physician may take the patient off of the aspirin altogether and might prescribe a second anti-platelet medication.","In another embodiment, no baseline readout is obtained.","In this situation where no baseline is obtained, the test involves performing one platelet aggregation assay whereby a platelet rich sample or a whole blood sample (in the case of flow cytometry) is obtained from an individual and is combined with synthetic collagen (e.g.","(at a concentration ranging from about 1.0 ng/mL to about 0.1 ng/mL) to form a treated sample.","The sample is measured for platelet aggregation, such as in an LTAA by placing it into a LTA aggregometer and the light transmission through the treated sample is obtained to get a readout to determine the individual's level of platelet aggregation).","In certain embodiments, an initial assay may be performed to check for spontaneous aggregation.","The results of this treated sample are used to determine the individual's aspirin response status.","For example, if the individual shows a significant reduction in platelet aggregation, then the individual may be characterized as normal or having an average aspirin sensitivity.","If the individual shows very little inhibition of platelet aggregation after taking aspirin (i.e.","the platelets still aggregated after the individual ingested the aspirin), then the individual may be characterized as being aspirin non-responsive.","If the individual showed an almost complete lack of platelet aggregation after ingesting the aspirin, then the individual may be characterized as being aspirin hypersensitive.","The readout from the LTAA may be Primary Slope, Primary Aggregation, Area Under the Curve, lag phase (LP), disaggregation (DA), final aggregatrion (FA) or a combination thereof.","D. Testing for Platelet Sensitivity to Aspirin in an Individual on Dual Anti-Platelet Medication Therapy Using Dilution Profile (Ignoring Effect of Anti-Platelet Medication) In another embodiment for testing platelet sensitivity to aspirin in an individual on a dual anti-platelet medication therapy, a dilution profile of synthetic collagen is utilized across a number of different platelet aggregation assays, such as LTAAs or flow cytometery run on an individual's PRP or whole blood sample.","In this embodiment, multiple different PRP or whole blood samples are obtained from the individual before the aspirin ingestion (to obtain a baseline dilution profile) and after the aspirin ingestion (to obtain a post aspirin dilution profile).","Each platelet sample is mixed with a different amount of synthetic collagen and a platelet aggregation assay, such as LTAA or flow cytometry, is performed on each sample to obtain a baseline dilution profile over the range of concentrations.","Then the individual is given the aspirin and sufficient time is allowed to pass to ensure the aspirin has been metabolized.","Multiple PRP or whole blood samples are then obtained from the individual post aspirin ingestion and mixed with different amounts of synthetic collagen.","In certain embodiments, the samples are aspirinated instead of having the patient ingest aspirin.","Platelet aggregation assay are performed on each sample to obtain a post-aspirin dilution profile.","The same concentrations of synthetic collagen that were used in the pre-aspirin baseline assays are preferably used in the post-aspirin assays.","Preferably the same type of platelet aggregation assay is used throughout the test.","For example, flow cytometry is used to measure platelet aggregation for each sample.","As another example, LTAAs are used to measure platelet aggregation for each sample.","The results are analyzed and the change in platelet aggregation as seen in changes in the PA, PS, AUC, LP, DA, or FA, or a combination thereof between the pre- and post-aspirin assays, as well as changes in the PA, PS, AUC, LP, DA, or FA, or a combination thereof over the differing amounts of synthetic collagen, are studied (often using an algorithm that categorizes the data or information and reports the data) to determine the individual's aspirin sensitivity response (whether the individual is aspirin hypersensitive, average aspirin sensitive or aspirin non-responsive and the degree of sensitivity therein).","In certain embodiments the results are characterized using the aggregometer's proprietary algorithm embedded in system software, which makes the results of the analysis easier for the diagnostician to understand and make appropriate clinical decisions.","In other embodiments, the pre-aspirin baseline is established with one platelet aggregation assay performed using one concentration of synthetic collagen (such as 0.5 ng/mL in one LTAA) on a pre-anti-platelet medication individual platelet sample, whereas multiple different concentrations of synthetic collagen are still used in different post aspirin platelet aggregation assays to create the post-aspirin dilution profile assays.","In this case, the platelet aggregation results are analyzed and compared against each other.","If LTAAs were used as the platelet aggregation assay, the change in PA, PS, AUC, LP, DA, or FA, or a combination thereof from differing amounts of synthetic collagen are studied, and/or compared against the baseline (pre-aspirin) LTAA to determine the donor's aspirin sensitivity response (whether aspirin hypersensitive, normal/average aspirin sensitive or aspirin non-responsive and the degree of sensitivity therein).","In other embodiments, a pre-aspirin baseline or pre aspirin dilution profile is not obtained.","This may be useful in the emergency clinical setting when it is not feasible to obtain a pre-aspirin medication baseline or whether one cannot determine from the patient whether he or she has been on aspirin therapy.","In this embodiment, multiple different platelet rich plasma samples or whole blood samples are obtained from the individual and each are mixed independently with a different synthetic collagen concentration to obtain multiple different treated samples for the dilution profile assays.","Platelet aggregation assays are performed for each of these samples to obtain a dilution profile over the range of different concentrations.","The data is obtained and measured.","In this case, the platelet aggregation results are analyzed and compared against each other.","If LTAAs were used as the platelet aggregation assay, the change in PA, PS, AUC, LP, DA, or FA, or a combination thereof from differing amounts of synthetic collagen are studied, and/or compared against the baseline (pre-aspirin) LTAA to determine the donor's aspirin sensitivity response (whether aspirin hypersensitive, normal/average aspirin sensitive or aspirin non-responsive and the degree of sensitivity therein).","In certain embodiments the results are analyzed using the aggregometer's proprietary algorithm embedded in system software.","The inventors have determined that this embodiment can be used to predict the donor's platelet aspirin response.","For individuals having an average or “normal” aspirin sensitivity, when looking at the slope, percentage aggregation and lag phase or the AUC, over the dilution profile, the slope, percentage aggregation or the AUC will show a corresponding decrease along with the decrease in the amount of synthetic collagen used.","Thus, for example, within a given range of various dilutions of synthetic collagen, as the concentration goes down, so will the slope, percentage aggregation, and the AUC.","There seems to be an almost linear decrease in slope, percentage aggregation and AUC that runs almost parallel or has almost a direct correlation with the concentration of synthetic collagen.","On the other hand, for individuals who are aspirin non-responders, instead of having a slope, percentage aggregation, and AUC that has a linear-like decrease that corresponds with the decrease in synthetic collagen, there is a point along the dilution profile where there is an increase in slope, an unexpected temporary increase in percentage aggregation and/or a temporary increase in AUC when there should be a decrease (because the concentration of synthetic collagen decreases).","Then, as the dilution profile continues to decrease, the slope and AUC “bounce back” down to where it should be (based on the dilution of synthetic collagen) and where it was before the temporary increase and then continues along decreasing.","The point at which the bounce back will occur will be at different concentrations of synthetic collagen, and will depend upon the aspirin dose, as well as the patient's metabolic and platelet receptor genetics.","Aspirin hypersensitive individuals will show increases in PA, PS and AUC compared to expected/normal results.","In certain embodiments of the invention utilizing the dilution profile LTAA concept, a series of 7, 6 or 5 different concentrations are used to develop a dilution profile, and in other embodiments, 4 different concentrations are used and yet in other embodiments, 3 or 2 different concentrations are used.","Dilution profiles, when presented graphically have distinctive shapes that may be further visually assessed rapidly much like an EKG.","Using too many different concentrations can make the test cumbersome and time consuming, whereas using too few concentrations reduces the amount of data obtained and limits the sensitivity analysis.","The range of synthetic collagen used is preferably within the “aspirin sensitive range,” which is defined herein as the range of concentrations in which in an average aspirin sensitive individual the measured platelet activity/aggregation is reduced corresponding with decreasing amounts of synthetic collagen concentrations (e.g.","the AUC and/or the slope decreases with the concentration of collagen).","In certain embodiments the different synthetic collagen dilution amounts comprise multiple different synthetic collagen amounts chosen from within a concentration range that is low enough to discount the effects of the anti-platelet medication but still pick up the effects of the aspirin.","In certain embodiments, there are different synthetic collagen amounts (2, 3, 4, 5, 6 or 7 different dilutions) each chosen from with the range of 0.01 ng/mL to 1.0 ng/mL; or chosen from with the range of 0.1 ng/mL to 0.5 ng/mL; or chosen from with the range of 0.1 ng/mL to 1.0 ng/mL; or chosen from with the range of 0.1 ng/mL to 1.5 ng/mL; or chosen from with the range of 0.5 ng/mL to 2.0 ng/mL.","As some non-limiting examples, some embodiments have 5 different dilutions chosen from within the range of 0.01 ng/mL to 1.0 ng/mL such as 0.01 ng/mL, 0.05 ng/mL, 0.1 ng/mL, 0.5 ng/mL, and 1.0 ng/mL.","As some non-limiting examples, some embodiments have 6 different dilutions chosen from within the range of 0.5 ng/mL to 2.0 ng/mL such as 0.5 ng/mL, 0.75 ng/mL, 1.0 ng/mL, 1.25 ng/mL, 1.75 ng/mL and 2.0 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.","E. Testing for Residual Platelet Activity in an Individual on Dual Anti-Platelet Medication Therapy (how Active are the Platelets after Exposure to Anti-Platelet Medication and Aspirin).","One embodiment of the present invention provides tests that can determine the individual's residual platelet activity to the dual therapy (aspirin and an anti-platelet medication) when the individual is on a dual anti-platelet medication therapy (i.e.","on aspirin and an anti-platelet medication).","In other words, in this embodiment, a level of synthetic collagen is used that is sensitive to both aspirin and the anti-platelet medication.","This test informs the physician the overall platelet sensitivity/reactivity in the individual.","This test is very useful in the emergency setting when the physician primarily just needs to know the patients platelet status and doesn't necessarily need to know the individual effect of the aspirin or the anti-platelet medication on the platelet reactivity.","Typically, anti-platelet medications have been broken down into 5 classes of anti-platelet drugs based on their mechanism of action.","The chart below provides some examples.","Note that although aspirin is considered an anti-platelet medication, in the present application when a dual therapy is referred to, it is meant as a therapy including aspirin and a second anti-platelet medication (that is not aspirin).","Class Example Therapeutic Basis 1 Aspirin Salicylate (COX Inhibitor) IUPAC Name: 2-acetyloxybenzoic acid 2 Dipyridimole Phosphodiesterase Inhibitor (cAMP and cAMP-inhibited cGMP 3′,5′- cyclic phosphodiesterase 10A Activity Inhibitor) IUPAC Name: 2-[[2- [bis(2-hydroxyethyl)amino]- 4,8-di(piperidin-1-yl)pyrimido[5,4- d]pyrimidin-6-yl]- (2-hydroxyethyl)amino]ethanol 3 Reopro ® Not listed as Pubchem Compound Immunoglobulin Fragment Fab Fragment Chimeric monoclonal antibody 7E3 (GP IIbIIIa receptor blocker) 4 Plavix ® Thienopiryridine (PY2 receptor inhibitor) IUPAC Name: methyl (2S)-2-(2- chlorophenyl)-2-(6,7-dihydro-4H- thieno[3,2-c]pyridin-5-yl)acetate 5 Brilinta ® Cyclopentyltriazolopyrimidine (P2Y12 Inhibitor) IUPAC Name: (1S,2S,3R,5S)- 3-[7-[[(1R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino]- 5-propylsulfanyltriazolo[4,5- d]pyrimidin-3-yl]-5- (2-hydroxyethoxy)cyclopentane-1,2-diol 6 Aggregnox ® Phosphodiesterase Inhibitor (cAMP-specific 3′,5′-cyclic phosphodiesterase 4A Inhibitor) IUPAC Name: 2-[[2-[bis(2-hydroxyethyl)amino]- 4,8-di(piperidin-1- yl)pyrimido[5,4-d]pyrimidin-6-yl]- (2-hydroxyethyl)amino]ethanol Note: some individuals consider Brilanta ® as a Class 4 drug because of chemical similarities This method of the present invention involves performing one platelet aggregation study, preferably a LTAA, whereby a platelet rich sample is obtained from an individual and is combined with synthetic collagen to form a treated sample.","The sample is placed into a LTA aggregometer and the light transmission through the treated sample is obtained to get a readout to determine the individual's percent aggregation.","In certain embodiments, an initial LTA may be performed to check for spontaneous aggregation to test for whether the platelets have any inherent hyperactivity.","Then, depending upon the levels of aggregation or (as read through PA, PS, AUC, LP, DA, or FA), if the individual shows a significant reduction in platelet aggregation, then the individual may be characterized as normal or having an average platelet reactivity/sensitivity.","If the individual shows very little inhibition of platelet aggregation (shows high platelet activity) (i.e.","the platelets still aggregated after the individual ingested the dual anti-platelet medication), then the individual may be characterized as being non-responsive.","If the individual showed an almost complete lack of platelet aggregation after ingesting the dual anti-platelet medication, then the individual may be characterized as being hypersensitive.","The readout from the LTA may be slope, primary aggregation, area under the curve, lag phase, disaggregation (DA) or final aggregation (FA), or a combination thereof.","In certain embodiments, an algorithm that combines and categorizes this data, into an actionable form useful to the physician may be employed.","In other words, this tests the residual platelet activity—how reactive are the platelets (likely to aggregate) after the patient has ingested the dual therapy of an anti-platelet medication and aspirin.","In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.","Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 ng/mL to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 ng/mL to 12.5 ng/mL; or ranges from about 2.0 ng/mL to about 25 ng/mL; or ranges from about 2.0 ng/mL to about 35 ng/mL; or ranges from about 2.0 ng/mL to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 ng/mL to about 25 ng/mL; or ranges from about 12.5 ng/mL to about 35 ng/mL; or ranges from about 12.5 ng/mL to about 39.0 ng/mL; or ranges from about 25 ng/mL to about 39 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.","F. Testing for Residual Platelet Activity in Patient on Dual Therapy Using a Dilution Profile In another embodiment for testing residual platelet activity in an individual on a dual anti-platelet medication therapy, a dilution profile of synthetic collagen is utilized across a number of different platelet aggregation assays, such as LTAAs or flow cytometery run on an individual's PRP or whole blood sample.","In this embodiment, a baseline aggregation assay is performed before the patient begins the dual therapy.","The baseline aggregation assay may be one test or may be a dilution profile baseline.","The baseline results of the individual test or dilution profile are compared against the dilution profile results obtained after the patient has been on the dual therapy.","In this embodiment, multiple different PRP or whole blood samples are obtained from the individual and each platelet sample is mixed with a different amount of synthetic collagen and a platelet aggregation assay, such as LTAA or flow cytometry, is performed on each sample to obtain a dilution profile.","Preferably the same type of platelet aggregation assay is used throughout the test.","For example, LTAAs are used to measure platelet aggregation for each sample.","Also, if a dilution profile is used for the baseline, preferably the same dilutions are used to test the platelets after the patient has been on the dual therapy.","The results are analyzed and the change in platelet aggregation as seen in changes in the PA, PS, AUC, LP, DA, or FA, from the baseline compared to the tests after the patient has been on the dual therapy, as well as a comparison of aggregation over the differing amounts of synthetic collagen, are studied (often using an algorithm that categorizes the data or information and reports the data) to determine the individual's residual platelet reactivity.","In certain embodiments the results are characterized using the aggregometer's proprietary algorithm embedded in system software, which makes the results of the analysis easier for the diagnostician to understand and make appropriate clinical decisions.","In other embodiments, a pre-dual therapy baseline or baseline profile is not obtained.","This may be useful in the emergency clinical setting when it is not feasible to obtain a pre-dual therapy medication baseline or whether one cannot determine from the patient whether he or she has been on a dual therapy.","In this embodiment, multiple different platelet rich plasma samples or whole blood samples are obtained from the individual and each are mixed independently with a different synthetic collagen concentration to obtain multiple different treated samples for the dilution profile assays.","Platelet aggregation assays are performed for each of these samples to obtain a dilution profile over the range of different concentrations.","The data is obtained and measured.","In this case, the platelet aggregation results are analyzed and compared against each other.","If LTAAs were used as the platelet aggregation assay, the change in PA, PS, AUC, LP, DA, or FA, or a combination thereof from differing amounts of synthetic collagen are studied, to determine the donor's residual platelet activity.","In certain embodiments the results are analyzed using the aggregometer's proprietary algorithm embedded in system software.","In certain embodiments of the invention utilizing the dilution profile LTAA concept, a series of 7, 6 or 5 different concentrations are used to develop a dilution profile, and in other embodiments, 4 different concentrations are used and yet in other embodiments, 3 or 2 different concentrations are used.","Dilution profiles, when presented graphically have distinctive shapes that may be further visually assessed rapidly much like an EKG.","Using too many different concentrations can make the test cumbersome and time consuming, whereas using too few concentrations reduces the amount of data obtained and limits the sensitivity analysis.","The range of synthetic collagen used is preferably within the “aspirin sensitive range,” which is defined herein as the range of concentrations in which in an average aspirin sensitive individual the measured platelet activity/aggregation is reduced corresponding with decreasing amounts of synthetic collagen concentrations (e.g.","the AUC and/or the slope decreases with the concentration of collagen).","In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.","In certain embodiments, there are different synthetic collagen amounts (2, 3, 4, 5, 6 or 7 different dilutions) each chosen from within the range of about 2.0 ng/mL to about 12.5 ng/mL; or from within the range of about 2.0 ng/mL to about 25 ng/mL; or from within the range of about 2.0 ng/mL to about 35 ng/mL; or from within the range of about 2.0 ng/mL to about 39 ng/mL; or from within the range of about 12.5 ng/mL to about 25 ng/mL; from within the range of about 12.5 ng/mL to about 39.0 ng/mL; or from within the range of about 25 ng/mL to about 39 ng/mL.","As a non-limiting example, 5 different concentrations are used chosen from within the range of 12.5 ng/mL to about 35 ng/mL are as follows: 12.5 ng/mL, 20 ng/mL, 25 ng/mL, 30 ng/mL and 35 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.","G. Combination of Tests Any of the tests described above can be combined for a more in-depth analysis of an individual's platelet activity in response to the dual anti-platelet medication therapy.","For a particular patient, for an example, an LTAA could be run using an amount of synthetic collagen that provides the physician with an insight as to how the anti-platelet medication alone affects the platelet reactivity (e.g.","about 50 ng/mL final in-test concentration of synthetic collagen)(by discounting the aspirin effects on the platelets).","Then the physician could run another LTAA using an amount of synthetic collagen that provides the physician with an insight as to how the aspirin alone affects the platelet reactivity (e.g.","about 1.0 ng/mL to about 0.1 ng/mL)(by discounting the anti-platelet medication effects on the platelets).","Then finally, the physician could run another LTAA using an amount of synthetic collagen that provides the physician with an insight as to how the combination of the aspirin and the anti-platelet medication affects the platelet reactivity (e.g.","about 25 ng/mL to 35 ng/mL), and thus provides information about the residual platelet activity.","In any of these tests or combinations, a baseline may be obtained prior to ingesting the medication or aspirin, and further the tests may be run using the dilution profile concept described herein above.","H. Compliance Testing The present invention also provides tests that can be used to check the patient for compliance with the aspirin, anti-platelet medication and/or the dual therapy.","As mentioned above, compliance means both taking the medication and taking the medicine at the right time (according to the prescribed dosing schedule).","For example, the patient may be complying with the anti-platelet medication but may not be complying with the aspirin therapy or vice versa.","The present invention provides a mechanism to test the patient for his compliance.","Non-compliance includes not taking the medication, not taking the proper dose or not staying with the effective dosing (time) schedule.","Recent studies have shown that a large problem in health care is patient noncompliance with aspirin and other therapies.","Current thinking is that what was once thought to be aspirin resistance may instead be a manifestation of non-compliance complicated by the use of multiple, non-standardized laboratory tests to evaluate platelets inhibited response to aspirin.","I.","Compliance of Aspirin Therapy Regimen Accordingly, to measure compliance the patient can be routinely tested, such as once a week, bi-monthly, monthly, every 3 months, etc., and the results compared against each other.","If the aggregation results vary widely from one test to another, the patient can be further tested to determine if aspirin resistance has developed or the patient could be questioned as to his compliance in taking the prescribed doses of aspirin.","If it is suspected that the patient has not been taking the aspirin or not taking it within the dosing window, the patient's plasma can be treated with aspirin and then tested.","If aggregation appears in the aspirinated sample, then it may be concluded that the patient had not been taking the aspirin as directed.","In some cases, the patient may be taking the aspirin sporadically and not at the same time each day.","The aggregation tests may reveal variability from test to test and this variability could be used as an indicator that the patient has not been following the prescribed regular dosing regimen (either not taking the dose every day or taking the dose at different times of the day).","It has been found that a patient on aspirin therapy that does not comply with the therapy but not taking the aspirin every day or taking it at different times of the day actually puts the patient at a higher than baseline levels for risk of a thrombotic event.","If aggregation does not appear in the aspirinated sample, it could be that the patient had developed aspirin resistance.","Further testing could be performed to determine if the patient should be on a different dual therapy of two different anti-platelet medication or perhaps a regimen a different anti-platelet medication altogether without aspirin.","In these tests, the concentration of synthetic collagen would be is low enough to be insensitive to the effects of the anti-platelet medication on platelet activity but high enough to be sensitive to the effects of aspirin on platelet activity.","In other words, in these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.","The concentration of synthetic collagen in this is aspect is a low range and is actually so low that a biological collagen could not be diluted to this low concentration.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","J.","Compliance of Anti-Platelet Medication Therapy Regimen If the aggregation results vary widely from one test to another, the patient can be further tested to determine if resistance has developed to the anti-platelet medication or the patient could be questioned as to his compliance in taking the prescribed doses of the anti-platelet medication.","If it is suspected that the patient has not been taking the anti-platelet medication or not taking it within the dosing window, the patient's plasma can be treated with the anti-platelet medication and then tested.","If aggregation appears in the treated sample, then it may be concluded that the patient had not been taking the anti-platelet medication as directed.","In some cases, the patient may be taking the aspirin sporadically and not at the same time each day.","If aggregation does not appear in the treated sample, it could be that the patient had developed resistance to the anti-platelet medication.","Further testing could be performed to determine if the patient should be on a different dual therapy of two different anti-platelet medication or perhaps a regimen a different anti-platelet medication altogether without aspirin.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","K. Compliance of the Dual Therapy If the aggregation results vary widely from one test to another, the patient can be further tested to determine if resistance has developed to the dual therapy or the patient could be questioned as to his compliance in taking the prescribed doses of the dual therapy.","If it is suspected that the patient has not been taking the dual therapy or not taking it within the prescribed dosing window, the patient's plasma can be treated with the anti-platelet medication and then tested and can also be treated with aspirin and then tested.","If aggregation appears in the treated sample, then it may be concluded that the patient had not been taking the medication(s) as directed.","In some cases, the patient may be taking the aspirin and/or anti-platelet medication sporadically and not at the same time each day.","If aggregation does not appear in the treated sample, it could be that the patient had developed resistance to the dual therapy.","Further testing could be performed to determine if the patient should be on a different dual therapy of two different anti-platelet medication or perhaps a regimen a different anti-platelet medication altogether without aspirin.","In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.","Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 ng/mL to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 ng/mL to 12.5 ng/mL; or ranges from about 2.0 ng/mL to about 25 ng/mL; or ranges from about 2.0 ng/mL to about 35 ng/mL; or ranges from about 2.0 ng/mL to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 ng/mL to about 25 ng/mL; or ranges from about 12.5 ng/mL to about 35 ng/mL; or ranges from about 12.5 ng/mL to about 39.0 ng/mL; or ranges from about 25 ng/mL to about 39 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","In the methods/assays of the present invention, instead of having the patient ingest aspirin and thereafter take a blood sample, a sample of blood can be taken before any aspirin is ingested and the sample can be “aspirinated” (or “aspirinized”)(that is, an aspirin solution (may also be the lysine salt of aspirin or Aspisol®) is added to the PRP and then tested).","It has been determined that in the all of the methods/assays of the present, either the patient can ingest the aspirin or the sample can be aspirinated.","This can speed up the testing because the patient does not need to ingest the aspirin and have time pass to allow the aspirin to get into the patient's system.","Instead, the blood is drawn and a PRP sample is obtained, and one part is aspirinated and the other part is not, thus also allowing the two samples to be tested side by side.","In some cases, the aspirinized portion of the test can be manufactured by adding aspirin to the PRP to a desired final concentration.","In certain embodiments, the concentration of the aspirin ranges from 25 to 150 μM, 25-100 μM, 50-150 μM, 50-100 μM, 75-150 μM, 75-100 μM and preferably a final concentration of 100 μM.","L. Method of Predicting Patient's Response to Aspirin, an Anti-Platelet Medication or Dual Therapy The present invention also provides a method of determining or calculating whether a patient would benefit from a certain prescription of aspirin, anti-platelet or dual therapy as well as what class of anti-platelet drug is best suited for the patient (personalized medicine/therapy).","L1.Predicting Effectiveness of Aspirin Therapy For example, if a physician was contemplating starting a patient on aspirin therapy, the patient's PRP sample (or whole blood sample) can be aspirinated (or aspirinized) and then can be tested for platelet aggregation using means known in the art, such as LTAAs.","If the resulting platelet aggregation tests showed that the platelets did not aggregate to a desired healthy level after being treated with aspirin, then the physician may not want prescribe an aspirin therapy since the patient would seem to be insensitive to aspirin.","In other words, the physician could use the results of the LTAAs to predict whether aspirin therapy would be beneficial or detrimental to the patient based on the amount of platelet aggregation that occurred in the presence of the synthetic collagen and the aspirin.","In some instances, it may be that the patient's platelets aggregated too strongly and contained no residual activity.","In this case, the physician may not prescribe an aspirin therapy regimen as this patient may be susceptible to bleeding complications.","In this case the physician would predict that the aspirin was too effective in inhibiting platelet aggregation, would choose another anti-platelet drug.","In this embodiment, the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","L2.Predicting Effectiveness of Dual-Therapy Regimen In addition, since the inventors have developed tests that can discount the effect of an anti-platelet medication on platelet aggregation by using a certain concentration range of synthetic collagen in the platelet aggregation assays, tests of the present invention can be used on patients who are currently on an anti-platelet medication and whom the physician might be considering supplementing with an aspirin therapy regimen.","Thus, the present invention provides a method of predicting the effectiveness of a dual therapy regimen (predicting the effect of adding aspirin to a patient's anti-platelet medication therapy regimen).","In this situation, a whole blood sample or PRP sample is taken from the patient while he is on the anti-platelet medication.","The samples are then aspirinized and tested for platelet aggregation.","If the resulting platelet aggregation tests showed that the platelets did not aggregate to a desired healthy level after being treated with aspirin, then the physician may not prescribe an aspirin therapy since the patient would seem to be insensitive to aspirin (the tests predicts that the aspirin therapy would not be effective).","If the patient's platelets aggregated too strongly and contained no residual activity, the physician may not prescribe an aspirin therapy regimen as this patient may be susceptible to bleeding complications (the tests predicts that the aspirin therapy would be too effective).","If the platelets showed an acceptable level of aggregation, then the physician may consider prescribing the dual therapy of the anti-platelet medication and the aspirin therapy (the tests predict a desired or acceptable level of platelet aggregation).","In this embodiment, the concentration of synthetic collagen is low enough to be insensitive to the effects of the anti-platelet medication on platelet activity but high enough to be sensitive to the effects of aspirin on platelet activity.","In other words, in these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","L3.Predicting Effectiveness of Anti-Platelet Medication (when Patient is on Aspirin Therapy) Further, the present invention also provides assays that discount the effect of aspirin on platelet aggregation and can test the effect of an anti-platelet medication on the platelet activity.","Thus, if a patient were on an aspirin therapy and the physician was considering starting the patient on a dual therapy by adding an anti-platelet medication, the patient's PRP or whole blood sample could be taken and treated with an anti-platelet medication.","After adding synthetic collagen, platelet aggregation is studied.","If it is determined that the level of platelet aggregation is acceptable, then the physician may prescribe that medication.","Or if the level of platelet aggregation was not acceptable, the physician may test and prescribe a different anti-platelet medication.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.","Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","L4.Predicting Effectiveness of Anti-Platelet Therapy Further, the present invention also provides assays that predict the effectiveness of an anti-platelet medication on platelet activity.","See example 2.Thus, if a physician was considering starting a patient on an anti-platelet medication, the patient's PRP or whole blood sample could be taken and treated with an anti-platelet medication.","After adding synthetic collagen, platelet aggregation is studied with or without aspirin in the sample.","If it is determined that the level of platelet aggregation is acceptable, then the physician may prescribe that medication.","Or if the level of platelet aggregation was not acceptable, the physician may test and prescribe a different anti-platelet medication.","In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 12.5 ng/mL to about 100 ng/mL; or from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","The concentration of medicine that is used in the test depends on the medication and the concentration of the synthetic collagen.","Because synthetic collagen induced platelet aggregation is a functional test, there is no need to have genetic and metabolic test data available prior to prescribing the individualized anti-platelet therapy.","The concentration of medicine that is used may depend on the dosing that is given to a patient and the desired levels obtained in the plasma.","To determine the best concentrations to use in the method of the invention, one skilled in the art could follow example 2 and obtain healthy donors and test varying ranges of the anti-platelet medication and the synthetic collagen, using the plasma levels as a guide to determine the best ranges (the most sensitive and most reliable across a collection of healthy donors) of anti-platelet medication and synthetic collagen.","L5.Predicting Residual Platelet Activity when Patient is on Dual Therapy In another embodiment, the physician may wish to test the residual platelet activity that remains after the plates have been exposed to aspirin and the anti-platelet medication as a method of predicting a patient's residual platelet activity while on a dual therapy regimen.","In this case the patient may be on aspirin therapy and the sample is treated with an anti-platelet medication, or the patient may be on an anti-platelet medication and the sample is treated with aspirin or it may be that the patient may already be on a dual therapy.","In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.","Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 ng/mL to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 ng/mL to 12.5 ng/mL; or ranges from about 2.0 ng/mL to about 25 ng/mL; or ranges from about 2.0 ng/mL to about 35 ng/mL; or ranges from about 2.0 ng/mL to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 ng/mL to about 25 ng/mL; or ranges from about 12.5 ng/mL to about 35 ng/mL; or ranges from about 12.5 ng/mL to about 39.0 ng/mL; or ranges from about 25 ng/mL to about 39 ng/mL.","These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.","In any of the tests described herein, any measurement of platelet aggregation or inhibition of platelet aggregation may be used.","In certain preferred embodiments, LTAAs are used.","In certain other preferred embodiments, flow cytometry is used to measure platelet aggregation.","As seen from the discussion above concerning the various embodiments, it is apparent that varying amounts of synthetic collagen can be used, depending upon the test to be performed or the clinician's request for an assessment.","The amount of synthetic collagen used is about two or more orders of magnitude less than what is generally used when performing LTAAs with biological source collagen.","For example, usually LTAAs using calf skin biological collagen generally use 0.19 mg/mL (milligrams/mL) collagen (as the “in-test” concentration); and LTAAs using equine tendon collagen generally use 2.0 μg/mL (micrograms/mL) collagen in the LTAA test (as the “in-test” concentration), whereas generally the methods of the present invention utilize from about 500 ng/mL to about 0.10 ng/mL (nanogram/mL) of synthetic collagen in each LTAA test (as the “in-test” concentration).","When testing platelet aggregation using flow cytometry, the usual concentrations of biological collagen ranges from 0.01-100 μg/mL, with 20 μg/mL to be most common.","However, using synthetic collagen, the amounts used are much lower, ranging from about 2.0 ng/mL to about 640 ng/mL.","Although there are ranges included hereinabove, the present invention is not limited by the recitation of the first and last endpoint to only mean the first and last, but expressly includes the first and last endpoint as well as all of the concentrations within the endpoints.","It would be just too cumbersome herein to list every concentration that falls within the recited ranges.","The inventors have contemplated using more than one concentration, and more than one range as well as more than one concentration within the recited range to produce the most sensitive and accurate results.","The ability to use such low concentrations as well as dilution profiles of collagen is only available with the synthetic collagen.","When the inventors tried to dilute biological collagen down to similar low concentrations, it became physically impossible to dilute down the biological collagen to the levels anywhere close to that used in the LTAAs of the present invention with synthetic collagen.","Biological collagen is an insoluble, viscous, heterogeneous material, and has long structured fibrous proteins wound into a triple helix.","These physical properties precluded the ability to dilute the biological collagen to any low concentration even 100 fold close to the synthetic collagen or to have any such dilution perform in a predictable or useful manner.","Further the LTAAs did not work (no aggregation occurred) when using calf skin collagen at a concentration a little lower than 0.19 mg/mL (milligrams/mL) (as the “in-test” concentration); nor when using equine tendon collagen a little lower than 2.0 μg/mL (micrograms/mL).","In tests performed on whole blood, using the whole blood mode of the Chrono Log aggregometer it was shown that diluting biological collagen did not produce any viable results but synthetic collagen could be diluted from 100 ng/mL to 12.5 ng/mL and still elicit the same response.","See FIGS.","14 and 15.Synthetic Collagen In certain embodiments the synthetic collagen is described in U.S. patent application Ser.","No.","12/520,508, which is herein incorporated by reference in its entirety.","In certain embodiments, the synthetic collagen is a synthetic collagen that has the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic type I collagen (allows the synthetic collagen to be recognized or function as type I collagen).","In certain embodiments the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) -(Pro-X-Gly)n (I) wherein X represents Hyp; and n represents an integer of from 20 to 5,000; and wherein the polypeptide has a molecular weight at a range of from 10,000 to 500,000,000.In certain embodiments, the synthetic collagen having the structure of formula (I) has the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic type I collagen.","It is preferred that synthetic collagen used in all the assays of the present invention have the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic human type I collagen.","In certain embodiments, the synthetic collagen that is used is described in U.S. Pat.","No.","7,262,275.The synthetic collagen molecule was made by the method described in U.S. Pat.","No.","7,262,275 (See e.g.","Example 6 and Example 7).","The molecular weight of the molecule was measured by the method described in the example section in the same patent as was over 1,000,000.In certain embodiments the synthetic collagen has the following values based on GPC-MALs (gel permeation chromatography—multi-angle laser light scattering); Average molecular weight (Mn) 1.3×104; Mw (weight average molecular weight)=1.6×104; size average molecular weight (Mz) 2.0×104.In other embodiments, the synthetic collagen as has the following values based on GPC-MALs (gel permeation chromatography—multi-angle laser light scattering); Average molecular weight (Mn) 2.8×104; Mw (weight average molecular weight)=4.1×104; size average molecular weight (Mz) 6.1×104.The synthetic collagen can be measured by GPC-Mals.","The synthetic collagen molecules tested in the present invention were measured using the HLC-8120GPC device manufactured by Tosoh with the following conditions.","Column: TSKgel α-M (7.8 mm I.D.×30 cm)×2 (manufactured by Tosoh).","Density Detector: Differential refractometer (RI detector), polarity=(+).","MALS: DAWN HELEOS (manufactured by Wyatt Technology).","MALS Laser wave: 658 nm.","Eluent: HFIP (1,1,1,3,3,3-Hexfloro-2-propanol) manufactured by central glass +5 mM-CF3COONa (1st class manufactured by Wako Pure Chemical).","Flow Speed: 0.6 mL/min.","Column Temp.",": 40° C. RI detector Temp.",": 40° C. MALS Temp.",": Room Temp.","Sample density: 2 mg/mL.","Sample amount: 100 μL.","Pre-treatment of sample: After weighing the samples, they were dissolved by adding a given amount of eluent and left at room temperature overnight.","The samples gently mixed and then were then filtered through a 0.5 μm PTFE cartridge filter.","In certain embodiments n is an integer of 20 to 250.In certain embodiments n is an integer of 20 to 200.In certain embodiments n is an integer of 20 to 150.In certain embodiments n is an integer of 30 to 100.In certain embodiments n is an integer of 20 to 2,500; of 20 to 2,000; of 20 to 1,500; of 20 to 1,000; of 20 to 500; or of 20 to 250; 30 to 2,500; of 30 to 2,000; of 30 to 1,500; of 30 to 1,000; of 30 to 500; or of 30 to 250.It is preferred that the synthetic collagen molecules discussed above have the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic type I collagen.","Two factors to consider in choosing the synthetic collagen is solubility and ease of handling.","If the molecular weight is too small, the synthetic collagen may have poor solubility characteristics.","If the molecular weight is too large, the synthetic collagen may not have good handling characteristics (may be too viscous and may have poor dispersibility).","Thus, a preferred synthetic collagen of the formula (I) [-(Pro-X-Gly)n] has both good solubility and good handling characteristics.","The following synthetic collagen molecules were tested: n=24 (Mn=6,300); n=28 (Mw=7,500); n=49 (Mn=13,000); n=60 (Mw=16,000); n=75 (Mz=20,000); n=105 (Mn=28,000); n=153 (Mw=41,000); n=229 (Mz=61,000).","When testing various synthetic molecules, those having the n value from between 49-75 showed the best combination of desirable solubility and handling characteristics.","In certain embodiments of the invention, the synthetic collagen may be all one length (for example where n=49 for all synthetic molecules and in certain embodiments, the synthetic collagen may be a mixture of many different lengths (for example, but not limited to, the synthetic collagen is a mixture of molecule having n from 49-75).","Kits The present invention also provides kits useful for testing platelet aggregation, comprising a synthetic collagen.","The synthetic collagen is as described above and can be at many different concentrations.","In addition, the kit may comprise one or more diluents as well as controls.","The synthetic collagen can be supplied at a higher concentration in the vial than what would be used as the “in-test” concentration.","In certain embodiments, the synthetic collagen in the vial is preferably more than 10 times the amount of the final “in-test” concentration desired.","In certain embodiments the synthetic collagen is supplied in the kit at the concentration contemplated for use in the methods of the present invention to bypass the need to create dilutions of the synthetic collagen.","In other words, the synthetic collagen is provided so that it is in the concentration that would be used directly in the methods of the present inventions.","In other embodiments the vial could contain a higher concentration amount and the directions included in the kit would provide instructions on the desired concentration to use in the assay to achieve the desired final “in-test” concentration of synthetic collagen.","In other embodiments, the kit contains at least one single use vial and/or at least one multiple use vial of synthetic collagen.","For a single use vial, the vial would contain only the amount of synthetic collagen needed for one test.","For a multiple use vial, the synthetic collagen may be supplied at the desired in-test concentration, but the vial contains more than the amount of volume needed for more than one test.","The kits of the present invention preferably contain instructions for use of the synthetic collagen in the light transmission assay using methods described herein.","In other embodiments, kits of the present invention contain more than one vial of synthetic collagen at the same concentration or in other embodiments, the kits contain more than one vial at a different concentration.","Kits having more than one vial at different concentrations would be useful in the dilution profile tests of the present invention.","For example, one kit of the present invention may contain vials having 7, 6, 5, 4, or 3 different concentrations of synthetic collagen ranging.","Each vial would, in certain embodiments, provide the synthetic collagen at the desired final “in-test” concentration and could be supplied as a single use or a multiple use vial.","The present invention is based on measuring platelet aggregation capacity along with dilution profiles generated (in certain embodiments) using synthetic collagen and subsequent data analysis and actionable report.","Other methods for measuring platelet response and other measurements to one or more anti-platelet and aspirin therapy regimens using the synthetic collagen are also expected to be useful, such as, for example, the whole blood and point of care platelet function analyzers, methods, and technologies such as impedance and multiple electrode impedance aggregometry, high shear stress, cone and plate, flow cytometry, and other-point-of care technologies and assays of platelet function or reactivity.","The inventors have discovered that the nature of the vial used to store synthetic collagen can affect the collagen by activating the collagen to some unpredictable degree.","It is preferable that the container used to store the synthetic collagen does not activate the collagen to ensure that when the synthetic collagen is removed from the vial and is introduced into a test system, the degree of activation and adherence of the synthetic collagen is predictable and due only to that test system.","In other words, artifacts caused by unintentional activation by the interaction of the collagen with the container are not introduced into the tests.","Collagens, including synthetic collagen, stored in generic polypropylene vials or other containers are activated to an unknown degree, subsequently adhere to the container, and are thus not available to participate in the test system.","The amount of collagen unavailable to the test system because it has adhered to the container and/or cap is unknown and, based on stability data, is variable.","The inventors have discovered that the use of synthetic collagen that has been prepared and stored in a homopolymeric container eliminates a significant degree of variability in test results.","Accordingly, it is preferred that the synthetic collagen is prepared and stored in a homopolymeric container.","Most containers that are noted as polypropylene are not a single plastic but rather are a family of plastics whose performance can be modified by including various additives during the manufacturing process.","Thus, the manufacturing process itself could produce different variations of polypropylene.","Further, the nature of the additives is largely unknown or disclosed to the purchaser/public as this information is considered proprietary by the manufacturers.","In addition, mold release agents add another variable that could not be assessed.","The inventors discovered that containers that have the best long term stability and do not interact with the synthetic collagen have the following characteristics: a) the chemical structure is based on a specific, identical monomer that is repeated (a homopolymer—a polypropylene polymer consisting of identical monomer units); b) caps are made of the same material as the tubes; and c) the caps have an additional internal seal such as a silicone O ring or washer or have a secondary seal molded therein.","Exemplary vials include cryovials and caps obtained from Simport (T310 Series); Lake Charles Manufacturing (54A series), and BD Falcon tubes 352096 series).","In addition, the inventors discovered that better stability was achieved when the synthetic collagen was diluted with physiologic saline instead of purified water.","In certain embodiments (including the methods described herein and the kits), the synthetic collagen is supplied and/or stored in a polypropylene homomer.","In certain embodiments, the cap is the same material as the vial/tube.","In certain embodiments, the container has an additional internal seal or a cap having a secondary seal molded therein.","In certain embodiments, the container contains all of the above described characteristics.","EXAMPLES Example 1: Evaluate the Use of Synthetic Collagen to Detect the Antiplatelet Activity of Ticagrelor, Cilostazol and Abciximab in Normal and Aspirinized Human Platelet Rich Plasma Materials: Antiplatelet Drugs Ticagrelor (Brilinta®, Astra-Zeneca, London, UK; lot AL0153, expiration February 2014) was obtained as 90 mg tablets from the Loyola University Health System inpatient pharmacy.","Tablets were ground using a mortar and pestle and subsequently dissolved in DMSO at a concentration of 10 mg/mL.","The stock solution was diluted in deionized water to make working solutions of 0.5, 0.1 and 0.05 mg/mL.","Cilostazol (Pletal®, Otsuka Laboratories, Tokushima, Japan; lot 0B91M) was obtained as a powder.","Cilostazol was dissolved in DMSO to make a stock solution of 5 mM.","The stock solution was diluted in deionized water to make working solutions of 250, 125 and 50 μM.","Abciximab (ReoPro®, Eli-Lilly, Indianapolis, Ind.","; lot 12D09AA, expiration May 2015) was obtained as a 2 mg/mL solution which was diluted in physiologic saline to make working solutions of 12.5, 25 and 50 μg/mL.","Aspirin powder was dissolved in 100% methanol to make a stock solution of 100 mM.","The stock solution was diluted with deionized water to make a 1 mM working solution.","Materials: Platelet Agonists ADP was obtained from Bio/Data Corporation, Horsham, Pa. Each vial was reconstituted with 1 mL of deionized water to make a 100 μM working solution.","The final concentration of ADP in the aggregation cuvette was 10 μM.","Arachidonic acid was obtained from Bio/Data Corporation, Horsham, Pa. Each vial was reconstituted with 0.5 mL deionized water to make a 5 mg/mL working solution.","The final concentration of arachidonic acid in the aggregation cuvette was 500 μg/mL.","Biological Collagen was obtained from Bio/Data Corporation, Horsham, Pa. Each vial was reconstituted with 0.5 mL deionized water to make a 1.9 mg/mL working solution.","The final concentration of Bio/Data collagen in the aggregation cuvette was 190 μg/mL.","Biological Collagen was obtained from Chrono Log Corporation, Havertown, Pa. as a 1 mg/mL solution.","A working solution of 100 μg/mL was made by dilution with physiologic saline.","The final concentration of Chrono Log collagen in the aggregation cuvette was 10 μg/mL.","Synthetic collagen was provided by JNC Corporation, Yokohama, Japan at working concentrations of 80, 160, 320 and 640 ng/mL.","The final concentrations of synthetic collagen in the aggregation cuvette were 64, 32, 16 and 8 ng/mL.","Methods: Blood Collection Approval for the collection of whole blood from healthy human volunteers was granted from the Institutional Review Board of the Health Sciences Division of Loyola University Chicago.","Whole blood was drawn using a double syringe technique from the antecubital vein and anticoagulated by the addition of 1 part 3.2% sodium citrate to (9 parts blood to 1 part citrate).","Citrated blood was centrifuged at 80×g at room temperature for 15 minutes to make platelet rich plasma (PRP).","Supernatant PRP was collected and kept at room temperature in capped tubes.","The remaining citrated blood was recentrifuged at 1,100×g for 15 minutes to make platelet poor plasma (PPP).","The platelet count of the PRP was determined using an ICHOR II Analyzer, Helena Laboratories, Beaumont, Tex.","Platelet count in the PRP was adjusted to 250,000-300,000/μl by the addition of homologous PPP.","Six blood donors were used for this study.","Each was drawn on separate days for the ‘non-aspirinized’ and ‘aspirinized’ portions of the protocol.","For the ‘non-aspirinized’ portion of the protocol, one donor (CS) was excluded from the final analysis as the aggregation responses were markedly different from that of the other 5 donors.","For the ‘aspirinized’ portion of the protocol, three donors had taken aspirin orally <48 hours prior to blood draw.","For the other three donors, aspirin was supplemented to the PRP in vitro at a final concentration of 100 μM.","Methods: Platelet Aggregation Platelet aggregation was measured using a PAP 8E platelet aggregometer (Bio/Data).","Each well was blanked using PPP.","25 μl of saline or antiplatelet drug and 200 μl of PRP were added to cuvettes containing magnetic stir bars and incubated for three minutes to equilibrate the sample to 37° C. 25 μl of agonist was added to each cuvette and the aggregation profile was monitored until a plateau was achieved.","Results were tabulated in terms of maximal aggregation level.","Under some reaction conditions, reversible aggregation was observed.","This was most commonly observed with ADP and arachidonic acid-induced aggregation in the presence of ticagrelor or cilostazol.","Final aggregation levels were also tabulated.","Results: Ticagrelor In non-aspirinized plasma, ADP-induced aggregation was strongly inhibited (FIG.","8).","Arachidonic acid-induced aggregation was inhibited to a similar extent.","Neither Bio/Data collagen, Chrono Log collagen nor 64 ng/mL synthetic collagen was markedly impacted by ticagrelor.","The antiplatelet effects of Ticagrelor® could be identified when aggregation was induced by synthetic collagen at concentrations of 32 ng/mL and lower.","The sensitivity for ticagrelor detection appeared to increase with decreasing synthetic collagen concentration.","The addition of aspirin did not affect the ADP-induced aggregation response (FIG.","9).","In contrast, an anti-platelet effect was no longer observed in arachidonic acid and 8 ng/mL synthetic collagen-induced aggregation assays and the effect in 16 and 32 ng/mL synthetic collagen-induced aggregation assays was reduced.","Cilostazol In non-aspirinized plasma, the most marked effect of cilostazol was on arachidonic acid-induced aggregation (FIG.","10), where aggregation levels of ˜20% were observed at concentrations ≥12.5 μM (vs. 95% in the absence of cilostazol).","ADP-induced aggregation was minimally affected (˜30% inhibition at 25 μM).","Cilostazol at concentrations up to 25 μM did not inhibit aggregation induced by Bio/Data collagen, Chrono Log collagen or the 64 ng/mL concentration of synthetic collagen.","At lower concentrations of synthetic collagen, the anti-platelet effect of higher concentrations of cilostazol could be observed.","Addition of aspirin to the PRP negated the ability to detect cilostazol (FIG.","11).","Abciximab In non-aspirinized plasma, abciximab produced a concentration-dependent inhibition of agonist-induced aggregation over the concentration range tested (1.25-5 μg/mL) (FIG.","12).","Arachidonic acid and synthetic collagen (8 and 16 ng/mL) were the most sensitive for detecting the presence of abciximab.","Inhibition of Bio/Data and Chrono Log collagen-induced aggregation was only observed at the 5 μg/mL concentration.","In aspirinized plasma, the response to arachidonic acid was nearly completely blunted (<20% aggregation) (FIG.","13).","The addition of abciximab to aspirinized plasma resulted in complete inhibition of arachidonic acid-induced aggregation.","Aggregation induced by 10 μM ADP and by 0.19 mg/mL Bio/Data collagen appeared to me minimally affected by the presence of aspirin.","Although, aspirin did not inhibit 10 μg/mL Chrono Log collagen-induced aggregation, abciximab produced a stronger inhibition of Chrono Log collagen-induced aggregation in aspirinized PRP.","At all concentrations tested, the synthetic collagen reagent produced lower levels of aggregation in aspirinized plasma than in non-aspirinized plasma.","Discussion: ADP, arachidonic acid and biological collagen are commonly used agonists to study platelet function.","Ticagrelor inhibited aggregation induced by ADP and arachidonic acid, but had little effect on biological collagen-induced aggregation.","Cilostazol strongly inhibited arachidonic acid-induced aggregation and produced a weaker, concentration-dependent inhibition of ADP-induced aggregation.","Biological collagen-induced aggregation was unaffected by cilostazol.","Abciximab inhibited aggregation induced by ADP, arachidonic acid and biological collagen, though ADP and arachidonic acid were more sensitive.","The synthetic collagen reagent was tested at concentrations ranging from 8 to 64 ng/mL.","Aggregation induced by the 64 ng/mL concentration of the synthetic collagen was comparable to that of the Bio/Data and Chrono Log biological collagen reagents in that there was minimal effect of ticagrelor or cilostazol on the aggregation response.","Aggregation induced by collagen or the 64 ng/mL synthetic collagen was inhibited by abciximab to a comparable degree.","At lower concentrations of synthetic collagen, the antiplatelet effect of ticagrelor, cilostazol and abciximab were readily apparent.","At the concentrations tested, aggregation induced by Bio/Data collagen or Chrono Log collagen was not inhibited by aspirin.","While the synthetic collagen reagent exhibited a higher sensitivity to aspirin in the absence of other antiplatelet drugs than either biological collagen, the presence of aspirin affected the ability of the synthetic collagen at these concentrations to detect the presence of ticagrelor or cilostazol.","Conclusion: Abciximab is readily detectable in the presence of aspirin using the synthetic collagen concentrations provided for this study.","Ticagrelor can be detected, but the concentration-dependence isn't as well defined as it is with abciximab.","Example 2: Testing for Platelet Aggregation Using LTAAs and Synthetic Collagen and Adding Anti-Platelet Medication to the PRP Sample Abciximab (ReoPro®) Two healthy donors supplied the PRP samples.","A panel of four different synthetic collagen concentrations were tested (12.5 ng/mL, 25 ng/mL, 50 ng/mL and 100 ng/mL Abciximab was added to the each of the four panels of different synthetic collagen concentrations.","In one panel, saline was added as the control to each of the four synthetic collagen concentrations.","In the second panel, 12.5 μg/mL (micrograms/mL) of abciximab was added to each of the four synthetic collagen concentrations.","In a third panel, 25 μg/mL of abciximab was added to each of the four synthetic collagen concentrations.","In a fourth panel, 50 μg/mL of abciximab was added to each of the four synthetic collagen concentrations.","LTAAs were run for each and the PA, PS, SA, SS AUC, LP, DA, MA and FA was measured for each.","The tests were run on each of the donors' samples.","Ticagrelor (Brilinta®) Two healthy donors supplied the PRP samples.","A panel of four different synthetic collagen concentrations were tested (12.5 ng/mL (nanograms/mL), 25 ng/mL, 50 ng/mL and 100 ng/mL.","Ticarelor was added to the each of the four panels of different synthetic collagen concentrations.","In one panel, saline was added as the control to each of the four synthetic collagen concentrations.","In the second panel, 0.05 mg/mL (milligrams/mL) of Ticagrelor was added to each of the four synthetic collagen concentrations.","In a third panel, 0.1 mg/mL of Ticagrelor was added to each of the four synthetic collagen concentrations.","In a fourth panel, 0.5 mg/mL of Ticagrelor was added to each of the four synthetic collagen concentrations.","LTAAs were run for each and the PA, PS, SA, SS AUC, LP, DA, MA and FA was measured for each.","The tests were run on each of the donors' samples.","The results showed that the synthetic collagen detected the drugs at the four different concentrations.","The synthetic collagen and the two drugs caused the platelets to aggregate.","The results also showed that the different dilutions of the two drugs worked with all four dilutions of synthetic collagen to cause the platelets to aggregate.","The tests also revealed that certain combinations of synthetic collagen in combination with certain drug dilutions were more sensitive than others.","Abciximab and Ticagrelor are two different classes of drugs and yet the assays worked with both.","In another test, the samples could also be aspirinized to test for the effect of the dual therapy of the anti-platelet medication and the aspirin on a donor's platelets.","Example 3: Use of Flow Cytometry to Test for Platelet Aggregation A vial of Bio/Data calf skin collagen was reconstituted with 0.5 ml of water to make a 1.9 mg/ml solution.","A vial of synthetic collagen was reconstituted with 1 ml of synthetic collagen diluent to make a 0.0005 mg/ml solution.","Chrono Log collagen was diluted with saline to make a 100 μg/ml solution.","A stock 2% paraformaldehyde solution was diluted with calcium-free Tyrode's buffer to make a 1% paraformaldehyde solution.","A set of tubes containing 1 ml of 1% paraformaldehyde was prepared.","A second set of tubes which contained 30 μl of collagen reagent and 30 μl of antiplatelet drug was prepared and set in a 37° C. heating block.","Whole blood was drawn from healthy individuals into sodium citrate.","240 μl of citrated blood was added to the tubes at 15-20 second intervals and gently mixed.","After a 3 minute incubation period, 50 μl of activated blood was transferred to the corresponding paraformaldehyde-containing tube.","After a 30 minute incubation at 4° C., the samples were centrifuged at 1,600 rpm for 10 minutes and the supernatant was removed.","The cell pellet was resuspended in 750 μl of Tyrode's buffer.","10 μl each of CD61FITC and CD62PE (BD Biosciences) was added to a set of clean tubes.","100 μl of resuspended cells was added to the antibody tubes.","After a 30 minute incubation period in the dark at room temperature, 700 μl of Tyrode's buffer was added to each tube and the samples were analyzed on the flow cytometer (EPICS-XL, Beckman-Coulter).","Platelet activation was assessed in terms of the percentage of platelets expressing P-selectin and the percentage of aggregated platelets."]],"string":"[\n [\n \"DUAL ANTI-PLATELET MEDICATION/ASPIRIN RESPONSE AND REACTIVITY TEST USING SYNTHETIC COLLAGEN\",\n \"The present invention provides tests that measures functional platelet aggregation such as by using Light Transmission Aggregometry Assays (LTAAs) or flow cytometry, using synthetic, self-assembling human type I collagen, methods of predicting and measuring an individual's platelet anti-platelet medication sensitivity and residual platelet activity status when the individual is on a dual anti-platelet therapy of aspirin and anti-platelet medication and kits useful in the assays and methods.\"\n ],\n [\n \"1.A platelet aggregation assay comprising a light transmission aggregometry assay for determining an individual's anti-platelet medication sensitivity status, when the individual is on a dual therapy of aspirin and an anti-platelet medication that is not aspirin, the assay comprising the use of synthetic collagen at a final concentration in the light transmission aggregometry assay from about 40 ng/mL to about 500 ng/mL, wherein the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) -(Pro-X-Gly)n (I) wherein X represents Hyp; and n represents an integer of from 20 to 250.2.The method of claim 1 wherein platelet aggregation is analyzed with light transmission aggregometry assays and wherein the patient sample is platelet rich plasma.\"\n ],\n [\n \"<SOH> BACKGROUND OF THE INVENTION <EOH>The conventional, primary need for an effective assessment of platelet response and reactivity is in the field of cardiology.\",\n \"The public health incidence and burden of heart attack, stroke and related cardiovascular and thrombotic diseases are well known.\",\n \"The medical community has long recommended the use of aspirin in primary care to reduce cardiovascular, stroke and certain other risks.\",\n \"The use of Aspirin in other area such as DVT prophylaxis, oncology, orthopedics and prevention is driving a renewed interest in and use of Aspirin alone or in combination with other drugs.\",\n \"Additionally compliance testing and personalized medicine initiatives increase the unmet medical need for a test which can provide Aspirin presence and response, presence and efficacy of a second antiplatelet drug and the residual reactivity of a patient's platelet reactivity.\",\n \"Aspirin (salicylate based compounds) ingestion or exposure inhibits the COX 1 pathway and modifies COX 2 enzymatic processes, which then precludes all subsequent events necessary for platelet aggregation.\",\n \"Since the ingestion of or exposure to aspirin can inhibit platelet aggregation, it has been given as a therapy to prevent undesired platelet aggregation, which can be a source of many heart attacks, strokes and other thrombotic events.\",\n \"Despite the benefits of aspirin therapy in many individuals, aspirin therapy is not effective enough in some individuals as it does not cause the desired inhibition of platelet aggregation or its effect is shorter than the dosing interval (some patients may only get 6 to 12 hours of protection rather than 24 hours resulting in an above baseline risk for the patient in the time between doses).\",\n \"In these individuals the residual platelet reactivity is high and the patient's risk is not mitigated.\",\n \"In other individuals, aspirin therapy can be harmful as it creates an increased risk of unwanted bleeding complications because the aspirin seems to block platelet activity altogether so that the blood does not clot when physiologically necessary.\",\n \"Recently, two elements of Aspirin's pharmacodynamic behavior have entered the clinical mindset: Aspirin must be taken at the same time every day to maintain its antiplatelet effectiveness; and the thrombotic risk from failure to keep this schedule is greater than the patient's baseline risk.\",\n \"Thus, physicians often prescribe a course of treatment involving both low dose aspirin and an anti-platelet medication to inhibit unwanted platelet aggregation.\",\n \"This is often called a “dual therapy.” Not all patients will respond to the dual therapy or the individual anti-platelet medication in the same way.\",\n \"Selecting and monitoring Aspirin in dual treatment protocols is also necessary because certain antiplatelet drugs like ticagrelor lose their effectiveness if the Aspirin dose is greater than 100 mg.\",\n \"There currently is not an effective way to measure a patient's response to dual anti-platelet medication therapy or to determine the patient's residual platelet reactivity.\",\n \"Thus, there is an unmet need for a reliable tool to assess and manage the anti-platelet medication response and reactivity on platelet aggregation when a patient is on a dual anti-platelet medication therapy, as well as checking patient compliance with the treatment regimen.\",\n \"Traditionally, a patient's response to aspirin and other anti-platelet medication therapy is assessed by testing platelet activity using a series of platelet aggregation test.\",\n \"The “gold standard” of platelet aggregation tests, light transmission aggregometry (LTA), utilizes collagen from biological sources as the agonist to bring about platelet aggregation, as a measure of the degree or extent of platelet response or inhibition to aggregation.\",\n \"However, there are multiple issues as well as the risk of infectious disease transmission when using biological material.\",\n \"Biologically derived products, whether ‘natural,’ processed, manufactured by fermentation, cell culture or similar processes, or recombinant, all share the following drawbacks: carry a risk of infectious disease transmission; have lot to lot variability (regarding the ratio of active materials, performance, chemical characteristics, solubility, stability, moisture content, and process contaminants); differing bio-profiles depending upon the location the product was made; differences caused by processing; and environment, geographic and dietary differences affecting the source animal or culture.\",\n \"Biological collagens cannot be diluted to enhance sensitivity or to generate dilution profiles, both of which easily performed with synthetic collagen.\",\n \"It is widely believed that anti-platelet therapy contributes to the reduction of major atherothrombotic complications in cardiovascular, neurovascular and other diseases.\",\n \"In the treatment of percutaneous coronary intervention and acute coronary syndromes, dual anti-platelet therapy when performed at optimal dosing and timing has significantly lowered the risk of thrombotic complications and contributed to positive outcomes.\",\n \"However, an important clinical problem of increased incidence of major adverse clinical events (“MACE”) and confounding differences in patient outcomes relates to the variability in patient response to anti-platelet treatments, especially in a dual antiplatelet therapy (a combination of Aspirin and a second agent such as clopidogrel or ticagrelor).\",\n \"Understanding the mechanisms underlying this phenomenon is important to individualizing and improving patient care, long term (maintenance—sometimes referred to as chronic therapy in the literature) therapy and consistent (positive) outcomes.\",\n \"However, a clear and reliable predictive model for responsiveness to anti-platelet therapy is currently not available.\",\n \"Attempts have been made to characterize the efficacy of anti-platelet therapy using platelet function testing but based on current information, and dependence on biological agonists, its routine use is not recommended particularly as costs, complexities and cost effectiveness have not been established, and lack of correlation, standardization and agreement between laboratory methods, and their respective results, is well documented in the literature.\",\n \"Tobias Geislera et al., Circulation 2010; 122:1049-1052.In addition, the inhibitory effects of aspirin on platelets decreases over time in patients on long term or chronic therapy.\",\n \"Violi, F. et al., J Am Cardio, Vol.\",\n \"43, No.\",\n \"6, 2004.Further, as evidenced in AstraZeneca's complete prescribing information on ticagrelor (trade name Brilinta® in the US, Brilique® and Possia® in Europe), Aspirin doses greater than 100 mg reduce the ability of ticagrelor to inhibit platelet aggregation.\",\n \"This conflicts with current clinical care guidelines in which increasing doses of Aspirin to ‘overcome’ Aspirin resistance is recommended.\",\n \"Thus, there remains a need for a quantitative, functional platelet activity test that does not use an animal derived collagen as the agonist.\",\n \"There remains a need for a test that is able to measure the platelet response to an anti-platelet medication when the patient is on a dual therapy of aspirin and an anti-platelet medication, as well as a test to monitor patient compliance with the dual therapy regimen.\",\n \"Dual antiplatelet therapy is the global practice standard.\",\n \"There is also a need for a test that can measure residual platelet activity (that is the platelet activity that remains even while the patient is on a dual anti-platelet medication therapy) rather than platelet inhibition, which is the result for currently available tests.\",\n \"Platelet inhibition does not equal residual platelet reactivity.\",\n \"Residual platelet reactivity is what determines patient outcome and thus is the better measurement.\",\n \"The present invention meets these needs.\"\n ],\n [\n \"<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provide tests for determining a donor's platelet combined sensitivity status when the individual is on a dual therapy of aspirin and an anti-platelet medication comprising the use of synthetic collagen.\",\n \"Exemplary tests include the use of platelet aggregation studies using for example, light transmission aggregation assays (LTAAs) and flow Cytometry, and to a lesser degree, methods based on measuring aggregation by impedance or whole blood aggregometry.\",\n \"The tests of the present invention use synthetic collagen as the agonist.\",\n \"Tests of the invention provide assays that “discount” or “ignore” the effect of the aspirin on platelet aggregation, but still measure the effect of the anti-platelet medication on the platelet aggregation.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.\",\n \"Further, the invention provides tests that “discount” or “ignore” the effect of the anti-platelet medication, but still measure the effect of the aspirin on platelet aggregation.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.\",\n \"The methods of the present invention are able to test the ability of the individual's platelets to aggregate after the individual has ingested an anti-platelet medication and aspirin.\",\n \"In other words, this tests the residual platelet activity—how reactive are the platelets (likely to aggregate) after the patient has ingested the dual therapy of an anti-platelet medication and aspirin.\",\n \"In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.\",\n \"Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 to 12.5 ng/mL; or ranges from about 2.0 to about 25 ng/mL; or ranges from about 2.0 to about 35 ng/mL; or ranges from about 2.0 to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 to about 25 ng/mL; or ranges from about 12.5 to about 35 ng/mL; or ranges from about 12.5 to about 39.0 ng/mL; or ranges from about 25 to about 39 ng/mL.\",\n \"The literature shows that 30-70% of patients do not comply with taking their medication or taking it as directed, and there is no current compliance test.\",\n \"There is developing thought that ‘resistance’ may be due, at least in part, to non-compliance.\",\n \"The present invention also provides a method of testing patient compliance, with the dual therapy regimen.\",\n \"The DAPT results will show noncompliance for Aspirin therapy as well as deviation from the scheduled dosing window.\",\n \"The present invention also provides a method of testing patient compliance for the aspirin therapy aspect while on a dual therapy, or testing patient compliance for the anti-platelet medication aspect while on a dual therapy.\",\n \"The present invention also provides methods of predicting the effectiveness of aspirin therapy, of an anti-platelet medication therapy, or a dual therapy.\",\n \"In certain embodiments, the synthetic collagen is a synthetic collagen that has the ability to self-assemble into a triple helix to form fibrils and which mimics human type I collagen.\",\n \"In certain embodiments the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"lead\\\"?\",\n \"-(Pro-X-Gly) n (I) in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"tail\\\"?\",\n \"wherein X represents Hyp; and n represents an integer of from 20 to 5,000; and wherein the polypeptide has a molecular weight at a range of from 10,000 to 500,000.In certain embodiments, n=20-250.The present invention also provides kits for testing platelet aggregation in a light transmission assay, comprising a vial of synthetic collagen; and instructions for use of the synthetic collagen in the dual anti-platelet therapy test (DAPT) of the present invention.\",\n \"In certain embodiments (including the methods described herein and the kits), the synthetic collagen is supplied and/or stored in a polypropylene homomer container.\",\n \"In certain embodiments, the cap is the same material as the vial/tube.\",\n \"In certain embodiments, the container has an additional internal seal or a cap having a secondary seal molded therein.\",\n \"In certain embodiments, the container contains all of the above described characteristics\"\n ],\n [\n \"This application is a divisional of U.S. patent application Ser.\",\n \"No.\",\n \"14/419,880 filed on Feb. 5, 2015 (pending), which is a U.S. National Phase under 35 U.S.C.\",\n \"§ 371 of International Application PCT/US2013/053612, filed on Aug. 5, 2013, which claims priority to U.S.\",\n \"Provisional Application 61/680,111, filed on Aug. 6, 2012, and U.S.\",\n \"Provisional Applications 61/681,485 filed on Aug. 9, 2012, which are incorporated herein in their entirety.\",\n \"This application also claims priority to PCT application, PCT/US13/49418, filed on Jul.\",\n \"5, 2013.All publications, patents, patent applications, databases and other references cited in this application, all related applications referenced herein, and all references cited therein, are incorporated by reference in their entirety as if restated here in full and as if each individual publication, patent, patent application, database or other reference were specifically and individually indicated to be incorporated by reference.\",\n \"BACKGROUND OF THE INVENTION The conventional, primary need for an effective assessment of platelet response and reactivity is in the field of cardiology.\",\n \"The public health incidence and burden of heart attack, stroke and related cardiovascular and thrombotic diseases are well known.\",\n \"The medical community has long recommended the use of aspirin in primary care to reduce cardiovascular, stroke and certain other risks.\",\n \"The use of Aspirin in other area such as DVT prophylaxis, oncology, orthopedics and prevention is driving a renewed interest in and use of Aspirin alone or in combination with other drugs.\",\n \"Additionally compliance testing and personalized medicine initiatives increase the unmet medical need for a test which can provide Aspirin presence and response, presence and efficacy of a second antiplatelet drug and the residual reactivity of a patient's platelet reactivity.\",\n \"Aspirin (salicylate based compounds) ingestion or exposure inhibits the COX 1 pathway and modifies COX 2 enzymatic processes, which then precludes all subsequent events necessary for platelet aggregation.\",\n \"Since the ingestion of or exposure to aspirin can inhibit platelet aggregation, it has been given as a therapy to prevent undesired platelet aggregation, which can be a source of many heart attacks, strokes and other thrombotic events.\",\n \"Despite the benefits of aspirin therapy in many individuals, aspirin therapy is not effective enough in some individuals as it does not cause the desired inhibition of platelet aggregation or its effect is shorter than the dosing interval (some patients may only get 6 to 12 hours of protection rather than 24 hours resulting in an above baseline risk for the patient in the time between doses).\",\n \"In these individuals the residual platelet reactivity is high and the patient's risk is not mitigated.\",\n \"In other individuals, aspirin therapy can be harmful as it creates an increased risk of unwanted bleeding complications because the aspirin seems to block platelet activity altogether so that the blood does not clot when physiologically necessary.\",\n \"Recently, two elements of Aspirin's pharmacodynamic behavior have entered the clinical mindset: Aspirin must be taken at the same time every day to maintain its antiplatelet effectiveness; and the thrombotic risk from failure to keep this schedule is greater than the patient's baseline risk.\",\n \"Thus, physicians often prescribe a course of treatment involving both low dose aspirin and an anti-platelet medication to inhibit unwanted platelet aggregation.\",\n \"This is often called a “dual therapy.” Not all patients will respond to the dual therapy or the individual anti-platelet medication in the same way.\",\n \"Selecting and monitoring Aspirin in dual treatment protocols is also necessary because certain antiplatelet drugs like ticagrelor lose their effectiveness if the Aspirin dose is greater than 100 mg.\",\n \"There currently is not an effective way to measure a patient's response to dual anti-platelet medication therapy or to determine the patient's residual platelet reactivity.\",\n \"Thus, there is an unmet need for a reliable tool to assess and manage the anti-platelet medication response and reactivity on platelet aggregation when a patient is on a dual anti-platelet medication therapy, as well as checking patient compliance with the treatment regimen.\",\n \"Traditionally, a patient's response to aspirin and other anti-platelet medication therapy is assessed by testing platelet activity using a series of platelet aggregation test.\",\n \"The “gold standard” of platelet aggregation tests, light transmission aggregometry (LTA), utilizes collagen from biological sources as the agonist to bring about platelet aggregation, as a measure of the degree or extent of platelet response or inhibition to aggregation.\",\n \"However, there are multiple issues as well as the risk of infectious disease transmission when using biological material.\",\n \"Biologically derived products, whether ‘natural,’ processed, manufactured by fermentation, cell culture or similar processes, or recombinant, all share the following drawbacks: carry a risk of infectious disease transmission; have lot to lot variability (regarding the ratio of active materials, performance, chemical characteristics, solubility, stability, moisture content, and process contaminants); differing bio-profiles depending upon the location the product was made; differences caused by processing; and environment, geographic and dietary differences affecting the source animal or culture.\",\n \"Biological collagens cannot be diluted to enhance sensitivity or to generate dilution profiles, both of which easily performed with synthetic collagen.\",\n \"It is widely believed that anti-platelet therapy contributes to the reduction of major atherothrombotic complications in cardiovascular, neurovascular and other diseases.\",\n \"In the treatment of percutaneous coronary intervention and acute coronary syndromes, dual anti-platelet therapy when performed at optimal dosing and timing has significantly lowered the risk of thrombotic complications and contributed to positive outcomes.\",\n \"However, an important clinical problem of increased incidence of major adverse clinical events (“MACE”) and confounding differences in patient outcomes relates to the variability in patient response to anti-platelet treatments, especially in a dual antiplatelet therapy (a combination of Aspirin and a second agent such as clopidogrel or ticagrelor).\",\n \"Understanding the mechanisms underlying this phenomenon is important to individualizing and improving patient care, long term (maintenance—sometimes referred to as chronic therapy in the literature) therapy and consistent (positive) outcomes.\",\n \"However, a clear and reliable predictive model for responsiveness to anti-platelet therapy is currently not available.\",\n \"Attempts have been made to characterize the efficacy of anti-platelet therapy using platelet function testing but based on current information, and dependence on biological agonists, its routine use is not recommended particularly as costs, complexities and cost effectiveness have not been established, and lack of correlation, standardization and agreement between laboratory methods, and their respective results, is well documented in the literature.\",\n \"Tobias Geislera et al., Circulation 2010; 122:1049-1052.In addition, the inhibitory effects of aspirin on platelets decreases over time in patients on long term or chronic therapy.\",\n \"Violi, F. et al., J Am Cardio, Vol.\",\n \"43, No.\",\n \"6, 2004.Further, as evidenced in AstraZeneca's complete prescribing information on ticagrelor (trade name Brilinta® in the US, Brilique® and Possia® in Europe), Aspirin doses greater than 100 mg reduce the ability of ticagrelor to inhibit platelet aggregation.\",\n \"This conflicts with current clinical care guidelines in which increasing doses of Aspirin to ‘overcome’ Aspirin resistance is recommended.\",\n \"Thus, there remains a need for a quantitative, functional platelet activity test that does not use an animal derived collagen as the agonist.\",\n \"There remains a need for a test that is able to measure the platelet response to an anti-platelet medication when the patient is on a dual therapy of aspirin and an anti-platelet medication, as well as a test to monitor patient compliance with the dual therapy regimen.\",\n \"Dual antiplatelet therapy is the global practice standard.\",\n \"There is also a need for a test that can measure residual platelet activity (that is the platelet activity that remains even while the patient is on a dual anti-platelet medication therapy) rather than platelet inhibition, which is the result for currently available tests.\",\n \"Platelet inhibition does not equal residual platelet reactivity.\",\n \"Residual platelet reactivity is what determines patient outcome and thus is the better measurement.\",\n \"The present invention meets these needs.\",\n \"SUMMARY OF THE INVENTION The present invention provide tests for determining a donor's platelet combined sensitivity status when the individual is on a dual therapy of aspirin and an anti-platelet medication comprising the use of synthetic collagen.\",\n \"Exemplary tests include the use of platelet aggregation studies using for example, light transmission aggregation assays (LTAAs) and flow Cytometry, and to a lesser degree, methods based on measuring aggregation by impedance or whole blood aggregometry.\",\n \"The tests of the present invention use synthetic collagen as the agonist.\",\n \"Tests of the invention provide assays that “discount” or “ignore” the effect of the aspirin on platelet aggregation, but still measure the effect of the anti-platelet medication on the platelet aggregation.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.\",\n \"Further, the invention provides tests that “discount” or “ignore” the effect of the anti-platelet medication, but still measure the effect of the aspirin on platelet aggregation.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.\",\n \"The methods of the present invention are able to test the ability of the individual's platelets to aggregate after the individual has ingested an anti-platelet medication and aspirin.\",\n \"In other words, this tests the residual platelet activity—how reactive are the platelets (likely to aggregate) after the patient has ingested the dual therapy of an anti-platelet medication and aspirin.\",\n \"In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.\",\n \"Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 to 12.5 ng/mL; or ranges from about 2.0 to about 25 ng/mL; or ranges from about 2.0 to about 35 ng/mL; or ranges from about 2.0 to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 to about 25 ng/mL; or ranges from about 12.5 to about 35 ng/mL; or ranges from about 12.5 to about 39.0 ng/mL; or ranges from about 25 to about 39 ng/mL.\",\n \"The literature shows that 30-70% of patients do not comply with taking their medication or taking it as directed, and there is no current compliance test.\",\n \"There is developing thought that ‘resistance’ may be due, at least in part, to non-compliance.\",\n \"The present invention also provides a method of testing patient compliance, with the dual therapy regimen.\",\n \"The DAPT results will show noncompliance for Aspirin therapy as well as deviation from the scheduled dosing window.\",\n \"The present invention also provides a method of testing patient compliance for the aspirin therapy aspect while on a dual therapy, or testing patient compliance for the anti-platelet medication aspect while on a dual therapy.\",\n \"The present invention also provides methods of predicting the effectiveness of aspirin therapy, of an anti-platelet medication therapy, or a dual therapy.\",\n \"In certain embodiments, the synthetic collagen is a synthetic collagen that has the ability to self-assemble into a triple helix to form fibrils and which mimics human type I collagen.\",\n \"In certain embodiments the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) -(Pro-X-Gly)n (I) wherein X represents Hyp; and n represents an integer of from 20 to 5,000; and wherein the polypeptide has a molecular weight at a range of from 10,000 to 500,000.In certain embodiments, n=20-250.The present invention also provides kits for testing platelet aggregation in a light transmission assay, comprising a vial of synthetic collagen; and instructions for use of the synthetic collagen in the dual anti-platelet therapy test (DAPT) of the present invention.\",\n \"In certain embodiments (including the methods described herein and the kits), the synthetic collagen is supplied and/or stored in a polypropylene homomer container.\",\n \"In certain embodiments, the cap is the same material as the vial/tube.\",\n \"In certain embodiments, the container has an additional internal seal or a cap having a secondary seal molded therein.\",\n \"In certain embodiments, the container contains all of the above described characteristics BRIEF DESCRIPTION OF THE FIGURES FIG.\",\n \"1 provides graphs showing the use of a high concentration of synthetic collagen, which shows at high concentrations, the synthetic collagen has no sensitivity to aspirin.\",\n \"FIG.\",\n \"2 provides graphs showing the use of a low concentration of synthetic collagen, which shows that at low concentrations synthetic collagen is sensitive to aspirin.\",\n \"It is this unique property of the synthetic collagen that is the basis for responsiveness and residual reactivity determinations as well as the concurrent assessment of multiple classes of anti-platelet medications.\",\n \"FIG.\",\n \"3 shows the results of LTAs run using synthetic collagen.\",\n \"This figure shows that synthetic collagen provides the ability to measure the effect of other anti-platelet medications in patients on a dual anti-platelet therapy (when one medication is aspirin).\",\n \"FIG.\",\n \"4 provides a graph of test (with the readout as area under the curve (“AUC”)) run on an individual known to be aspirin resistant before and after aspirin ingestion.\",\n \"The tests were run over various dilutions of synthetic collagen.\",\n \"A “bounce back” is seen between 1.0 ng/mL and 0.1 ng/mL.\",\n \"This bounce back is where the line showing the AUC should be decreasing down to correspond with the decreasing concentration of synthetic collagen, but instead bounces up and then bounces down to where it should be (decreasing).\",\n \"FIG.\",\n \"5 provides a graph of test (with the readout as area under the curve (“AUC”)) run on an individual known to be a normal or average aspirin responder before and after aspirin ingestion.\",\n \"The tests were run over various dilutions of synthetic collagen.\",\n \"As expected the AUC decreases as the concentration of synthetic collagen decreases.\",\n \"There is no pronounced “bounce back” as seen in the aspirin resistant individual.\",\n \"FIG.\",\n \"6 provides the test results shown as AUC on a known normal/average aspirin responder using Chrono-Log (Horm) collagen before and after aspirin ingestion.\",\n \"This figure shows that the Chrono-Log (Horm) collagen is insensitive to aspirin because the pre-aspirin and post aspirin AUCs are very similar and would be difficult if not impossible to distinguish.\",\n \"This insensitivity to aspirin in one reason why Chrono-Log (Horm) collagen could not be used to determine the combined effect of aspirin and an anti-platelet medication on platelet activity/aggregation.\",\n \"Further, the non dilutability of biological collagen limits its sensitivity and usefulness in assessing anti-platelet medication effectiveness.\",\n \"FIG.\",\n \"7 provides a block diagram of a dual anti-platelet medication therapy test.\",\n \"FIGS.\",\n \"8-13 show the results of tests where synthetic collagen was used to detect anti-platelet activity of various anti-platelet medications.\",\n \"In these tests, light transmission assays using Bio/Data's PAP 8E platelet aggregometer was used.\",\n \"The ICHOR II impedance cell counter was used to count the platelets.\",\n \"See Example 1.FIG.\",\n \"8 shows the effect of ticagrelor on agonist-induced platelet aggregation.\",\n \"FIG.\",\n \"9 shows the effect of ticagrelor on agonist-induced platelet aggregation in aspirinized plasma.\",\n \"FIG.\",\n \"10 shows the effect of cilostazol on agonist-induced platelet aggregation.\",\n \"FIG.\",\n \"11 shows the effect of cilostazol on agonist-induced platelet aggregation in aspirinized plasma.\",\n \"FIG.\",\n \"12 shows the effect of abciximab on agonist-induced platelet aggregation.\",\n \"FIG.\",\n \"13 shows the effect of abciximab on agonist-induced platelet aggregation in aspirinized plasma.\",\n \"FIG.\",\n \"14 shows biological collagen at 5 and 2 μg/mL.\",\n \"In using the whole blood mode of the Chrono Log aggregometer, a test measuring platelet aggregation on whole blood (impedance aggregation), at 5 μg/mL, the biological collagen gets a response.\",\n \"At 2 μg/mL, there is no response.\",\n \"As an aside, even though called “whole blood mode” by the manufacture, most often whole blood is actually diluted whole blood (usually a 1:1 or greater dilution).\",\n \"FIG.\",\n \"15 shows that synthetic collagen can be diluted from 100 ng/mL to 12.5 ng/mL and still elicit the same response using the whole blood mode of the Chrono Log aggregometer, a test measuring platelet aggregation on whole blood (impedance aggregation).\",\n \"DETAILED DESCRIPTION OF THE INVENTION The present invention provides dual anti-platelet therapy tests (“DAPT™”).\",\n \"The DAPT™ test is a unique, quantitative, functional test, based on different synthetic collagen concentrations, that measures the patient's response to different classes of anti-platelet medications administered concurrently with aspirin, as well as the combined residual platelet reactivity of the aspirin and anti-platelet medication inhibited patient platelets.\",\n \"The test results provide the physician with information about the patient's response to the combination of aspiring and anti-platelet medication as well as discreet and combined residual platelet activity.\",\n \"The dual anti-platelet therapy tests of the present invention use platelet aggregation assays to measure platelet aggregation or inhibition of platelet aggregation, which include, but are not limited to light transmission aggregometry (LTA) (which uses platelet rich plasma (“PRP”)); flow cytometry (which uses whole blood); whole blood impedance aggregometry.\",\n \"The present invention also provides a method for testing a patient's compliance with a dual therapy regimen by monitoring the patient's platelet response over time.\",\n \"Compliance with the dual therapy means both taking both the medications (aspirin and an anti-platelet medication), and taking them at the proper time to maintain its risk-reducing anti-platelet effect.\",\n \"It is also known that tailoring the second drug (the anti-platelet medication) in dual therapy is important because the pathways that process the anti-platelet drugs also process other drugs.\",\n \"For example, in a patient on dual anti-platelet therapy in which one drug is ticagrelor, the plasma level of statins is increased and may be above the therapeutic level.\",\n \"High dose statin therapy avoidance is recommended by the FDA.\",\n \"Other drugs, such as digoxin, must be regularly monitored when a patient is on dual antiplatelet therapy.\",\n \"Incidentally, the aspirin dose must not go over 100 mg, or ticagrelor effectiveness decreases and MACE risk increases.\",\n \"Residual platelet activity is the activity (functionality) of the platelets after they have been exposed to the dual anti-platelet medication therapy.\",\n \"No therapeutic dose will impair 100% of the platelets, nor would any combination reach 100% (nor would this be desirable).\",\n \"In this case the major adverse clinical event (MACE) would be severe bleeding.\",\n \"However, the reactivity of these non-impaired platelets is a key factor in understanding the individual's complete platelet response and MACE risk.\",\n \"For instance if the dual anti-platelet medication therapy were to impair 80% of the platelets (keep 80% platelets from aggregation), there is still 20% of the individual's platelets that could cause thrombotic risk if they were to be extremely active or alternatively, could pose a risk of bleeding to death if the platelets were not active and would not aggregate (and thus would not clot).\",\n \"The present invention provides a method for determining an individual's functional response to an anti-platelet medication when the individual is on, or is a candidate for a dual anti-platelet medication therapy regimen.\",\n \"A dual anti-platelet therapy regimen means an anti-platelet aggregation regimen involving the administration of a low or patient specific dose of aspirin and at least one other anti-platelet medication, typically a first generation thienopyridine such as clopidogrel or increasingly, ticagrelor—a cyclopentyltriazolopyrimidine.\",\n \"Aspirin is a common drug whose active ingredient is acetylsalicylic acid (ASA or ASS).\",\n \"It is a weak acid that is absorbed across the mucosal lining of the stomach and small intestine.\",\n \"After absorption, ASA is (metabolized) hydrolyzed to acetic acid and salicylic acid.\",\n \"In most individuals, aspirin causes inhibition of platelet aggregation and thus, aspirin is used in many therapies where it is desired to minimize platelet aggregation.\",\n \"These individuals are sometimes referred to as normal or average aspirin sensitive.\",\n \"However, in some individuals, even after taking aspirin, the platelets will still aggregate, and hence aspirin therapy would not be beneficial or at the very least would not be beneficial alone.\",\n \"These individuals are often referred to as aspirin resistant or aspirin non-responsive, or high on treatment platelet reactivity (platelets are still highly reactive while patient is on therapy).\",\n \"In this situation, it is important for the physician to know if the patient is compliant or non-compliant in their therapy regimen rather than being non-responsive to aspirin.\",\n \"Several studies report patient noncompliance to range from 30-70%.\",\n \"Noncompliance, which is currently only documented by patient interviews, may be a major reason for outcome variability.\",\n \"In yet other individuals, even very small doses of aspirin cause a severe inhibition of platelet aggregation that could lead to serious bleeding issues.\",\n \"These individuals can be called aspirin hypersensitive.\",\n \"For these individuals aspirin therapy may cause more harm than good because of the increased bleeding risk.\",\n \"In other individuals, aspirin administration causes a life threatening anaphylactic reaction.\",\n \"These individuals are said to be aspirin intolerant.\",\n \"Thus, it is very desirable to be able to test a patient/donor for their response to aspirin to see what effects the aspirin will have on the patient's platelet aggregation to determine whether the aspirin therapy will be useful for preventing unwanted platelet aggregation or whether aspirin therapy should be avoided altogether or perhaps instead be used with another drug to enhance the aspirin effect.\",\n \"Low-dose aspirin (81 mg) is the most common dose used as a preventative regimen against a heart attack or a stroke.\",\n \"However, the dose for daily aspirin can range from 81 mg to 500 mg. Tablets marketed as “low-dose aspirin” contain 81 mg aspirin.\",\n \"One adult-strength tablet contains about 325 mg aspirin, and “advanced” extra strength contains 500 mg.\",\n \"Patient specific aspirin doses can vary from 81 mg to 500 mg. Resistance or insensitivity can occur at any of these doses.\",\n \"Antiplatelet medications are known and include, but are not limited to, abciximab (Reopro®), anagrelide (Agrylin®), apixoban (Eliquis®), clopidogrel bisulfate (Plavix®), eptifabatide (Integrilin®), tirofiban (Aggrastat®), dipyridamole/aspirin (ASA) (Aggrenox®), cilostazol (Pletal®); dipyridamole (Persantine®), ticlopidine (Ticlid®), ticagrelor (Brilinta®), Aloxiprin (aluminum acetylsalicylate), Carbasalate calcium (mixture of calcium acetylsalicylate and urea), Cloricromen, Clorindione, Ditazole, Indobufen, Picotamide, Ramatroban, Terbogrel, Terutroban, and triflusal, as well as those in similar drug classes that are in various stages of development like cangrelor, elinogrel, prasugrel, and others.\",\n \"Aspirin is also considered an anti-platelet medication.\",\n \"For purposes of this application, when referring to a “dual therapy” it is meant as a therapy that includes aspirin and an anti-platelet medication (that is not aspirin).\",\n \"The methods of the present invention are able to test the ability of the individual's platelets to aggregate after the individual has ingested an anti-platelet medication and aspirin.\",\n \"In addition, methods of the invention provide assays that “discount” or “ignore” the effect of the aspirin on platelet aggregation, but still measure the effect of the anti-platelet medication on the platelet aggregation.\",\n \"Further, the invention provides assays that “discount” or “ignore” the effect of the anti-platelet medication, but still measure the effect of the aspirin on platelet aggregation.\",\n \"In most individuals, various anti-platelet medications will cause a variable degree of inhibition of platelet aggregation.\",\n \"These individuals are sometimes referred to as having an average/normal response or “low on therapy platelet reactivity.” However, in some individuals, even after taking the standard dose of anti-platelet medication, the platelets will still aggregate, and hence the particular anti-platelet medication would not be beneficial, but rather detrimental since the thrombotic risk would not be controlled, reduced or evident to the clinician.\",\n \"These individuals are often referred to being non-responsive.\",\n \"In such individuals, the clinician might change medication doses, try another drug class or even add a third drug to the anti-platelet regimen if the bleeding risk is reasonable.\",\n \"In yet other individuals, even very small doses of anti-platelet medication causes a severe inhibition of platelet aggregation that could lead to bleeding issues, which in some cases are life threatening or life ending.\",\n \"These individuals can be called hypersensitive.\",\n \"For these individuals a particular anti-platelet medication therapy may cause more harm than good because of the known bleeding risk attendant to the use of these types of medications.\",\n \"Thus, it is very desirable to be able to test a patient/individual for their response to a particular anti-platelet medication to see what effects the anti-platelet medications will have on the patient's platelet aggregation and residual platelet reactivity to determine whether the anti-platelet medication therapy will be useful for preventing unwanted platelet aggregation or whether the particular anti-platelet medication therapy should be avoided because of bleeding, interference with other drug therapies, or other serious risks.\",\n \"In addition, the tests can be used to monitor patient compliance in taking the prescribed anti-platelet medication.\",\n \"Non-compliance has been identified in multiple studies as a significant occurrence and carries a very high risk for the patient.\",\n \"The preceding is the basis for the increasing shift to a personalized medicine focus, a key element of selecting the right drug or combination of drugs for the individual patient.\",\n \"The DAPT meets this currently unmet need.\",\n \"Embodiments of the invention can test for platelet aggregation using methods known in the art, including, but not limited to flow cytometery and light transmission aggregometry (LTA) and whole blood impedance aggregometry.\",\n \"Flow cytometry uses whole blood and can be used to detect platelet aggregation.\",\n \"Light Transmission Aggregometry (LTA) studies, which are known as the “gold standard” in testing platelet aggregation.\",\n \"Light Transmission Aggregometry (LTA) is an in vitro diagnostic functional assay that measures quantitatively multiple optical parameters from changes in light transmission through Platelet Rich Plasma (PRP) following the addition of an agonist (such as, collagen, ADP, epinephrine, Ristocetin, Arachidonic Acid, thrombin and TRAP) (e.g.\",\n \"more light passes through a sample where there has been platelet aggregation as compared to a sample with no platelet aggregation).\",\n \"Often a blank is used for the comparison, which is the donor's plasma with no platelets present, which is often called “platelet poor plasma” (“PPP”).\",\n \"An agonist is a material that when added to platelet rich plasma, causes the platelets to aggregate.\",\n \"In the methods of the present invention the agonist is synthetic collagen.\",\n \"In LTAA, the PRP is usually stirred in a cuvette at 37° C., and the cuvette sits between a light course and a photocell.\",\n \"After an agonist is added to platelet rich plasma (PRP), the platelets aggregate and absorb less light, so the light transmission increases and is detected by the photocell.\",\n \"LTAAs generate data in the form of aggregation patterns.\",\n \"The LTAA generates parameters plotted on an x/y grid.\",\n \"The x axis is usually a linear time base (typically—minutes).\",\n \"The y axis is a logarithmic scale based upon light transmittance.\",\n \"This light transmittance is equated to percent (%) aggregation.\",\n \"As the LTAA pattern or curve is generated (primary data), various derived measurements are calculated, including Slope (Sa); Maximum Aggregation; Final Aggregation; Area Under the Curve (AUC), Area Under the Slope (AUS) and others.\",\n \"In some embodiments of the present invention AUC is a preferred measurement aspect, because it appears more sensitive than the others.\",\n \"Slope of aggregation (Sa) is a measurement of the rate at which the reaction is proceeding.\",\n \"Dilution profile (DUP) is an incremental change in concentration of the reactants in a test mixture.\",\n \"In collagen testing, the DUP is comprised of the changes to the concentration of the collagen reagent used.\",\n \"Other dilution profiles may be defined and used in analyses.\",\n \"Slope of the dilution Profile (Sd) is generally the regression analysis of the change in concentration.\",\n \"Slope of the reaction profile (Sr) is generally the regression analysis of the change of reaction to change of dilution.\",\n \"The regression analysis may be linear, polynomial or other models.\",\n \"Area under the curve (AUC) is a receiver operating curve that is the calculated graphical volume from the start of the reaction to the end of the reaction as defined by the aggregation and slope of aggregation (Sa).\",\n \"The use of the AUC parameter increases the sensitivity of the DAPT assay(s).\",\n \"This may be considered as the “Power” generated by the reaction.\",\n \"The present invention utilizes synthetic collagen, which it turns out is much more sensitive, potent, predictive and precise than biological collagen, and further is dilutable, which allows extremely low amounts of synthetic collagen to be used.\",\n \"Using synthetic collagen, the methods of the present invention are able measure the degree to which the patient's platelets resist aggregation after the patient has ingested aspirin and an anti-platelet medication.\",\n \"This is a key element, which permits the clinician to accurately assess thrombotic risk avoid MACE and improve patient outcome.\",\n \"In addition, as will be described below in more detail, because the synthetic collagen is dilutable and can be used at many different concentrations, (thereby the right concentration for maximum sensitivity) the tests can be manipulated using different concentrations of the collagen to test for residual platelet activity, to test the effect the anti-platelet medication is having on platelet activity, and to test the effect that the aspirin is having on platelet activity.\",\n \"Further, synthetic collagen provides a means of quantitatively assessing residual platelet reactivity, which is the key indicator of prognostic risk, and is, therefore, more useful information than the currently available, qualitative and highly variable parameter called platelet inhibition.\",\n \"It is important to note that inhibition of aggregation does not equal residual platelet reactivity.\",\n \"Until recently, “platelet inhibition” was the global term and test parameter that was accepted for understanding how platelets behaved when exposed to an anti-platelet drug.\",\n \"The percent aggregation or percent inhibition of aggregation was simply adopted because that is how platelet aggregation was reported.\",\n \"So, inhibition was simply the difference between the patient's original aggregation result and the post treatment result.\",\n \"If the patient's original aggregation result was 82% and the post treatment aggregation result was, 23%, the percent inhibition was reported as 59%.\",\n \"It was then assumed that the other 41% of the platelets were not inhibited.\",\n \"The target was to get the percentage of inhibition between 60 and 80% because that would mean the patient would neither clot nor bleed (ideal outcome).\",\n \"However, it has now been determined that this simplistic construct or understanding does not tell the whole story and thus not work because it does nothing to aid in the understanding of the residual platelet reactivity (that is, the reactivity of the platelets that did not respond to the ingested medicine).\",\n \"There simply is no direct, measurable or predictable relationship between percent inhibition and residual platelet reactivity.\",\n \"Physicians have discovered that patient outcomes to various treatments would vary even when they shared the same percent inhibition.\",\n \"For example, two patients who showed 41 percent inhibition (and thus had 59% aggregation) in an LTA might respond very differently (one may still have problems with unwanted clotting and the other may have problems with bleeding).\",\n \"This observation has slowly led to the realization that although the percent inhibition number (the number of remaining or uninhibited platelets) could be identical, the patient responses could be very different.\",\n \"This has recently spawned the use of terms such as hyper and hypoactive, hyper and hypo-responders, platelet reactivity, residual platelet reactivity, and High on Treatment Platelet Reactivity.\",\n \"The point is that percent inhibition is not the same as residual platelet reactivity.\",\n \"It is clear that platelet response is the measurable effect of a challenge on platelet function, i.e., how a particular drug interferes with a platelet function pathway (platelet and metabolic genetics, drug action and pharmacokinetics, and other factors all come in to play for residual platelet reactivity).\",\n \"The present invention can measure residual platelet reactivity, which is a combination of three things wrapped up into basically a single measurement.\",\n \"The first component is a dose response based on the primary drug (e.g.\",\n \"an anti-platelet medication) to show what portion of the patient's platelets are rendered partially or non-functional based on the that particular patient's individual response to that drug and dose.\",\n \"The second component relates to how reactive the remaining platelets are.\",\n \"These platelets, like the ones that are inhibited, could be hyperactive, hypoactive or anywhere on the continuum between those two points to a different medicine.\",\n \"The third component provides information about the effect of the second drug (e.g.\",\n \"aspirin), which has all the same considerations of the first drug.\",\n \"Synthetic collagen has a unique ability to be insensitive to aspirin at certain concentrations, which allows for the assessment of the second anti-platelet medication, along with its residual platelet reactivity and yet can be used at extremely low concentrations to allow assessment of aspirin sensitivity alone (see FIGS.\",\n \"1 and 2) and further, at other concentrations, can be used to assess residual platelet activity (the activity of the platelets remaining in response to both the anti-platelet medication and the aspirin.\",\n \"FIG.\",\n \"1 shows no aspirin sensitivity when the synthetic collagen concentration is high.\",\n \"FIG.\",\n \"2 shows aspirin sensitivity when the synthetic collagen is low.\",\n \"The insensitivity to aspirin is a key factor in measuring the second anti-platelet drug while the sensitivity to aspirin is needed to assess the residual platelet activity (the activity remaining despite the separate effects of the two drugs).\",\n \"In one aspect, the synthetic collagen is used at a concentration that causes the test to ignore or discount the effect that that aspirin might be having on platelet activity, but still allows one to measure the effect of the anti-platelet medication on platelet activity.\",\n \"In this aspect, the concentration is greater than 40 ng/mL and preferably greater than 50 ng/mL.\",\n \"In another aspect, the synthetic collagen is used at a concentration that causes the test to ignore or discount the effect that the anti-platelet medication might be having on the platelets but still allows one to measure the effect of the aspirin on platelet activity.\",\n \"In another aspect, the amount of synthetic collagen is used at a concentration that tests the residual activity of the platelets after being exposed to the aspirin and the anti-platelet medication.\",\n \"In this aspect, the concentration of synthetic collagen is between about 25 ng/mL to about 35 ng/mL.\",\n \"There are ranges of platelet aggregation that occur after an individual consumes an anti-platelet medication and these ranges can be used to characterize an individual as having a hypersensitive response, a normal/average response, or having a non-response to the anti-platelet medication.\",\n \"Different individuals respond to a particular anti platelet medications differently, so the present invention provides a way of measuring the response to the anti-platelet medication as well as residual platelet reactivity.\",\n \"If the individual does not respond to the medication as desired, the physician can then change the dose, prescribe a different anti-platelet medication or even add a third drug.\",\n \"The present invention also provides embodiments that capitalize on the repeatability and sensitivity of the synthetic collagen as well as its ability to be reproducibly diluted over a range of concentrations and thus, employs multiple dilutions of synthetic collagen (referred to herein as “dilution profiles”) to aid a physician in determining not only whether an individual is sensitive to the anti-platelet medication and/or aspirin, but to further understand an individual's anti-platelet medication and/or aspirin sensitivity status (e.g.\",\n \"the degree to which an individual is anti-platelet medication and/or aspirin sensitive, non-responsive or hypersensitive).\",\n \"This information may be useful for the physician to determine an appropriate dose (patient specific) of anti-platelet medication and/or aspirin in the prescribed therapeutic regimen, or perhaps whether a second or third therapeutic medicine is required, or whether to consider abandoning the use of the anti-platelet medication and/or aspirin altogether for an alternative therapy.\",\n \"Further capitalizing on the sensitivity of synthetic collagen and further using the dilution profile concept, the present invention also provides embodiments where an individual's anti-platelet medication and/or aspirin sensitivity can be predicted even before the donor ingests the anti-platelet medication.\",\n \"Aspirin and anti-platelet medication non-responder (resistant) donors have a distinct response (referred to herein as the “bounce back”) to LTAAs run over varying concentrations of synthetic collagen, which can be used to diagnose a donor's response to the aspirin and the anti-platelet medication.\",\n \"This and other embodiments are discussed more fully herein below.\",\n \"As mentioned above, LTAAs use Platelet Rich Plasma (PRP), which is prepared from properly anti-coagulated whole blood.\",\n \"The individual's blood is collected and spun down to obtain the PRP.\",\n \"Since platelets are very sensitive and can be readily activated during the preparation of PRP, the individual's blood is usually collected in a tube containing a particular anticoagulant.\",\n \"For example, venous blood is obtained and collected into 3.2% sodium citrate in a ratio of 1:9 (1 part anticoagulant to 9 parts blood).\",\n \"Whole blood samples should be processed within 4 hours of collection and blood samples for platelet aggregation testing must be stored at room temperature as cooling the platelets can lead to activation and erroneous test results.\",\n \"PRP is usually prepared by centrifugation at 20° C. for 10-15 minutes at 150-200 g, or, with platelet function centrifuge such as the PDQ companion centrifuge for the PAP 8E, PRP can be prepared in under 4 minutes.\",\n \"The PRP is carefully removed and placed into a stoppered plastic tube.\",\n \"PRP must be stored at room temperature.\",\n \"Platelet poor plasma (PPP) can be then prepared by further centrifugation of the remaining plasma at 2700 g for 15 minutes.\",\n \"Platelet poor plasma (PPP) contains no platelets or other cellular material, and is often used as a blank in LTA sample analyses.\",\n \"By using the PDQ platelet function centrifuge, this time can be reduced to about three minutes.\",\n \"In certain embodiments a special centrifuge that can repeatedly generate PRP and PPP in about 5 minutes instead of the typical 45-60 minutes is employed.\",\n \"This makes the LTAA even more practical for emergency and critical care situations or for a high throughput clinical setting.\",\n \"In addition to the rapid sample preparation, the use of certain concentrations of synthetic collagen can be used to generate the patient's global residual platelet reactivity on an emergency basis.\",\n \"Addition of a platelet agonist to the PRP usually leads to platelet activation, and leads to a change in their shape from discoid to spiny spheres, which is associated with a transient increase in optical density.\",\n \"Exceptions to this are epinephrine in which there is no shape change, and ristocetin, which causes platelet agglutination rather than aggregation, i.e.\",\n \"there is no binding of fibrinogen.\",\n \"Agonists are usually classified as strong agonists or weak agonists.\",\n \"Strong Agonists (e.g.\",\n \"Collagen, thrombin, TRAP, high concentration ADP, and U46619 (an analog of TxA2)) directly induce platelet aggregation, TxA2 synthesis and platelet granule secretion.\",\n \"Weak Agonists (e.g.\",\n \"low concentration ADP & epinephrine) induce platelet aggregation without inducing secretion.\",\n \"In general, LTAs are performed at 37° C. The aggregometer is calibrated by: 1) a cuvette containing PRP, which equates to 0% light transmission; and 2) a second cuvette containing PPP, which equates to 100% light transmission.\",\n \"Since platelets will normally only aggregate if they are activated (with an agonist) and in contact with each other, they must be stirred whilst testing is taking place.\",\n \"Absence of stirring will lead to an absence of, or at least a significant reduction in, aggregation.\",\n \"The present invention utilizes synthetic collagen as the agonist instead of collagen obtained from biological sources in the light transmission aggregometry (“LTA”).\",\n \"The use of synthetic collagen provides many unexpected benefits over the use of biological collagen, which is described herein.\",\n \"In certain embodiments, Bio/Data's PAP 8E LTA is employed (See U.S. Pat.\",\n \"No.\",\n \"7,453,555) as the LTA used in the LTAAs of the present invention.\",\n \"Normally a test for spontaneous platelet aggregation (“SPA”) is performed.\",\n \"SPA is rare in healthy individuals, but occurs in people with hyperactive platelets and is also recognized as an independent marker for some pro-thrombotic conditions, in some cases of von Willebrand Disease (vWD), in some patients with diabetes, in some lipid disorders and in a variety of other disorders.\",\n \"The presence of SPA is tested by placing undiluted PRP in the aggregometer and stirring for 15 minutes.\",\n \"In cases of SPA, dilution of the PRP may abolish this and if the platelet count remains >200×109/L then aggregation testing can proceed.\",\n \"In general, about 225 μL of PRP is added to the aggregometry test cuvette and warmed at 37° C. Then 25 μL of the agonist is added and the response recorded.\",\n \"The typical readouts or responses recorded include primary aggregation (“PA”) (which usually provides a value indicating the amount of aggregation), primary slope (“PS”)(which usually provides a value relating to the speed of aggregation) and area under the curve (“AUC”)(which generally provides a value relating to a combination of PA and PS).\",\n \"Aggregometry analyzers used in the field typically will provide these readouts along with a pictorial graph of the aggregation.\",\n \"Each aggregometer or system calculates the values a bit differently and may use a proprietary formulae embedded in the system software.\",\n \"For example, % maximal aggregation may be calculated by measuring the distance between the baseline [0% aggregation−platelet rich plasma] and platelet poor plasma [100% aggregation] [Y] and dividing this number by the maximal aggregation [X].\",\n \"So if the Y=100 mm and X=89 mm then percentage maximal aggregation=X/Y=89%.\",\n \"In the methods/assays of the present invention, instead of having the patient ingest aspirin and thereafter take a blood sample, a sample of blood can be taken before any aspirin is ingested and the sample can be “aspirinated” (or “aspirinized”)(that is, an aspirin solution (may also be the lysine salt of aspirin or Aspisol®) is added to the PRP and then tested).\",\n \"It has been determined that in the all of the methods/assays of the present, either the patient can ingest the aspirin or the sample can be aspirinated.\",\n \"This can speed up the testing because the patient does not need to ingest the aspirin and have time pass to allow the aspirin to get into the patient's system.\",\n \"Instead, the blood is drawn and a PRP sample is obtained, and one part is aspirinated and the other part is not, thus also allowing the two samples to be tested side by side.\",\n \"A.\",\n \"Testing for Platelet Sensitivity to Anti-Platelet Medication in an Individual on Dual Anti-Platelet Medication Therapy (Ignoring the Effect of Aspirin at this Stage of the Assay, but can be Measured at Another Stage) One embodiment of the present invention provides tests that can determine the individual's platelet sensitivity to an anti-platelet medication when the individual is on a dual anti-platelet medication therapy (i.e.\",\n \"on aspirin and an anti-platelet medication).\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.\",\n \"This method involves performing one or more platelet aggregation assays, such as light transmission assays or flow cytometry whereby a first platelet rich sample or whole blood sample is obtained from an individual and is combined with synthetic collagen to form a first treated sample.\",\n \"For the first treated sample, the individual has not ingested the anti-platelet medication for a time period of about 24 hours, preferably 72-96 hours.\",\n \"The idea is to make sure that the individual will not have any anti-platelet medication in his system to affect the platelet aggregation tests.\",\n \"The first treated sample is tested/measured for platelet aggregation to get a first readout to determine the individual's baseline level of platelet aggregation in the absence of ingested anti-platelet medication.\",\n \"If LTA is used, the sample is placed into a LTA aggregometer and light transmission through the first treated sample is obtained to get the first readout.\",\n \"In certain embodiments, an initial LTAA or other platelet aggregation assay may be performed to check for spontaneous aggregation to test for whether the platelets have any inherent hyperactivity.\",\n \"Then the individual is given the anti-platelet medication (presumably the individual is already on aspirin therapy and has ingested aspirin) and a time period sufficient to allow the anti-platelet medication to be metabolized (e.g.\",\n \"at least about 2 hours to about 16 hours) is allowed to pass before a second platelet rich plasma sample is obtained from the donor.\",\n \"Another platelet aggregation assay such as LTAA is performed on the second platelet rich plasma sample by treating it with synthetic collagen to form a second treated sample.\",\n \"Platelet aggregation is measured to obtain a second readout.\",\n \"If LTAA is the assay used to measure platelet aggregation, light transmission through the second sample is measured to obtain the second readout.\",\n \"It is preferred that the same type of platelet aggregation assay is used throughout the process.\",\n \"For example, if LTAA is used for the first treated sample, then preferably LTAA is used for the second treated sample.\",\n \"The baseline level readout of platelet aggregation in the absence of ingested anti-platelet medication is compared with the second treated sample readout (obtained after the anti-platelet medication ingestion) and the results of this comparison will determine the individual's anti-platelet medication response status.\",\n \"For example, if the individual shows a significant reduction in platelet aggregation after the anti-platelet medication ingestion (in the second sample) as compared to the baseline sample, then the individual may be characterized as normal or having an average anti-platelet medication sensitivity.\",\n \"If the individual shows very little difference in the platelet aggregation after taking the anti-platelet medication (i.e.\",\n \"the platelets still aggregated after the individual ingested the anti-platelet medication), then the individual may be characterized as being anti-platelet medication non-responsive.\",\n \"If the individual showed an almost complete lack of platelet aggregation after ingesting the anti-platelet medication, then the individual may be characterized as being anti-platelet medication hypersensitive, which itself is a very high risk state for the patient.\",\n \"In certain embodiments, the test uses LTAA for platelet aggregation measurements.\",\n \"The readout from the LTAA may be slope, primary aggregation, area under the curve, lag phase disaggregation or a combination thereof.\",\n \"For example, when using the Bio/Data's PAP 8E aggregometer, and when using an “in-test” concentration of 50 ng/mL of synthetic collagen, for an anti-platelet medication hypersensitive individual, the baseline for PA will range from 40% to 100%.\",\n \"The baseline for PS will range from 20 to 60.The baseline for AUC will range from 300 to 700.After the anti-platelet medication, the AUC will range from 100 to 400.PS, PA and LP, will be different from their respective baselines.\",\n \"The anti-platelet medication sensitive and the anti-platelet medication non-responders will show differences from baselines; sensitive individuals will show less aggregation.\",\n \"In certain embodiments, an algorithm that combines and categorizes this data, into an actionable form useful to the physician is.\",\n \"In these tests, the individual may or may not have also consumed aspirin for the test.\",\n \"In one embodiment, the individual does not consume aspirin before the first platelet sample is obtained for the baseline readout, but then ingests aspirin before the second assay is run.\",\n \"In another embodiment, the individual was already on aspirin therapy and had ingested aspirin before the baseline readout was obtained and continued taking the aspirin during the testing.\",\n \"Since this test uses synthetic collagen at a range where it is insensitive to the effects of aspirin on platelets, it does not matter for the test results if the individual consumes aspirin.\",\n \"The beauty of the test is that any inhibition of platelet aggregation seen in the test occurs because of the effect of the anti-platelet medication on the platelet activity and not the aspirin.\",\n \"In another embodiment, no baseline readout is obtained.\",\n \"In this situation, it may be desirable, but is not necessary, to use a previous test run for this individual before the individual started the dual anti-platelet medication therapy as the baseline readout.\",\n \"In the situation where no baseline was obtained, the assay involves performing one or more tests, such as light transmission assays, whereby a first platelet rich sample is obtained from an individual and is combined with synthetic collagen to form a treated sample.\",\n \"The sample is tested and in the case of LTAA is placed into a LTA aggregometer and the light transmission through the treated sample is obtained to get a readout to determine the individual's level of platelet aggregation.\",\n \"In certain embodiments, an initial test may be performed to check for spontaneous aggregation.\",\n \"The results of this treated sample assay are used to determine the individual's anti-platelet medication response status.\",\n \"For example, if the individual shows a significant reduction in platelet aggregation, then the individual may be characterized as normal or having an average anti-platelet medication sensitivity.\",\n \"If the individual shows very little inhibition of platelet aggregation after taking the anti-platelet medication (i.e.\",\n \"the platelets still aggregated after the individual ingested the anti-platelet medication), then the individual may be characterized as being anti-platelet medication non-responsive.\",\n \"If the individual showed an almost complete lack of platelet aggregation after ingesting the anti-platelet medication, then the individual may be characterized as being anti-platelet medication hypersensitive.\",\n \"If the test used LTAAs then the readout of platelet aggregation from the LTAA may be slope, primary aggregation, area under the curve, lag phase, disaggregation, final aggregation or a combination thereof.\",\n \"B.\",\n \"Testing for Platelet Sensitivity to an Anti-Platelet Medication in an Individual on Dual Anti-Platelet Medication Therapy Using a Dilution Profile (Ignoring the Effect of Aspirin on the Platelets) In another embodiment, a dilution profile of synthetic collagen is utilized across a number of different platelet aggregation tests run on an individual's whole blood or PRP sample.\",\n \"In this embodiment of the invention, more than two reactions (more than just the baseline test before the anti-platelet medication ingestion and the test after the anti-platelet medication) are run.\",\n \"A series of platelet aggregation tests, such as a series of LTAAs, are run using multiple differing amounts of synthetic collagen.\",\n \"This is referred to herein as the “dilution profile assays” or “dilution profiles.” In this embodiment, multiple different whole blood or PRP samples are obtained from the individual before the anti-platelet medication ingestion (to obtain a baseline dilution profile) and after the anti-platelet medication ingestion (to obtain a post anti-platelet medication dilution profile).\",\n \"Each individual pre-anti-platelet medication platelet sample is mixed with a different amount of synthetic collagen and a platelet aggregation assay, such as LTAA, is performed on each sample to obtain a baseline dilution profile over the range of concentrations.\",\n \"Then the individual is given the anti-platelet medication and sufficient time is allowed to pass to ensure the anti-platelet medication has been metabolized.\",\n \"Multiple whole blood or PRP samples are obtained from the individual post anti-platelet medication ingestion and mixed with different amounts of synthetic collagen.\",\n \"Platelet aggregation tests, such as LTAAs, are performed on each different sample to obtain a post-anti-platelet medication dilution profile.\",\n \"The same concentrations of synthetic collagen that were used in the pre-anti-platelet medication baseline platelet aggregation tests are preferably used in the post-anti-platelet medication platelet aggregation tests.\",\n \"The results are analyzed and the change in platelet aggregation between the pre- and post-anti-platelet medication tests as well as the change of aggregation over the differing amounts of synthetic collagen are studied to determine the individual's anti-platelet medication sensitivity response (whether the individual is anti-platelet medication hypersensitive, average anti-platelet medication sensitive or anti-platelet medication non-responsive and the degree of sensitivity therein).\",\n \"If the tests utilized LTAAs then the PA, PS or AUC or a combination thereof between the pre- and post-anti-platelet medication LTAs, as well as changes in the PA, PS or AUC or a combination thereof over the differing amounts of synthetic collagen, are studied (often using an algorithm that categorizes the data or information and reports the data) to determine the individual's anti-platelet medication sensitivity response (whether the individual is anti-platelet medication hypersensitive, average anti-platelet medication sensitive or anti-platelet medication non-responsive and the degree of sensitivity therein).\",\n \"In certain embodiments, the results are characterized using the aggregometer's proprietary algorithm embedded in system software, which makes the analysis easier for the diagnostician to understand and make appropriate clinical decisions.\",\n \"In other embodiments, the pre-anti-platelet medication baseline is established with one platelet aggregation test (such as an LTAA) performed using one concentration of synthetic collagen (such as 50 ng/mL) in the LTAA on an individual pre-anti-platelet medication platelet sample, whereas multiple different concentrations of synthetic collagen are still used in different post anti-platelet medication platelet aggregation tests, such as LTAAs, to create the post-anti-platelet medication dilution profile.\",\n \"In this case, the results are analyzed and the change in platelet aggregation seen in the different amounts of synthetic collagen are studied, and compared against each other as well as to against the baseline (pre-anti-platelet medication) to determine the donor's anti-platelet medication sensitivity response (whether anti-platelet medication hypersensitive, normal/average anti-platelet medication sensitive or anti-platelet medication non-responsive and the degree of sensitivity therein).\",\n \"When the platelet aggregation tests use LTAAs, the PA, PS, AUC, or a combination thereof from differing amounts of synthetic collagen are studied, and compared against each other as well as to against the baseline (pre-anti-platelet medication) LTAA to determine the donor's anti-platelet medication sensitivity response.\",\n \"In other embodiments, a pre-anti-platelet medication baseline or pre-anti-platelet medication dilution profile is not obtained.\",\n \"This may be useful in the emergency clinical setting when it is not feasible to obtain a pre-anti-platelet medication baseline or whether one cannot determine from the patient whether he or she has been on anti-platelet medication therapy.\",\n \"In this embodiment, multiple different platelet rich plasma samples or whole blood samples are obtained from the individual and each are mixed independently with a different synthetic collagen concentration to obtain multiple different treated samples for the dilution profile tests.\",\n \"Platelet aggregation tests, such as LTAAs, are performed for each of these samples to obtain a dilution profile over the range of different concentrations.\",\n \"The data is obtained and measured.\",\n \"When the platelet aggregation tests are LTAAs, the AUC, PA, and/or PS or combination therefore are obtained and analyzed over the different ranges of synthetic collagen.\",\n \"In certain embodiments, the results are analyzed using the aggregometer's proprietary algorithm embedded in system software.\",\n \"The inventors have determined that this embodiment can be used to predict the donor's platelet the anti-platelet medication response.\",\n \"For individuals having an average or “normal” anti-platelet medication sensitivity, when looking at the slope, percentage aggregation and/or the AUC, over the dilution profile, the slope, percentage aggregation and/or the AUC will show a corresponding decrease along with the decrease in the amount of synthetic collagen used.\",\n \"Thus, for example, within a given range of various dilutions of synthetic collagen, as the concentration goes down, so will the slope, percentage aggregation, and the AUC.\",\n \"There seems to be an almost linear decrease in slope, percentage aggregation and AUC that runs almost parallel or has almost a direct correlation with the concentration of synthetic collagen.\",\n \"On the other hand, for individuals who are anti-platelet medication non-responders, instead of having a slope, percentage aggregation, and/or the AUC that has a linear-like decrease that corresponds with the decrease in synthetic collagen, there is a point along the dilution profile where there is an increase in slope, an unexpected temporary increase in percentage aggregation and/or a temporary increase in AUC when there should be a decrease (because the concentration of synthetic collagen decreases).\",\n \"Then, as the dilution profile continues to decrease, the slope and AUC “bounce back” down to where it should be (based on the dilution of synthetic collagen) and where it was before the temporary increase and then continues along decreasing.\",\n \"The point at which the bounce back will occur will be at different concentrations of synthetic collagen, and will depend upon the medication class and dose, as well as the patient's metabolic and platelet receptor genetics.\",\n \"Anti-platelet medication hypersensitive individuals will show increases in PA, PS and AUC compared to expected/normal results.\",\n \"In certain embodiments of the invention utilizing the dilution profile concept, a series of 7, 6 or 5 different concentrations are used to develop a dilution profile, and in other embodiments, 4 different concentrations are used and yet in other embodiments, 3 or 2 different concentrations are used.\",\n \"Using too many different concentrations can make the test cumbersome and time consuming, whereas using too few concentrations reduces the amount of data obtained and limits the sensitivity analysis.\",\n \"The range of synthetic collagen used is the dilution profile is preferably within the “anti-platelet medication sensitive range,” which is defined herein as the range of concentrations in which in an average anti-platelet medication sensitive individual the measured platelet activity/aggregation is reduced corresponding with decreasing amounts of synthetic collagen concentrations (e.g.\",\n \"the AUC and/or the slope decreases with the concentration of collagen).\",\n \"In these embodiments the final in-test concentration of synthetic collagen used in the dilution profiles tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.\",\n \"In certain embodiments the different synthetic collagen dilution amounts comprise multiple different synthetic collagen amounts chosen from within the concentration range from about 50 ng/mL to about 500 ng/mL or the range from about 50 ng/mL to about 250 ng/mL.\",\n \"For example, in certain embodiments there are seven different synthetic collagen amounts as the final “in test” concentration as follows: 500 ng/mL; 325 ng/mL; 250 ng/mL; 150 ng/mL; 100 ng/mL; 75 ng/mL; and 50 ng/mL.\",\n \"In other embodiments, there are different synthetic collagen amounts (2, 3, 4, 5, 6 or 7 different dilutions) each chosen from within the range of about 50 ng/mL to about 500 ng/mL or each chosen from within the range of about 50 ng/mL to about about 250 ng/mL, or chosen within the range of about 40 ng/mL to about 500 ng/mL.\",\n \"As some non-limiting examples, in certain embodiments, there are 7 different concentrations (50 ng/mL, 75 ng/mL, 100 ng/mL, 150 ng/mL, 250 ng/mL, 325 ng/mL, and 500 ng/mL).\",\n \"In certain embodiments there are 6 different concentrations (50 ng/mL, 100 ng/mL, 150 ng/mL, 200 ng/mL, 250 ng/mL, and 300 ng/mL).\",\n \"In certain embodiments, there are 5 different concentrations (100 ng/mL, 200 ng/mL, 300 ng/mL, 400 ng/mL, and 500 ng/mL).\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.\",\n \"C. Testing for Platelet Sensitivity to Aspirin in an Individual on Dual Anti-Platelet Medication Therapy (Ignoring Effect of Anti-Platelet Medication) One method of the present invention provides tests that can determine an individual's platelet sensitivity to aspirin when the individual is on a dual anti-platelet medication therapy.\",\n \"In this embodiment, the concentration of synthetic collagen is low enough to be insensitive to the effects of the antiplatelet medication on platelet activity but high enough to be sensitive to the effects of aspirin on platelet activity.\",\n \"In other words, in these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.\",\n \"The concentration of synthetic collagen in this is aspect is a low range and is actually so low that a biological collagen could not be diluted to this low concentration.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"This method involves performing one or more platelet aggregation tests, such as light transmission assays, whereby a first platelet rich sample or whole blood sample is obtained from an individual and is combined with synthetic collagen to form a first treated sample.\",\n \"For this first treated sample, the individual has not ingested the aspirin for a time period of about 24 hours, preferably 72-96 hours (presumably the patient is on an anti-platelet medication).\",\n \"The idea is to make sure that the individual will not have any aspirin in his system to affect the platelet aggregation tests.\",\n \"The sample is measured, such as by placing into a LTA aggregometer and the light transmission through the first treated sample is obtained, to get a first readout to determine the individual's baseline level in the absence of ingested aspirin.\",\n \"In certain embodiments, an initial platelet aggregation assay may be performed to check for spontaneous aggregation to test for whether the platelets have any inherent hyperactivity.\",\n \"Then the individual's is given the aspirin and a time period sufficient to allow the aspirin to be metabolized (e.g.\",\n \"at least about 2 hours to about 16 hours) is allowed to pass before a second platelet rich plasma sample or whole blood sample is obtained from the donor.\",\n \"A platelet aggregation study, such as LTAA, is performed on the second platelet rich plasma sample by treating it with synthetic collagen to form a second treated sample.\",\n \"The second sample is assayed such as in an LTAA by measuring light transmission through the second treated sample to obtain a second readout.\",\n \"The baseline level readout in the absence of ingested aspirin is compared with the second treated sample readout (obtained after the aspirin ingestion) and the results of this comparison will determine the individual's aspirin response status.\",\n \"For example, if the individual shows a significant reduction in platelet aggregation after the aspirin ingestion (in the second sample) as compared to the baseline sample, then the individual may be characterized as normal or having an average aspirin sensitivity.\",\n \"If the individual shows very little difference in the platelet aggregation after taking the aspirin (i.e.\",\n \"the platelets still aggregated after the individual ingested the aspirin), then the individual may be characterized as being aspirin non-responsive.\",\n \"If the individual showed an almost complete lack of platelet aggregation after ingesting the aspirin, then the individual may be characterized as being aspirin hypersensitive.\",\n \"Instead of having the patient ingest the aspirin, the sample can be aspirinated (a solution of aspirin is added to the PRP sample (or whole blood sample).\",\n \"If the platelet aggregation tests used LTAAs, then the readout from the LTA may be slope, primary aggregation, area under the curve, or a combination thereof.\",\n \"The aspirin sensitive and the aspirin non-responders will show differences from baselines; sensitive individuals will show less aggregation.\",\n \"In certain embodiments, an algorithm that combines and categorizes this data, into an actionable form useful to the physician is employed.\",\n \"During these tests the individual is also preferably taking an anti-platelet medication.\",\n \"Because the amount of synthetic collagen used is so low, the test is insensitive to any action of the anti-platelet medication on the platelets.\",\n \"This allows the tester to analyze the effects of the aspirin on platelet activity, while the individual is on the dual anti-platelet medication therapy.\",\n \"This can provide useful information, for example, in cases where the individual turns out to be an aspirin non-responder.\",\n \"In this case, the physician might take the patient off of the aspirin altogether and might prescribe a second anti-platelet medication.\",\n \"Or it could turn out that the patient is hypersensitive to aspirin, which may render the patient at a high risk to unwanted bleeding complications.\",\n \"In this case, the physician may take the patient off of the aspirin altogether and might prescribe a second anti-platelet medication.\",\n \"In another embodiment, no baseline readout is obtained.\",\n \"In this situation where no baseline is obtained, the test involves performing one platelet aggregation assay whereby a platelet rich sample or a whole blood sample (in the case of flow cytometry) is obtained from an individual and is combined with synthetic collagen (e.g.\",\n \"(at a concentration ranging from about 1.0 ng/mL to about 0.1 ng/mL) to form a treated sample.\",\n \"The sample is measured for platelet aggregation, such as in an LTAA by placing it into a LTA aggregometer and the light transmission through the treated sample is obtained to get a readout to determine the individual's level of platelet aggregation).\",\n \"In certain embodiments, an initial assay may be performed to check for spontaneous aggregation.\",\n \"The results of this treated sample are used to determine the individual's aspirin response status.\",\n \"For example, if the individual shows a significant reduction in platelet aggregation, then the individual may be characterized as normal or having an average aspirin sensitivity.\",\n \"If the individual shows very little inhibition of platelet aggregation after taking aspirin (i.e.\",\n \"the platelets still aggregated after the individual ingested the aspirin), then the individual may be characterized as being aspirin non-responsive.\",\n \"If the individual showed an almost complete lack of platelet aggregation after ingesting the aspirin, then the individual may be characterized as being aspirin hypersensitive.\",\n \"The readout from the LTAA may be Primary Slope, Primary Aggregation, Area Under the Curve, lag phase (LP), disaggregation (DA), final aggregatrion (FA) or a combination thereof.\",\n \"D. Testing for Platelet Sensitivity to Aspirin in an Individual on Dual Anti-Platelet Medication Therapy Using Dilution Profile (Ignoring Effect of Anti-Platelet Medication) In another embodiment for testing platelet sensitivity to aspirin in an individual on a dual anti-platelet medication therapy, a dilution profile of synthetic collagen is utilized across a number of different platelet aggregation assays, such as LTAAs or flow cytometery run on an individual's PRP or whole blood sample.\",\n \"In this embodiment, multiple different PRP or whole blood samples are obtained from the individual before the aspirin ingestion (to obtain a baseline dilution profile) and after the aspirin ingestion (to obtain a post aspirin dilution profile).\",\n \"Each platelet sample is mixed with a different amount of synthetic collagen and a platelet aggregation assay, such as LTAA or flow cytometry, is performed on each sample to obtain a baseline dilution profile over the range of concentrations.\",\n \"Then the individual is given the aspirin and sufficient time is allowed to pass to ensure the aspirin has been metabolized.\",\n \"Multiple PRP or whole blood samples are then obtained from the individual post aspirin ingestion and mixed with different amounts of synthetic collagen.\",\n \"In certain embodiments, the samples are aspirinated instead of having the patient ingest aspirin.\",\n \"Platelet aggregation assay are performed on each sample to obtain a post-aspirin dilution profile.\",\n \"The same concentrations of synthetic collagen that were used in the pre-aspirin baseline assays are preferably used in the post-aspirin assays.\",\n \"Preferably the same type of platelet aggregation assay is used throughout the test.\",\n \"For example, flow cytometry is used to measure platelet aggregation for each sample.\",\n \"As another example, LTAAs are used to measure platelet aggregation for each sample.\",\n \"The results are analyzed and the change in platelet aggregation as seen in changes in the PA, PS, AUC, LP, DA, or FA, or a combination thereof between the pre- and post-aspirin assays, as well as changes in the PA, PS, AUC, LP, DA, or FA, or a combination thereof over the differing amounts of synthetic collagen, are studied (often using an algorithm that categorizes the data or information and reports the data) to determine the individual's aspirin sensitivity response (whether the individual is aspirin hypersensitive, average aspirin sensitive or aspirin non-responsive and the degree of sensitivity therein).\",\n \"In certain embodiments the results are characterized using the aggregometer's proprietary algorithm embedded in system software, which makes the results of the analysis easier for the diagnostician to understand and make appropriate clinical decisions.\",\n \"In other embodiments, the pre-aspirin baseline is established with one platelet aggregation assay performed using one concentration of synthetic collagen (such as 0.5 ng/mL in one LTAA) on a pre-anti-platelet medication individual platelet sample, whereas multiple different concentrations of synthetic collagen are still used in different post aspirin platelet aggregation assays to create the post-aspirin dilution profile assays.\",\n \"In this case, the platelet aggregation results are analyzed and compared against each other.\",\n \"If LTAAs were used as the platelet aggregation assay, the change in PA, PS, AUC, LP, DA, or FA, or a combination thereof from differing amounts of synthetic collagen are studied, and/or compared against the baseline (pre-aspirin) LTAA to determine the donor's aspirin sensitivity response (whether aspirin hypersensitive, normal/average aspirin sensitive or aspirin non-responsive and the degree of sensitivity therein).\",\n \"In other embodiments, a pre-aspirin baseline or pre aspirin dilution profile is not obtained.\",\n \"This may be useful in the emergency clinical setting when it is not feasible to obtain a pre-aspirin medication baseline or whether one cannot determine from the patient whether he or she has been on aspirin therapy.\",\n \"In this embodiment, multiple different platelet rich plasma samples or whole blood samples are obtained from the individual and each are mixed independently with a different synthetic collagen concentration to obtain multiple different treated samples for the dilution profile assays.\",\n \"Platelet aggregation assays are performed for each of these samples to obtain a dilution profile over the range of different concentrations.\",\n \"The data is obtained and measured.\",\n \"In this case, the platelet aggregation results are analyzed and compared against each other.\",\n \"If LTAAs were used as the platelet aggregation assay, the change in PA, PS, AUC, LP, DA, or FA, or a combination thereof from differing amounts of synthetic collagen are studied, and/or compared against the baseline (pre-aspirin) LTAA to determine the donor's aspirin sensitivity response (whether aspirin hypersensitive, normal/average aspirin sensitive or aspirin non-responsive and the degree of sensitivity therein).\",\n \"In certain embodiments the results are analyzed using the aggregometer's proprietary algorithm embedded in system software.\",\n \"The inventors have determined that this embodiment can be used to predict the donor's platelet aspirin response.\",\n \"For individuals having an average or “normal” aspirin sensitivity, when looking at the slope, percentage aggregation and lag phase or the AUC, over the dilution profile, the slope, percentage aggregation or the AUC will show a corresponding decrease along with the decrease in the amount of synthetic collagen used.\",\n \"Thus, for example, within a given range of various dilutions of synthetic collagen, as the concentration goes down, so will the slope, percentage aggregation, and the AUC.\",\n \"There seems to be an almost linear decrease in slope, percentage aggregation and AUC that runs almost parallel or has almost a direct correlation with the concentration of synthetic collagen.\",\n \"On the other hand, for individuals who are aspirin non-responders, instead of having a slope, percentage aggregation, and AUC that has a linear-like decrease that corresponds with the decrease in synthetic collagen, there is a point along the dilution profile where there is an increase in slope, an unexpected temporary increase in percentage aggregation and/or a temporary increase in AUC when there should be a decrease (because the concentration of synthetic collagen decreases).\",\n \"Then, as the dilution profile continues to decrease, the slope and AUC “bounce back” down to where it should be (based on the dilution of synthetic collagen) and where it was before the temporary increase and then continues along decreasing.\",\n \"The point at which the bounce back will occur will be at different concentrations of synthetic collagen, and will depend upon the aspirin dose, as well as the patient's metabolic and platelet receptor genetics.\",\n \"Aspirin hypersensitive individuals will show increases in PA, PS and AUC compared to expected/normal results.\",\n \"In certain embodiments of the invention utilizing the dilution profile LTAA concept, a series of 7, 6 or 5 different concentrations are used to develop a dilution profile, and in other embodiments, 4 different concentrations are used and yet in other embodiments, 3 or 2 different concentrations are used.\",\n \"Dilution profiles, when presented graphically have distinctive shapes that may be further visually assessed rapidly much like an EKG.\",\n \"Using too many different concentrations can make the test cumbersome and time consuming, whereas using too few concentrations reduces the amount of data obtained and limits the sensitivity analysis.\",\n \"The range of synthetic collagen used is preferably within the “aspirin sensitive range,” which is defined herein as the range of concentrations in which in an average aspirin sensitive individual the measured platelet activity/aggregation is reduced corresponding with decreasing amounts of synthetic collagen concentrations (e.g.\",\n \"the AUC and/or the slope decreases with the concentration of collagen).\",\n \"In certain embodiments the different synthetic collagen dilution amounts comprise multiple different synthetic collagen amounts chosen from within a concentration range that is low enough to discount the effects of the anti-platelet medication but still pick up the effects of the aspirin.\",\n \"In certain embodiments, there are different synthetic collagen amounts (2, 3, 4, 5, 6 or 7 different dilutions) each chosen from with the range of 0.01 ng/mL to 1.0 ng/mL; or chosen from with the range of 0.1 ng/mL to 0.5 ng/mL; or chosen from with the range of 0.1 ng/mL to 1.0 ng/mL; or chosen from with the range of 0.1 ng/mL to 1.5 ng/mL; or chosen from with the range of 0.5 ng/mL to 2.0 ng/mL.\",\n \"As some non-limiting examples, some embodiments have 5 different dilutions chosen from within the range of 0.01 ng/mL to 1.0 ng/mL such as 0.01 ng/mL, 0.05 ng/mL, 0.1 ng/mL, 0.5 ng/mL, and 1.0 ng/mL.\",\n \"As some non-limiting examples, some embodiments have 6 different dilutions chosen from within the range of 0.5 ng/mL to 2.0 ng/mL such as 0.5 ng/mL, 0.75 ng/mL, 1.0 ng/mL, 1.25 ng/mL, 1.75 ng/mL and 2.0 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.\",\n \"E. Testing for Residual Platelet Activity in an Individual on Dual Anti-Platelet Medication Therapy (how Active are the Platelets after Exposure to Anti-Platelet Medication and Aspirin).\",\n \"One embodiment of the present invention provides tests that can determine the individual's residual platelet activity to the dual therapy (aspirin and an anti-platelet medication) when the individual is on a dual anti-platelet medication therapy (i.e.\",\n \"on aspirin and an anti-platelet medication).\",\n \"In other words, in this embodiment, a level of synthetic collagen is used that is sensitive to both aspirin and the anti-platelet medication.\",\n \"This test informs the physician the overall platelet sensitivity/reactivity in the individual.\",\n \"This test is very useful in the emergency setting when the physician primarily just needs to know the patients platelet status and doesn't necessarily need to know the individual effect of the aspirin or the anti-platelet medication on the platelet reactivity.\",\n \"Typically, anti-platelet medications have been broken down into 5 classes of anti-platelet drugs based on their mechanism of action.\",\n \"The chart below provides some examples.\",\n \"Note that although aspirin is considered an anti-platelet medication, in the present application when a dual therapy is referred to, it is meant as a therapy including aspirin and a second anti-platelet medication (that is not aspirin).\",\n \"Class Example Therapeutic Basis 1 Aspirin Salicylate (COX Inhibitor) IUPAC Name: 2-acetyloxybenzoic acid 2 Dipyridimole Phosphodiesterase Inhibitor (cAMP and cAMP-inhibited cGMP 3′,5′- cyclic phosphodiesterase 10A Activity Inhibitor) IUPAC Name: 2-[[2- [bis(2-hydroxyethyl)amino]- 4,8-di(piperidin-1-yl)pyrimido[5,4- d]pyrimidin-6-yl]- (2-hydroxyethyl)amino]ethanol 3 Reopro ® Not listed as Pubchem Compound Immunoglobulin Fragment Fab Fragment Chimeric monoclonal antibody 7E3 (GP IIbIIIa receptor blocker) 4 Plavix ® Thienopiryridine (PY2 receptor inhibitor) IUPAC Name: methyl (2S)-2-(2- chlorophenyl)-2-(6,7-dihydro-4H- thieno[3,2-c]pyridin-5-yl)acetate 5 Brilinta ® Cyclopentyltriazolopyrimidine (P2Y12 Inhibitor) IUPAC Name: (1S,2S,3R,5S)- 3-[7-[[(1R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino]- 5-propylsulfanyltriazolo[4,5- d]pyrimidin-3-yl]-5- (2-hydroxyethoxy)cyclopentane-1,2-diol 6 Aggregnox ® Phosphodiesterase Inhibitor (cAMP-specific 3′,5′-cyclic phosphodiesterase 4A Inhibitor) IUPAC Name: 2-[[2-[bis(2-hydroxyethyl)amino]- 4,8-di(piperidin-1- yl)pyrimido[5,4-d]pyrimidin-6-yl]- (2-hydroxyethyl)amino]ethanol Note: some individuals consider Brilanta ® as a Class 4 drug because of chemical similarities This method of the present invention involves performing one platelet aggregation study, preferably a LTAA, whereby a platelet rich sample is obtained from an individual and is combined with synthetic collagen to form a treated sample.\",\n \"The sample is placed into a LTA aggregometer and the light transmission through the treated sample is obtained to get a readout to determine the individual's percent aggregation.\",\n \"In certain embodiments, an initial LTA may be performed to check for spontaneous aggregation to test for whether the platelets have any inherent hyperactivity.\",\n \"Then, depending upon the levels of aggregation or (as read through PA, PS, AUC, LP, DA, or FA), if the individual shows a significant reduction in platelet aggregation, then the individual may be characterized as normal or having an average platelet reactivity/sensitivity.\",\n \"If the individual shows very little inhibition of platelet aggregation (shows high platelet activity) (i.e.\",\n \"the platelets still aggregated after the individual ingested the dual anti-platelet medication), then the individual may be characterized as being non-responsive.\",\n \"If the individual showed an almost complete lack of platelet aggregation after ingesting the dual anti-platelet medication, then the individual may be characterized as being hypersensitive.\",\n \"The readout from the LTA may be slope, primary aggregation, area under the curve, lag phase, disaggregation (DA) or final aggregation (FA), or a combination thereof.\",\n \"In certain embodiments, an algorithm that combines and categorizes this data, into an actionable form useful to the physician may be employed.\",\n \"In other words, this tests the residual platelet activity—how reactive are the platelets (likely to aggregate) after the patient has ingested the dual therapy of an anti-platelet medication and aspirin.\",\n \"In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.\",\n \"Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 ng/mL to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 ng/mL to 12.5 ng/mL; or ranges from about 2.0 ng/mL to about 25 ng/mL; or ranges from about 2.0 ng/mL to about 35 ng/mL; or ranges from about 2.0 ng/mL to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 ng/mL to about 25 ng/mL; or ranges from about 12.5 ng/mL to about 35 ng/mL; or ranges from about 12.5 ng/mL to about 39.0 ng/mL; or ranges from about 25 ng/mL to about 39 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.\",\n \"F. Testing for Residual Platelet Activity in Patient on Dual Therapy Using a Dilution Profile In another embodiment for testing residual platelet activity in an individual on a dual anti-platelet medication therapy, a dilution profile of synthetic collagen is utilized across a number of different platelet aggregation assays, such as LTAAs or flow cytometery run on an individual's PRP or whole blood sample.\",\n \"In this embodiment, a baseline aggregation assay is performed before the patient begins the dual therapy.\",\n \"The baseline aggregation assay may be one test or may be a dilution profile baseline.\",\n \"The baseline results of the individual test or dilution profile are compared against the dilution profile results obtained after the patient has been on the dual therapy.\",\n \"In this embodiment, multiple different PRP or whole blood samples are obtained from the individual and each platelet sample is mixed with a different amount of synthetic collagen and a platelet aggregation assay, such as LTAA or flow cytometry, is performed on each sample to obtain a dilution profile.\",\n \"Preferably the same type of platelet aggregation assay is used throughout the test.\",\n \"For example, LTAAs are used to measure platelet aggregation for each sample.\",\n \"Also, if a dilution profile is used for the baseline, preferably the same dilutions are used to test the platelets after the patient has been on the dual therapy.\",\n \"The results are analyzed and the change in platelet aggregation as seen in changes in the PA, PS, AUC, LP, DA, or FA, from the baseline compared to the tests after the patient has been on the dual therapy, as well as a comparison of aggregation over the differing amounts of synthetic collagen, are studied (often using an algorithm that categorizes the data or information and reports the data) to determine the individual's residual platelet reactivity.\",\n \"In certain embodiments the results are characterized using the aggregometer's proprietary algorithm embedded in system software, which makes the results of the analysis easier for the diagnostician to understand and make appropriate clinical decisions.\",\n \"In other embodiments, a pre-dual therapy baseline or baseline profile is not obtained.\",\n \"This may be useful in the emergency clinical setting when it is not feasible to obtain a pre-dual therapy medication baseline or whether one cannot determine from the patient whether he or she has been on a dual therapy.\",\n \"In this embodiment, multiple different platelet rich plasma samples or whole blood samples are obtained from the individual and each are mixed independently with a different synthetic collagen concentration to obtain multiple different treated samples for the dilution profile assays.\",\n \"Platelet aggregation assays are performed for each of these samples to obtain a dilution profile over the range of different concentrations.\",\n \"The data is obtained and measured.\",\n \"In this case, the platelet aggregation results are analyzed and compared against each other.\",\n \"If LTAAs were used as the platelet aggregation assay, the change in PA, PS, AUC, LP, DA, or FA, or a combination thereof from differing amounts of synthetic collagen are studied, to determine the donor's residual platelet activity.\",\n \"In certain embodiments the results are analyzed using the aggregometer's proprietary algorithm embedded in system software.\",\n \"In certain embodiments of the invention utilizing the dilution profile LTAA concept, a series of 7, 6 or 5 different concentrations are used to develop a dilution profile, and in other embodiments, 4 different concentrations are used and yet in other embodiments, 3 or 2 different concentrations are used.\",\n \"Dilution profiles, when presented graphically have distinctive shapes that may be further visually assessed rapidly much like an EKG.\",\n \"Using too many different concentrations can make the test cumbersome and time consuming, whereas using too few concentrations reduces the amount of data obtained and limits the sensitivity analysis.\",\n \"The range of synthetic collagen used is preferably within the “aspirin sensitive range,” which is defined herein as the range of concentrations in which in an average aspirin sensitive individual the measured platelet activity/aggregation is reduced corresponding with decreasing amounts of synthetic collagen concentrations (e.g.\",\n \"the AUC and/or the slope decreases with the concentration of collagen).\",\n \"In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.\",\n \"In certain embodiments, there are different synthetic collagen amounts (2, 3, 4, 5, 6 or 7 different dilutions) each chosen from within the range of about 2.0 ng/mL to about 12.5 ng/mL; or from within the range of about 2.0 ng/mL to about 25 ng/mL; or from within the range of about 2.0 ng/mL to about 35 ng/mL; or from within the range of about 2.0 ng/mL to about 39 ng/mL; or from within the range of about 12.5 ng/mL to about 25 ng/mL; from within the range of about 12.5 ng/mL to about 39.0 ng/mL; or from within the range of about 25 ng/mL to about 39 ng/mL.\",\n \"As a non-limiting example, 5 different concentrations are used chosen from within the range of 12.5 ng/mL to about 35 ng/mL are as follows: 12.5 ng/mL, 20 ng/mL, 25 ng/mL, 30 ng/mL and 35 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"However, they may also be used in other analyzers, including flow cytometers and impedance aggregometers or their equivalents.\",\n \"G. Combination of Tests Any of the tests described above can be combined for a more in-depth analysis of an individual's platelet activity in response to the dual anti-platelet medication therapy.\",\n \"For a particular patient, for an example, an LTAA could be run using an amount of synthetic collagen that provides the physician with an insight as to how the anti-platelet medication alone affects the platelet reactivity (e.g.\",\n \"about 50 ng/mL final in-test concentration of synthetic collagen)(by discounting the aspirin effects on the platelets).\",\n \"Then the physician could run another LTAA using an amount of synthetic collagen that provides the physician with an insight as to how the aspirin alone affects the platelet reactivity (e.g.\",\n \"about 1.0 ng/mL to about 0.1 ng/mL)(by discounting the anti-platelet medication effects on the platelets).\",\n \"Then finally, the physician could run another LTAA using an amount of synthetic collagen that provides the physician with an insight as to how the combination of the aspirin and the anti-platelet medication affects the platelet reactivity (e.g.\",\n \"about 25 ng/mL to 35 ng/mL), and thus provides information about the residual platelet activity.\",\n \"In any of these tests or combinations, a baseline may be obtained prior to ingesting the medication or aspirin, and further the tests may be run using the dilution profile concept described herein above.\",\n \"H. Compliance Testing The present invention also provides tests that can be used to check the patient for compliance with the aspirin, anti-platelet medication and/or the dual therapy.\",\n \"As mentioned above, compliance means both taking the medication and taking the medicine at the right time (according to the prescribed dosing schedule).\",\n \"For example, the patient may be complying with the anti-platelet medication but may not be complying with the aspirin therapy or vice versa.\",\n \"The present invention provides a mechanism to test the patient for his compliance.\",\n \"Non-compliance includes not taking the medication, not taking the proper dose or not staying with the effective dosing (time) schedule.\",\n \"Recent studies have shown that a large problem in health care is patient noncompliance with aspirin and other therapies.\",\n \"Current thinking is that what was once thought to be aspirin resistance may instead be a manifestation of non-compliance complicated by the use of multiple, non-standardized laboratory tests to evaluate platelets inhibited response to aspirin.\",\n \"I.\",\n \"Compliance of Aspirin Therapy Regimen Accordingly, to measure compliance the patient can be routinely tested, such as once a week, bi-monthly, monthly, every 3 months, etc., and the results compared against each other.\",\n \"If the aggregation results vary widely from one test to another, the patient can be further tested to determine if aspirin resistance has developed or the patient could be questioned as to his compliance in taking the prescribed doses of aspirin.\",\n \"If it is suspected that the patient has not been taking the aspirin or not taking it within the dosing window, the patient's plasma can be treated with aspirin and then tested.\",\n \"If aggregation appears in the aspirinated sample, then it may be concluded that the patient had not been taking the aspirin as directed.\",\n \"In some cases, the patient may be taking the aspirin sporadically and not at the same time each day.\",\n \"The aggregation tests may reveal variability from test to test and this variability could be used as an indicator that the patient has not been following the prescribed regular dosing regimen (either not taking the dose every day or taking the dose at different times of the day).\",\n \"It has been found that a patient on aspirin therapy that does not comply with the therapy but not taking the aspirin every day or taking it at different times of the day actually puts the patient at a higher than baseline levels for risk of a thrombotic event.\",\n \"If aggregation does not appear in the aspirinated sample, it could be that the patient had developed aspirin resistance.\",\n \"Further testing could be performed to determine if the patient should be on a different dual therapy of two different anti-platelet medication or perhaps a regimen a different anti-platelet medication altogether without aspirin.\",\n \"In these tests, the concentration of synthetic collagen would be is low enough to be insensitive to the effects of the anti-platelet medication on platelet activity but high enough to be sensitive to the effects of aspirin on platelet activity.\",\n \"In other words, in these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.\",\n \"The concentration of synthetic collagen in this is aspect is a low range and is actually so low that a biological collagen could not be diluted to this low concentration.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"J.\",\n \"Compliance of Anti-Platelet Medication Therapy Regimen If the aggregation results vary widely from one test to another, the patient can be further tested to determine if resistance has developed to the anti-platelet medication or the patient could be questioned as to his compliance in taking the prescribed doses of the anti-platelet medication.\",\n \"If it is suspected that the patient has not been taking the anti-platelet medication or not taking it within the dosing window, the patient's plasma can be treated with the anti-platelet medication and then tested.\",\n \"If aggregation appears in the treated sample, then it may be concluded that the patient had not been taking the anti-platelet medication as directed.\",\n \"In some cases, the patient may be taking the aspirin sporadically and not at the same time each day.\",\n \"If aggregation does not appear in the treated sample, it could be that the patient had developed resistance to the anti-platelet medication.\",\n \"Further testing could be performed to determine if the patient should be on a different dual therapy of two different anti-platelet medication or perhaps a regimen a different anti-platelet medication altogether without aspirin.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"K. Compliance of the Dual Therapy If the aggregation results vary widely from one test to another, the patient can be further tested to determine if resistance has developed to the dual therapy or the patient could be questioned as to his compliance in taking the prescribed doses of the dual therapy.\",\n \"If it is suspected that the patient has not been taking the dual therapy or not taking it within the prescribed dosing window, the patient's plasma can be treated with the anti-platelet medication and then tested and can also be treated with aspirin and then tested.\",\n \"If aggregation appears in the treated sample, then it may be concluded that the patient had not been taking the medication(s) as directed.\",\n \"In some cases, the patient may be taking the aspirin and/or anti-platelet medication sporadically and not at the same time each day.\",\n \"If aggregation does not appear in the treated sample, it could be that the patient had developed resistance to the dual therapy.\",\n \"Further testing could be performed to determine if the patient should be on a different dual therapy of two different anti-platelet medication or perhaps a regimen a different anti-platelet medication altogether without aspirin.\",\n \"In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.\",\n \"Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 ng/mL to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 ng/mL to 12.5 ng/mL; or ranges from about 2.0 ng/mL to about 25 ng/mL; or ranges from about 2.0 ng/mL to about 35 ng/mL; or ranges from about 2.0 ng/mL to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 ng/mL to about 25 ng/mL; or ranges from about 12.5 ng/mL to about 35 ng/mL; or ranges from about 12.5 ng/mL to about 39.0 ng/mL; or ranges from about 25 ng/mL to about 39 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"In the methods/assays of the present invention, instead of having the patient ingest aspirin and thereafter take a blood sample, a sample of blood can be taken before any aspirin is ingested and the sample can be “aspirinated” (or “aspirinized”)(that is, an aspirin solution (may also be the lysine salt of aspirin or Aspisol®) is added to the PRP and then tested).\",\n \"It has been determined that in the all of the methods/assays of the present, either the patient can ingest the aspirin or the sample can be aspirinated.\",\n \"This can speed up the testing because the patient does not need to ingest the aspirin and have time pass to allow the aspirin to get into the patient's system.\",\n \"Instead, the blood is drawn and a PRP sample is obtained, and one part is aspirinated and the other part is not, thus also allowing the two samples to be tested side by side.\",\n \"In some cases, the aspirinized portion of the test can be manufactured by adding aspirin to the PRP to a desired final concentration.\",\n \"In certain embodiments, the concentration of the aspirin ranges from 25 to 150 μM, 25-100 μM, 50-150 μM, 50-100 μM, 75-150 μM, 75-100 μM and preferably a final concentration of 100 μM.\",\n \"L. Method of Predicting Patient's Response to Aspirin, an Anti-Platelet Medication or Dual Therapy The present invention also provides a method of determining or calculating whether a patient would benefit from a certain prescription of aspirin, anti-platelet or dual therapy as well as what class of anti-platelet drug is best suited for the patient (personalized medicine/therapy).\",\n \"L1.Predicting Effectiveness of Aspirin Therapy For example, if a physician was contemplating starting a patient on aspirin therapy, the patient's PRP sample (or whole blood sample) can be aspirinated (or aspirinized) and then can be tested for platelet aggregation using means known in the art, such as LTAAs.\",\n \"If the resulting platelet aggregation tests showed that the platelets did not aggregate to a desired healthy level after being treated with aspirin, then the physician may not want prescribe an aspirin therapy since the patient would seem to be insensitive to aspirin.\",\n \"In other words, the physician could use the results of the LTAAs to predict whether aspirin therapy would be beneficial or detrimental to the patient based on the amount of platelet aggregation that occurred in the presence of the synthetic collagen and the aspirin.\",\n \"In some instances, it may be that the patient's platelets aggregated too strongly and contained no residual activity.\",\n \"In this case, the physician may not prescribe an aspirin therapy regimen as this patient may be susceptible to bleeding complications.\",\n \"In this case the physician would predict that the aspirin was too effective in inhibiting platelet aggregation, would choose another anti-platelet drug.\",\n \"In this embodiment, the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"L2.Predicting Effectiveness of Dual-Therapy Regimen In addition, since the inventors have developed tests that can discount the effect of an anti-platelet medication on platelet aggregation by using a certain concentration range of synthetic collagen in the platelet aggregation assays, tests of the present invention can be used on patients who are currently on an anti-platelet medication and whom the physician might be considering supplementing with an aspirin therapy regimen.\",\n \"Thus, the present invention provides a method of predicting the effectiveness of a dual therapy regimen (predicting the effect of adding aspirin to a patient's anti-platelet medication therapy regimen).\",\n \"In this situation, a whole blood sample or PRP sample is taken from the patient while he is on the anti-platelet medication.\",\n \"The samples are then aspirinized and tested for platelet aggregation.\",\n \"If the resulting platelet aggregation tests showed that the platelets did not aggregate to a desired healthy level after being treated with aspirin, then the physician may not prescribe an aspirin therapy since the patient would seem to be insensitive to aspirin (the tests predicts that the aspirin therapy would not be effective).\",\n \"If the patient's platelets aggregated too strongly and contained no residual activity, the physician may not prescribe an aspirin therapy regimen as this patient may be susceptible to bleeding complications (the tests predicts that the aspirin therapy would be too effective).\",\n \"If the platelets showed an acceptable level of aggregation, then the physician may consider prescribing the dual therapy of the anti-platelet medication and the aspirin therapy (the tests predict a desired or acceptable level of platelet aggregation).\",\n \"In this embodiment, the concentration of synthetic collagen is low enough to be insensitive to the effects of the anti-platelet medication on platelet activity but high enough to be sensitive to the effects of aspirin on platelet activity.\",\n \"In other words, in these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of the anti-platelet medication on platelet aggregation but still measures the effect of the aspirin on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 0.01 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 0.5 ng/mL; or ranges from about 0.1 ng/mL to about 1.0 ng/mL; or ranges from about 0.1 ng/mL to about 1.5 ng/mL; or is from about 0.5 ng/mL or less; or ranges from about 0.5 ng/mL to about 2.0 ng/mL; or is less than 2.0 ng/mL; or is less than 10 ng/mL; or is less than 5 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"L3.Predicting Effectiveness of Anti-Platelet Medication (when Patient is on Aspirin Therapy) Further, the present invention also provides assays that discount the effect of aspirin on platelet aggregation and can test the effect of an anti-platelet medication on the platelet activity.\",\n \"Thus, if a patient were on an aspirin therapy and the physician was considering starting the patient on a dual therapy by adding an anti-platelet medication, the patient's PRP or whole blood sample could be taken and treated with an anti-platelet medication.\",\n \"After adding synthetic collagen, platelet aggregation is studied.\",\n \"If it is determined that the level of platelet aggregation is acceptable, then the physician may prescribe that medication.\",\n \"Or if the level of platelet aggregation was not acceptable, the physician may test and prescribe a different anti-platelet medication.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) and is at a concentration where the test ignores the effect of aspirin on platelet aggregation but still measures the effect of the anti-platelet medication on the platelet aggregation.\",\n \"Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"L4.Predicting Effectiveness of Anti-Platelet Therapy Further, the present invention also provides assays that predict the effectiveness of an anti-platelet medication on platelet activity.\",\n \"See example 2.Thus, if a physician was considering starting a patient on an anti-platelet medication, the patient's PRP or whole blood sample could be taken and treated with an anti-platelet medication.\",\n \"After adding synthetic collagen, platelet aggregation is studied with or without aspirin in the sample.\",\n \"If it is determined that the level of platelet aggregation is acceptable, then the physician may prescribe that medication.\",\n \"Or if the level of platelet aggregation was not acceptable, the physician may test and prescribe a different anti-platelet medication.\",\n \"In these embodiments the final in-test concentration of synthetic collagen that is used tests the ability of the platelets to aggregate in the presence of an agonist (synthetic collagen) Preferably, in these embodiments the final in-test concentration of synthetic collagen used ranges from about 12.5 ng/mL to about 100 ng/mL; or from about 50 ng/mL to about 500 ng/mL; or is >40 ng/mL; or is >50 ng/mL; or ranges from about 40 to about 500 ng/mL; or ranges from about 40 to about 400 ng/mL; or ranges from about 40 to 300 ng/mL; or ranges from about 40 to about 200 ng/mL; or ranges from about 40 to about 100 ng/mL; or ranges from about 40 to about 90 ng/mL; or ranges from about 40 to about 80 ng/mL; or ranges from about 40 to about 70 ng/mL; or ranges from about 40 to about 60 ng/mL; or ranges from about 50 to about 400 ng/mL; or ranges from about 50 to about 300 ng/mL; or ranges from about 50 to about 200 ng/mL; or ranges from about 50 to about 100 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"The concentration of medicine that is used in the test depends on the medication and the concentration of the synthetic collagen.\",\n \"Because synthetic collagen induced platelet aggregation is a functional test, there is no need to have genetic and metabolic test data available prior to prescribing the individualized anti-platelet therapy.\",\n \"The concentration of medicine that is used may depend on the dosing that is given to a patient and the desired levels obtained in the plasma.\",\n \"To determine the best concentrations to use in the method of the invention, one skilled in the art could follow example 2 and obtain healthy donors and test varying ranges of the anti-platelet medication and the synthetic collagen, using the plasma levels as a guide to determine the best ranges (the most sensitive and most reliable across a collection of healthy donors) of anti-platelet medication and synthetic collagen.\",\n \"L5.Predicting Residual Platelet Activity when Patient is on Dual Therapy In another embodiment, the physician may wish to test the residual platelet activity that remains after the plates have been exposed to aspirin and the anti-platelet medication as a method of predicting a patient's residual platelet activity while on a dual therapy regimen.\",\n \"In this case the patient may be on aspirin therapy and the sample is treated with an anti-platelet medication, or the patient may be on an anti-platelet medication and the sample is treated with aspirin or it may be that the patient may already be on a dual therapy.\",\n \"In these embodiments, the concentration of synthetic collagen is such that the effect of both the anti-platelet medication and the aspirin on platelet aggregation is taken into account and the activity of the platelets is the activity that remains after the medications have had their effect.\",\n \"Preferably in these embodiments the final in-test concentration of synthetic collagen used preferably ranges from about 25 ng/mL to 35 ng/mL; or is about 2.0 ng/mL; or ranges from 2.0 ng/mL to 12.5 ng/mL; or ranges from about 2.0 ng/mL to about 25 ng/mL; or ranges from about 2.0 ng/mL to about 35 ng/mL; or ranges from about 2.0 ng/mL to about 39 ng/mL; or is about 12.5 ng/mL; or ranges from about 12.5 ng/mL to about 25 ng/mL; or ranges from about 12.5 ng/mL to about 35 ng/mL; or ranges from about 12.5 ng/mL to about 39.0 ng/mL; or ranges from about 25 ng/mL to about 39 ng/mL.\",\n \"These values and ranges are preferably used when the platelet aggregation tests are light transmission assays and the sample is a PRP sample that is tested.\",\n \"In any of the tests described herein, any measurement of platelet aggregation or inhibition of platelet aggregation may be used.\",\n \"In certain preferred embodiments, LTAAs are used.\",\n \"In certain other preferred embodiments, flow cytometry is used to measure platelet aggregation.\",\n \"As seen from the discussion above concerning the various embodiments, it is apparent that varying amounts of synthetic collagen can be used, depending upon the test to be performed or the clinician's request for an assessment.\",\n \"The amount of synthetic collagen used is about two or more orders of magnitude less than what is generally used when performing LTAAs with biological source collagen.\",\n \"For example, usually LTAAs using calf skin biological collagen generally use 0.19 mg/mL (milligrams/mL) collagen (as the “in-test” concentration); and LTAAs using equine tendon collagen generally use 2.0 μg/mL (micrograms/mL) collagen in the LTAA test (as the “in-test” concentration), whereas generally the methods of the present invention utilize from about 500 ng/mL to about 0.10 ng/mL (nanogram/mL) of synthetic collagen in each LTAA test (as the “in-test” concentration).\",\n \"When testing platelet aggregation using flow cytometry, the usual concentrations of biological collagen ranges from 0.01-100 μg/mL, with 20 μg/mL to be most common.\",\n \"However, using synthetic collagen, the amounts used are much lower, ranging from about 2.0 ng/mL to about 640 ng/mL.\",\n \"Although there are ranges included hereinabove, the present invention is not limited by the recitation of the first and last endpoint to only mean the first and last, but expressly includes the first and last endpoint as well as all of the concentrations within the endpoints.\",\n \"It would be just too cumbersome herein to list every concentration that falls within the recited ranges.\",\n \"The inventors have contemplated using more than one concentration, and more than one range as well as more than one concentration within the recited range to produce the most sensitive and accurate results.\",\n \"The ability to use such low concentrations as well as dilution profiles of collagen is only available with the synthetic collagen.\",\n \"When the inventors tried to dilute biological collagen down to similar low concentrations, it became physically impossible to dilute down the biological collagen to the levels anywhere close to that used in the LTAAs of the present invention with synthetic collagen.\",\n \"Biological collagen is an insoluble, viscous, heterogeneous material, and has long structured fibrous proteins wound into a triple helix.\",\n \"These physical properties precluded the ability to dilute the biological collagen to any low concentration even 100 fold close to the synthetic collagen or to have any such dilution perform in a predictable or useful manner.\",\n \"Further the LTAAs did not work (no aggregation occurred) when using calf skin collagen at a concentration a little lower than 0.19 mg/mL (milligrams/mL) (as the “in-test” concentration); nor when using equine tendon collagen a little lower than 2.0 μg/mL (micrograms/mL).\",\n \"In tests performed on whole blood, using the whole blood mode of the Chrono Log aggregometer it was shown that diluting biological collagen did not produce any viable results but synthetic collagen could be diluted from 100 ng/mL to 12.5 ng/mL and still elicit the same response.\",\n \"See FIGS.\",\n \"14 and 15.Synthetic Collagen In certain embodiments the synthetic collagen is described in U.S. patent application Ser.\",\n \"No.\",\n \"12/520,508, which is herein incorporated by reference in its entirety.\",\n \"In certain embodiments, the synthetic collagen is a synthetic collagen that has the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic type I collagen (allows the synthetic collagen to be recognized or function as type I collagen).\",\n \"In certain embodiments the synthetic collagen comprises a polypeptide having a peptide fragment represented by the formula (I) -(Pro-X-Gly)n (I) wherein X represents Hyp; and n represents an integer of from 20 to 5,000; and wherein the polypeptide has a molecular weight at a range of from 10,000 to 500,000,000.In certain embodiments, the synthetic collagen having the structure of formula (I) has the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic type I collagen.\",\n \"It is preferred that synthetic collagen used in all the assays of the present invention have the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic human type I collagen.\",\n \"In certain embodiments, the synthetic collagen that is used is described in U.S. Pat.\",\n \"No.\",\n \"7,262,275.The synthetic collagen molecule was made by the method described in U.S. Pat.\",\n \"No.\",\n \"7,262,275 (See e.g.\",\n \"Example 6 and Example 7).\",\n \"The molecular weight of the molecule was measured by the method described in the example section in the same patent as was over 1,000,000.In certain embodiments the synthetic collagen has the following values based on GPC-MALs (gel permeation chromatography—multi-angle laser light scattering); Average molecular weight (Mn) 1.3×104; Mw (weight average molecular weight)=1.6×104; size average molecular weight (Mz) 2.0×104.In other embodiments, the synthetic collagen as has the following values based on GPC-MALs (gel permeation chromatography—multi-angle laser light scattering); Average molecular weight (Mn) 2.8×104; Mw (weight average molecular weight)=4.1×104; size average molecular weight (Mz) 6.1×104.The synthetic collagen can be measured by GPC-Mals.\",\n \"The synthetic collagen molecules tested in the present invention were measured using the HLC-8120GPC device manufactured by Tosoh with the following conditions.\",\n \"Column: TSKgel α-M (7.8 mm I.D.×30 cm)×2 (manufactured by Tosoh).\",\n \"Density Detector: Differential refractometer (RI detector), polarity=(+).\",\n \"MALS: DAWN HELEOS (manufactured by Wyatt Technology).\",\n \"MALS Laser wave: 658 nm.\",\n \"Eluent: HFIP (1,1,1,3,3,3-Hexfloro-2-propanol) manufactured by central glass +5 mM-CF3COONa (1st class manufactured by Wako Pure Chemical).\",\n \"Flow Speed: 0.6 mL/min.\",\n \"Column Temp.\",\n \": 40° C. RI detector Temp.\",\n \": 40° C. MALS Temp.\",\n \": Room Temp.\",\n \"Sample density: 2 mg/mL.\",\n \"Sample amount: 100 μL.\",\n \"Pre-treatment of sample: After weighing the samples, they were dissolved by adding a given amount of eluent and left at room temperature overnight.\",\n \"The samples gently mixed and then were then filtered through a 0.5 μm PTFE cartridge filter.\",\n \"In certain embodiments n is an integer of 20 to 250.In certain embodiments n is an integer of 20 to 200.In certain embodiments n is an integer of 20 to 150.In certain embodiments n is an integer of 30 to 100.In certain embodiments n is an integer of 20 to 2,500; of 20 to 2,000; of 20 to 1,500; of 20 to 1,000; of 20 to 500; or of 20 to 250; 30 to 2,500; of 30 to 2,000; of 30 to 1,500; of 30 to 1,000; of 30 to 500; or of 30 to 250.It is preferred that the synthetic collagen molecules discussed above have the ability to self-assemble into a triple helix to form fibrils, which allows the synthetic collagen to mimic type I collagen.\",\n \"Two factors to consider in choosing the synthetic collagen is solubility and ease of handling.\",\n \"If the molecular weight is too small, the synthetic collagen may have poor solubility characteristics.\",\n \"If the molecular weight is too large, the synthetic collagen may not have good handling characteristics (may be too viscous and may have poor dispersibility).\",\n \"Thus, a preferred synthetic collagen of the formula (I) [-(Pro-X-Gly)n] has both good solubility and good handling characteristics.\",\n \"The following synthetic collagen molecules were tested: n=24 (Mn=6,300); n=28 (Mw=7,500); n=49 (Mn=13,000); n=60 (Mw=16,000); n=75 (Mz=20,000); n=105 (Mn=28,000); n=153 (Mw=41,000); n=229 (Mz=61,000).\",\n \"When testing various synthetic molecules, those having the n value from between 49-75 showed the best combination of desirable solubility and handling characteristics.\",\n \"In certain embodiments of the invention, the synthetic collagen may be all one length (for example where n=49 for all synthetic molecules and in certain embodiments, the synthetic collagen may be a mixture of many different lengths (for example, but not limited to, the synthetic collagen is a mixture of molecule having n from 49-75).\",\n \"Kits The present invention also provides kits useful for testing platelet aggregation, comprising a synthetic collagen.\",\n \"The synthetic collagen is as described above and can be at many different concentrations.\",\n \"In addition, the kit may comprise one or more diluents as well as controls.\",\n \"The synthetic collagen can be supplied at a higher concentration in the vial than what would be used as the “in-test” concentration.\",\n \"In certain embodiments, the synthetic collagen in the vial is preferably more than 10 times the amount of the final “in-test” concentration desired.\",\n \"In certain embodiments the synthetic collagen is supplied in the kit at the concentration contemplated for use in the methods of the present invention to bypass the need to create dilutions of the synthetic collagen.\",\n \"In other words, the synthetic collagen is provided so that it is in the concentration that would be used directly in the methods of the present inventions.\",\n \"In other embodiments the vial could contain a higher concentration amount and the directions included in the kit would provide instructions on the desired concentration to use in the assay to achieve the desired final “in-test” concentration of synthetic collagen.\",\n \"In other embodiments, the kit contains at least one single use vial and/or at least one multiple use vial of synthetic collagen.\",\n \"For a single use vial, the vial would contain only the amount of synthetic collagen needed for one test.\",\n \"For a multiple use vial, the synthetic collagen may be supplied at the desired in-test concentration, but the vial contains more than the amount of volume needed for more than one test.\",\n \"The kits of the present invention preferably contain instructions for use of the synthetic collagen in the light transmission assay using methods described herein.\",\n \"In other embodiments, kits of the present invention contain more than one vial of synthetic collagen at the same concentration or in other embodiments, the kits contain more than one vial at a different concentration.\",\n \"Kits having more than one vial at different concentrations would be useful in the dilution profile tests of the present invention.\",\n \"For example, one kit of the present invention may contain vials having 7, 6, 5, 4, or 3 different concentrations of synthetic collagen ranging.\",\n \"Each vial would, in certain embodiments, provide the synthetic collagen at the desired final “in-test” concentration and could be supplied as a single use or a multiple use vial.\",\n \"The present invention is based on measuring platelet aggregation capacity along with dilution profiles generated (in certain embodiments) using synthetic collagen and subsequent data analysis and actionable report.\",\n \"Other methods for measuring platelet response and other measurements to one or more anti-platelet and aspirin therapy regimens using the synthetic collagen are also expected to be useful, such as, for example, the whole blood and point of care platelet function analyzers, methods, and technologies such as impedance and multiple electrode impedance aggregometry, high shear stress, cone and plate, flow cytometry, and other-point-of care technologies and assays of platelet function or reactivity.\",\n \"The inventors have discovered that the nature of the vial used to store synthetic collagen can affect the collagen by activating the collagen to some unpredictable degree.\",\n \"It is preferable that the container used to store the synthetic collagen does not activate the collagen to ensure that when the synthetic collagen is removed from the vial and is introduced into a test system, the degree of activation and adherence of the synthetic collagen is predictable and due only to that test system.\",\n \"In other words, artifacts caused by unintentional activation by the interaction of the collagen with the container are not introduced into the tests.\",\n \"Collagens, including synthetic collagen, stored in generic polypropylene vials or other containers are activated to an unknown degree, subsequently adhere to the container, and are thus not available to participate in the test system.\",\n \"The amount of collagen unavailable to the test system because it has adhered to the container and/or cap is unknown and, based on stability data, is variable.\",\n \"The inventors have discovered that the use of synthetic collagen that has been prepared and stored in a homopolymeric container eliminates a significant degree of variability in test results.\",\n \"Accordingly, it is preferred that the synthetic collagen is prepared and stored in a homopolymeric container.\",\n \"Most containers that are noted as polypropylene are not a single plastic but rather are a family of plastics whose performance can be modified by including various additives during the manufacturing process.\",\n \"Thus, the manufacturing process itself could produce different variations of polypropylene.\",\n \"Further, the nature of the additives is largely unknown or disclosed to the purchaser/public as this information is considered proprietary by the manufacturers.\",\n \"In addition, mold release agents add another variable that could not be assessed.\",\n \"The inventors discovered that containers that have the best long term stability and do not interact with the synthetic collagen have the following characteristics: a) the chemical structure is based on a specific, identical monomer that is repeated (a homopolymer—a polypropylene polymer consisting of identical monomer units); b) caps are made of the same material as the tubes; and c) the caps have an additional internal seal such as a silicone O ring or washer or have a secondary seal molded therein.\",\n \"Exemplary vials include cryovials and caps obtained from Simport (T310 Series); Lake Charles Manufacturing (54A series), and BD Falcon tubes 352096 series).\",\n \"In addition, the inventors discovered that better stability was achieved when the synthetic collagen was diluted with physiologic saline instead of purified water.\",\n \"In certain embodiments (including the methods described herein and the kits), the synthetic collagen is supplied and/or stored in a polypropylene homomer.\",\n \"In certain embodiments, the cap is the same material as the vial/tube.\",\n \"In certain embodiments, the container has an additional internal seal or a cap having a secondary seal molded therein.\",\n \"In certain embodiments, the container contains all of the above described characteristics.\",\n \"EXAMPLES Example 1: Evaluate the Use of Synthetic Collagen to Detect the Antiplatelet Activity of Ticagrelor, Cilostazol and Abciximab in Normal and Aspirinized Human Platelet Rich Plasma Materials: Antiplatelet Drugs Ticagrelor (Brilinta®, Astra-Zeneca, London, UK; lot AL0153, expiration February 2014) was obtained as 90 mg tablets from the Loyola University Health System inpatient pharmacy.\",\n \"Tablets were ground using a mortar and pestle and subsequently dissolved in DMSO at a concentration of 10 mg/mL.\",\n \"The stock solution was diluted in deionized water to make working solutions of 0.5, 0.1 and 0.05 mg/mL.\",\n \"Cilostazol (Pletal®, Otsuka Laboratories, Tokushima, Japan; lot 0B91M) was obtained as a powder.\",\n \"Cilostazol was dissolved in DMSO to make a stock solution of 5 mM.\",\n \"The stock solution was diluted in deionized water to make working solutions of 250, 125 and 50 μM.\",\n \"Abciximab (ReoPro®, Eli-Lilly, Indianapolis, Ind.\",\n \"; lot 12D09AA, expiration May 2015) was obtained as a 2 mg/mL solution which was diluted in physiologic saline to make working solutions of 12.5, 25 and 50 μg/mL.\",\n \"Aspirin powder was dissolved in 100% methanol to make a stock solution of 100 mM.\",\n \"The stock solution was diluted with deionized water to make a 1 mM working solution.\",\n \"Materials: Platelet Agonists ADP was obtained from Bio/Data Corporation, Horsham, Pa. Each vial was reconstituted with 1 mL of deionized water to make a 100 μM working solution.\",\n \"The final concentration of ADP in the aggregation cuvette was 10 μM.\",\n \"Arachidonic acid was obtained from Bio/Data Corporation, Horsham, Pa. Each vial was reconstituted with 0.5 mL deionized water to make a 5 mg/mL working solution.\",\n \"The final concentration of arachidonic acid in the aggregation cuvette was 500 μg/mL.\",\n \"Biological Collagen was obtained from Bio/Data Corporation, Horsham, Pa. Each vial was reconstituted with 0.5 mL deionized water to make a 1.9 mg/mL working solution.\",\n \"The final concentration of Bio/Data collagen in the aggregation cuvette was 190 μg/mL.\",\n \"Biological Collagen was obtained from Chrono Log Corporation, Havertown, Pa. as a 1 mg/mL solution.\",\n \"A working solution of 100 μg/mL was made by dilution with physiologic saline.\",\n \"The final concentration of Chrono Log collagen in the aggregation cuvette was 10 μg/mL.\",\n \"Synthetic collagen was provided by JNC Corporation, Yokohama, Japan at working concentrations of 80, 160, 320 and 640 ng/mL.\",\n \"The final concentrations of synthetic collagen in the aggregation cuvette were 64, 32, 16 and 8 ng/mL.\",\n \"Methods: Blood Collection Approval for the collection of whole blood from healthy human volunteers was granted from the Institutional Review Board of the Health Sciences Division of Loyola University Chicago.\",\n \"Whole blood was drawn using a double syringe technique from the antecubital vein and anticoagulated by the addition of 1 part 3.2% sodium citrate to (9 parts blood to 1 part citrate).\",\n \"Citrated blood was centrifuged at 80×g at room temperature for 15 minutes to make platelet rich plasma (PRP).\",\n \"Supernatant PRP was collected and kept at room temperature in capped tubes.\",\n \"The remaining citrated blood was recentrifuged at 1,100×g for 15 minutes to make platelet poor plasma (PPP).\",\n \"The platelet count of the PRP was determined using an ICHOR II Analyzer, Helena Laboratories, Beaumont, Tex.\",\n \"Platelet count in the PRP was adjusted to 250,000-300,000/μl by the addition of homologous PPP.\",\n \"Six blood donors were used for this study.\",\n \"Each was drawn on separate days for the ‘non-aspirinized’ and ‘aspirinized’ portions of the protocol.\",\n \"For the ‘non-aspirinized’ portion of the protocol, one donor (CS) was excluded from the final analysis as the aggregation responses were markedly different from that of the other 5 donors.\",\n \"For the ‘aspirinized’ portion of the protocol, three donors had taken aspirin orally <48 hours prior to blood draw.\",\n \"For the other three donors, aspirin was supplemented to the PRP in vitro at a final concentration of 100 μM.\",\n \"Methods: Platelet Aggregation Platelet aggregation was measured using a PAP 8E platelet aggregometer (Bio/Data).\",\n \"Each well was blanked using PPP.\",\n \"25 μl of saline or antiplatelet drug and 200 μl of PRP were added to cuvettes containing magnetic stir bars and incubated for three minutes to equilibrate the sample to 37° C. 25 μl of agonist was added to each cuvette and the aggregation profile was monitored until a plateau was achieved.\",\n \"Results were tabulated in terms of maximal aggregation level.\",\n \"Under some reaction conditions, reversible aggregation was observed.\",\n \"This was most commonly observed with ADP and arachidonic acid-induced aggregation in the presence of ticagrelor or cilostazol.\",\n \"Final aggregation levels were also tabulated.\",\n \"Results: Ticagrelor In non-aspirinized plasma, ADP-induced aggregation was strongly inhibited (FIG.\",\n \"8).\",\n \"Arachidonic acid-induced aggregation was inhibited to a similar extent.\",\n \"Neither Bio/Data collagen, Chrono Log collagen nor 64 ng/mL synthetic collagen was markedly impacted by ticagrelor.\",\n \"The antiplatelet effects of Ticagrelor® could be identified when aggregation was induced by synthetic collagen at concentrations of 32 ng/mL and lower.\",\n \"The sensitivity for ticagrelor detection appeared to increase with decreasing synthetic collagen concentration.\",\n \"The addition of aspirin did not affect the ADP-induced aggregation response (FIG.\",\n \"9).\",\n \"In contrast, an anti-platelet effect was no longer observed in arachidonic acid and 8 ng/mL synthetic collagen-induced aggregation assays and the effect in 16 and 32 ng/mL synthetic collagen-induced aggregation assays was reduced.\",\n \"Cilostazol In non-aspirinized plasma, the most marked effect of cilostazol was on arachidonic acid-induced aggregation (FIG.\",\n \"10), where aggregation levels of ˜20% were observed at concentrations ≥12.5 μM (vs. 95% in the absence of cilostazol).\",\n \"ADP-induced aggregation was minimally affected (˜30% inhibition at 25 μM).\",\n \"Cilostazol at concentrations up to 25 μM did not inhibit aggregation induced by Bio/Data collagen, Chrono Log collagen or the 64 ng/mL concentration of synthetic collagen.\",\n \"At lower concentrations of synthetic collagen, the anti-platelet effect of higher concentrations of cilostazol could be observed.\",\n \"Addition of aspirin to the PRP negated the ability to detect cilostazol (FIG.\",\n \"11).\",\n \"Abciximab In non-aspirinized plasma, abciximab produced a concentration-dependent inhibition of agonist-induced aggregation over the concentration range tested (1.25-5 μg/mL) (FIG.\",\n \"12).\",\n \"Arachidonic acid and synthetic collagen (8 and 16 ng/mL) were the most sensitive for detecting the presence of abciximab.\",\n \"Inhibition of Bio/Data and Chrono Log collagen-induced aggregation was only observed at the 5 μg/mL concentration.\",\n \"In aspirinized plasma, the response to arachidonic acid was nearly completely blunted (<20% aggregation) (FIG.\",\n \"13).\",\n \"The addition of abciximab to aspirinized plasma resulted in complete inhibition of arachidonic acid-induced aggregation.\",\n \"Aggregation induced by 10 μM ADP and by 0.19 mg/mL Bio/Data collagen appeared to me minimally affected by the presence of aspirin.\",\n \"Although, aspirin did not inhibit 10 μg/mL Chrono Log collagen-induced aggregation, abciximab produced a stronger inhibition of Chrono Log collagen-induced aggregation in aspirinized PRP.\",\n \"At all concentrations tested, the synthetic collagen reagent produced lower levels of aggregation in aspirinized plasma than in non-aspirinized plasma.\",\n \"Discussion: ADP, arachidonic acid and biological collagen are commonly used agonists to study platelet function.\",\n \"Ticagrelor inhibited aggregation induced by ADP and arachidonic acid, but had little effect on biological collagen-induced aggregation.\",\n \"Cilostazol strongly inhibited arachidonic acid-induced aggregation and produced a weaker, concentration-dependent inhibition of ADP-induced aggregation.\",\n \"Biological collagen-induced aggregation was unaffected by cilostazol.\",\n \"Abciximab inhibited aggregation induced by ADP, arachidonic acid and biological collagen, though ADP and arachidonic acid were more sensitive.\",\n \"The synthetic collagen reagent was tested at concentrations ranging from 8 to 64 ng/mL.\",\n \"Aggregation induced by the 64 ng/mL concentration of the synthetic collagen was comparable to that of the Bio/Data and Chrono Log biological collagen reagents in that there was minimal effect of ticagrelor or cilostazol on the aggregation response.\",\n \"Aggregation induced by collagen or the 64 ng/mL synthetic collagen was inhibited by abciximab to a comparable degree.\",\n \"At lower concentrations of synthetic collagen, the antiplatelet effect of ticagrelor, cilostazol and abciximab were readily apparent.\",\n \"At the concentrations tested, aggregation induced by Bio/Data collagen or Chrono Log collagen was not inhibited by aspirin.\",\n \"While the synthetic collagen reagent exhibited a higher sensitivity to aspirin in the absence of other antiplatelet drugs than either biological collagen, the presence of aspirin affected the ability of the synthetic collagen at these concentrations to detect the presence of ticagrelor or cilostazol.\",\n \"Conclusion: Abciximab is readily detectable in the presence of aspirin using the synthetic collagen concentrations provided for this study.\",\n \"Ticagrelor can be detected, but the concentration-dependence isn't as well defined as it is with abciximab.\",\n \"Example 2: Testing for Platelet Aggregation Using LTAAs and Synthetic Collagen and Adding Anti-Platelet Medication to the PRP Sample Abciximab (ReoPro®) Two healthy donors supplied the PRP samples.\",\n \"A panel of four different synthetic collagen concentrations were tested (12.5 ng/mL, 25 ng/mL, 50 ng/mL and 100 ng/mL Abciximab was added to the each of the four panels of different synthetic collagen concentrations.\",\n \"In one panel, saline was added as the control to each of the four synthetic collagen concentrations.\",\n \"In the second panel, 12.5 μg/mL (micrograms/mL) of abciximab was added to each of the four synthetic collagen concentrations.\",\n \"In a third panel, 25 μg/mL of abciximab was added to each of the four synthetic collagen concentrations.\",\n \"In a fourth panel, 50 μg/mL of abciximab was added to each of the four synthetic collagen concentrations.\",\n \"LTAAs were run for each and the PA, PS, SA, SS AUC, LP, DA, MA and FA was measured for each.\",\n \"The tests were run on each of the donors' samples.\",\n \"Ticagrelor (Brilinta®) Two healthy donors supplied the PRP samples.\",\n \"A panel of four different synthetic collagen concentrations were tested (12.5 ng/mL (nanograms/mL), 25 ng/mL, 50 ng/mL and 100 ng/mL.\",\n \"Ticarelor was added to the each of the four panels of different synthetic collagen concentrations.\",\n \"In one panel, saline was added as the control to each of the four synthetic collagen concentrations.\",\n \"In the second panel, 0.05 mg/mL (milligrams/mL) of Ticagrelor was added to each of the four synthetic collagen concentrations.\",\n \"In a third panel, 0.1 mg/mL of Ticagrelor was added to each of the four synthetic collagen concentrations.\",\n \"In a fourth panel, 0.5 mg/mL of Ticagrelor was added to each of the four synthetic collagen concentrations.\",\n \"LTAAs were run for each and the PA, PS, SA, SS AUC, LP, DA, MA and FA was measured for each.\",\n \"The tests were run on each of the donors' samples.\",\n \"The results showed that the synthetic collagen detected the drugs at the four different concentrations.\",\n \"The synthetic collagen and the two drugs caused the platelets to aggregate.\",\n \"The results also showed that the different dilutions of the two drugs worked with all four dilutions of synthetic collagen to cause the platelets to aggregate.\",\n \"The tests also revealed that certain combinations of synthetic collagen in combination with certain drug dilutions were more sensitive than others.\",\n \"Abciximab and Ticagrelor are two different classes of drugs and yet the assays worked with both.\",\n \"In another test, the samples could also be aspirinized to test for the effect of the dual therapy of the anti-platelet medication and the aspirin on a donor's platelets.\",\n \"Example 3: Use of Flow Cytometry to Test for Platelet Aggregation A vial of Bio/Data calf skin collagen was reconstituted with 0.5 ml of water to make a 1.9 mg/ml solution.\",\n \"A vial of synthetic collagen was reconstituted with 1 ml of synthetic collagen diluent to make a 0.0005 mg/ml solution.\",\n \"Chrono Log collagen was diluted with saline to make a 100 μg/ml solution.\",\n \"A stock 2% paraformaldehyde solution was diluted with calcium-free Tyrode's buffer to make a 1% paraformaldehyde solution.\",\n \"A set of tubes containing 1 ml of 1% paraformaldehyde was prepared.\",\n \"A second set of tubes which contained 30 μl of collagen reagent and 30 μl of antiplatelet drug was prepared and set in a 37° C. heating block.\",\n \"Whole blood was drawn from healthy individuals into sodium citrate.\",\n \"240 μl of citrated blood was added to the tubes at 15-20 second intervals and gently mixed.\",\n \"After a 3 minute incubation period, 50 μl of activated blood was transferred to the corresponding paraformaldehyde-containing tube.\",\n \"After a 30 minute incubation at 4° C., the samples were centrifuged at 1,600 rpm for 10 minutes and the supernatant was removed.\",\n \"The cell pellet was resuspended in 750 μl of Tyrode's buffer.\",\n \"10 μl each of CD61FITC and CD62PE (BD Biosciences) was added to a set of clean tubes.\",\n \"100 μl of resuspended cells was added to the antibody tubes.\",\n \"After a 30 minute incubation period in the dark at room temperature, 700 μl of Tyrode's buffer was added to each tube and the samples were analyzed on the flow cytometer (EPICS-XL, Beckman-Coulter).\",\n \"Platelet activation was assessed in terms of the percentage of platelets expressing P-selectin and the percentage of aggregated platelets.\"\n ]\n]","isConversational":false},"source":{"kind":"string","value":"Patent_15874780"}}},{"rowIdx":4494699,"cells":{"text":{"kind":"list like","value":[["Dynamic Bridging of Interface Protocols","Systems and methods for protocol bridging for a system level modeling simulation (SLMS), such as a SYSTEMC simulation where the components communicate using a TLM2.0 application programming interface (API).","The method includes accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.","Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.","The run-time bridging logic is inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component."],["1.A method for a system level modeling simulation (SLMS) using a mapping registry that includes information related to mapping of attributes between different communication protocols of a plurality of communication protocols, the method comprising: generating, at initialization of the SLMS and using a portion of the information from the mapping registry, run-time bridging logic for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and inserting, at the initialization of the SLMS, the run-time bridging logic between a first representation of a first hardware block that uses the first communication protocol and a second representation of a second hardware block that uses the second communication protocol, the run-time bridging logic configured to bridge the first communication protocol of the first representation of the first hardware block and the second communication protocol of the second representation of the second hardware block.","2.The method of claim 1, wherein the portion of the information from the mapping registry includes an attribute mapping callback for translating a protocol specific attribute specific to a communication protocol of the plurality of communication protocols from the communication protocol to another communication protocol of the plurality of communication protocols.","3.The method of claim 1, wherein generating the run-time bridging logic further comprises: identifying in the mapping registry the portion of the information for translating communications between the first communication protocol and the second communication protocol; and including the identified portion of the information into the run-time bridging logic.","4.The method of claim 1, wherein generating the run-time bridging logic further comprises: identifying in the mapping registry a portion of other information for mapping of states between the different communications protocols; and including the identified portion of the other information into the run-time bridging logic.","5.The method of claim 4, further comprising: mapping, with the run-time bridging logic, a first protocol state of the first communication protocol to a second protocol state of the second communication protocol using the portion of the other information.","6.The method of claim 1, further comprising: receiving a request from the second representation of the second hardware block for a protocol specific attribute that is specific to the second communication protocol; and invoking, with the run-time bridging logic and without accessing the mapping registry during the SLMS, an attribute mapping callback from the portion of the information that includes logic to map attribute information in a payload to the protocol specific attribute that is specific to the second communication protocol, the payload being formatted for the first communication protocol and sent from the first representation of the first hardware block to the second representation of the second hardware block.","7.The method of claim 6, further comprising: sending the protocol specific attribute to the second representation of the second hardware block.","8.A method for protocol bridging for a system level modeling simulation (SLMS), the method comprising: creating a mapping registry prior to initialization of the SLMS by including in the mapping registry information related to mapping of attributes between different communication protocols of a plurality of communication protocols.","9.The method of claim 8, further comprising: identifying in the mapping registry a portion of the information for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and including the identified portion of the information into run-time bridging logic for translating communications between the first communication protocol and the second communication protocol.","10.The method of claim 8, further comprising: creating, within the mapping registry prior to the initialization of the SLMS, a state translation table that includes mappings of states between the different communication protocols.","11.The method of claim 8, further comprising: including, in the mapping registry prior to the initialization of the SLMS, other information for mapping of states between the different communication protocols.","12.The method of claim 11, further comprising: generating, at the initialization of the SLMS and using a portion of the information from the mapping registry, run-time bridging logic for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and inserting, at the initialization of the SLMS, the run-time bridging logic between a first representation of a first hardware block that uses the first communication protocol and a second representation of a second hardware block that uses the second communication protocol, the run-time bridging logic configured to bridge the first communication protocol of the first representation of the first hardware block and the second communication protocol of the second representation of the second hardware block.","13.The method of claim 12, further comprising: accessing, during the SLMS, at least one communication payload formatted for the first communication protocol sent from the first representation of the first hardware block to the second representation of the second hardware block; and translating, by the run-time bridging logic during the SLMS, the at least one communication payload from the first communication protocol to the second communication protocol using the portion of the information.","14.The method of claim 13, further comprising: receiving a request from the second representation of the second hardware block for a protocol specific attribute that is specific to the second communication protocol; and invoking, with the run-time bridging logic and without accessing the mapping registry during the SLMS, an attribute mapping callback from the portion of the information that includes logic to map attribute information in the at least one communication payload to the protocol specific attribute that is specific to the second communication protocol.","15.The method of claim 13, wherein the at least one communication payload includes a first protocol state of the first communication protocol, and the method further comprising: mapping, with the run-time bridging logic, the first protocol state of the first communication protocol to a second protocol state of the second communication protocol using the portion of the other information.","16.A non-transitory computer readable medium storing processor executable instructions for a system level modeling simulation (SLMS) using a mapping registry that includes information related to mapping of attributes between different communication protocols of a plurality of communication protocols, the instructions comprising instructions for: generating, at initialization of the SLMS and using a portion of the information from the mapping registry, run-time bridging logic for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and inserting, at the initialization of the SLMS, the run-time bridging logic between a first representation of a first hardware block that uses the first communication protocol and a second representation of a second hardware block that uses the second communication protocol, the run-time bridging logic configured to bridge the first communication protocol of the first representation of the first hardware block and the second communication protocol of the second representation of the second hardware block.","17.The computer readable medium of claim 16, wherein the portion of the information from the mapping registry includes an attribute mapping callback for translating a protocol specific attribute specific to a communication protocol of the plurality of communication protocols from the communication protocol to another communication protocol of the plurality of communication protocols.","18.The computer readable medium of claim 16, the instructions further comprising instructions for: identifying in the mapping registry the portion of the information for translating communications between the first communication protocol and the second communication protocol; and including the identified portion of the information into the run-time bridging logic.","19.The computer readable medium of claim 16, the instructions further comprising instructions for: identifying in the mapping registry a portion of other information for mapping of states between the different communications protocols; and including the identified portion of the other information into the run-time bridging logic.","20.The computer readable medium of claim 16, the instructions further comprising instructions for: receiving a request from the second representation of the second hardware block for a protocol specific attribute that is specific to the second communication protocol; and invoking, with the run-time bridging logic and without accessing the mapping registry during the SLMS, an attribute mapping callback from the portion of the information that includes logic to map attribute information in a payload to the protocol specific attribute that is specific to the second communication protocol, the payload being formatted for the first communication protocol and sent from the first representation of the first hardware block to the second representation of the second hardware block."],["<SOH> BACKGROUND <EOH>As computer systems have advanced, processing power and speed have increased substantially.","At the same time, computer system complexity and the number of components included in a computer system have increased significantly.","System design has correspondingly increased in complexity as more and more increasingly complex components are used in a given computer system.","In order to accelerate the development process, computer systems and the corresponding components are simulated.","A computer system may have several buses that allow the various components of the computer system to communicate.","Unfortunately, many component simulations have been designed around different protocols and are not able to natively communicate with each other.","Conventional solutions have involved creation of dedicated conversion components to handle conversion of communications between the numerous protocols of the components.","These conversion components need to be created for each protocol pair resulting in complex conversions and a large validation space to ensure protocol compliance at both ends.","For example, for n communication protocols a total of 2*(n*(n−1) conversion components need to be developed and verified.","The use of a large number of conversion components often negatively impacts the efficiency of the simulation.","Often such components are custom and hard coded involving significant development time and reducing flexibility thereby necessitating significant reworking for interface changes.","Thus, a need exists for a solution to allow conversion of communication protocols without dedicated fixed logic conversion components."],["<SOH> SUMMARY <EOH>Embodiments of the present disclosure overcome the need for creating dedicated logic and insertion of the dedicated logic in a design for bridging different communication protocols for on and off-chip communications components.","An efficient mechanism for bridging of protocols or interface protocols, semantics, and application program interfaces (APIs) within system level modeling simulations is thus provided.","Embodiments of the present disclosure are operable to model an interconnect network of a simulated computer system.","In one embodiment disclosed is a method of protocol bridging for a system level modeling simulation (SLMS).","The method comprises accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.","Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.","The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.","In one embodiment, the SLMS is a SYSTEMC simulation where the components communicate using a Transaction Level Modeling 2.0 (TLM2.0) compliant API.","In one embodiment, disclosed is a non-transitory computer readable medium storing processor executable instructions for protocol bridging for a system level modeling simulation (SLMS).","The instructions comprise instructions for accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.","Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.","The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component."],["CROSS REFERENCE TO RELATED U.S.","APPLICATIONS This application claims benefit of and priority to U.S. provisional patent application 61/658,322, entitled “DYNAMIC BRIDGING OF IEEE 1666 TLM 2.0 BASED INTERFACE PROTOCOLS” and filed on Jun.","11, 2012, the contents of which are incorporated by reference herein in its entirety.","This application also claims benefit of and priority to U.S. provisional patent application 61/789,688, entitled “SYSTEM AND METHOD FOR DYNAMIC BRIDGING OF INTERFACE PROTOCOLS” and filed on Mar.","15, 2013, the contents of which are incorporated by reference herein in its entirety FIELD OF THE DISCLOSURE Embodiments of the present disclosure are generally related to simulated systems.","BACKGROUND As computer systems have advanced, processing power and speed have increased substantially.","At the same time, computer system complexity and the number of components included in a computer system have increased significantly.","System design has correspondingly increased in complexity as more and more increasingly complex components are used in a given computer system.","In order to accelerate the development process, computer systems and the corresponding components are simulated.","A computer system may have several buses that allow the various components of the computer system to communicate.","Unfortunately, many component simulations have been designed around different protocols and are not able to natively communicate with each other.","Conventional solutions have involved creation of dedicated conversion components to handle conversion of communications between the numerous protocols of the components.","These conversion components need to be created for each protocol pair resulting in complex conversions and a large validation space to ensure protocol compliance at both ends.","For example, for n communication protocols a total of 2*(n*(n−1) conversion components need to be developed and verified.","The use of a large number of conversion components often negatively impacts the efficiency of the simulation.","Often such components are custom and hard coded involving significant development time and reducing flexibility thereby necessitating significant reworking for interface changes.","Thus, a need exists for a solution to allow conversion of communication protocols without dedicated fixed logic conversion components.","SUMMARY Embodiments of the present disclosure overcome the need for creating dedicated logic and insertion of the dedicated logic in a design for bridging different communication protocols for on and off-chip communications components.","An efficient mechanism for bridging of protocols or interface protocols, semantics, and application program interfaces (APIs) within system level modeling simulations is thus provided.","Embodiments of the present disclosure are operable to model an interconnect network of a simulated computer system.","In one embodiment disclosed is a method of protocol bridging for a system level modeling simulation (SLMS).","The method comprises accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.","Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.","The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.","In one embodiment, the SLMS is a SYSTEMC simulation where the components communicate using a Transaction Level Modeling 2.0 (TLM2.0) compliant API.","In one embodiment, disclosed is a non-transitory computer readable medium storing processor executable instructions for protocol bridging for a system level modeling simulation (SLMS).","The instructions comprise instructions for accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.","Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.","The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.","BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the present disclosure are illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements.","FIG.","1 shows a computer system in accordance with one embodiment of the present disclosure.","FIG.","2 shows an exemplary simulated component coupling in a simulated computer system in accordance with one embodiment of the present disclosure.","FIG.","3 shows a block diagram of an exemplary component communication in accordance with one embodiment of the present disclosure.","FIG.","4 shows protocol specifications and registration of callbacks to create the mapping registry, in accordance with an embodiment of the present disclosure.","FIG.","5 is a flowchart of a process for run-time protocol translation, according to an embodiment.","FIG.","6A shows a flowchart of a process for protocol state mapping in accordance with one embodiment of the present disclosure.","FIG.","6B shows a flowchart of a process for attribute mapping in accordance with one embodiment of the present disclosure.","FIG.","7 shows a block diagram of exemplary computer system and corresponding modules, in accordance with one embodiment of the present disclosure.","DETAILED DESCRIPTION Reference will now be made in detail to the preferred embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings.","While the disclosure will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the disclosure to these embodiments.","On the contrary, the disclosure is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the disclosure as defined by the appended claims.","Furthermore, in the following detailed description of embodiments of the present disclosure, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure.","However, it will be recognized by one of ordinary skill in the art that the present disclosure may be practiced without these specific details.","In other instances, well-known methods, procedures, components, and circuits have not been described in detail as not to unnecessarily obscure aspects of the embodiments of the present disclosure.","Notation and Nomenclature Some portions of the detailed descriptions, which follow, are presented in terms of procedures, steps, logic blocks, processing, and other symbolic representations of operations on data bits within a computer memory.","These descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art.","A procedure, computer executed step, logic block, process, etc., is here, and generally, conceived to be a self-consistent sequence of steps or instructions leading to a desired result.","The steps are those requiring physical manipulations of physical quantities.","Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated in a computer system.","It has proven convenient at times, principally for reasons of common usage, to refer to these signals as bits, values, elements, symbols, characters, terms, numbers, or the like.","It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities.","Unless specifically stated otherwise as apparent from the following discussions, it is appreciated that throughout the present disclosure, discussions utilizing terms such as “ processing” or “accessing” or “ executing” or “ storing” or “rendering” or the like, refer to the action and processes of an integrated circuit (e.g., computing system 100 of FIG.","1), or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices.","Exemplary Computer System Environment FIG.","1 shows an exemplary computer system 100 in accordance with one embodiment of the present disclosure.","FIG.","1 depicts an embodiment of a computer system operable to execute embodiments of the present disclosure and a computer system operable to be simulated in conjunction with embodiments of the present disclosure, as described herein.","Computer system 100 depicts the components of a generic computer system in accordance with embodiments of the present disclosure providing the execution platform for certain hardware-based and software-based functionality.","In general, computer system 100 comprises at least one CPU 101, a system memory 115, and at least one graphics processor unit (GPU) 110.The CPU 101 can be coupled to the system memory 115 via a bridge component/memory controller (not shown) or can be directly coupled to the system memory 115 via a memory controller (not shown) internal to the CPU 101.The GPU 110 may be coupled to a display 112.One or more additional GPUs can optionally be coupled to system 100 to further increase its computational power.","The GPU(s) 110 is coupled to the CPU 101 and the system memory 115.The GPU 110 can be implemented as a discrete component, a discrete graphics card designed to couple to the computer system 100 via a connector (e.g., AGP slot, PCI-Express slot, etc.","), a discrete integrated circuit die (e.g., mounted directly on a motherboard), or as an integrated GPU included within the integrated circuit die of a computer system chipset component (not shown).","Additionally, a local graphics memory 114 can be included for the GPU 110 for high bandwidth graphics data storage.","The CPU 101 and the GPU 110 can also be integrated into a single integrated circuit die and the CPU and GPU may share various resources, such as instruction logic, buffers, functional units and so on, or separate resources may be provided for graphics and general-purpose operations.","The GPU may further be integrated into a core logic component.","Accordingly, any or all the circuits and/or functionality described herein as being associated with the GPU 110 can also be implemented in, and performed by, a suitably equipped CPU 101.Additionally, while embodiments herein may make reference to a GPU, it should be noted that the described circuits and/or functionality can also be implemented and other types of processors (e.g., general purpose or other special-purpose coprocessors) or within a CPU.","System 100 can be implemented as, for example, a desktop computer system or server computer system having a powerful general-purpose CPU 101 coupled to a dedicated graphics rendering GPU 110.In such an embodiment, components can be included that add peripheral buses, specialized audio/video components, 10 devices, and the like.","Similarly, system 100 can be implemented as a handheld device (e.g., cellphone, smartphone, etc.","), direct broadcast satellite (DBS)/terrestrial set-top box or a set-top video game console device such as, for example, the Xbox®, available from Microsoft Corporation of Redmond, Washington, or the PlayStation3®, available from Sony Computer Entertainment Corporation of Tokyo, Japan.","System 100 can also be implemented as a “system on a chip (SoC)”, where the electronics (e.g., the components 101, 115, 110, 114, and the like) of a computing device are wholly contained within a single integrated circuit die.","Examples include a hand-held instrument with a display, a car navigation system, a portable entertainment system, and the like.","Exemplary Systems and Methods Embodiments of the present disclosure overcome the need for creating dedicated logic and insertion of the dedicated logic in a design for bridging different communication protocols for on and off-chip communications components.","An efficient mechanism for bridging of protocols or interface protocols, semantics, and APIs within SYSTEMC simulations is thus provided.","Embodiments of the present disclosure are operable to model an interconnect network of a simulated computer system.","Embodiments of the present disclosure provide a framework in which bridging logic is dynamically inserted at various interface points based on a design configuration.","Due to the run time nature, embodiments of the present disclosure allow for on-the-fly or dynamic re-configurability of the design.","In one embodiment, the framework is based on SYSTEMC transaction level modeling (e.g., IEEE 1666 TLM2.0) semantics and operable with communicating entities using TLM2.0 semantics while adhering to detailed protocol specifications.","Embodiments of the present disclosure thereby eliminate the need for creation and verification of dedicated logic blocks for bridging of various protocols.","Embodiments of the present disclosure thus eliminate the need for inserting and wiring up additional components that perform logic conversion at design creation time.","Embodiments of the present disclosure further significantly ease the design creation of a heterogeneous SoC and reduce model availability problems relating to various protocol bridging models.","Dynamic generation of the dynamic bridging logic may include looking up mappings in a central registry for adding/morphing or deleting interface method calls and state transitions across two communicating entities mimicking the peer part of the protocol handling of the protocol.","Embodiments of the present disclosure also perform mapping of attributes on demand when requested by a destination component to reduce simulation time.","FIG.","2 shows a component coupling in a simulated computer system 200 in accordance with one embodiment of the present disclosure.","Exemplary simulated computer system 200 includes components 202-210 and interconnect component 220.In one embodiment, a component refers to the simulation representation of a real synthesizable hardware block that provides the specified logical functionality in a computer system.","In one embodiment, the simulated computer system 200 can represent the computer system 100 from FIG.","1.The simulation of the simulated computer system 200 can be carried out on a host system, which can also resemble the computer system 100 from FIG.","1.Components 202-210 may be any of a variety of computer or system on a chip (SoC) components including, but not limited to, an Ethernet interface, a wireless network interface, an audio controller, a memory controller, a storage controller, a modem controller, a display controller, a graphics processing unit, a central processing unit, a coprocessor, a digital signal processor, an analog signal processor, a USB controller, a IEEE 1394 controller, available from Apple Corporation of Cupertino, Calif., a thunderbolt™ controller, available from Intel Corporation of Santa Clara, Calif., etc.","Interconnection component 220 may be a simulated interconnect or bus of a simulated computer system.","In one embodiment, an interconnect is a central component that acts as a communication backbone of a computer system which enables routing of information amongst different components in the system.","In one embodiment, components are simulated with SYSTEMC.","SYSTEMC is a system-level modeling language that is approved by the Institute of Electrical and Electronics Engineers (IEEE) Standards Association as IEEE 1666.SYSTEMC allows describing a system at different levels of abstraction.","More specifically, SYSTEMC is a language built in standard C++ by extending the language with the use of class libraries.","SYSTEMC addresses the need for a system design and verification language that spans hardware and software.","The language is particularly suited for modeling a system's partitioning, for evaluating and verifying the assignment of blocks to either hardware or software implementations, and for architecting and measuring the interactions between and among functional blocks.","Throughout the specification, SYSTEMC will be used as an example of a system-level modeling language, but the principles described herein are applicable to any system-level modeling language.","The applications programming interface (API) (e.g., IEEE 1666 TLM2.0) for modeling with SYSTEMC at the transaction level has been standardized and is referred to as TLM2.0 (Transaction Level Modeling 2.0).","TLM2.0 APIs of SYSTEMC provide a generic approach to defining communication protocols or the models for the actual protocols.","The API can thus be used to setup a protocol for components to communicate.","However models of components may come from different places, be designed for different protocols, or different abstractions of the same protocol in more or less detail.","Components 202-210 may each be designed or configured for communication by communication protocols 1-5, respectively.","Interconnect component 220 is configured to communicate by communication protocol 6.In one embodiment, a communication protocol establishes rules (e.g.","as a state machine) for the information interchange semantics, the format, and context of the information exchanged between two components in order to achieve system level behavior.","Examples of communication protocols include the Advanced High Performance Bus (AHB) and the Advanced Extensible Interface (AXI).","Components communicate with each other during a simulation by invoking interface method calls of a TLM 2.0 send API (which can be part of the components) and using the API to transmit a communication payload that is formatted according to an appropriate communication protocol.","In one embodiment, a communication payload includes payload attributes and protocol state attributes.","Payload attributes are elements carrying information in the payload.","There are generally two types of payload attributes: generic attributes and protocol specific attributes.","Generic attributes are protocol agnostic and used by many protocols.","Examples of generic attributes are data and address attributes.","Protocol specific attributes are specific to a particular protocol.","Examples of protocol specific attributes are a burstSize attribute specifying the size of each data beat or a burstLen attribute specifying the number of data beats in a given transaction.","It is noted that often a protocol specific attribute for one protocol may correspond to a protocol specific attribute in a different protocol and should be interpreted correctly for correct functionality.","Protocol state attributes indicate different protocol phases that are needed in order to complete a transaction.","Protocol communications are typically performed in different logical phases.","Examples of protocol phases include an address phase, a data exchange phase, and a completion phase.","Different protocols may use different protocol phases.","In other words, different protocols may have different required states and transactions according to protocol semantics.","In one embodiment protocol states attributes may be considered a type of protocol specific state attribute.","In one embodiment, a formal specification of a protocol definition may comprise: 1) specification of any protocol specific payload attributes (e.g., if needed) and 2) specification of a protocol state attribute.","The specification of the protocol state attribute comprises possible state values and allowed state transitions.","Embodiments of the present disclosure facilitate communication between two components (e.g.","component 202 and interconnect component 220, or any other components) operating with different protocols.","The components may have different semantics and protocols.","Embodiments of the present disclosure are further operable to modify communications between two components operating with different communication protocols.","In other words, each component may have been originally designed with different protocols or semantics and the different communication protocols need to be bridged to allow communication between the components.","Embodiments of the present disclosure are operable for dynamic generation of run-time bridging logic based on formal protocol specification and run time translation.","Embodiments further provide run-time interception and translation of communication calls and mapping between payloads and protocol states of different protocols.","Run time interception may refer to the capture of information when the system (e.g., simulated computer system) is working such that the captured information can be inspected and if needed transformed before reaching the destination.","Embodiments of the present disclosure are further operable to support bridging or translation of communications where a component changes the protocol being used during run time.","Processes and components shown in FIG.","3-7 may be used to translate communications between different protocols, as described herein.","FIG.","3 shows a block diagram of component communication in accordance with one embodiment of the present disclosure.","Diagram 300 includes component 202 and interconnect component 220, a run-time bridging (RTB) logic 310 inserted between component 202 and interconnect component 220, a mapping registry 450 accessed by the RTB logic 310, and attribute mapping callbacks 352.FIG.","3 depicts exemplary conceptual communication of two simulated components and interception of communications between the simulated components.","In other embodiments, the RTB logic 310 may be inserted between any of the components shown in FIG.","2.Mapping registry 450 can be a database that stores information about the attributes of the various protocols and information about mapping payloads from one protocol (e.g., protocol 1) to a different protocol (e.g., protocol 6).","It may also include logic to determine what attribute mapping callbacks 352 should be invoked based on attributes requested at run-time.","As shown, mapping registry 450 includes an attribute-callback mapping table 340 and a protocol state translation table 342.Attribute-callback mapping table 340 includes a list of protocol specific attributes and references to attribute mapping callbacks 352 that are registered for those attributes.","An attribute mapping callback 352 is logic that maps attribute information from a communication payload into a protocol specific attribute for a destination protocol (e.g., protocol 6).","Each attribute mapping callback 352 can be used for mapping into a different protocol specific attribute.","For example, callback 352a can be used for mapping into a protocol specific attribute for protocol 1, callback 352b can be used for mapping into a protocol specific attribute for protocol 2, etc.","An attribute mapping callback 352 can expect a specific set of inputs and returns a specific set of outputs in a specified format.","For example, attribute mapping callback 352 can receive all the payload attributes of a communication payload and process those attributes to return a protocol specific attribute for a destination protocol (e.g., protocol 6).","In one embodiment, each attribute mapping callback 352 performs a formal one to one attribute mapping of attributes from one protocol to attributes for another protocol, such as value mappings.","The mapping is independent of the source protocol, meaning that a single attribute mapping callback 352 can be used to extract a protocol specific attribute regardless of the source protocol.","For example, a single attribute mapping callback 352c can be used to extract a protocol specific attribute for protocol 6 from a payload regardless of whether the payload is formatted for protocol 1, protocol 2, protocol 3, etc.","In one embodiment, the attribute mapping callbacks 352 may be stateless and do not need information about prior communications to perform attribute translation.","In one embodiment, the attribute mapping callbacks may be invoked by the RTB logic 310 on an as needed basis.","State translation table 342 includes a mapping of states between many different protocols in the form of a rule table.","For example, the state translation table 342 can include a mapping of states between protocol 1 and protocol 6, between protocol 1 and protocol 2, etc.","In one embodiment, each transformation in the state translation table 342 may be specified as a combination of a particular state value for the source and the destination protocol and a group of associated payload attribute(s).","State mapping can be done using a combination of payload attributes and state attributes.","This allows specification of a unique mapping to destination protocol state transitions.","For example, a mapping of states from the TLM2.0 Generic protocol to Advanced eXtensible Interface (AXI) for a write transaction may be specified as: PAYLOAD ATTRIBUTES={CMD=WRITE, PHASE=BEGIN_REQ} AXI_STATES={AWVALID, AWREADY, WVALID, WREADY, WVALID_LAST, WREADY_LAST} This example shows that the attributes in a TLM 2.0 generic protocol, used as the source protocol, are CMD having a value WRITE and PHASE having a value of BEGIN_REQ.","When the payload attribute CMD has the value of WRITE and the payload attribute of PHASE has the value of BEGIN_REQ, the resulting AXI state values that are mapped to are AWVALID, AWREADY, WVALID, WREADY, WVALID_LAST, WREADY_LAST.","So one set of input state values maps to multiple output state values.","In this example, AWVALID will be sent to the destination component, and destination will respond with AWREADY.","WVALID will be sent to the destination component, and the destination will responds with WREADY.","WVALID_LAST will be sent to the destination component, and the destination will respond with WREADY_LAST.","WVALID will be sent multiple times depending on a length attribute in the payload (not shown).","Payload attributes & state attributes may allow for merging and splitting of states across protocols that have differing capabilities.","For example, bridging a protocol having shared read and write paths to a protocol having dedicated read and write paths may necessitate state splitting.","As an example, mapping between TLM2.0 generic protocol which has a single request and response path and AXI which has dedicated request and response paths for reads and writes, would need splitting of an incoming generic protocol request to either READ_REQUESTS or WRITE_REQUESTS on the AXI side.","In one embodiment, attribute-callback table 340 and state translation table 342 are populated at the time of protocol specification prior to simulation initialization or run time.","Additional protocol mappings can be defined dynamically at anytime during run time and the additional protocol mappings are pluggable into the simulation framework of embodiments of the present disclosure.","For example, the state translation table 342 may be centrally available to the simulation framework at run time for dynamic insertion of conversion semantics on a communication interface.","The state translation tables 342 may be provided to the simulation framework in a plug and play manner such that additional translations can be added or plugged in at any time (e.g., dynamically during runtime).","Component 202 is designed to communicate based on protocol 1 and component 220 is designed to communicate based on protocol 6.For purposes of explanation, component 202 will be referred to as a source component and interconnect component 220 will be referred to as a destination component.","The protocol used by the source component 202 may be referred to as a source protocol and the protocol used by the destination component 220 may be referred to as a destination protocol.","However, as communications are inherently bi-directional, either component 202 and component 220 may be a source or a destination of a communication payload depending on which component is generating the communication payload.","At initialization of a SYSTEMC simulation, run time bridging block 310 is inserted between the source component 202 and destination component 220 bridge communications between the source protocol and the destination protocol.","Run time bridging logic 310 can intercept communication payloads transmitted between the source component 202 and the destination component 220 and translate the communication payloads for the destination protocol.","In one embodiment, RTB logic 310 is inserted between two communicating entities by modifying the implementation of the TLM 2.0 API in both components 202 and 220 such that the RTB logic 310 can intercept payloads that are transmitted between components 202 and 220.RTB logic 310 is dynamically generated using the information in the attribute-callback table and the state translation table 342 that is appropriate for translating communications between the source/destination protocols.","The RTB logic 310 is dynamically generated at initialization of a SYSTEMC simulation.","The RTB bridging logic is generated with all the necessary logic needed to do state translation between the source/destination protocols and all the necessary logic needed to locate callbacks 352 for attribute translation between the source/destination protocols.","Once generated, the RTB logic 310 no longer needs to access the mapping registry 450 during run-time to perform protocol translations.","In one embodiment, generating the run-time bridging logic can include identifying specific portions of the state translation table 342 and attribute-callback table 340 that are appropriate for translation between the source/destination protocols and then using these portions of the tables to create a decision tree in the run time bridging logic 310.In one embodiment, after intercepting a payload from the source component 202 that is formatted for the source protocol, the RTB logic 310 maps the state of the source protocol into a state of the destination protocol, modifies the state in the payload with the state of the destination protocol, and forwards the modified payload on to the destination component 220.However, RTB logic 310 does not provide mapped attributes to the destination component 220 until the destination component 220 requests it.","In one embodiment, the destination component 220 will request an attribute from the payload.","A payload in SYSTEMC can be stored as an object from which information can be requested from.","Making a request to the payload implicitly invokes the RTB logic 310 and causes the RTB logic 310 to process the request.","For example, when destination component 302 requests a certain attribute from the payload which is not present but another corresponding attribute which has a mapping defined to the requested attribute is present then RTB logic 310 performs mapping of the attribute and the data is returned to the destination component 310 as if it were present in the payload natively.","Performing translation on-demand reduces the amount of time required to process each payload.","In other embodiments, the RTB logic 310 may provide translated attributes to the destination component 220 with every intercepted payload.","Once the mapped states and attributes are provided to the destination component 220, the destination component 220 is free to morph/update the attribute as per the protocol semantics.","On completion of the processing the destination component 220 updates the payload and returns the payload to the source component 202.On the reverse intercept path, the RTB logic 310 re-translates the state and attributes for the source protocol of the source component 202.FIG.","4 shows protocol specifications and registration of callbacks to create the mapping registry 450, in accordance with an embodiment of the present disclosure.","The registration of callbacks typically occurs prior to initialization of a simulation.","In other embodiments, the registration can occur during simulation run-time.","As shown, there are four different protocol specifications 402, 410, 420 and 430 for four different protocols.","As previously described, protocols can communicate information with generic attributes and protocol specific attributes.","Generic attributes are attributes common to all protocols and are used in any computer system (e.g., address and data).","Protocol specific attributes may be attributes specific to a protocol.","In more detail, protocol specification 402 for protocol 1 includes generic attributes 404 (address) and 406 (data) and protocol specific attribute 408 (attr1).","Protocol specification 410 for protocol 2 includes generic attribute 404 (address) and 406 (data) and protocol specific attributes 416 (attr2-1) and 418 (attr2-2) .","Protocol 420 includes generic attributes 404 (address) and 406 (data) and protocol specific attribute 428 (attr3).","Protocol 430 includes generic attributes 404 (address) and 406 (data) and protocol specific attribute 438 (attr4).","Each protocol specific attribute and its associated mapping callback 352 is registered with the mapping registry 450 to create the attribute-callback table 340.This registration typically occurs prior to initialization of a simulation.","The mapping callbacks 352 are written by a designer that is familiar with what type of logic is needed in order to obtain a protocol specific attribute from a payload.","A different mapping callback 352 can be registered for each protocol specific attribute.","Registration of the mapping callbacks 352 enables the appropriate mapping callback 352 to be identified at run-time when attribute translation is needed.","With reference to FIG.","5, 6A and 6B, flowcharts 500, 600 and 650 illustrate example functions used by various embodiments of the present disclosure.","Although specific function blocks (“blocks”) are disclosed in flowcharts 500, 600 and 650, such steps are examples.","That is, embodiments are well suited to performing various other blocks or variations of the blocks recited in flowcharts 500, 600 and 650.It is appreciated that the blocks in flowcharts 500, 600 and 650 may be performed in an order different than presented, and that not all of the blocks in flowcharts 500, 600 and 650 may be performed.","FIG.","5 is a flowchart 500 of a process for run-time protocol translation, during a simulation, according to an embodiment.","The run-time protocol translation is divided into two stages: simulation initialization and simulation run-time.","In step 552, during initialization of a SYSTEMC simulation, design configuration information describing the configuration of a target system (e.g., computer system, system on chip, etc) to be simulated is accessed.","An example of a system is the one shown in FIG.","2.The system includes several components that communicate with different protocols and has been prepared by a system designer prior to the simulation.","Design configuration information may include a connectivity map describing how components are connected to each other.","Design configuration information may also include information describing the specific protocols used by those components.","In step 554, desired protocol specifications are identified based on the protocols specified in the design configuration information.","For example, knowing that one component uses AHB and another component uses AXI, an AXI protocol specification and an AHB protocol specification can be identified from a database of protocol specifications.","For example, the protocol specifications may be the protocol specifications shown in FIG.","4.In step 556, RTB logic 310 is dynamically generated based on the desired protocol specifications.","In one embodiment, generating RTB logic can involve the following steps.","Based on the source and destination protocol specifications, portions of the state translation table 342 that can be used to translate between the source and destination protocol states are identified.","The state translation table 342 can include information useful for translating between many different destination protocols and many different source protocols.","Only a small portion of the state translation table 342 may be useful in configuring the RTB logic for operating with a specific destination protocol and a specific source protocol.","These portions of the state translation table 342 are identified and then used to generate state decision logic of the RTB logic 310.Additionally, portions of the attribute-callback table 340 that reference callbacks 352 that are useful for translation into the attributes of the source and destination protocols are identified and added to the RTB logic 310.In one embodiment, the final RTB 310 can be viewed as a local translation table for state mapping and references to the attribute mapping callbacks 352 that can be used to invoke the attribute mapping callbacks 352 on demand.","In step 558, RTB logic 310 is inserted into the system for components specified by the design configuration information that use different protocols.","RTB logic 310 only needs to be inserted between two components when the components communicate using different protocols.","It is not needed when two components communicate with the same protocol.","In one embodiment, inserting the RTB logic 310 involves overriding the interface implementation of a TLM 2.0 API in the components, such as by modifying interface method calls of the TLM 2.0 API.","In step 560, during simulation run-time, the RTB logic 310 intercepts communication payloads generated by a source component that are formatted for a source protocol.","The RTB logic 310 also accesses the communication payloads to perform translation of communication payloads into a destination protocol.","Because the RTB logic is configured to behave in accordance with the information from the mapping registry 450, it may not need to access the mapping registry 450 anymore during simulation run-time.","The translation can be performed on demand in response to a request from the destination component 220.The run-time translation can include mapping of states from the source protocol to the destination protocol.","The run-time translation can also include mapping of attributes from the source protocol to the destination protocol.","The run-time translation step 560 is further described by reference to FIGS.","5 and 6.FIG.","6A shows a flowchart 600 of a process for protocol state mapping in accordance with one embodiment of the present disclosure.","Flowchart 600 depicts a process for mapping of a protocol state of one protocol to another protocol state of another protocol and may be performed by the RTB logic 310.In one embodiment, state mapping may be coupled with attribute mapping (e.g., process 650) thereby allowing for seamless translation of any two protocols for the payload and the corresponding protocol state machines.","At block 601 an intercepted communication payload is received at the RTB logic 310.The communication payload may generated by a source component 202 that is sent to a destination component 220 and intercepted by the RTB logic 310 at run time.","The communication payload is formatted for the protocol of the source component 202.At block 602, a current protocol state for the destination protocol of the destination component 302 is accessed by the RTB logic 310.The protocol state for the destination protocol may be a protocol state queried from the destination component 302.At block 604, whether a mapped state is found is determined by the RTB logic 310.If there is no mapping from the protocol state of the payload (e.g.","of the source component 202) to a protocol state for the destination component 220, block 614 is performed.","If a mapped state is found, block 606 is performed.","In some embodiments, the current destination state may be used during step 604 to determine whether the state for the source protocol can be mapped to a state for the destination protocol.","At block 606, once a mapped state is found, the payload modified with the mapped state for the destination component, and the modified payload is forwarded to the destination component.","In one embodiment, after the destination component 202 receives the modified payload with the mapped state, it then makes a request for an attribute as shown in FIG.","6B.","At block 614, when a mapped state is not found, the next protocol state for the source protocol is injected into the payload and the payload is returned back to the source component.","The next protocol state is determined by the RTB logic 310.Notably, the payload is not forwarded to the destination when a mapped state is not found.","This is because the destination component 220 is not able to use the payload if no mapped state can be found.","Thus, instead of forwarding the payload to the destination component 220, the protocol state of the source component 202 is advanced to the next state.","FIG.","6B shows a flowchart 650 of a process for attribute mapping during simulation run-time in accordance with one embodiment of the present disclosure.","Flowchart 650 depicts a process for mapping of attributes from a source protocol to a destination protocol and may be performed in logic such as the RTB logic 310 or the callbacks 352.In one embodiment, the steps in flowchart 650 of FIG.","6B are performed after the steps of flowchart 600 of FIG.","6A.","At block 654, the RTB logic 310 receives a request from a destination component 220 to access an attribute.","The attribute requested may be a request for a generic attribute or a protocol specific attribute that is specific to the destination protocol of the destination component 220.At block 656, the RTB logic 310 determines whether the requested attribute is present in the payload.","In one embodiment, the semantics of the source protocol are determined from the payload.","Whether an attribute is present may be based on whether a requested attribute is common to the source protocol of the source component and the destination protocol of the destination component.","For example, if the attribute is a generic attribute it may be common to both protocols, whereas protocol specific attributes may not be common to both protocols.","If an attribute is present in the payload then block 664 is performed.","If an attribute is not present in the payload then block 658 is performed.","At block 664, the RTB logic 310 accesses the attribute and returns the attribute to the destination component 220 if it is present in the payload.","When a destination component 220 attempts to access a generic attribute and the attribute is present in the payload, the attribute is identified as common and the value of the attribute is returned to the destination component 220 that attempted to access it.","For example, if the destination component 220 attempts to access a generic address attribute, the value of the address attribute is returned.","At block 658, the RTB logic 310 invokes an attribute mapping callback for a requested attribute if the requested attribute is not present in the payload.","Requested attributes are typically not present in the payload when they are protocol specific attributes.","In one embodiment, if a destination component 220 attempts to access an attribute that is not present in the payload, an attribute mapping callback 352 that is associated with the protocol specific attribute is invoked to map an attribute from the payload into a protocol specific attribute for the destination protocol of the destination component 220.At block 660, the attribute mapping callback 352 maps the attribute in the payload from the source protocol of the source component 202 to the destination protocol of the destination component 220.The attribute mapping results in an attribute value for the requested attribute.","It is noted that the attribute mappings may be performed in other ways and embodiments of the present disclosure are not limited to performing mapping using attribute mapping callbacks 352.At block 662, the RTB logic 310 sends the mapped attribute value to the destination component 220 that requested the attribute, thereby returning the requested attribute.","The destination component 220 may then request another attribute or perform internal logic operations using the attribute and generate a return payload.","The return payload is processed by the RTB logic 310 in the same manner as that shown in FIG.","6A and 6B, except that attributes and states will now be mapped from the destination protocol to the source protocol.","FIG.","7 illustrates example components used by various embodiments of the present disclosure.","Although specific components are disclosed in computing system environment 700, it should be appreciated that such components are examples.","That is, embodiments of the present disclosure are well suited to having various other components or variations of the components recited in computing system environment 700.It is appreciated that the components in computing system environment 700 may operate with other components than those presented, and that not all of the components of system 700 may be required to achieve the goals of computing system environment 700.FIG.","7 shows a block diagram of an exemplary computing system environment 700, in accordance with one embodiment of the present disclosure.","With reference to FIG.","7, an exemplary system module for implementing embodiments includes a general purpose computing system environment, such as computing system environment 700.Computing system environment 700 may include, but is not limited to, servers, desktop computers, laptops, tablet PCs, mobile devices, and smartphones.","In one embodiment, computing system environment 700 is computer system 100.In its most basic configuration, computing system environment 700 typically includes at least one processing unit 702 and non-transitory computer readable storage medium 704.Depending on the exact configuration and type of computing system environment, computer readable storage medium 704 may be volatile (such as RAM), non-volatile (such as ROM, flash memory, etc.)","or some combination of the two.","Portions of computer readable storage medium 704 includes processor executable instructions that when executed facilitate communication bridging (e.g., processes 500, 600, 650).","Additionally, computing system environment 700 may also have additional features/functionality.","For example, computing system environment 700 may also include additional storage (removable and/or non-removable) including, but not limited to, magnetic or optical disks or tape.","Such additional storage is illustrated in FIG.","7 by removable storage 708 and non-removable storage 710.Computer storage media includes volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data.","Computer readable medium 704, removable storage 708 and nonremovable storage 710 are all examples of computer storage media.","Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can be accessed by computing system environment 700.Any such computer storage media may be part of computing system environment 700.Computing system environment 700 may also contain communications connection(s) 712 that allow it to communicate with other devices.","Communications connection(s) 712 is an example of communication media.","Communication media typically embodies computer readable instructions, data structures, program modules or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media.","The term computer readable media as used herein includes both storage media and communication media.","Communications connection(s) 712 may allow computing system environment 700 to communication over various networks types including, but not limited to, fibre channel, small computer system interface (SCSI), Bluetooth, Ethernet, Wi-fi, Infrared Data Association (IrDA), Local area networks (LAN), Wireless Local area networks (WLAN), wide area networks (WAN) such as the internet, serial, and universal serial bus (USB).","It is appreciated the various network types that communication connection(s) 712 connect to may run a plurality of network protocols including, but not limited to, transmission control protocol (TCP), internet protocol (IP), real-time transport protocol (RTP), real-time transport control protocol (RTCP), file transfer protocol (FTP), and hypertext transfer protocol (HTTP).","Computing system environment 700 may also have input device(s) 714 such as a keyboard, mouse, pen, voice input device, touch input device, remote control, etc.","Output device(s) 716 such as a display, speakers, etc.","may also be included.","All these devices are well known in the art and are not discussed at length.","In one embodiment, computer readable storage medium 704 includes bridging module 706.Bridging module 706 includes communication intercept module 720, attribute mapping module 730, protocol state mapping module 740, forwarding module 750, mapping registry access module 760, and protocol state translation table access module 770.Run-time communication intercept module 720 is operable to intercept communications between a first component and a second component where the first component is operable to communicate based on a first protocol and the second component is operable to communicate based on a second protocol.","Run-time communication intercept module 720 is further operable to intercept communications between the first component and the second component at run time.","In one exemplary embodiment, run-time communication intercept module 720 is operable to intercept communication between a first component and second component which are part of a system level modeling simulation, such as a SYSTEMC simulation.","In one embodiment, run-time communication intercept module 720 also intercepts a return communication from a component (e.g., a return payload or communication from the second component).","Attribute mapping module 730 is operable to map a first attribute of a payload of the first protocol to a second attribute of the second protocol, as described herein.","On a return path, attribute mapping module 730 is further operable to map a third attribute of the return communication (e.g., return payload) to a fourth attribute of the first protocol, as described herein.","A protocol state mapping module 740 is operable to map a first state of the first protocol to a second protocol state of the second protocol.","In one embodiment, protocol state mapping module 740 includes protocol state determination module 742 which is operable to determine a protocol state for a destination component.","Protocol state mapping module 740 further includes next protocol state determination module 744 which is operable to determine a next protocol state of a component.","Run-time intercept module 720, attribute mapping module 730, and protocol state mapping module 740 may together include the functionality of the run-time bridging logic 310.In one exemplary embodiment, protocol state mapping module 740 is operable to inject a next protocol state of the second protocol if the first protocol state of the first protocol does not correspond to the second protocol state of the second protocol.","Protocol state mapping module 740 is further operable to map a third protocol state of a return communication to a fourth protocol state of the first protocol, as described herein.","Forwarding module 750 is operable to forward (i.e.","send) payloads, values of mapped attributes, and values of mapped states to component.","Mapping registry access module 760 is operable to provide access to attribute callback table 340 of the mapping registry 450(e.g., for use by attribute mapping module 730 and protocol state mapping module 740).","Protocol state translation table access module 770 is operable to provide access to a protocol state translation table, as described herein (e.g., for use by protocol state mapping module 740).","The foregoing descriptions of specific embodiments of the present disclosure have been presented for purposes of illustration and description.","They are not intended to be exhaustive or to limit the disclosure to the precise forms disclosed, and many modifications and variations are possible in light of the above teaching.","The embodiments were chosen and described in order to best explain the principles of the disclosure and its practical application, to thereby enable others skilled in the art to best utilize the disclosure and various embodiments with various modifications as are suited to the particular use contemplated.","It is intended that the scope of the disclosure be defined by the claims appended hereto and their equivalents."]],"string":"[\n [\n \"Dynamic Bridging of Interface Protocols\",\n \"Systems and methods for protocol bridging for a system level modeling simulation (SLMS), such as a SYSTEMC simulation where the components communicate using a TLM2.0 application programming interface (API).\",\n \"The method includes accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.\",\n \"Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.\",\n \"The run-time bridging logic is inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.\"\n ],\n [\n \"1.A method for a system level modeling simulation (SLMS) using a mapping registry that includes information related to mapping of attributes between different communication protocols of a plurality of communication protocols, the method comprising: generating, at initialization of the SLMS and using a portion of the information from the mapping registry, run-time bridging logic for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and inserting, at the initialization of the SLMS, the run-time bridging logic between a first representation of a first hardware block that uses the first communication protocol and a second representation of a second hardware block that uses the second communication protocol, the run-time bridging logic configured to bridge the first communication protocol of the first representation of the first hardware block and the second communication protocol of the second representation of the second hardware block.\",\n \"2.The method of claim 1, wherein the portion of the information from the mapping registry includes an attribute mapping callback for translating a protocol specific attribute specific to a communication protocol of the plurality of communication protocols from the communication protocol to another communication protocol of the plurality of communication protocols.\",\n \"3.The method of claim 1, wherein generating the run-time bridging logic further comprises: identifying in the mapping registry the portion of the information for translating communications between the first communication protocol and the second communication protocol; and including the identified portion of the information into the run-time bridging logic.\",\n \"4.The method of claim 1, wherein generating the run-time bridging logic further comprises: identifying in the mapping registry a portion of other information for mapping of states between the different communications protocols; and including the identified portion of the other information into the run-time bridging logic.\",\n \"5.The method of claim 4, further comprising: mapping, with the run-time bridging logic, a first protocol state of the first communication protocol to a second protocol state of the second communication protocol using the portion of the other information.\",\n \"6.The method of claim 1, further comprising: receiving a request from the second representation of the second hardware block for a protocol specific attribute that is specific to the second communication protocol; and invoking, with the run-time bridging logic and without accessing the mapping registry during the SLMS, an attribute mapping callback from the portion of the information that includes logic to map attribute information in a payload to the protocol specific attribute that is specific to the second communication protocol, the payload being formatted for the first communication protocol and sent from the first representation of the first hardware block to the second representation of the second hardware block.\",\n \"7.The method of claim 6, further comprising: sending the protocol specific attribute to the second representation of the second hardware block.\",\n \"8.A method for protocol bridging for a system level modeling simulation (SLMS), the method comprising: creating a mapping registry prior to initialization of the SLMS by including in the mapping registry information related to mapping of attributes between different communication protocols of a plurality of communication protocols.\",\n \"9.The method of claim 8, further comprising: identifying in the mapping registry a portion of the information for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and including the identified portion of the information into run-time bridging logic for translating communications between the first communication protocol and the second communication protocol.\",\n \"10.The method of claim 8, further comprising: creating, within the mapping registry prior to the initialization of the SLMS, a state translation table that includes mappings of states between the different communication protocols.\",\n \"11.The method of claim 8, further comprising: including, in the mapping registry prior to the initialization of the SLMS, other information for mapping of states between the different communication protocols.\",\n \"12.The method of claim 11, further comprising: generating, at the initialization of the SLMS and using a portion of the information from the mapping registry, run-time bridging logic for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and inserting, at the initialization of the SLMS, the run-time bridging logic between a first representation of a first hardware block that uses the first communication protocol and a second representation of a second hardware block that uses the second communication protocol, the run-time bridging logic configured to bridge the first communication protocol of the first representation of the first hardware block and the second communication protocol of the second representation of the second hardware block.\",\n \"13.The method of claim 12, further comprising: accessing, during the SLMS, at least one communication payload formatted for the first communication protocol sent from the first representation of the first hardware block to the second representation of the second hardware block; and translating, by the run-time bridging logic during the SLMS, the at least one communication payload from the first communication protocol to the second communication protocol using the portion of the information.\",\n \"14.The method of claim 13, further comprising: receiving a request from the second representation of the second hardware block for a protocol specific attribute that is specific to the second communication protocol; and invoking, with the run-time bridging logic and without accessing the mapping registry during the SLMS, an attribute mapping callback from the portion of the information that includes logic to map attribute information in the at least one communication payload to the protocol specific attribute that is specific to the second communication protocol.\",\n \"15.The method of claim 13, wherein the at least one communication payload includes a first protocol state of the first communication protocol, and the method further comprising: mapping, with the run-time bridging logic, the first protocol state of the first communication protocol to a second protocol state of the second communication protocol using the portion of the other information.\",\n \"16.A non-transitory computer readable medium storing processor executable instructions for a system level modeling simulation (SLMS) using a mapping registry that includes information related to mapping of attributes between different communication protocols of a plurality of communication protocols, the instructions comprising instructions for: generating, at initialization of the SLMS and using a portion of the information from the mapping registry, run-time bridging logic for translating communications between a first communication protocol and a second communication protocol of the plurality of communication protocols; and inserting, at the initialization of the SLMS, the run-time bridging logic between a first representation of a first hardware block that uses the first communication protocol and a second representation of a second hardware block that uses the second communication protocol, the run-time bridging logic configured to bridge the first communication protocol of the first representation of the first hardware block and the second communication protocol of the second representation of the second hardware block.\",\n \"17.The computer readable medium of claim 16, wherein the portion of the information from the mapping registry includes an attribute mapping callback for translating a protocol specific attribute specific to a communication protocol of the plurality of communication protocols from the communication protocol to another communication protocol of the plurality of communication protocols.\",\n \"18.The computer readable medium of claim 16, the instructions further comprising instructions for: identifying in the mapping registry the portion of the information for translating communications between the first communication protocol and the second communication protocol; and including the identified portion of the information into the run-time bridging logic.\",\n \"19.The computer readable medium of claim 16, the instructions further comprising instructions for: identifying in the mapping registry a portion of other information for mapping of states between the different communications protocols; and including the identified portion of the other information into the run-time bridging logic.\",\n \"20.The computer readable medium of claim 16, the instructions further comprising instructions for: receiving a request from the second representation of the second hardware block for a protocol specific attribute that is specific to the second communication protocol; and invoking, with the run-time bridging logic and without accessing the mapping registry during the SLMS, an attribute mapping callback from the portion of the information that includes logic to map attribute information in a payload to the protocol specific attribute that is specific to the second communication protocol, the payload being formatted for the first communication protocol and sent from the first representation of the first hardware block to the second representation of the second hardware block.\"\n ],\n [\n \"<SOH> BACKGROUND <EOH>As computer systems have advanced, processing power and speed have increased substantially.\",\n \"At the same time, computer system complexity and the number of components included in a computer system have increased significantly.\",\n \"System design has correspondingly increased in complexity as more and more increasingly complex components are used in a given computer system.\",\n \"In order to accelerate the development process, computer systems and the corresponding components are simulated.\",\n \"A computer system may have several buses that allow the various components of the computer system to communicate.\",\n \"Unfortunately, many component simulations have been designed around different protocols and are not able to natively communicate with each other.\",\n \"Conventional solutions have involved creation of dedicated conversion components to handle conversion of communications between the numerous protocols of the components.\",\n \"These conversion components need to be created for each protocol pair resulting in complex conversions and a large validation space to ensure protocol compliance at both ends.\",\n \"For example, for n communication protocols a total of 2*(n*(n−1) conversion components need to be developed and verified.\",\n \"The use of a large number of conversion components often negatively impacts the efficiency of the simulation.\",\n \"Often such components are custom and hard coded involving significant development time and reducing flexibility thereby necessitating significant reworking for interface changes.\",\n \"Thus, a need exists for a solution to allow conversion of communication protocols without dedicated fixed logic conversion components.\"\n ],\n [\n \"<SOH> SUMMARY <EOH>Embodiments of the present disclosure overcome the need for creating dedicated logic and insertion of the dedicated logic in a design for bridging different communication protocols for on and off-chip communications components.\",\n \"An efficient mechanism for bridging of protocols or interface protocols, semantics, and application program interfaces (APIs) within system level modeling simulations is thus provided.\",\n \"Embodiments of the present disclosure are operable to model an interconnect network of a simulated computer system.\",\n \"In one embodiment disclosed is a method of protocol bridging for a system level modeling simulation (SLMS).\",\n \"The method comprises accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.\",\n \"Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.\",\n \"The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.\",\n \"In one embodiment, the SLMS is a SYSTEMC simulation where the components communicate using a Transaction Level Modeling 2.0 (TLM2.0) compliant API.\",\n \"In one embodiment, disclosed is a non-transitory computer readable medium storing processor executable instructions for protocol bridging for a system level modeling simulation (SLMS).\",\n \"The instructions comprise instructions for accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.\",\n \"Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.\",\n \"The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED U.S.\",\n \"APPLICATIONS This application claims benefit of and priority to U.S. provisional patent application 61/658,322, entitled “DYNAMIC BRIDGING OF IEEE 1666 TLM 2.0 BASED INTERFACE PROTOCOLS” and filed on Jun.\",\n \"11, 2012, the contents of which are incorporated by reference herein in its entirety.\",\n \"This application also claims benefit of and priority to U.S. provisional patent application 61/789,688, entitled “SYSTEM AND METHOD FOR DYNAMIC BRIDGING OF INTERFACE PROTOCOLS” and filed on Mar.\",\n \"15, 2013, the contents of which are incorporated by reference herein in its entirety FIELD OF THE DISCLOSURE Embodiments of the present disclosure are generally related to simulated systems.\",\n \"BACKGROUND As computer systems have advanced, processing power and speed have increased substantially.\",\n \"At the same time, computer system complexity and the number of components included in a computer system have increased significantly.\",\n \"System design has correspondingly increased in complexity as more and more increasingly complex components are used in a given computer system.\",\n \"In order to accelerate the development process, computer systems and the corresponding components are simulated.\",\n \"A computer system may have several buses that allow the various components of the computer system to communicate.\",\n \"Unfortunately, many component simulations have been designed around different protocols and are not able to natively communicate with each other.\",\n \"Conventional solutions have involved creation of dedicated conversion components to handle conversion of communications between the numerous protocols of the components.\",\n \"These conversion components need to be created for each protocol pair resulting in complex conversions and a large validation space to ensure protocol compliance at both ends.\",\n \"For example, for n communication protocols a total of 2*(n*(n−1) conversion components need to be developed and verified.\",\n \"The use of a large number of conversion components often negatively impacts the efficiency of the simulation.\",\n \"Often such components are custom and hard coded involving significant development time and reducing flexibility thereby necessitating significant reworking for interface changes.\",\n \"Thus, a need exists for a solution to allow conversion of communication protocols without dedicated fixed logic conversion components.\",\n \"SUMMARY Embodiments of the present disclosure overcome the need for creating dedicated logic and insertion of the dedicated logic in a design for bridging different communication protocols for on and off-chip communications components.\",\n \"An efficient mechanism for bridging of protocols or interface protocols, semantics, and application program interfaces (APIs) within system level modeling simulations is thus provided.\",\n \"Embodiments of the present disclosure are operable to model an interconnect network of a simulated computer system.\",\n \"In one embodiment disclosed is a method of protocol bridging for a system level modeling simulation (SLMS).\",\n \"The method comprises accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.\",\n \"Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.\",\n \"The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.\",\n \"In one embodiment, the SLMS is a SYSTEMC simulation where the components communicate using a Transaction Level Modeling 2.0 (TLM2.0) compliant API.\",\n \"In one embodiment, disclosed is a non-transitory computer readable medium storing processor executable instructions for protocol bridging for a system level modeling simulation (SLMS).\",\n \"The instructions comprise instructions for accessing design configuration information describing a first component of the SLMS that uses a first communication protocol and a second component of the SLMS that uses a second communication protocol.\",\n \"Run-time bridging logic is inserted between the first component and the second component based on the design configuration information.\",\n \"The run-time bridging logic inserted at initialization of the SLMS and configured to bridge the first communication protocol of the first component and the second communication protocol of the second component.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the present disclosure are illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements.\",\n \"FIG.\",\n \"1 shows a computer system in accordance with one embodiment of the present disclosure.\",\n \"FIG.\",\n \"2 shows an exemplary simulated component coupling in a simulated computer system in accordance with one embodiment of the present disclosure.\",\n \"FIG.\",\n \"3 shows a block diagram of an exemplary component communication in accordance with one embodiment of the present disclosure.\",\n \"FIG.\",\n \"4 shows protocol specifications and registration of callbacks to create the mapping registry, in accordance with an embodiment of the present disclosure.\",\n \"FIG.\",\n \"5 is a flowchart of a process for run-time protocol translation, according to an embodiment.\",\n \"FIG.\",\n \"6A shows a flowchart of a process for protocol state mapping in accordance with one embodiment of the present disclosure.\",\n \"FIG.\",\n \"6B shows a flowchart of a process for attribute mapping in accordance with one embodiment of the present disclosure.\",\n \"FIG.\",\n \"7 shows a block diagram of exemplary computer system and corresponding modules, in accordance with one embodiment of the present disclosure.\",\n \"DETAILED DESCRIPTION Reference will now be made in detail to the preferred embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings.\",\n \"While the disclosure will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the disclosure to these embodiments.\",\n \"On the contrary, the disclosure is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the disclosure as defined by the appended claims.\",\n \"Furthermore, in the following detailed description of embodiments of the present disclosure, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure.\",\n \"However, it will be recognized by one of ordinary skill in the art that the present disclosure may be practiced without these specific details.\",\n \"In other instances, well-known methods, procedures, components, and circuits have not been described in detail as not to unnecessarily obscure aspects of the embodiments of the present disclosure.\",\n \"Notation and Nomenclature Some portions of the detailed descriptions, which follow, are presented in terms of procedures, steps, logic blocks, processing, and other symbolic representations of operations on data bits within a computer memory.\",\n \"These descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art.\",\n \"A procedure, computer executed step, logic block, process, etc., is here, and generally, conceived to be a self-consistent sequence of steps or instructions leading to a desired result.\",\n \"The steps are those requiring physical manipulations of physical quantities.\",\n \"Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated in a computer system.\",\n \"It has proven convenient at times, principally for reasons of common usage, to refer to these signals as bits, values, elements, symbols, characters, terms, numbers, or the like.\",\n \"It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities.\",\n \"Unless specifically stated otherwise as apparent from the following discussions, it is appreciated that throughout the present disclosure, discussions utilizing terms such as “ processing” or “accessing” or “ executing” or “ storing” or “rendering” or the like, refer to the action and processes of an integrated circuit (e.g., computing system 100 of FIG.\",\n \"1), or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices.\",\n \"Exemplary Computer System Environment FIG.\",\n \"1 shows an exemplary computer system 100 in accordance with one embodiment of the present disclosure.\",\n \"FIG.\",\n \"1 depicts an embodiment of a computer system operable to execute embodiments of the present disclosure and a computer system operable to be simulated in conjunction with embodiments of the present disclosure, as described herein.\",\n \"Computer system 100 depicts the components of a generic computer system in accordance with embodiments of the present disclosure providing the execution platform for certain hardware-based and software-based functionality.\",\n \"In general, computer system 100 comprises at least one CPU 101, a system memory 115, and at least one graphics processor unit (GPU) 110.The CPU 101 can be coupled to the system memory 115 via a bridge component/memory controller (not shown) or can be directly coupled to the system memory 115 via a memory controller (not shown) internal to the CPU 101.The GPU 110 may be coupled to a display 112.One or more additional GPUs can optionally be coupled to system 100 to further increase its computational power.\",\n \"The GPU(s) 110 is coupled to the CPU 101 and the system memory 115.The GPU 110 can be implemented as a discrete component, a discrete graphics card designed to couple to the computer system 100 via a connector (e.g., AGP slot, PCI-Express slot, etc.\",\n \"), a discrete integrated circuit die (e.g., mounted directly on a motherboard), or as an integrated GPU included within the integrated circuit die of a computer system chipset component (not shown).\",\n \"Additionally, a local graphics memory 114 can be included for the GPU 110 for high bandwidth graphics data storage.\",\n \"The CPU 101 and the GPU 110 can also be integrated into a single integrated circuit die and the CPU and GPU may share various resources, such as instruction logic, buffers, functional units and so on, or separate resources may be provided for graphics and general-purpose operations.\",\n \"The GPU may further be integrated into a core logic component.\",\n \"Accordingly, any or all the circuits and/or functionality described herein as being associated with the GPU 110 can also be implemented in, and performed by, a suitably equipped CPU 101.Additionally, while embodiments herein may make reference to a GPU, it should be noted that the described circuits and/or functionality can also be implemented and other types of processors (e.g., general purpose or other special-purpose coprocessors) or within a CPU.\",\n \"System 100 can be implemented as, for example, a desktop computer system or server computer system having a powerful general-purpose CPU 101 coupled to a dedicated graphics rendering GPU 110.In such an embodiment, components can be included that add peripheral buses, specialized audio/video components, 10 devices, and the like.\",\n \"Similarly, system 100 can be implemented as a handheld device (e.g., cellphone, smartphone, etc.\",\n \"), direct broadcast satellite (DBS)/terrestrial set-top box or a set-top video game console device such as, for example, the Xbox®, available from Microsoft Corporation of Redmond, Washington, or the PlayStation3®, available from Sony Computer Entertainment Corporation of Tokyo, Japan.\",\n \"System 100 can also be implemented as a “system on a chip (SoC)”, where the electronics (e.g., the components 101, 115, 110, 114, and the like) of a computing device are wholly contained within a single integrated circuit die.\",\n \"Examples include a hand-held instrument with a display, a car navigation system, a portable entertainment system, and the like.\",\n \"Exemplary Systems and Methods Embodiments of the present disclosure overcome the need for creating dedicated logic and insertion of the dedicated logic in a design for bridging different communication protocols for on and off-chip communications components.\",\n \"An efficient mechanism for bridging of protocols or interface protocols, semantics, and APIs within SYSTEMC simulations is thus provided.\",\n \"Embodiments of the present disclosure are operable to model an interconnect network of a simulated computer system.\",\n \"Embodiments of the present disclosure provide a framework in which bridging logic is dynamically inserted at various interface points based on a design configuration.\",\n \"Due to the run time nature, embodiments of the present disclosure allow for on-the-fly or dynamic re-configurability of the design.\",\n \"In one embodiment, the framework is based on SYSTEMC transaction level modeling (e.g., IEEE 1666 TLM2.0) semantics and operable with communicating entities using TLM2.0 semantics while adhering to detailed protocol specifications.\",\n \"Embodiments of the present disclosure thereby eliminate the need for creation and verification of dedicated logic blocks for bridging of various protocols.\",\n \"Embodiments of the present disclosure thus eliminate the need for inserting and wiring up additional components that perform logic conversion at design creation time.\",\n \"Embodiments of the present disclosure further significantly ease the design creation of a heterogeneous SoC and reduce model availability problems relating to various protocol bridging models.\",\n \"Dynamic generation of the dynamic bridging logic may include looking up mappings in a central registry for adding/morphing or deleting interface method calls and state transitions across two communicating entities mimicking the peer part of the protocol handling of the protocol.\",\n \"Embodiments of the present disclosure also perform mapping of attributes on demand when requested by a destination component to reduce simulation time.\",\n \"FIG.\",\n \"2 shows a component coupling in a simulated computer system 200 in accordance with one embodiment of the present disclosure.\",\n \"Exemplary simulated computer system 200 includes components 202-210 and interconnect component 220.In one embodiment, a component refers to the simulation representation of a real synthesizable hardware block that provides the specified logical functionality in a computer system.\",\n \"In one embodiment, the simulated computer system 200 can represent the computer system 100 from FIG.\",\n \"1.The simulation of the simulated computer system 200 can be carried out on a host system, which can also resemble the computer system 100 from FIG.\",\n \"1.Components 202-210 may be any of a variety of computer or system on a chip (SoC) components including, but not limited to, an Ethernet interface, a wireless network interface, an audio controller, a memory controller, a storage controller, a modem controller, a display controller, a graphics processing unit, a central processing unit, a coprocessor, a digital signal processor, an analog signal processor, a USB controller, a IEEE 1394 controller, available from Apple Corporation of Cupertino, Calif., a thunderbolt™ controller, available from Intel Corporation of Santa Clara, Calif., etc.\",\n \"Interconnection component 220 may be a simulated interconnect or bus of a simulated computer system.\",\n \"In one embodiment, an interconnect is a central component that acts as a communication backbone of a computer system which enables routing of information amongst different components in the system.\",\n \"In one embodiment, components are simulated with SYSTEMC.\",\n \"SYSTEMC is a system-level modeling language that is approved by the Institute of Electrical and Electronics Engineers (IEEE) Standards Association as IEEE 1666.SYSTEMC allows describing a system at different levels of abstraction.\",\n \"More specifically, SYSTEMC is a language built in standard C++ by extending the language with the use of class libraries.\",\n \"SYSTEMC addresses the need for a system design and verification language that spans hardware and software.\",\n \"The language is particularly suited for modeling a system's partitioning, for evaluating and verifying the assignment of blocks to either hardware or software implementations, and for architecting and measuring the interactions between and among functional blocks.\",\n \"Throughout the specification, SYSTEMC will be used as an example of a system-level modeling language, but the principles described herein are applicable to any system-level modeling language.\",\n \"The applications programming interface (API) (e.g., IEEE 1666 TLM2.0) for modeling with SYSTEMC at the transaction level has been standardized and is referred to as TLM2.0 (Transaction Level Modeling 2.0).\",\n \"TLM2.0 APIs of SYSTEMC provide a generic approach to defining communication protocols or the models for the actual protocols.\",\n \"The API can thus be used to setup a protocol for components to communicate.\",\n \"However models of components may come from different places, be designed for different protocols, or different abstractions of the same protocol in more or less detail.\",\n \"Components 202-210 may each be designed or configured for communication by communication protocols 1-5, respectively.\",\n \"Interconnect component 220 is configured to communicate by communication protocol 6.In one embodiment, a communication protocol establishes rules (e.g.\",\n \"as a state machine) for the information interchange semantics, the format, and context of the information exchanged between two components in order to achieve system level behavior.\",\n \"Examples of communication protocols include the Advanced High Performance Bus (AHB) and the Advanced Extensible Interface (AXI).\",\n \"Components communicate with each other during a simulation by invoking interface method calls of a TLM 2.0 send API (which can be part of the components) and using the API to transmit a communication payload that is formatted according to an appropriate communication protocol.\",\n \"In one embodiment, a communication payload includes payload attributes and protocol state attributes.\",\n \"Payload attributes are elements carrying information in the payload.\",\n \"There are generally two types of payload attributes: generic attributes and protocol specific attributes.\",\n \"Generic attributes are protocol agnostic and used by many protocols.\",\n \"Examples of generic attributes are data and address attributes.\",\n \"Protocol specific attributes are specific to a particular protocol.\",\n \"Examples of protocol specific attributes are a burstSize attribute specifying the size of each data beat or a burstLen attribute specifying the number of data beats in a given transaction.\",\n \"It is noted that often a protocol specific attribute for one protocol may correspond to a protocol specific attribute in a different protocol and should be interpreted correctly for correct functionality.\",\n \"Protocol state attributes indicate different protocol phases that are needed in order to complete a transaction.\",\n \"Protocol communications are typically performed in different logical phases.\",\n \"Examples of protocol phases include an address phase, a data exchange phase, and a completion phase.\",\n \"Different protocols may use different protocol phases.\",\n \"In other words, different protocols may have different required states and transactions according to protocol semantics.\",\n \"In one embodiment protocol states attributes may be considered a type of protocol specific state attribute.\",\n \"In one embodiment, a formal specification of a protocol definition may comprise: 1) specification of any protocol specific payload attributes (e.g., if needed) and 2) specification of a protocol state attribute.\",\n \"The specification of the protocol state attribute comprises possible state values and allowed state transitions.\",\n \"Embodiments of the present disclosure facilitate communication between two components (e.g.\",\n \"component 202 and interconnect component 220, or any other components) operating with different protocols.\",\n \"The components may have different semantics and protocols.\",\n \"Embodiments of the present disclosure are further operable to modify communications between two components operating with different communication protocols.\",\n \"In other words, each component may have been originally designed with different protocols or semantics and the different communication protocols need to be bridged to allow communication between the components.\",\n \"Embodiments of the present disclosure are operable for dynamic generation of run-time bridging logic based on formal protocol specification and run time translation.\",\n \"Embodiments further provide run-time interception and translation of communication calls and mapping between payloads and protocol states of different protocols.\",\n \"Run time interception may refer to the capture of information when the system (e.g., simulated computer system) is working such that the captured information can be inspected and if needed transformed before reaching the destination.\",\n \"Embodiments of the present disclosure are further operable to support bridging or translation of communications where a component changes the protocol being used during run time.\",\n \"Processes and components shown in FIG.\",\n \"3-7 may be used to translate communications between different protocols, as described herein.\",\n \"FIG.\",\n \"3 shows a block diagram of component communication in accordance with one embodiment of the present disclosure.\",\n \"Diagram 300 includes component 202 and interconnect component 220, a run-time bridging (RTB) logic 310 inserted between component 202 and interconnect component 220, a mapping registry 450 accessed by the RTB logic 310, and attribute mapping callbacks 352.FIG.\",\n \"3 depicts exemplary conceptual communication of two simulated components and interception of communications between the simulated components.\",\n \"In other embodiments, the RTB logic 310 may be inserted between any of the components shown in FIG.\",\n \"2.Mapping registry 450 can be a database that stores information about the attributes of the various protocols and information about mapping payloads from one protocol (e.g., protocol 1) to a different protocol (e.g., protocol 6).\",\n \"It may also include logic to determine what attribute mapping callbacks 352 should be invoked based on attributes requested at run-time.\",\n \"As shown, mapping registry 450 includes an attribute-callback mapping table 340 and a protocol state translation table 342.Attribute-callback mapping table 340 includes a list of protocol specific attributes and references to attribute mapping callbacks 352 that are registered for those attributes.\",\n \"An attribute mapping callback 352 is logic that maps attribute information from a communication payload into a protocol specific attribute for a destination protocol (e.g., protocol 6).\",\n \"Each attribute mapping callback 352 can be used for mapping into a different protocol specific attribute.\",\n \"For example, callback 352a can be used for mapping into a protocol specific attribute for protocol 1, callback 352b can be used for mapping into a protocol specific attribute for protocol 2, etc.\",\n \"An attribute mapping callback 352 can expect a specific set of inputs and returns a specific set of outputs in a specified format.\",\n \"For example, attribute mapping callback 352 can receive all the payload attributes of a communication payload and process those attributes to return a protocol specific attribute for a destination protocol (e.g., protocol 6).\",\n \"In one embodiment, each attribute mapping callback 352 performs a formal one to one attribute mapping of attributes from one protocol to attributes for another protocol, such as value mappings.\",\n \"The mapping is independent of the source protocol, meaning that a single attribute mapping callback 352 can be used to extract a protocol specific attribute regardless of the source protocol.\",\n \"For example, a single attribute mapping callback 352c can be used to extract a protocol specific attribute for protocol 6 from a payload regardless of whether the payload is formatted for protocol 1, protocol 2, protocol 3, etc.\",\n \"In one embodiment, the attribute mapping callbacks 352 may be stateless and do not need information about prior communications to perform attribute translation.\",\n \"In one embodiment, the attribute mapping callbacks may be invoked by the RTB logic 310 on an as needed basis.\",\n \"State translation table 342 includes a mapping of states between many different protocols in the form of a rule table.\",\n \"For example, the state translation table 342 can include a mapping of states between protocol 1 and protocol 6, between protocol 1 and protocol 2, etc.\",\n \"In one embodiment, each transformation in the state translation table 342 may be specified as a combination of a particular state value for the source and the destination protocol and a group of associated payload attribute(s).\",\n \"State mapping can be done using a combination of payload attributes and state attributes.\",\n \"This allows specification of a unique mapping to destination protocol state transitions.\",\n \"For example, a mapping of states from the TLM2.0 Generic protocol to Advanced eXtensible Interface (AXI) for a write transaction may be specified as: PAYLOAD ATTRIBUTES={CMD=WRITE, PHASE=BEGIN_REQ} AXI_STATES={AWVALID, AWREADY, WVALID, WREADY, WVALID_LAST, WREADY_LAST} This example shows that the attributes in a TLM 2.0 generic protocol, used as the source protocol, are CMD having a value WRITE and PHASE having a value of BEGIN_REQ.\",\n \"When the payload attribute CMD has the value of WRITE and the payload attribute of PHASE has the value of BEGIN_REQ, the resulting AXI state values that are mapped to are AWVALID, AWREADY, WVALID, WREADY, WVALID_LAST, WREADY_LAST.\",\n \"So one set of input state values maps to multiple output state values.\",\n \"In this example, AWVALID will be sent to the destination component, and destination will respond with AWREADY.\",\n \"WVALID will be sent to the destination component, and the destination will responds with WREADY.\",\n \"WVALID_LAST will be sent to the destination component, and the destination will respond with WREADY_LAST.\",\n \"WVALID will be sent multiple times depending on a length attribute in the payload (not shown).\",\n \"Payload attributes & state attributes may allow for merging and splitting of states across protocols that have differing capabilities.\",\n \"For example, bridging a protocol having shared read and write paths to a protocol having dedicated read and write paths may necessitate state splitting.\",\n \"As an example, mapping between TLM2.0 generic protocol which has a single request and response path and AXI which has dedicated request and response paths for reads and writes, would need splitting of an incoming generic protocol request to either READ_REQUESTS or WRITE_REQUESTS on the AXI side.\",\n \"In one embodiment, attribute-callback table 340 and state translation table 342 are populated at the time of protocol specification prior to simulation initialization or run time.\",\n \"Additional protocol mappings can be defined dynamically at anytime during run time and the additional protocol mappings are pluggable into the simulation framework of embodiments of the present disclosure.\",\n \"For example, the state translation table 342 may be centrally available to the simulation framework at run time for dynamic insertion of conversion semantics on a communication interface.\",\n \"The state translation tables 342 may be provided to the simulation framework in a plug and play manner such that additional translations can be added or plugged in at any time (e.g., dynamically during runtime).\",\n \"Component 202 is designed to communicate based on protocol 1 and component 220 is designed to communicate based on protocol 6.For purposes of explanation, component 202 will be referred to as a source component and interconnect component 220 will be referred to as a destination component.\",\n \"The protocol used by the source component 202 may be referred to as a source protocol and the protocol used by the destination component 220 may be referred to as a destination protocol.\",\n \"However, as communications are inherently bi-directional, either component 202 and component 220 may be a source or a destination of a communication payload depending on which component is generating the communication payload.\",\n \"At initialization of a SYSTEMC simulation, run time bridging block 310 is inserted between the source component 202 and destination component 220 bridge communications between the source protocol and the destination protocol.\",\n \"Run time bridging logic 310 can intercept communication payloads transmitted between the source component 202 and the destination component 220 and translate the communication payloads for the destination protocol.\",\n \"In one embodiment, RTB logic 310 is inserted between two communicating entities by modifying the implementation of the TLM 2.0 API in both components 202 and 220 such that the RTB logic 310 can intercept payloads that are transmitted between components 202 and 220.RTB logic 310 is dynamically generated using the information in the attribute-callback table and the state translation table 342 that is appropriate for translating communications between the source/destination protocols.\",\n \"The RTB logic 310 is dynamically generated at initialization of a SYSTEMC simulation.\",\n \"The RTB bridging logic is generated with all the necessary logic needed to do state translation between the source/destination protocols and all the necessary logic needed to locate callbacks 352 for attribute translation between the source/destination protocols.\",\n \"Once generated, the RTB logic 310 no longer needs to access the mapping registry 450 during run-time to perform protocol translations.\",\n \"In one embodiment, generating the run-time bridging logic can include identifying specific portions of the state translation table 342 and attribute-callback table 340 that are appropriate for translation between the source/destination protocols and then using these portions of the tables to create a decision tree in the run time bridging logic 310.In one embodiment, after intercepting a payload from the source component 202 that is formatted for the source protocol, the RTB logic 310 maps the state of the source protocol into a state of the destination protocol, modifies the state in the payload with the state of the destination protocol, and forwards the modified payload on to the destination component 220.However, RTB logic 310 does not provide mapped attributes to the destination component 220 until the destination component 220 requests it.\",\n \"In one embodiment, the destination component 220 will request an attribute from the payload.\",\n \"A payload in SYSTEMC can be stored as an object from which information can be requested from.\",\n \"Making a request to the payload implicitly invokes the RTB logic 310 and causes the RTB logic 310 to process the request.\",\n \"For example, when destination component 302 requests a certain attribute from the payload which is not present but another corresponding attribute which has a mapping defined to the requested attribute is present then RTB logic 310 performs mapping of the attribute and the data is returned to the destination component 310 as if it were present in the payload natively.\",\n \"Performing translation on-demand reduces the amount of time required to process each payload.\",\n \"In other embodiments, the RTB logic 310 may provide translated attributes to the destination component 220 with every intercepted payload.\",\n \"Once the mapped states and attributes are provided to the destination component 220, the destination component 220 is free to morph/update the attribute as per the protocol semantics.\",\n \"On completion of the processing the destination component 220 updates the payload and returns the payload to the source component 202.On the reverse intercept path, the RTB logic 310 re-translates the state and attributes for the source protocol of the source component 202.FIG.\",\n \"4 shows protocol specifications and registration of callbacks to create the mapping registry 450, in accordance with an embodiment of the present disclosure.\",\n \"The registration of callbacks typically occurs prior to initialization of a simulation.\",\n \"In other embodiments, the registration can occur during simulation run-time.\",\n \"As shown, there are four different protocol specifications 402, 410, 420 and 430 for four different protocols.\",\n \"As previously described, protocols can communicate information with generic attributes and protocol specific attributes.\",\n \"Generic attributes are attributes common to all protocols and are used in any computer system (e.g., address and data).\",\n \"Protocol specific attributes may be attributes specific to a protocol.\",\n \"In more detail, protocol specification 402 for protocol 1 includes generic attributes 404 (address) and 406 (data) and protocol specific attribute 408 (attr1).\",\n \"Protocol specification 410 for protocol 2 includes generic attribute 404 (address) and 406 (data) and protocol specific attributes 416 (attr2-1) and 418 (attr2-2) .\",\n \"Protocol 420 includes generic attributes 404 (address) and 406 (data) and protocol specific attribute 428 (attr3).\",\n \"Protocol 430 includes generic attributes 404 (address) and 406 (data) and protocol specific attribute 438 (attr4).\",\n \"Each protocol specific attribute and its associated mapping callback 352 is registered with the mapping registry 450 to create the attribute-callback table 340.This registration typically occurs prior to initialization of a simulation.\",\n \"The mapping callbacks 352 are written by a designer that is familiar with what type of logic is needed in order to obtain a protocol specific attribute from a payload.\",\n \"A different mapping callback 352 can be registered for each protocol specific attribute.\",\n \"Registration of the mapping callbacks 352 enables the appropriate mapping callback 352 to be identified at run-time when attribute translation is needed.\",\n \"With reference to FIG.\",\n \"5, 6A and 6B, flowcharts 500, 600 and 650 illustrate example functions used by various embodiments of the present disclosure.\",\n \"Although specific function blocks (“blocks”) are disclosed in flowcharts 500, 600 and 650, such steps are examples.\",\n \"That is, embodiments are well suited to performing various other blocks or variations of the blocks recited in flowcharts 500, 600 and 650.It is appreciated that the blocks in flowcharts 500, 600 and 650 may be performed in an order different than presented, and that not all of the blocks in flowcharts 500, 600 and 650 may be performed.\",\n \"FIG.\",\n \"5 is a flowchart 500 of a process for run-time protocol translation, during a simulation, according to an embodiment.\",\n \"The run-time protocol translation is divided into two stages: simulation initialization and simulation run-time.\",\n \"In step 552, during initialization of a SYSTEMC simulation, design configuration information describing the configuration of a target system (e.g., computer system, system on chip, etc) to be simulated is accessed.\",\n \"An example of a system is the one shown in FIG.\",\n \"2.The system includes several components that communicate with different protocols and has been prepared by a system designer prior to the simulation.\",\n \"Design configuration information may include a connectivity map describing how components are connected to each other.\",\n \"Design configuration information may also include information describing the specific protocols used by those components.\",\n \"In step 554, desired protocol specifications are identified based on the protocols specified in the design configuration information.\",\n \"For example, knowing that one component uses AHB and another component uses AXI, an AXI protocol specification and an AHB protocol specification can be identified from a database of protocol specifications.\",\n \"For example, the protocol specifications may be the protocol specifications shown in FIG.\",\n \"4.In step 556, RTB logic 310 is dynamically generated based on the desired protocol specifications.\",\n \"In one embodiment, generating RTB logic can involve the following steps.\",\n \"Based on the source and destination protocol specifications, portions of the state translation table 342 that can be used to translate between the source and destination protocol states are identified.\",\n \"The state translation table 342 can include information useful for translating between many different destination protocols and many different source protocols.\",\n \"Only a small portion of the state translation table 342 may be useful in configuring the RTB logic for operating with a specific destination protocol and a specific source protocol.\",\n \"These portions of the state translation table 342 are identified and then used to generate state decision logic of the RTB logic 310.Additionally, portions of the attribute-callback table 340 that reference callbacks 352 that are useful for translation into the attributes of the source and destination protocols are identified and added to the RTB logic 310.In one embodiment, the final RTB 310 can be viewed as a local translation table for state mapping and references to the attribute mapping callbacks 352 that can be used to invoke the attribute mapping callbacks 352 on demand.\",\n \"In step 558, RTB logic 310 is inserted into the system for components specified by the design configuration information that use different protocols.\",\n \"RTB logic 310 only needs to be inserted between two components when the components communicate using different protocols.\",\n \"It is not needed when two components communicate with the same protocol.\",\n \"In one embodiment, inserting the RTB logic 310 involves overriding the interface implementation of a TLM 2.0 API in the components, such as by modifying interface method calls of the TLM 2.0 API.\",\n \"In step 560, during simulation run-time, the RTB logic 310 intercepts communication payloads generated by a source component that are formatted for a source protocol.\",\n \"The RTB logic 310 also accesses the communication payloads to perform translation of communication payloads into a destination protocol.\",\n \"Because the RTB logic is configured to behave in accordance with the information from the mapping registry 450, it may not need to access the mapping registry 450 anymore during simulation run-time.\",\n \"The translation can be performed on demand in response to a request from the destination component 220.The run-time translation can include mapping of states from the source protocol to the destination protocol.\",\n \"The run-time translation can also include mapping of attributes from the source protocol to the destination protocol.\",\n \"The run-time translation step 560 is further described by reference to FIGS.\",\n \"5 and 6.FIG.\",\n \"6A shows a flowchart 600 of a process for protocol state mapping in accordance with one embodiment of the present disclosure.\",\n \"Flowchart 600 depicts a process for mapping of a protocol state of one protocol to another protocol state of another protocol and may be performed by the RTB logic 310.In one embodiment, state mapping may be coupled with attribute mapping (e.g., process 650) thereby allowing for seamless translation of any two protocols for the payload and the corresponding protocol state machines.\",\n \"At block 601 an intercepted communication payload is received at the RTB logic 310.The communication payload may generated by a source component 202 that is sent to a destination component 220 and intercepted by the RTB logic 310 at run time.\",\n \"The communication payload is formatted for the protocol of the source component 202.At block 602, a current protocol state for the destination protocol of the destination component 302 is accessed by the RTB logic 310.The protocol state for the destination protocol may be a protocol state queried from the destination component 302.At block 604, whether a mapped state is found is determined by the RTB logic 310.If there is no mapping from the protocol state of the payload (e.g.\",\n \"of the source component 202) to a protocol state for the destination component 220, block 614 is performed.\",\n \"If a mapped state is found, block 606 is performed.\",\n \"In some embodiments, the current destination state may be used during step 604 to determine whether the state for the source protocol can be mapped to a state for the destination protocol.\",\n \"At block 606, once a mapped state is found, the payload modified with the mapped state for the destination component, and the modified payload is forwarded to the destination component.\",\n \"In one embodiment, after the destination component 202 receives the modified payload with the mapped state, it then makes a request for an attribute as shown in FIG.\",\n \"6B.\",\n \"At block 614, when a mapped state is not found, the next protocol state for the source protocol is injected into the payload and the payload is returned back to the source component.\",\n \"The next protocol state is determined by the RTB logic 310.Notably, the payload is not forwarded to the destination when a mapped state is not found.\",\n \"This is because the destination component 220 is not able to use the payload if no mapped state can be found.\",\n \"Thus, instead of forwarding the payload to the destination component 220, the protocol state of the source component 202 is advanced to the next state.\",\n \"FIG.\",\n \"6B shows a flowchart 650 of a process for attribute mapping during simulation run-time in accordance with one embodiment of the present disclosure.\",\n \"Flowchart 650 depicts a process for mapping of attributes from a source protocol to a destination protocol and may be performed in logic such as the RTB logic 310 or the callbacks 352.In one embodiment, the steps in flowchart 650 of FIG.\",\n \"6B are performed after the steps of flowchart 600 of FIG.\",\n \"6A.\",\n \"At block 654, the RTB logic 310 receives a request from a destination component 220 to access an attribute.\",\n \"The attribute requested may be a request for a generic attribute or a protocol specific attribute that is specific to the destination protocol of the destination component 220.At block 656, the RTB logic 310 determines whether the requested attribute is present in the payload.\",\n \"In one embodiment, the semantics of the source protocol are determined from the payload.\",\n \"Whether an attribute is present may be based on whether a requested attribute is common to the source protocol of the source component and the destination protocol of the destination component.\",\n \"For example, if the attribute is a generic attribute it may be common to both protocols, whereas protocol specific attributes may not be common to both protocols.\",\n \"If an attribute is present in the payload then block 664 is performed.\",\n \"If an attribute is not present in the payload then block 658 is performed.\",\n \"At block 664, the RTB logic 310 accesses the attribute and returns the attribute to the destination component 220 if it is present in the payload.\",\n \"When a destination component 220 attempts to access a generic attribute and the attribute is present in the payload, the attribute is identified as common and the value of the attribute is returned to the destination component 220 that attempted to access it.\",\n \"For example, if the destination component 220 attempts to access a generic address attribute, the value of the address attribute is returned.\",\n \"At block 658, the RTB logic 310 invokes an attribute mapping callback for a requested attribute if the requested attribute is not present in the payload.\",\n \"Requested attributes are typically not present in the payload when they are protocol specific attributes.\",\n \"In one embodiment, if a destination component 220 attempts to access an attribute that is not present in the payload, an attribute mapping callback 352 that is associated with the protocol specific attribute is invoked to map an attribute from the payload into a protocol specific attribute for the destination protocol of the destination component 220.At block 660, the attribute mapping callback 352 maps the attribute in the payload from the source protocol of the source component 202 to the destination protocol of the destination component 220.The attribute mapping results in an attribute value for the requested attribute.\",\n \"It is noted that the attribute mappings may be performed in other ways and embodiments of the present disclosure are not limited to performing mapping using attribute mapping callbacks 352.At block 662, the RTB logic 310 sends the mapped attribute value to the destination component 220 that requested the attribute, thereby returning the requested attribute.\",\n \"The destination component 220 may then request another attribute or perform internal logic operations using the attribute and generate a return payload.\",\n \"The return payload is processed by the RTB logic 310 in the same manner as that shown in FIG.\",\n \"6A and 6B, except that attributes and states will now be mapped from the destination protocol to the source protocol.\",\n \"FIG.\",\n \"7 illustrates example components used by various embodiments of the present disclosure.\",\n \"Although specific components are disclosed in computing system environment 700, it should be appreciated that such components are examples.\",\n \"That is, embodiments of the present disclosure are well suited to having various other components or variations of the components recited in computing system environment 700.It is appreciated that the components in computing system environment 700 may operate with other components than those presented, and that not all of the components of system 700 may be required to achieve the goals of computing system environment 700.FIG.\",\n \"7 shows a block diagram of an exemplary computing system environment 700, in accordance with one embodiment of the present disclosure.\",\n \"With reference to FIG.\",\n \"7, an exemplary system module for implementing embodiments includes a general purpose computing system environment, such as computing system environment 700.Computing system environment 700 may include, but is not limited to, servers, desktop computers, laptops, tablet PCs, mobile devices, and smartphones.\",\n \"In one embodiment, computing system environment 700 is computer system 100.In its most basic configuration, computing system environment 700 typically includes at least one processing unit 702 and non-transitory computer readable storage medium 704.Depending on the exact configuration and type of computing system environment, computer readable storage medium 704 may be volatile (such as RAM), non-volatile (such as ROM, flash memory, etc.)\",\n \"or some combination of the two.\",\n \"Portions of computer readable storage medium 704 includes processor executable instructions that when executed facilitate communication bridging (e.g., processes 500, 600, 650).\",\n \"Additionally, computing system environment 700 may also have additional features/functionality.\",\n \"For example, computing system environment 700 may also include additional storage (removable and/or non-removable) including, but not limited to, magnetic or optical disks or tape.\",\n \"Such additional storage is illustrated in FIG.\",\n \"7 by removable storage 708 and non-removable storage 710.Computer storage media includes volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data.\",\n \"Computer readable medium 704, removable storage 708 and nonremovable storage 710 are all examples of computer storage media.\",\n \"Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can be accessed by computing system environment 700.Any such computer storage media may be part of computing system environment 700.Computing system environment 700 may also contain communications connection(s) 712 that allow it to communicate with other devices.\",\n \"Communications connection(s) 712 is an example of communication media.\",\n \"Communication media typically embodies computer readable instructions, data structures, program modules or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media.\",\n \"The term computer readable media as used herein includes both storage media and communication media.\",\n \"Communications connection(s) 712 may allow computing system environment 700 to communication over various networks types including, but not limited to, fibre channel, small computer system interface (SCSI), Bluetooth, Ethernet, Wi-fi, Infrared Data Association (IrDA), Local area networks (LAN), Wireless Local area networks (WLAN), wide area networks (WAN) such as the internet, serial, and universal serial bus (USB).\",\n \"It is appreciated the various network types that communication connection(s) 712 connect to may run a plurality of network protocols including, but not limited to, transmission control protocol (TCP), internet protocol (IP), real-time transport protocol (RTP), real-time transport control protocol (RTCP), file transfer protocol (FTP), and hypertext transfer protocol (HTTP).\",\n \"Computing system environment 700 may also have input device(s) 714 such as a keyboard, mouse, pen, voice input device, touch input device, remote control, etc.\",\n \"Output device(s) 716 such as a display, speakers, etc.\",\n \"may also be included.\",\n \"All these devices are well known in the art and are not discussed at length.\",\n \"In one embodiment, computer readable storage medium 704 includes bridging module 706.Bridging module 706 includes communication intercept module 720, attribute mapping module 730, protocol state mapping module 740, forwarding module 750, mapping registry access module 760, and protocol state translation table access module 770.Run-time communication intercept module 720 is operable to intercept communications between a first component and a second component where the first component is operable to communicate based on a first protocol and the second component is operable to communicate based on a second protocol.\",\n \"Run-time communication intercept module 720 is further operable to intercept communications between the first component and the second component at run time.\",\n \"In one exemplary embodiment, run-time communication intercept module 720 is operable to intercept communication between a first component and second component which are part of a system level modeling simulation, such as a SYSTEMC simulation.\",\n \"In one embodiment, run-time communication intercept module 720 also intercepts a return communication from a component (e.g., a return payload or communication from the second component).\",\n \"Attribute mapping module 730 is operable to map a first attribute of a payload of the first protocol to a second attribute of the second protocol, as described herein.\",\n \"On a return path, attribute mapping module 730 is further operable to map a third attribute of the return communication (e.g., return payload) to a fourth attribute of the first protocol, as described herein.\",\n \"A protocol state mapping module 740 is operable to map a first state of the first protocol to a second protocol state of the second protocol.\",\n \"In one embodiment, protocol state mapping module 740 includes protocol state determination module 742 which is operable to determine a protocol state for a destination component.\",\n \"Protocol state mapping module 740 further includes next protocol state determination module 744 which is operable to determine a next protocol state of a component.\",\n \"Run-time intercept module 720, attribute mapping module 730, and protocol state mapping module 740 may together include the functionality of the run-time bridging logic 310.In one exemplary embodiment, protocol state mapping module 740 is operable to inject a next protocol state of the second protocol if the first protocol state of the first protocol does not correspond to the second protocol state of the second protocol.\",\n \"Protocol state mapping module 740 is further operable to map a third protocol state of a return communication to a fourth protocol state of the first protocol, as described herein.\",\n \"Forwarding module 750 is operable to forward (i.e.\",\n \"send) payloads, values of mapped attributes, and values of mapped states to component.\",\n \"Mapping registry access module 760 is operable to provide access to attribute callback table 340 of the mapping registry 450(e.g., for use by attribute mapping module 730 and protocol state mapping module 740).\",\n \"Protocol state translation table access module 770 is operable to provide access to a protocol state translation table, as described herein (e.g., for use by protocol state mapping module 740).\",\n \"The foregoing descriptions of specific embodiments of the present disclosure have been presented for purposes of illustration and description.\",\n \"They are not intended to be exhaustive or to limit the disclosure to the precise forms disclosed, and many modifications and variations are possible in light of the above teaching.\",\n \"The embodiments were chosen and described in order to best explain the principles of the disclosure and its practical application, to thereby enable others skilled in the art to best utilize the disclosure and various embodiments with various modifications as are suited to the particular use contemplated.\",\n \"It is intended that the scope of the disclosure be defined by the claims appended hereto and their equivalents.\"\n 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[
"METHOD FOR MODULATING A BIOLOGICAL ACTIVITY OF A TARGET STRUCTURE BY ENERGY GENERATION IN-SITU WITHIN A MEDIUM",
"A system and method for light stimulation within a medium.",
"Products, compositions, systems, and methods for modifying a target structure which mediates or is associated with a biologic... | Patent_15874426 |
[
[
"Combination Of Dopamine Agonists Plus First Phase Insulin Secretagogues For The Treatment Of Metabolic Disorders",
"The present invention is directed to a method of treating a metabolic disorder or key elements of a metabolic disorder such method comprising the use of an agent(s) that increases central d... | Patent_15874430 |
[
[
"DE-DUPLICATED VIRTUAL MACHINE IMAGE TRANSFER",
"Technologies are generally described for a system and method effective to copy virtual machine images from a source to a destination memory.",
"A processor may copy a first block corresponding to a first virtual machine image from an interim memory to t... | Patent_15874433 |
[
[
"Endoscopic Surgical Devices and Other Surgical Devices and Methods of Making, Especially Using Polyarylamides, Polyetherimides, Polyether Ether Ketones, and Liquid Crystal Polymers",
"An endoscopic surgical device having a windowed blade case featuring an interior surface that is black or dark plastic, p... | Patent_15874442 |
[
[
"MULTI-LAYER CAST FILM",
"A multi-layer polymer film comprising a core layer and a sealing layer, said sealing layer comprises a propylene copolymer composition, said propylene copolymer composition has a comonomer content in the range of 3.0 to 8.0 wt.-%, the comonomers are C5 to C12 α-olefins, comprises... | Patent_15874443 |
[
[
"SECURITY APPARATUS",
"A security apparatus for a portable electronic device includes a locking head having a base and an engagement element extending from the base and adapted to be inserted into an aperture of the portable electronic device.",
"The engagement element includes a wedge-shaped engageme... | Patent_15874445 |
[
[
"MICRONUTRIENT COMPOSITIONS AND SYSTEMS AND METHODS OF USING SAME",
"An agricultural spray may be produced by admixing citric acid and glutamic acid with a metal salt and a pesticide or other agricultural chemical containing components capable of precipitating with the metal salt in the admixture.",
"... | Patent_15874447 |
[
[
"INFERENTIAL USER MATCHING SYSTEM",
"An inferential user matching system can determine a mutual interest between a first user and a second user based on inferred trends corresponding to a set of usage behaviors by a plurality of users utilizing the system.",
"Based on determining the mutual interest, ... | Patent_15874453 |
[
[
"HIGH CAPACITY LITHIUM RICH CATHODE MATERIAL AND METHOD OF PRODUCING THE SAME",
"A composite material for a battery electrode and a method of producing thereof have been disclosed.",
"In particular, the composite material is used as a cathode for lithium ion batteries.",
"The cathode material is a... | Patent_15874456 |
[
[
"CIRCUIT AND METHOD FOR BANDWIDTH MEASUREMENT",
"A circuit for measuring a bandwidth of an amplifier includes first and second capacitors, first through third switches, and a pulse generator.",
"First terminals of the capacitors are coupled to an amplifier input, and a second terminal of the second ca... | Patent_15874459 |
[
[
"PRE-POSITIONING PRE-STORED CONTENT IN A CONTENT DISTRIBUTION SYSTEM",
"A method for execution by one or more processing modules of one or more computing devices of a dispersed storage network (DSN), the method begins by selecting a plurality of network edge units for staging public pillar encoded data sl... | Patent_15874461 |
[
[
"POROUS MATERIAL AND DEVICES FOR PERFORMING SEPARATIONS, FILTRATIONS, AND CATALYSIS AND EK PUMPS, AND METHODS OF MAKING AND USING THE SAME",
"Embodiments of the present invention are directed to a porous monolith polymeric composition having utility in catalysis, chromatography, filtration, and electro-ki... | Patent_15874469 |
[
[
"MONOMERIC CXCL121 PEPTIDE AND USE THEREOF",
"The present invention provides a CXCL121 peptide engineered to resist peptide-induced dimerization by maintaining steric repulsion of the chemokine helix, pharmaceutical compositions thereof, and methods of using said dimer in the treatment of cancer, inflamma... | Patent_15874476 |
[
[
"MODULAR VALVE ASSEMBLY",
"A wet piping system modular valve assembly includes a single piece valve body with a check valve within the valve body.",
"The check valve is movable between a closed position and an open position according to a pressure differential across the check valve.",
"A drain va... | Patent_15874479 |
[
[
"HYDRAULIC DRIVE WITH RAPID STROKE AND LOAD STROKE",
"A hydraulic drive including at least one hydraulic cylinder that includes a piston chamber, an annulus, and a piston that separates the piston chamber from the annulus.",
"The hydraulic drive also includes a first hydraulic pump hydraulically conne... | Patent_15874482 |
[
[
"MODULAR ELECTRICAL WIRING DEVICE SYSTEM",
"The present invention is directed to a method including the steps of providing a frame member configured to be disposed over a device wall box, the frame member including at least one frame opening having a lip member configured to substantially extend into an i... | Patent_15874487 |
[
[
"Electronic Device Module Comprising an Ethylene Multi-Block Copolymer",
"An electronic device module comprises: A.",
"At least one electronic device, e.g., a solar cell, and B.",
"A polymeric material in intimate contact with at least one surface of the electronic device, the polymeric material c... | Patent_15874492 |
[
[
"SUBSTRATE SUPPORT ASSEMBLY HAVING A PLASMA RESISTANT PROTECTIVE LAYER",
"A substrate support assembly comprises a ceramic body and a thermally conductive base bonded to a lower surface of the ceramic body.",
"The substrate support assembly further comprises a protective layer covering an upper surfac... | Patent_15874495 |
[
[
"MAGNESIUM FLUORIDE SINTERED COMPACT, METHOD FOR MANUFACTURING MAGNESIUM FLUORIDE SINTERED COMPACT, NEUTRON MODERATOR, AND METHOD FOR MANUFACTURING NEUTRON MODERATOR",
"According to an aspect, a magnesium fluoride sintered compact includes a disc-shaped magnesium fluoride sintered compact having a through... | Patent_15874496 |
[
[
"PROGRAMMABLE GAME-BASED HAPTIC ENABLED GUN CONTROLLER",
"Various systems, game controllers, and methods for simulating various objects such as weapons are provided.",
"For example, a game controller may include a trigger, a processor within the body that receives a trigger signal when the trigger is ... | Patent_15874517 |
[
[
"SHOE FOR USE ON ANIMALS",
"A shoe for the foot (5) of an animal.",
"The shoe includes a sole (10) and an upper part (20) that are connected to each other, and where the upper part (20) has an opening with a tightening mechanism (70) to tighten the shoe against the foot (5).",
"The tightening mech... | Patent_15874518 |
[
[
"CRYSTALLIZED GLASS AND CRYSTALLIZED GLASS SUBSTRATE",
"Provided is a high-strength crystallized glass or substrate having a high visible light transmittance and a good color balance, which is suitable for use in protecting members of portable electronic devices, optical devices and the like.",
"Provi... | Patent_15874520 |
[
[
"CORTICOSTERIOD CONTAINING FOAM COMPOSITIONS",
"The present invention provides a method of manufacturing foamable, corticosteroid containing compositions as well as methods for treating various skin diseases."
],
[
"1.A foamable pharmaceutical composition comprising: a) a corticosteroid or a pharm... | Patent_15874521 |
[
[
"DETERMINING SOFT DATA FOR FRACTIONAL DIGIT MEMORY CELLS",
"Apparatuses and methods for determining soft data for fractional digit memory cells are provided.",
"One example apparatus can include a controller to determine states of memory cells of a group of memory cells operated as fractional digit me... | Patent_15874529 |
[
[
"Mounting Tool for a Brake Retaining Clip with a Securing Arrangement of a Disc Brake, Disc Brake, and Brake Pad Set",
"A mounting tool for mounting a brake retaining clip to and/or removing the brake retaining clip from a securing arrangement of a disc brake, wherein the securing arrangement has a securi... | Patent_15874530 |
[
[
"APPARATUS AND METHOD FOR DECODING OR ENCODING AN AUDIO SIGNAL USING ENERGY INFORMATION VALUES FOR A RECONSTRUCTION BAND",
"An apparatus for decoding an encoded audio signal having an encoded representation of a first set of first spectral portions and an encoded representation of parametric data indicati... | Patent_15874536 |
[
[
"Polypeptides Having Endoglucanase Activity and Polynucleotides Encoding Same",
"The present invention relates to isolated polypeptides having endoglucanase activity and isolated polynucleotides encoding the polypeptides.",
"The invention also relates to nucleic acid constructs, vectors, and host cell... | Patent_15874540 |
[
[
"COMPRESSED TABLET CONTAINING CANNABIDIOL, METHOD FOR ITS MANUFACTURE AND USE OF SUCH TABLET IN ORAL TREATMENT OF PSYCHOSIS OR ANXIETY DISORDERS",
"The present invention relates to compressed tablets for peroral delivery of the cannabinoid cannabidiol (CBD).",
"More particularly, the invention provide... | Patent_15874544 |
[
[
"BATTERY SYSTEM",
"A battery system includes a battery module having a plurality of assembled batteries.",
"Battery monitoring circuits are provided to correspond to each of the assembled batteries of the battery module.",
"A control circuit controls operation of the battery monitoring circuits.",... | Patent_15874548 |
[
[
"SECURE START SYSTEM FOR AN AUTONOMOUS VEHICLE",
"A secure start system for an autonomous vehicle (AV) can transmit credentials to an authentication system based on detecting startup of the autonomous vehicle.",
"When the credentials are authenticated the system can receive a tunnel key from the authe... | Patent_15874549 |
[
[
"IMPLICIT CODING OF REFERENCE LINE INDEX USED IN INTRA PREDICTION",
"A device for decoding video data determines that a current block of video data is coded using a linear model prediction mode; for the luma component of the current block, determines reconstructed luma samples; based on luma samples in a ... | Patent_15874565 |
[
[
"NOVEL PAENIBACILLUS STRAIN, ANTIFUNGAL COMPOUNDS, AND METHODS FOR THEIR USE",
"The present invention relates to a composition comprising a biologically pure culture of a fungicidal Paenibacillus sp.",
"strain comprising a variant fusaricidin synthetase lacking a functional adenylation domain in the t... | Patent_15874577 |
[
[
"FOAM FUSE FILLER AND CARTRIDGE FUSE",
"Fuses having a melamine-coated-steatite foam filler are described.",
"In particular, melamine-coated-steatite foam filler for use in a fuse comprising steatite coated in a melamine compound (e.g., plasticized melamine resin) and then heated to form crystalline f... | Patent_15874579 |
[
[
"Variable Frequency Drive Motor Control",
"Various embodiments include a variable frequency drive motor control apparatus.",
"The apparatus includes a main controller having a first interface.",
"A motor controller is coupled to and controls an electric motor, the motor controller further coupled ... | Patent_15874581 |
[
[
"Engine Harmonic Enhancement Control",
"In a general aspect, a system includes circuitry for providing an engine harmonic scaling module and a summer.",
"The engine harmonic scaling module is configured to receive a torque signal and a throttle signal, process the torque signal to generate a calibrate... | Patent_15874583 |
[
[
"MANHOLE COVER ASSEMBLY",
"An example manhole cover assembly includes a manhole cover and a latch assembly.",
"The manhole cover is supportable by a seat of a manhole frame.",
"The latch assembly includes a latch housing fixedly coupled to the manhole cover.",
"A latch plunger is slidably coup... | Patent_15874584 |
[
[
"Method of Providing Pirfenidone Therapy to a Patient",
"The invention relates to methods for decreasing adverse events associated with pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) therapy.",
"The invention discloses an optimized dose escalation scheme that results in the patient having increased t... | Patent_15874590 |
[
[
"SILICON ON INSULATOR DEVICE WITH PARTIALLY RECESSED GATE",
"Transistors having partially recessed gates are constructed on silicon-on-insulator (SOI) semiconductor wafers provided with a buried oxide layer (BOX), for example, FD-SOI and UTBB devices.",
"An epitaxially grown channel region relaxes con... | Patent_15874591 |
[
[
"USE OF TETRAHYDROPYRIDINES IN THE TREATMENT OF SODIUM CHANNEL RELATED DISEASE AND DISORDERS",
"The present invention provides a method of treating one or more sodium channel related diseases or disorders in an individual, including related symptoms.",
"The method comprises administering to the indivi... | Patent_15874592 |
[
[
"REFLECTOR AND A LASER DIODE ASSEMBLY USING SAME",
"A laser diode assembly is disclosed, in which a transmissive reflector is used to redirect the laser beam upwards or to turn or rotate the laser beam.",
"The reflector has at least one Brewster transmissive surface and at least one total internal ref... | Patent_15874601 |
[
[
"METHOD FOR FABRICATING SEMICONDUCTOR PACKAGE AND SEMICONDUCTOR PACKAGE USING THE SAME",
"Provided are a method for fabricating a semiconductor package and a semiconductor package using the same, which can simplify a fabricating process of the semiconductor package by forming a lead frame on which a semic... | Patent_15874602 |
[
[
"NUTRITIONAL FORMULATIONS INCLUDING HUMAN MILK OLIGOSACCHARIDES AND ANTIOXIDANTS AND USES THEREOF",
"Disclosed are nutritional compositions including human milk oligosaccharides in combination with long chain polyunsaturated fatty acids and/or carotenoids that can be administered to preterm infants, term ... | Patent_15874604 |
[
[
"EDGE INJECTED SPEECH IN ELECTRONIC COMMUNICATIONS",
"Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for receiving an input from an agent during a call with a caller where the input directs one or more processors to inject a recorded statement in the age... | Patent_15874607 |
[
[
"TREATMENT TOOL FOR ENDOSCOPE",
"A treatment tool for an endoscope of the present invention includes a sheath, a balloon provided at the sheath and configured to be expandable to an inflated state from a reduced diameter state by injecting a fluid, a shaft member inserted through an inside of the balloon ... | Patent_15874608 |
[
[
"OPERATION METHOD OF COMMUNICATION NODE IN NETWORK",
"An operation method of communication node in a vehicle network is provided.",
"The operation method includes transitioning from a sleep mode to an active mode and generating a first message that includes a first information indicating at least one ... | Patent_15874609 |
[
[
"METHOD OF MANUFACTURING CORTICOSTERIOD CONTAINING FOAM COMPOSITIONS",
"The present invention provides a method of manufacturing foamable, corticosteroid containing compositions as well as methods for treating various skin diseases."
],
[
"1.A method for single-stream manufacture of a foamable com... | Patent_15874610 |
[
[
"SYSTEM AND METHOD FOR SYNTHESIS OF SPEECH FROM PROVIDED TEXT",
"A system and method are presented for the synthesis of speech from provided text.",
"Particularly, the generation of parameters within the system is performed as a continuous approximation in order to mimic the natural flow of speech as ... | Patent_15874612 |
[
[
"ATTACHMENT FOR ENDOSCOPE, ENDOSCOPE SYSTEM AND METHOD FOR INDWELLING INDWELLING TOOL IN LUMINAL TISSUE",
"An attachment for an endoscope includes: a tubular main body having a proximal end portion; a partition part provided in the main body, the partition part being provided at a position at which a dist... | Patent_15874620 |
[
[
"SKATE WITH INJECTED BOOT FORM",
"A boot form for a hockey skate is made of multiple plastic materials having different hardness properties, or different flexural moduli, and is formed via an injection-molding process or another similar process.",
"One or more of the plastic materials may be reinforce... | Patent_15874625 |
[
[
"GOLF BALL",
"An object of the present invention is to provide a golf ball traveling a great distance on driver shots.",
"The present invention provides a golf ball comprising a spherical core including an inner layer and an outer layer, an intermediate layer and a cover, wherein a difference (HX+1−HX... | Patent_15874628 |
[
[
"FOAMABLE RESIN COMPOSITION FOR FOAM SHEET, FOAM SHEET, PROCESS FOR PREPARING PARTICULATE POLYLACTIC ACID AND PROCESS FOR PREPARING FOAM SHEET",
"Disclosed herein is a foamable resin composition for a foam sheet including polylactic acid resin particles, each of the particles having a particle size of abo... | Patent_15874632 |
[
[
"SYSTEM AND METHOD FOR CONTROLLING LINEAR MOVEMENT USING A TAPERED MR VALVE",
"A tapered magnetorheological (MR) valve includes a first fixed housing that remains in a fixed position along a central axis of the tapered MR valve.",
"A second housing moves linearly along the central axis of the tapered ... | Patent_15874634 |
[
[
"HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN IL-4 RECEPTOR",
"The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R).",
"Also provided are expression vectors comprising nucleic acid mol... | Patent_15874635 |
[
[
"Display Control Method and Display Control Apparatus",
"Embodiments of the present application disclose a display control method and a display control apparatus, relating to the field of near-to-eye display technologies.",
"The method includes: determining a first display area, in the FOV of a user, ... | Patent_15874640 |
[
[
"COLLABORATIVE EXPERTISE NETWORKING SYSTEM AND METHOD",
"Embodiments are directed to an apparatus or method that includes among other features, a search engine configured to permit a user to search the profiles of other users, a storage medium configured to store the profile of the users such that the pro... | Patent_15874641 |
[
[
"PERFORMING A COMPARISON COMPUTATION IN A COMPUTER SYSTEM",
"A method and computer system are provided for performing a comparison computation, e.g.",
"for use in a check procedure for a reciprocal square root operation.",
"The comparison computation compares a multiplication of three values with ... | Patent_15874642 |
[
[
"MICROCARRIER PERFUSION CULTURING METHODS AND USES THEREOF",
"Provided herein are methods of perfusion culturing an adherent mammalian cell using a shake flask and a plurality of microcarriers, and various methods that utilize these culturing methods."
],
[
"1.A method of optimizing a manufacturin... | Patent_15874645 |
[
[
"GRADED-SEMICONDUCTOR IMAGE SENSOR",
"A method of image sensor fabrication includes growing a semiconductor material having an illuminated surface and a non-illuminated surface, where the semiconductor material includes silicon and germanium and a germanium concentration increases in a direction of the no... | Patent_15874648 |
[
[
"ADVANCED INTERCONNECT WITH AIR GAP",
"Ultra-low-k dielectric materials used as inter-layer dielectrics in high-performance integrated circuits are prone to be structurally unstable.",
"The Young's modulus of such materials is decreased, resulting in porosity, poor film strength, cracking, and voids."... | Patent_15874654 |
[
[
"DETECTION NETWORK SELF-DISCOVERY",
"Systems and methods for detecting the presence of a body in a network without fiducial elements, using signal absorption, and signal forward and reflected backscatter of radio frequency (RF) waves caused by the presence of a biological mass in a communications network.... | Patent_15874657 |
[
[
"Passenger Transport Carriers",
"A child transport carrier includes an upper frame member having a forward end and a rear end and a rear frame coupled to the upper frame member.",
"The rear frame includes a lower rear frame member, an upper rear frame member having an upper end fixedly coupled to the ... | Patent_15874658 |
[
[
"BATTERY MODULE COMPRESSED CELL ASSEMBLY",
"The present disclosure relates to a stacked cell manufacturing scheme for battery modules.",
"A disclosed method of manufacturing a battery module includes assembling a plurality of prismatic battery cells of the battery module into a cell stack.",
"The ... | Patent_15874661 |
[
[
"CURTAIN WALL SADDLE BRACKET AND CLIP ASSEMBLY",
"A bracket for securing insulation and/or a stiffener relative to a mullion or transom having a given width.",
"The bracket includes a pair of legs extending from a bridge to define a receiving channel having a width equal to or smaller than the given w... | Patent_15874663 |
[
[
"ARRANGEMENT WITH A MEMS DEVICE AND METHOD OF MANUFACTURING",
"An arrangement and a production method for the arrangement with at least one MEMS device, which comprises a package that closely encloses the MEMS device and seals it from ambient influences.",
"The package comprises as sealing a PFPE laye... | Patent_15874664 |
[
[
"VISUALIZING CHANGES IN A MULTI-DIMENSIONAL DATASET USING THREE-DIMENSIONAL CUBES",
"A method, system and computer program product for visualizing changes in a multi-dimensional dataset.",
"A multi-dimensional dataset of discrete data, such as online analytical processing based multi-dimensional data,... | Patent_15874667 |
[
[
"METHOD AND APPARATUS FOR TRANSMITTING ACK/NACK SIGNAL IN WIRELESS COMMUNICATION SYSTEM",
"The present invention relates to a method and apparatus for transmitting an acknowledgement/not-acknowledgement (ACK/NACK) signal in a wireless communication system.",
"The method includes the steps of: receivin... | Patent_15874668 |
[
[
"Method of improving measurement speed of distributed optical fiber sensor by adopting orthogonal signals and system thereof",
"A method of improving measurement speed of distributed optical fiber sensors by adopting orthogonal signals and the system thereof is disclosed, which is related to the optical f... | Patent_15874672 |
[
[
"POWER ADAPTATION BASED ON ERROR RATE",
"A host device is configured to increase the power output by an internal amplifier of its wireless chipset in response to requests from a remote device.",
"Once the internal amplifier has reached its maximum power, further requests for power increases from the r... | Patent_15874678 |
[
[
"SELF-ALIGNED REPLACEMENT METAL GATE SPACERLESS VERTICAL FIELD EFFECT TRANSISTOR",
"A method of making a vertical field effect transistor includes forming a semiconductor nanowire that extends from a substrate surface.",
"A first sacrificial layer is deposited over the substrate surface, and a second ... | Patent_15874680 |
[
[
"BACKLIGHT UNIT AND DISPLAY DEVICE HAVING BACKLIGHT UNIT",
"A display device including a display panel; a frame at a rear of the display panel, the frame including a bottom and a sidewall extending from the bottom; a substrate on the frame; a plurality of light sources mounted on the substrate; and a refl... | Patent_15874682 |
[
[
"IDENTIFICATION OF AREAS OF INTEREST DURING INTRAORAL SCANS",
"A processing device receives a first virtual 3D model and a second virtual 3D model, each comprising one or more teeth of a patient.",
"The processing device compares the first virtual 3D model to the second virtual 3D model and determines... | Patent_15874686 |
[
[
"SENSING FOR COMPENSATION OF PIXEL VOLTAGES",
"A display device may include rows of pixels that may display image data on a display and a circuit.",
"The circuit may perform a progressive scan across the rows of pixels to display the image data using a plurality of pixels, supply test data to a pixel ... | Patent_15874687 |
[
[
"DETECT AND DIFFERENTIATE TOUCHES FROM DIFFERENT SIZE CONDUCTIVE OBJECTS ON A CAPACITIVE BUTTON",
"Apparatuses and methods of distinguishing between a finger and stylus proximate to a touch surface are described.",
"One apparatus includes a first circuit to obtain capacitance measurements of sense ele... | Patent_15874705 |
[
[
"Service Takeover Method, Storage Device, And Service Takeover Apparatus",
"The present disclosure describes example service takeover methods, storage devices, and service takeover apparatuses.",
"In one example, when a communication fault occurs between two storage devices in a storage system, the tw... | Patent_15874722 |
[
[
"Decoding Instructions That Are Modified By One Or More Other Instructions",
"Methods and apparatus are provided for decoding instructions in a computer program wherein the instructions include one or more base instructions that are subject to modification by one or more other instructions.",
"A decod... | Patent_15874724 |
[
[
"METHOD AND DEVICE FOR SEPARATING AND TRANSFERRING PELLETS",
"A pellet column is formed in a metering duct.",
"The lowermost pellet is located in a connection point where an outlet duct is connected to the metering duct and leads transversely away therefrom.",
"A first duct, which opens into the m... | Patent_15874732 |
[
[
"POWER SUPPLY SYSTEM AND SHORT CIRCUIT AND/OR BAD CONNECTION DETECTION METHOD THEREOF, AND POWER CONVERTER THEREOF",
"The present invention discloses a short circuit and/or bad connection detection method for use in a power supply system.",
"The power supply system includes a power converter which con... | Patent_15874733 |
[
[
"METHOD AND APPARATUS FOR RECEIVING OR TRANSMITTING DOWNLINK CONTROL SIGNAL IN WIRELESS COMMUNICATION SYSTEM",
"Provided is a method for receiving a downlink signal by a user equipment (UE) in a wireless communication system according to one embodiment of the present disclosure, comprising: receiving a pl... | Patent_15874736 |
[
[
"DATA ENCODING AND DECODING",
"A video coding or decoding method using inter-image prediction to encode input video data in which each chrominance component has 1/Mth of the horizontal resolution of the luminance component and 1/Nth of the vertical resolution of the luminance component, where M and N are ... | Patent_15874737 |
[
[
"CAMERA CONTROL INTERFACE SLAVE DEVICE TO SLAVE DEVICE COMMUNICATION",
"In a shared bus where communications are managed by a master device, direct slave device to slave device (S2S) communications is implemented.",
"A first slave device wanting to communicate with a second slave device may make a S2S... | Patent_15874739 |
[
[
"PHASE SHIFT AND ATTENUATION CIRCUITS FOR USE WITH MULTIPLE-PATH AMPLIFIERS",
"Embodiments of circuits for use with an amplifier that includes multiple amplifier paths include a first circuit and a second circuit in parallel with the first circuit.",
"The first circuit includes a first input coupled t... | Patent_15874740 |
[
[
"REMANUFACTURING METHOD OF DEVELOPER ACCOMMODATING UNIT",
"Provided is a remanufacturing method of a developer accommodating unit including a flexible container provided with an opening and configured to accommodate developer, and a frame member configured to accommodate the flexible container.",
"The... | Patent_15874741 |
[
[
"SMART STORAGE OF TEMPERATURE SENSITIVE PHARMACEUTICALS",
"A refrigerator and/or freezer unit and system for storing, monitoring, and maintaining a supply of temperature sensitive pharmaceutical products in compliance with regulatory requirements.",
"The unit contains compartments for each product typ... | Patent_15874742 |
[
[
"PLASMA ETCHING DEVICE WITH PLASMA ETCH RESISTANT COATING",
"A method for coating a part body for use in a plasma processing chamber is provided.",
"The part body is received into a chamber.",
"At least part of a surface of the part body is coated by physical vapor deposition or chemical vapor dep... | Patent_15874744 |
[
[
"PREPARATION OF (R,R)-FENOTEROL AND (R,R)- OR (R,S)-FENOTEROL ANALOGUES AND THEIR USE IN TREATING CONGESTIVE HEART FAILURE",
"This disclosure concerns the discovery of (R,R)- and (R,S)-fenoterol analogues which are highly effective at binding β2-adrenergic receptors.",
"Exemplary chemical structures f... | Patent_15874747 |
[
[
"AUTONOMOUS FLUID INSTILLATION SYSTEM AND METHOD WITH TISSUE SITE PRESSURE MONITORING",
"A system and method for providing fluid to a tissue site is described.",
"The method fluidly couples an instillation therapy system to the tissue site and monitors a pressure supplied to the tissue site by a reduc... | Patent_15874749 |
[
[
"Linear Solid-State Lighting With Low Voltage Control Free Of Electric Shock And Fire Hazard",
"A linear light-emitting diode (LED) lamp comprising a housing, two lamp bases at two ends of the housing, a full-wave rectifier, an LED driving circuit, one or more LED arrays, at least two proximity sensors, a... | Patent_15874752 |
[
[
"HIGH CONDUCTIVITY GRAPHENE-METAL COMPOSITE",
"Embodiments of the present technology include graphene-metal composites.",
"An example graphene-metal composite comprises a porous metal foam substrate, a graphene layer deposited to the porous metal foam substrate, a metal layer applied to the graphene l... | Patent_15874753 |
[
[
"JUICE EXTRACTION MODULE FOR JUICER",
"A juice extraction module for a juicer is provided, which includes a container formed with a juice discharge port, a sieve positioned inside of the container, a screw positioned inside of the sieve to extract juice from a material, and a lid coupled to a top end of t... | Patent_15874756 |
[
[
"POSTERIOR CAPSULOTOMY USING LASER TECHNIQUES",
"A system and method are provided for removing a natural lens and inserting an Intraocular Lens (IOL) into the lens capsule of an eye.",
"Specifically, this is accomplished by inserting the IOL through an opening on the posterior capsule that is created ... | Patent_15874759 |
[
[
"APPLIANCE, MOTOR OR STATOR",
"A motor suited for use in a direct drive laundry machine.",
"The described motor has a stator core including an annular ring with an inner diameter between 120 mm and 250 mm, a radial width between 5 mm and 15 mm, and 24 or 27 stator poles projecting outward from the ann... | Patent_15874764 |
[
[
"SOFT LANDING NANOLAMINATES FOR ADVANCED PATTERNING",
"Methods for depositing nanolaminate protective layers over a core layer to enable deposition of high quality conformal films over the core layer for use in advanced multiple patterning schemes are provided.",
"In certain embodiments, the methods i... | Patent_15874766 |
[
[
"PYRIDINE COMPOUNDS",
"The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity.",
"The present invention provides a compound represented by the formula (I): wherein R1 represents a hydrogen... | Patent_15874768 |
[
[
"ROOFING SYSTEMS AND METHODS",
"A method includes providing a production line configured for continuous fabrication of polymer or predominantly polymer roofing boards by setting and expansion of precursor materials on a conveyor.",
"A first polymer or predominantly polymer material foam precursor is d... | Patent_15874770 |
[
[
"THREAT DETECTION AND MITIGATION THROUGH RUN-TIME INTROSPECTION AND INSTRUMENTATION",
"A graph of a plurality of resources in a computing environment is generated, with the graph associating a first resource of the plurality with a second resource of the plurality.",
"Based at least in part on measure... | Patent_15874771 |
[
[
"DRYERS FOR REMOVING SOLVENT FROM A DRUG-ELUTING COATING APPLIED TO MEDICAL DEVICES",
"A coating device for coating a medical device with a drug-eluting material uses an in-process drying station between coats to improve a drug release profile.",
"The drying station includes a dryer having a telescopi... | Patent_15874772 |
[
[
"TRANSFORMABLE SPEECH PROCESSOR MODULE FOR A HEARING PROSTHESIS",
"A method for operating an external component of a cochlear implant hearing system.",
"The external component includes a speech processor module operable in a stand-alone mode of operation and a body-worn mode of operation, and a protec... | Patent_15874774 |
[
[
"GROOVE PATTERN FOR A PUTTER HEAD",
"A putter head is provided.",
"The putter head includes a putter face defining a groove pattern extending in a heel-to-toe direction of the putter face.",
"The groove pattern includes multiple sets of grooves spaced apart from one another in a vertical direction... | Patent_15874776 |
[
[
"DUAL ANTI-PLATELET MEDICATION/ASPIRIN RESPONSE AND REACTIVITY TEST USING SYNTHETIC COLLAGEN",
"The present invention provides tests that measures functional platelet aggregation such as by using Light Transmission Aggregometry Assays (LTAAs) or flow cytometry, using synthetic, self-assembling human type ... | Patent_15874780 |
[
[
"Dynamic Bridging of Interface Protocols",
"Systems and methods for protocol bridging for a system level modeling simulation (SLMS), such as a SYSTEMC simulation where the components communicate using a TLM2.0 application programming interface (API).",
"The method includes accessing design configurati... | Patent_15874781 |